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Philip AE, Singh H, Nanjundiah SY, Samudrala PC, Theunissen DW, Robinson J, Banerjee I. Impact of Exercise on Perimenopausal Syndrome: A Systematic Review of Randomized Controlled Trials. Cureus 2025; 17:e80862. [PMID: 40255746 PMCID: PMC12008710 DOI: 10.7759/cureus.80862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2025] [Indexed: 04/22/2025] Open
Abstract
Exercise has been contemplated as a natural means to alleviate the symptoms of perimenopause. The need for this study arises from the lack of data regarding the impact of exercise on the perimenopausal population. The primary objective of this systematic review of randomized controlled trials was to evaluate the impact of exercise in improving various symptoms of perimenopause, including hot flushes, insomnia, paresthesia, myalgia, arthralgia, palpitations, fatigue, headache, depression, vaginal dryness, and irritability in perimenopausal women. An extensive literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, examining the impact of exercise on relieving perimenopausal syndrome. The assessment was based on the readings of the Blatt-Kupperman Index (KI), a scale in which 11 symptoms of perimenopause are rated from 0 (absence of symptom) to 3 (severe). Based on the studies, there was a considerable reduction in the total KI score from baseline by 15.7%. Paresthesia and irritability reduced by 2 points on the scale and showed the greatest improvement. Headache, myalgia, fatigue, hot flushes, and insomnia decreased from an average score of 2 to 1. There was no significant improvement in psychiatric disorders such as depression. Furthermore, its efficacy in treating hot flushes is yet to be established, as discrepancies exist in the results. Exercise has been proven effective in treating mild to moderate perimenopausal symptoms. However, skepticism remains regarding its effectiveness in treating vasomotor symptoms, and further scrutiny is needed to establish it as a viable and effective therapy.
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Affiliation(s)
- Ashima Elsa Philip
- Obstetrics and Gynaecology, Sir Seewoosagur Ramgoolam Medical College, Belle Rive, MUS
| | - Hutesh Singh
- Obstetrics and Gynaecology, Sir Seewoosagur Ramgoolam Medical College, Belle Rive, MUS
| | | | | | - De Wet Theunissen
- Obstetrics and Gynaecology, Sir Seewoosagur Ramgoolam Medical College, Belle Rive, MUS
| | - Jared Robinson
- Surgery, Sir Seewoosagur Ramgoolam Medical College, Belle Rive, MUS
| | - Indrajit Banerjee
- Pharmacology, Sir Seewoosagur Ramgoolam Medical College, Belle Rive, MUS
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2
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Zanini BM, de Avila BM, Garcia DN, Hense JD, Veiga GB, Barreto MM, Ashiqueali S, Mason JB, Yadav H, Masternak M, Schneider A. Dynamics of serum exosome microRNA profile altered by chemically induced estropause and rescued by estrogen therapy in female mice. GeroScience 2024; 46:5891-5909. [PMID: 38499957 PMCID: PMC11493931 DOI: 10.1007/s11357-024-01129-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 03/09/2024] [Indexed: 03/20/2024] Open
Abstract
The decline in the ovarian reserve leads to menopause and reduced serum estrogens. MicroRNAs are small non-coding RNAs, which can regulate gene expression and be secreted by cells and trafficked in serum via exosomes. Serum miRNAs regulate tissue function and disease development. Therefore, the aim of this study was to identify miRNA profiles in serum exosomes of mice induced to estropause and treated with 17β-estradiol (E2). Female mice were divided into three groups including control (CTL), injected with 4-Vinylcyclohexene diepoxide (VCD), and injected with VCD plus E2 (VCD + E2). Estropause was confirmed by acyclicity and a significant reduction in the number of ovarian follicles (p < 0.05). Body mass gain during estropause was higher in VCD and VCD + E2 compared to CTL females (p = 0.02). Sequencing of miRNAs was performed from exosomes extracted from serum, and 402 miRNAs were detected. Eight miRNAs were differentially regulated between CTL and VCD groups, seven miRNAs regulated between CTL and VCD + E2 groups, and ten miRNAs regulated between VCD and VCD + E2 groups. Only miR-200a-3p and miR-200b-3p were up-regulated in both serum exosomes and ovarian tissue in both VCD groups, suggesting that these exosomal miRNAs could be associated with ovarian activity. In the hepatic tissue, only miR-370-3p (p = 0.02) was up-regulated in the VCD + E2 group, as observed in serum. Our results suggest that VCD-induced estropause and E2 replacement have an impact on the profile of serum exosomal miRNAs. The miR-200 family was increased in serum exosomes and ovarian tissue and may be a candidate biomarker of ovarian function.
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Affiliation(s)
| | | | | | - Jéssica Damé Hense
- Faculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil
| | | | | | - Sarah Ashiqueali
- College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA
| | - Jeffrey B Mason
- College of Veterinary Medicine, Department of Veterinary Clinical and Life Sciences, Center for Integrated BioSystems, Utah State University, Logan, UT, USA
| | - Hariom Yadav
- USF Center for Microbiome Research, and Department of Neurosurgery and Brain Repair, Microbiomes Institute, University of South Florida, Tampa, FL, USA
| | - Michal Masternak
- Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL, USA
- Department of Head and Neck Surgery, Poznan University of Medical Sciences, Poznan, Poland
| | - Augusto Schneider
- Faculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
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Fathy N, Labib MA, Essam RM, El-Boghdady NA. The Interplay between MiR-134/BDNF and LKB1/AMPK/SIRT1 Accentuates the Antidepressant Efficacy of Empagliflozin in Ovariectomized Rats. ACS Chem Neurosci 2024. [PMID: 39350330 DOI: 10.1021/acschemneuro.4c00313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Major depressive disorder (MDD) is considered a major cause of suicide worldwide. As previous studies revealed that neuroinflammation is a significant factor in the etiology of MDD, this study proposed to unravel the possible antidepressant effect of Empagliflozin (EMPA) through targeting miRNA-134 (miR-134)/brain-derived neurotrophic factor (BDNF) and liver kinase B1 (LKB1)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) axes in ovariectomized (OVX) female rats. Rats were assigned randomly to four groups: Sham operation (SO), OVX, OVX + EMPA (10 mg/kg/day, p.o.), and OVX + EMPA + Dorsomorphin (DORSO) (25 μg/day/rat, i.v.). Drugs were administered for 28 days after 2 weeks of surgery. EMPA debilitated OVX-induced depressive-like behavior by mitigating the immobility time in the tail suspension test and forced swimming test. Moreover, EMPA curtailed OVX-induced alterations of serum estradiol, hippocampal serotonin, miR-134 expression, as well as BDNF. EMPA also dwindled OVX-induced changes of hippocampal p-LKB1/LKB1, p-AMPK/AMPK, SIRT1, and inflammatory markers (nuclear factor-kappa-B, interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha). Additionally, the EMPA-treated group exhibited marked improvement in different brain regions' histopathology. However, DORSO coadministration reversed most of EMPA's beneficial effects. The current study displayed the modulatory role of EMPA on miR-134/BDNF and LKB1/AMPK/SIRT1 axes, thus offering a partial explanation of its antidepressant efficacy and proposing EMPA as a novel therapeutic avenue for MDD.
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Affiliation(s)
- Nevine Fathy
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Merna A Labib
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Reham M Essam
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Biology Department, School of Pharmacy, Newgiza University, Giza 3296121, Egypt
| | - Noha A El-Boghdady
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
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Park H, Ha H, Lee H, Lee G, Go GW, Yoon TM, Kim TY, Kim W. Alleviation of Menopausal Symptoms by Yam (Dioscorea japonica Thunb.) and Gromwell (Lithospermum erythrorhizon Sieb. Et Zucc.) Extracts in Ovariectomized Mice. Mol Nutr Food Res 2024; 68:e2400158. [PMID: 38934532 DOI: 10.1002/mnfr.202400158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 06/12/2024] [Indexed: 06/28/2024]
Abstract
SCOPE The decline in estrogen during menopause contributes to a variety of menopausal symptoms, for which hormone replacement therapy (HRT) has been extensively applied. Regarding side effects and limited effectiveness of HRT for specific individuals, there is a growing interest in safe alternatives such as phytoestrogens which are structurally analogous to estrogens. This study aims to investigate the efficacy of yam and gromwell extracts, rich in bioactive compounds, and the synergistic effect of extracts on symptoms induced by estrogen deficiency in ovariectomized (OVX) mice. METHODS AND RESULTS OVX mice receive dietary intervention of either yam, gromwell extract, or their mixture for 14 weeks. Sham-operated mice and E2-injected OVX mice serve as positive controls. Following 14 weeks of oral administration, blood, adipose tissue, vagina, uterus, femurs, and tibias are harvested for further investigation. Consequently, yam and gromwell extracts ameliorate menopausal conditions such as weight gain, glucose intolerance, dyslipidemia, and osteoporosis in estrogen-deficient OVX mice. In addition, the mixture of yam and gromwell extracts synergistically aids in the relief of the indications. CONCLUSION These results indicate the potential use of yam and gromwell extracts, as well as their mixture, for the development of healthy functional foods to modulate menopausal symptoms.
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Affiliation(s)
- Hyejeong Park
- Department of Food Science and Biotechnology, Kyung Hee University, Yongin, 17104, Republic of Korea
| | - Hyunju Ha
- Department of Food Science and Biotechnology, Kyung Hee University, Yongin, 17104, Republic of Korea
| | - Hyeji Lee
- Department of Food Science and Biotechnology, Kyung Hee University, Yongin, 17104, Republic of Korea
| | - Gyeongwhan Lee
- Department of Food Science and Biotechnology, Kyung Hee University, Yongin, 17104, Republic of Korea
| | - Gwang-Woong Go
- Department of Food and Nutrition, Hanyang University, Seoul, 04763, Republic of Korea
| | - Tae Mi Yoon
- Antimicrobial Materials Lab., Dynesoze Co., Ltd., R&D Center, Yongin, 16827, Republic of Korea
| | - Tae Yeol Kim
- Antimicrobial Materials Lab., Dynesoze Co., Ltd., R&D Center, Yongin, 16827, Republic of Korea
| | - Wooki Kim
- Department of Food and Nutrition, Yonsei University, Seoul, 03722, Republic of Korea
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Lim AMW, Lim EU, Chen PL, Fann CSJ. Unsupervised clustering identified clinically relevant metabolic syndrome endotypes in UK and Taiwan Biobanks. iScience 2024; 27:109815. [PMID: 39040048 PMCID: PMC11260869 DOI: 10.1016/j.isci.2024.109815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 02/02/2024] [Accepted: 04/23/2024] [Indexed: 07/24/2024] Open
Abstract
Metabolic syndrome (MetS) is a collection of cardiovascular risk factors; however, the high prevalence and heterogeneity impede effective clinical management. We conducted unsupervised clustering on individuals from UK Biobank to reveal endotypes. Five MetS subgroups were identified: Cluster 1 (C1): non-descriptive, Cluster 2 (C2): hypertensive, Cluster 3 (C3): obese, Cluster 4 (C4): lipodystrophy-like, and Cluster 5 (C5): hyperglycemic. For all of the endotypes, we identified the corresponding cardiometabolic traits and their associations with clinical outcomes. Genome-wide association studies (GWASs) were conducted to identify associated genotypic traits. We then determined endotype-specific genotypic traits and constructed polygenic risk score (PRS) models specific to each endotype. GWAS of each MetS clusters revealed different genotypic traits. C1 GWAS revealed novel findings of TRIM63, MYBPC3, MYLPF, and RAPSN. Intriguingly, C1, C3, and C4 were associated with genes highly expressed in brain tissues. MetS clusters with comparable phenotypic and genotypic traits were identified in Taiwan Biobank.
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Affiliation(s)
- Aylwin Ming Wee Lim
- Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, Taiwan
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
- ASUS Intelligent Cloud Services (AICS), Taipei 112, Taiwan
| | - Evan Unit Lim
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
- College of Computing, Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Pei-Lung Chen
- Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 10617, Taiwan
- Department of Medical Genetics, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Cathy Shen Jang Fann
- Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, Taiwan
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
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Hsu JH, Lee JI, Huang SP, Chen SC, Geng JH. Coffee consumption was associated with a lower prevalence of airflow limitation in postmenopausal women. Respir Investig 2024; 62:623-630. [PMID: 38723441 DOI: 10.1016/j.resinv.2024.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 04/22/2024] [Accepted: 05/02/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND Several studies have suggested a potential correlation between menopause and airflow limitation. However, the presence of protective factors in postmenopausal women remains uncertain. Therefore, our study seeks to examine potential protective factors associated with a reduced prevalence of airflow limitation among postmenopausal women. METHODS Postmenopausal women were recruited from the Taiwan Biobank for this cross-sectional study. Airflow limitation was defined by a forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio <0.7. The participants were categorized into two groups: non-coffee drinkers and coffee drinkers, and the association between coffee consumption and airflow limitation was examined using binary logistic regression models. RESULTS A total of 8149 women with available information were enrolled. Compared to the non-coffee drinkers, the coffee drinkers had a significantly lower prevalence of airflow limitation (7% vs. 5%). The odds ratio (OR) for airflow limitation was lower in the coffee drinkers than in the non-coffee drinkers (OR = 0.77; 95% confidence interval [CI] = 0.63 to 0.94) after adjusting for confounding factors. We also examined the association between daily coffee consumption in cups and airflow limitation. The women who consumed ≥2 cups of coffee per day had an OR of 0.74 (95% CI = 0.59 to 0.94) compared to those who did not consume coffee. CONCLUSIONS Our results suggest that habitual coffee consumption is associated with a reduction in the prevalence of airflow limitation in postmenopausal women, warranting further prospective studies to explore possible causal effects and mechanisms.
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Affiliation(s)
- Jui-Hung Hsu
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Jia-In Lee
- Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
| | - Shu-Pin Huang
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University 807378, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; Institute of Medical Science and Technology, College of Medicine, National Sun Yat-Sen University, Kaohsiung 804201, Taiwan
| | - Szu-Chia Chen
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University 812015, Kaohsiung, Taiwan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Jiun-Hung Geng
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University 807378, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812015, Taiwan.
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7
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Corbi G, Comegna M, Vinciguerra C, Capasso A, Onorato L, Salucci AM, Rapacciuolo A, Cannavo A. Age and sex mediated effects of estrogen and Β3-adrenergic receptor on cardiovascular pathophysiology. Exp Gerontol 2024; 190:112420. [PMID: 38588751 DOI: 10.1016/j.exger.2024.112420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/29/2024] [Accepted: 04/05/2024] [Indexed: 04/10/2024]
Abstract
Sex differences are consistently identified in determining the prevalence, manifestation, and response to therapies in several systemic disorders, including those affecting the cardiovascular (CV), skeletal muscle, and nervous system. Interestingly, such differences are often more noticeable as we age. For example, premenopausal women experience a lower risk of CV disease than men of the same age. While at an advanced age, with menopause, the risk of cardiovascular diseases and adverse outcomes increases exponentially in women, exceeding that of men. However, this effect appears to be reversed in diseases such as pulmonary hypertension, where women are up to seven times more likely than men to develop an idiopathic form of the disease with symptoms developing ten years earlier than their male counterparts. Explaining this is a complex question. However, several factors and mechanisms have been identified in recent decades, including a role for sex hormones, particularly estrogens and their related receptors. Furthermore, an emerging role in these sex differences has also been suggested for β-adrenergic receptors (βARs), which are essential regulators of mammalian physiology. It has in fact been shown that βARs interact with estrogen receptors (ER), providing further demonstration of their involvement in determining sexual differences. Based on these premises, this review article focused on the β3AR subtype, which shows important activities in adipose tissue but with new and interesting roles in regulating the function of cardiomyocytes and vascular cells. In detail, we examined how β3AR and ER signaling are intertwined and whether there would be sex- and age-dependent specific effects of these receptor systems.
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Affiliation(s)
- Graziamaria Corbi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Marika Comegna
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy; CEINGE-Advanced Biotechnologies - Franco Salvatore, Naples, Italy
| | - Caterina Vinciguerra
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Alessio Capasso
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Luigi Onorato
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | | | - Antonio Rapacciuolo
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Alessandro Cannavo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
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Pszczołowska M, Walczak K, Miśków W, Mroziak M, Kozłowski G, Beszłej JA, Leszek J. Association between Female Reproductive Factors and Risk of Dementia. J Clin Med 2024; 13:2983. [PMID: 38792524 PMCID: PMC11122498 DOI: 10.3390/jcm13102983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/07/2024] [Accepted: 05/16/2024] [Indexed: 05/26/2024] Open
Abstract
Women have an over 50% greater risk of dementia than men, which is a main topic of much research. This review aims to investigate the impact of a woman's reproductive history on dementia risk. The consequences of stillbirth are long-term health and psychosocial problems for women. Because of the awareness of an endangered pregnancy, many parents experience deep anxiety and stress in subsequent pregnancies. There are contradictory conclusions from research about abortion and the risk of dementia correlation. When it comes to the late age of first birth, which is said to be above 35 years old, it was observed that older mothers have a decreased risk of dementia compared to those who gave birth in their 20s; however, being a child of the older mother is connected with a higher risk of developing dementia. Using hormonal contraception can result in decreased risk of dementia as estrogen stimulates microglia-related Aβ removal and reduces tau hyperphosphorylation. The influence of postmenopausal hormonal therapy and the duration of the reproductive period on developing dementia remains unclear. Although female disorders like endometriosis and polycystic ovary syndrome are reported to increase the risk of dementia, the research on this topic is very limited, especially when it comes to endometriosis, and needs further investigation. Interestingly, there is no conclusion on whether hypertensive disorders of pregnancy increase the risk of dementia, but most articles seem to confirm this theory.
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Affiliation(s)
| | - Kamil Walczak
- Faculty of Medicine, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Weronika Miśków
- Faculty of Medicine, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Magdalena Mroziak
- Faculty of Medicine, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Gracjan Kozłowski
- Faculty of Medicine, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Jan Aleksander Beszłej
- Clinic of Psychiatry, Department of Psychiatry, Medical Department, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Jerzy Leszek
- Clinic of Psychiatry, Department of Psychiatry, Medical Department, Wrocław Medical University, 50-367 Wrocław, Poland
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Joris A, Di Pietrantonio V, Praet J, Renard K, Verduyn AC, Buxant F, Rozenberg S. Randomized trial: treatment of genitourinary syndrome of menopause using radiofrequency. Climacteric 2024; 27:210-214. [PMID: 38251861 DOI: 10.1080/13697137.2024.2302425] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 12/20/2023] [Indexed: 01/23/2024]
Abstract
OBJECTIVE A randomized controlled study was conducted to evaluate the safety and efficacy of radiofrequency treatment in postmenopausal women not willing to use or presenting a contraindication for menopause hormone therapy (MHT) and suffering from genitourinary syndrome of menopause (GSM). METHODS A prospective randomized open study evaluated the effect of radiofrequency treatment versus a gel (control group) in postmenopausal women suffering from GSM. Patients were assessed at baseline and after 10-12 weeks of treatment for severity of vulvovaginal atrophy, dyspareunia, pH, vaginal smear maturation index, Vaginal Health Index and Female Sexual Function Index. The difference at baseline and after 10-12 weeks of treatment and the difference in improvement were tested between groups by a two-sample t-test and the Mann-Whitney test. RESULTS Due to the COVID-19 pandemic, we were only able to treat 48 patients (24 patients using radiofrequency and 24 patients using a gel). Globally, at the end of the study, there were no differences in changes of the measured outcomes between the group of women treated with radiofrequency and the control group. CONCLUSION Radiofrequency treatment was found to be safe, but was not superior to a gel, although the study lacked power. The study was registered at ClinicalTrials.gov (NCT03857893).
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Affiliation(s)
- A Joris
- Department of Obstetrics and Gynecology CHU St Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | - V Di Pietrantonio
- Department of Obstetrics and Gynecology CHU St Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | - J Praet
- Department of Obstetrics and Gynecology CHU St Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | - K Renard
- Department of Obstetrics and Gynecology CHU St Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | - A-C Verduyn
- Department of Obstetrics and Gynecology CHU St Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | - F Buxant
- Department of Obstetrics and Gynecology CHU St Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | - S Rozenberg
- Department of Obstetrics and Gynecology HIS, Université Libre de Bruxelles, Ixelles, Belgium
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10
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Na Z, Wei W, Xu Y, Li D, Yin B, Gu W. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis. Open Life Sci 2023; 18:20220759. [PMID: 38152576 PMCID: PMC10752002 DOI: 10.1515/biol-2022-0759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/08/2023] [Accepted: 10/02/2023] [Indexed: 12/29/2023] Open
Abstract
The use of menopausal hormone therapy (MHT) has declined due to concerns about its potential side effects. However, its pivotal role in managing postmenopausal osteoporosis is gaining increased recognition. In this article, we explore how MHT assists postmenopausal women in maintaining bone health and preventing fractures. Recent research indicates that MHT significantly reduces the risk of fractures in women. This benefit is evident regardless of a woman's bone mineral density or their use of progestogens. However, there is limited evidence suggesting that the skeletal benefits continue once the treatment is discontinued. Possible complications of MHT include heart attacks, clots, strokes, dementia, and breast cancer. The most suitable candidates for MHT are women who have recently entered menopause, are experiencing menopausal symptoms, and are below 60 years of age with a minimal baseline risk of adverse events. The treatment is available to those who meet these criteria. For women undergoing premature menopause, MHT can be considered as a means to protect bone health, especially if initiated before menopause or if accelerated bone loss is documented soon after menopause. Such decisions should be made after evaluating individual risk factors and benefits.
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Affiliation(s)
- Zhao Na
- Department of Gynecology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, 215500, China
| | - Wei Wei
- Department of Orthopaedics, Changshu Hospital Affiliated to Soochow University, First People’s Hospital of Changshu City, Changshu, 215500, China
| | - Yingfang Xu
- Department of Gynecology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, 215500, China
| | - Dong Li
- Department of Obstetrics and Gynecology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou No. 7 People’s Hospital, Changzhou, 213000, China
| | - Beili Yin
- Department of Gynecology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, 215500, China
| | - Weiqun Gu
- Department of Gynecology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, 215500, China
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Li J, Xiong M, Fu XH, Fan Y, Dong C, Sun X, Zheng F, Wang SW, Liu L, Xu M, Wang C, Ping J, Che S, Wang Q, Yang K, Zuo Y, Lu X, Zheng Z, Lan T, Wang S, Ma S, Sun S, Zhang B, Chen CS, Cheng KY, Ye J, Qu J, Xue Y, Yang YG, Zhang F, Zhang W, Liu GH. Determining a multimodal aging clock in a cohort of Chinese women. MED 2023; 4:825-848.e13. [PMID: 37516104 DOI: 10.1016/j.medj.2023.06.010] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/25/2023] [Accepted: 06/30/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND Translating aging rejuvenation strategies into clinical practice has the potential to address the unmet needs of the global aging population. However, to successfully do so requires precise quantification of aging and its reversal in a way that encompasses the complexity and variation of aging. METHODS Here, in a cohort of 113 healthy women, tiled in age from young to old, we identified a repertoire of known and previously unknown markers associated with age based on multimodal measurements, including transcripts, proteins, metabolites, microbes, and clinical laboratory values, based on which an integrative aging clock and a suite of customized aging clocks were developed. FINDINGS A unified analysis of aging-associated traits defined four aging modalities with distinct biological functions (chronic inflammation, lipid metabolism, hormone regulation, and tissue fitness), and depicted waves of changes in distinct biological pathways peak around the third and fifth decades of life. We also demonstrated that the developed aging clocks could measure biological age and assess partial aging deceleration by hormone replacement therapy, a prevalent treatment designed to correct hormonal imbalances. CONCLUSIONS We established aging metrics that capture systemic physiological dysregulation, a valuable framework for monitoring the aging process and informing clinical development of aging rejuvenation strategies. FUNDING This work was supported by the National Natural Science Foundation of China (32121001), the National Key Research and Development Program of China (2022YFA1103700 and 2020YFA0804000), the National Natural Science Foundation of China (81502304), and the Quzhou Technology Projects (2022K46).
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Affiliation(s)
- Jiaming Li
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Muzhao Xiong
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Xiang-Hong Fu
- Center for Reproductive Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China; Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Yanling Fan
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China
| | - Chen Dong
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing 100876, China
| | - Xiaoyan Sun
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Fang Zheng
- Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Si-Wei Wang
- Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Lixiao Liu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Ming Xu
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing 100876, China
| | - Cui Wang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Jiale Ping
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Shanshan Che
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Qiaoran Wang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Kuan Yang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Yuesheng Zuo
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaoyong Lu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Zikai Zheng
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Tian Lan
- Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Si Wang
- Aging Biomarker Consortium, Beijing 100101, China; Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Shuai Ma
- Aging Biomarker Consortium, Beijing 100101, China; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
| | - Shuhui Sun
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
| | - Bin Zhang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China
| | - Chen-Shui Chen
- Department of Respiratory and Critical Care Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China; Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Ke-Yun Cheng
- Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Jinlin Ye
- Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Jing Qu
- Aging Biomarker Consortium, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
| | - Yongbiao Xue
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China
| | - Yun-Gui Yang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
| | - Feng Zhang
- Center for Reproductive Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China; The Joint Innovation Center for Engineering in Medicine, Quzhou People's Hospital, Quzhou 324000, China; Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
| | - Weiqi Zhang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; Aging Biomarker Consortium, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China.
| | - Guang-Hui Liu
- Aging Biomarker Consortium, Beijing 100101, China; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
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12
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Ye B, Yuan Y, Liu R, Zhou H, Li Y, Sheng Z, Li T, Zhang B, Xu Z, Li Y, Liu Z. Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors. Mol Med 2023; 29:101. [PMID: 37491227 PMCID: PMC10369844 DOI: 10.1186/s10020-023-00697-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 07/09/2023] [Indexed: 07/27/2023] Open
Abstract
BACKGROUND Postpartum depression (PPD) is a prevalent mental disorder that negatively impacts mothers and infants. The mechanisms of vulnerability to affective illness in the postpartum period remain largely unknown. Drastic fluctuations in reproductive hormones during the perinatal period generally account for triggering PPD. However, the molecular mechanism underlying the PPD-like behaviors induced by the fluctuations in hormones has rarely been reported. METHODS We utilized hormones-simulated pseudopregnancy (HSP) and hormones-simulated postpartum period (HSPP) rat models to determine how drastic fluctuations in hormone levels affect adult neurotransmission and contribute to depressive-like behaviors. The electrophysiological response of CA1 pyramidal neurons was evaluated by whole-cell patch clamping to identify the hormone-induced modulations of neurotransmission. The statistical significance of differences was assessed with One-way ANOVA and t-test (p < 0.05 was considered significant). RESULTS Reproductive hormones withdrawal induced depressive-like behaviors and disturbed the balance of excitatory and inhibitory transmission in the pyramidal neurons in the hippocampus. Molecular analyses revealed that the blunted Wnt signaling might be responsible for the deficits of synaptic transmission and behaviors. Activation of Wnt signaling increased excitatory and inhibitory synaptic transmission in the hippocampus. Reactivation of Wnt signaling alleviated the anhedonic behaviors and abnormal synaptic transmission. CONCLUSIONS Restoring Wnt signaling in the hormones-simulated postpartum period rat models remediated depression-related anhedonia symptoms and rebalanced the excitation/inhibition ratio by collectively enhancing the plasticity of GABAergic and glutamatergic synapses. The investigations carried out in this research might provide an alternative and prospective treatment strategy for PPD.
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Affiliation(s)
- Binglu Ye
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
| | - Yawei Yuan
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
| | - Rui Liu
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
| | - Haitao Zhou
- State Key Laboratory of Drug Research and Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
- University of Chinese Academy of Sciences, No.9A Yuquan Road, Beijing, 100049, China
| | - Yujie Li
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
| | - Zhihao Sheng
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
| | - Tianyu Li
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
- State Key Laboratory of Drug Research and Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
| | - Bing Zhang
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China
| | - Zhendong Xu
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
| | - Yang Li
- State Key Laboratory of Drug Research and Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
- University of Chinese Academy of Sciences, No.9A Yuquan Road, Beijing, 100049, China.
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.
| | - Zhiqiang Liu
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
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Zaki ES, Sayed RH, Saad MA, El-Yamany MF. Roflumilast ameliorates ovariectomy-induced depressive-like behavior in rats via activation of AMPK/mTOR/ULK1-dependent autophagy pathway. Life Sci 2023:121806. [PMID: 37257579 DOI: 10.1016/j.lfs.2023.121806] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 05/14/2023] [Accepted: 05/23/2023] [Indexed: 06/02/2023]
Abstract
AIMS Roflumilast, a well-known phosphodiesterase-4 (PDE-4) inhibitor, possess an anti-inflammatory activity with approved indications in chronic obstructive pulmonary disease. This study aimed to evaluate the neuroprotective role of roflumilast in ovariectomy (OVX)-induced depressive-like behavior in female rats and to shed light on a potential autophagy enhancing effect. MAIN METHODS Rats were randomly divided into four groups: sham, OVX, OVX + roflumilast (1 mg/kg, p.o), and OVX + roflumilast + chloroquine (CQ) (50 mg/kg, i.p). Drugs were administered for 4 weeks starting 2 weeks after OVX. KEY FINDINGS Roflumilast improved the depressive-like behaviors observed in OVX rats as evidenced by decreasing both forced swimming and open field immobility times while, increasing % sucrose preference and number of open field crossed squares. Histopathological analysis provides further evidence of roflumilast's beneficial effects, demonstrating that roflumilast ameliorated the neuronal damage caused by OVX. Roflumilast antidepressant potential was mediated via restoring hippocampal cAMP and BDNF levels as well as down-regulating PDE4 expression. Moreover, roflumilast revealed anti-inflammatory and anti-apoptotic effects via hindering TNF-α level and diminishing Bax/Bcl2 ratio. Roflumilast restored the autophagic function via up-regulation of p-AMPK, p-ULK1, Beclin-1 and LC3II/I expression, along with downregulation of P62 level and p-mTOR protein expression. The autophagy inhibitor CQ was used to demonstrate the suggested pathway. SIGNIFICANCE The present study revealed that roflumilast showed an anti-depressant activity in OVX female rats via turning on AMPK/mTOR/ULK1-dependent autophagy pathway; and neurotrophic, anti-inflammatory, and anti-apoptotic activities. Roflumilast could offer a more secure alternative to hormone replacement therapy for postmenopausal depression treatment.
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Affiliation(s)
- Eman S Zaki
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Rabab H Sayed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Muhammed A Saad
- Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, 4184, United Arab Emirates; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
| | - Muhammed F El-Yamany
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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14
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Tian JS, Qin PF, Xu T, Gao Y, Zhou YZ, Gao XX, Qin XM, Ren Y. Chaigui granule exerts anti-depressant effects by regulating the synthesis of Estradiol and the downstream of CYP19A1-E2-ERKs signaling pathway in CUMS-induced depressed rats. Front Pharmacol 2022; 13:1005438. [PMID: 36353500 PMCID: PMC9637986 DOI: 10.3389/fphar.2022.1005438] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 10/10/2022] [Indexed: 09/05/2023] Open
Abstract
Background: There is a significant gender difference in the prevalence of depression. Recent studies have shown that estrogen plays a crucial role in depression. Therefore, studying the specific mechanism of estrogen's role in depression can provide new ideas to address the treatment of depression. Chaigui granule has been shown to have exact antidepressant efficacy, and the contents of saikosaponin (a, b1, b2, d) and paeoniflorin in Chaigui granule are about 0.737% and 0.641%, respectively. Some studies have found that they can improve depression-induced decrease in testosterone (T) levels (∼36.99% decrease compared to control). However, whether Chaigui granule can exert antidepressant efficacy by regulating estrogen is still unclear. This study aimed to elucidate the regulation of estrogen levels by Chaigui granule and the underlying mechanism of its anti-depressant effect. Methods: Eighty-four male Sprague-Dawley (SD) rats were modeled using a chronic unpredictable mild stress (CUMS) procedure. The administration method was traditional oral gavage administration, and behavioral indicators were used to evaluate the anti-depressant effect of Chaigui granule. Enzyme-linked immunosorbent assay (ELISA) was adopted to assess the modulating impact of Chaigui granule on sex hormones. Then, reverse transcription-quantitative PCR (RT-qPCR), and Western blot (WB) techniques were employed to detect extracellular regulated protein kinases (ERK) signaling-related molecules downstream of estradiol in the hippocampus tissue. Results: The administration of Chaigui granule significantly alleviated the desperate behavior of CUMS-induced depressed rats. According to the results, we found that Chaigui granule could upregulate the level of estradiol (E2) in the serum (∼46.56% increase compared to model) and hippocampus (∼26.03% increase compared to model) of CUMS rats and increase the levels of CYP19A1 gene and protein, which was the key enzyme regulating the synthesis of T into E2 in the hippocampus. Chaigui granule was also found to have a significant back-regulatory effect on the gene and protein levels of ERβ, ERK1, and ERK2. Conclusion: Chaigui granule can increase the synthesis of E2 in the hippocampus of CUMS-induced depressed rats and further exert antidepressant effects by activating the CYP19A1-E2-ERKs signaling pathway.
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Affiliation(s)
- Jun-sheng Tian
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Peng-fei Qin
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Teng Xu
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Yao Gao
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Yu-zhi Zhou
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Xiao-xia Gao
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Xue-mei Qin
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Yan Ren
- Department of Psychiatry, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Furtado Macruz C, Lima SMRR. Effects of Cimicifuga racemosa (L.) Nutt on sexual function in women receiving tamoxifen for breast cancer. J OBSTET GYNAECOL 2022; 42:3236-3240. [PMID: 35993523 DOI: 10.1080/01443615.2022.2111517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
To assess the effects of Cimicifuga racemosa (L.) Nutt on climacteric symptoms and sexual function in women receiving tamoxifen after breast cancer treatment. A prospective study of women treated at the Mastology Outpatient Clinic of the Department of Obstetrics and Gynecology of the Santa Casa de Sao Paulo School of Medical Science of the hospital was conducted between 2018 and 2021. Patients diagnosed with breast cancer that underwent surgical, radiotherapy and chemotherapy treatment more than one year prior, receiving tamoxifen, exhibited climacteric symptoms and were sexually active were selected. Total of 34 women were recruited and during outpatient visits completed sociodemographic questionnaire, Blatt-Kupperman Index (KI) and Female Sexual Function Index (FSFI). The group showed improvements in climacteric symptoms (p<.001) and sexual function (p=.011) after the 6-month follow-up. Cimicifuga racemosa (L.) Nutt promoted improvements in climacteric symptoms and sexual function in women surgically treated for breast cancer. Clinical Trials.gov ID: NCT02467686.Impact StatementWhat is already known on this subject? The medications used for the treatment of breast cancer can lead to important complaints of vasomotor manifestations with a negative impact on the success of their treatment, and cases have been described until their interruption. Cimicifuga racemosa (L.) Nutt. is described in several works as a therapy to alleviate these symptoms. Numerous works in the literature present climatic symptoms and sexual function with a selective approach to the themes.What do the results of this study add? Our study evaluated a group of women who were treated for breast cancer after menopause taking into account the following aspects: climacteric symptoms and sexual function. When we reviewed the literature, we did not find, so far, work similar to ours.What are the implications of these findings for clinical practice and/or further research? In clinical practice, assessing vasomotor symptoms and sexual response of breast cancer patients can contribute towards improving the lives of this patient group. Prescribing Cimicifuga racemosa (L.) Nutt in cases with climacteric complaints and poor sexual response can relieve distress and promote better health and life status for these women. Although the present investigation has generated important data on female breast cancer survivors, there are limitations regarding the number of participants. We recommend further clinical research with expansion of the sample studied and the results presented.
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Affiliation(s)
- Carolina Furtado Macruz
- Department of Obstetrics and Gynecology, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil
| | - Sônia Maria Rolim Rosa Lima
- Department of Obstetrics and Gynecology, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil
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Bi B, Jiang Y, Shi Y, Ruan F. Bazedoxifene plus conjugated estrogens improve menopausal symptoms in postmenopausal women: a systematic review and meta-analysis. Gynecol Endocrinol 2022; 38:813-821. [PMID: 36036169 DOI: 10.1080/09513590.2022.2117294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/15/2022] Open
Abstract
Our aim is to evaluate the efficacy of bazedoxifene (BZA) plus conjugated estrogens (CE) on menopausal symptoms in postmenopausal women. A series of databases including PubMed, EMBASE, Medline, Web of science, China national knowledge internet and Wanfang database up to 31 October 2021 were searched, and randomized controlled trials (RCTs) of BZA/CE for menopausal symptoms were included. Seven RCTs involving 5431 patients were included in this study. Compared with placebo group, there were significantly reduce in daily number of hot flushes, daily number of moderate or severe hot flushes, the percentages of parabasal cells and the time to fall sleep when patients treated with BZA/CE. Besides, there were significant improvement in sleep disturbance and total MENQOL. However, no significant improvements in sleep adequacy were observed in the three groups. Furthermore, BZA 20 mg/CE 0.625 mg was more effective than BZA 20 mg/CE 0.45 mg in improving the menopausal symptoms. Therefore, both bazedoxifene 20 mg plus conjugated estrogens 0.45 mg and bazedoxifene 20 mg plus conjugated estrogens 0.625 mg could significantly improve the menopause-related symptoms and MENQOL in postmenopausal women, and the curative effects of BZA 20 mg/CE 0.625 mg were better than that of BZA 20 mg/CE 0.45 mg. These findings need to be further confirmed by more high-quality RCTs.
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Affiliation(s)
- Beilei Bi
- Department of Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Yi Jiang
- Department of Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Yin Shi
- Department of Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Fan Ruan
- Department of Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, China
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Li HY, Wang J, Liang LF, Shen SY, Li W, Chen XR, Li B, Zhang YQ, Yu J. Sirtuin 3 Plays a Critical Role in the Antidepressant- and Anxiolytic-like Effects of Kaempferol. Antioxidants (Basel) 2022; 11:1886. [PMID: 36290610 PMCID: PMC9598871 DOI: 10.3390/antiox11101886] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 09/07/2022] [Accepted: 09/20/2022] [Indexed: 12/03/2022] Open
Abstract
An estimated 20% of women experience depression at some point during menopause. Hormone replacement therapy (HRT), as the main therapy for depression and other menopausal syndromes, comes with a few undesirable side effects and a potential increase in cancer and cardiovascular risk. Consequently, there is a dire need for the development of new therapies to treat menopausal depression. Oxidative stress combined with the decline in sex hormones might explain the occurrence of psychological symptoms characteristic of menopause. Therefore, antioxidants have been suggested as a promising therapy for aging-associated diseases, such as menopausal depression. As a flavonoid antioxidant, kaempferol might have a potential neuroprotective action. Hence, the study was conducted to assess the potential antidepressant action of kaempferol and clarify the underlying mechanism. The results show that kaempferol has potential beneficial effects on VCD-induced rodent model of menopausal depression and produces antioxidant effects as well as increases the deacetylation of superoxide dismutase 2 (SOD2) and the protein level of Sirtuin3 (Sirt3) in the hippocampus. On the contrary, Sirt3 depletion abrogated the antidepressant- and anxiolytic-like effects as well as antioxidant effects of kaempferol. In conclusion, kaempferol might produce antidepressant effects via upregulating the expression of Sirt3, the major deacetylase in mitochondria, and subsequently activate the mitochondrial antioxidases. These findings shed some light on the use of kaempferol or vegetables and herbs that contain kaempferol as a complementary therapy for menopausal depression.
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Affiliation(s)
- Hao-Yuan Li
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jing Wang
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Ling-Feng Liang
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Shi-Yu Shen
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Wei Li
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xiao-Rong Chen
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Bing Li
- Center Laboratories, Jinshan Hospital of Fudan University, Shanghai 201508, China
| | - Yu-Qiu Zhang
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jin Yu
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, China
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18
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Lu J, Hu D, Ma C, Shuai B. Advances in Our Understanding of the Mechanism of Action of Drugs (including Traditional Chinese Medicines) for the Intervention and Treatment of Osteoporosis. Front Pharmacol 2022; 13:938447. [PMID: 35774616 PMCID: PMC9237325 DOI: 10.3389/fphar.2022.938447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 05/23/2022] [Indexed: 12/12/2022] Open
Abstract
Osteoporosis (OP) is known as a silent disease in which the loss of bone mass and bone density does not cause obvious symptoms, resulting in insufficient treatment and preventive measures. The losses of bone mass and bone density become more severe over time and an only small percentage of patients are diagnosed when OP-related fractures occur. The high disability and mortality rates of OP-related fractures cause great psychological and physical damage and impose a heavy economic burden on individuals and society. Therefore, early intervention and treatment must be emphasized to achieve the overall goal of reducing the fracture risk. Anti-OP drugs are currently divided into three classes: antiresorptive agents, anabolic agents, and drugs with other mechanisms. In this review, research progress related to common anti-OP drugs in these three classes as well as targeted therapies is summarized to help researchers and clinicians understand their mechanisms of action and to promote pharmacological research and novel drug development.
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19
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Menopause Hormone Therapy in the Management of Postmenopausal Osteoporosis. Cancer J 2022; 28:204-207. [PMID: 35594468 DOI: 10.1097/ppo.0000000000000592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
ABSTRACT This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks.
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20
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Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate. Int J Mol Sci 2022; 23:ijms23074009. [PMID: 35409368 PMCID: PMC8999971 DOI: 10.3390/ijms23074009] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 12/30/2022] Open
Abstract
The medical community recognizes sex-related differences in pathophysiology and cardiovascular disease outcomes (CVD), culminating with heart failure. In general, pre-menopausal women tend to have a better prognosis than men. Explaining why this occurs is not a simple matter. For decades, sex hormones like estrogens (Es) have been identified as one of the leading factors driving these sex differences. Indeed, Es seem protective in women as their decline, during and after menopause, coincides with an increased CV risk and HF development. However, clinical trials demonstrated that E replacement in post-menopause women results in adverse cardiac events and increased risk of breast cancer. Thus, a deeper understanding of E-related mechanisms is needed to provide a vital gateway toward better CVD prevention and treatment in women. Of note, sphingolipids (SLs) and their metabolism are strictly related to E activities. Among the SLs, ceramide and sphingosine 1-phosphate play essential roles in mammalian physiology, particularly in the CV system, and appear differently modulated in males and females. In keeping with this view, here we explore the most recent experimental and clinical observations about the role of E and SL metabolism, emphasizing how these factors impact the CV system.
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21
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Costanian C, Farah R, Salameh R, Meisner BA, Aoun Bahous S, Sibai AM. The Influence of Female Reproductive Factors on Longevity: A Systematized Narrative Review of Epidemiological Studies. Gerontol Geriatr Med 2022; 8:23337214221138663. [DOI: 10.1177/23337214221138663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 10/22/2022] [Accepted: 10/27/2022] [Indexed: 11/19/2022] Open
Abstract
Purpose: This systematized review presents a synthesis of epidemiological studies that examine the association between female reproductive factors and longevity indicators. Methods: A comprehensive literature search was conducted using four bibliographic databases: OVID Medline, Web of Science, PubMed, and Google Scholar, including English language articles published until March 2022. Results from the search strategy yielded 306 articles, 37 of which were included for review based on eligibility criteria. Results were identified within the following nine themes: endogenous androgens and estrogens, age at first childbirth, age at last childbirth, parity, reproductive lifespan, menopause-related factors, hormone therapy use, age at menarche, and offspring gender. Results: Evidence that links reproductive factors and long lifespan is limited. Several female reproductive factors are shown to be significantly associated with longevity, yet findings remain inconclusive. The most consistent association was between parity (fertility and fecundity) and increased female lifespan. Age at first birth and parity were consistently associated with increased longevity. Associations between age at menarche and menopause, premature menopause, reproductive lifespan, offspring gender and longevity are inconclusive. Conclusion: There is not enough evidence to consider sex a longevity predictor. To understand the mechanisms that predict longevity outcomes, it is imperative to consider sex-specific within-population differences.
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Affiliation(s)
| | | | | | | | | | - Abla M. Sibai
- Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
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22
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Della Torre S, Vegeto E, Ciana P. The Use of ERE-Luc Reporter Mice to Monitor Estrogen Receptor Transcriptional Activity in a Spatio-Temporal Dimension. Methods Mol Biol 2022; 2418:153-172. [PMID: 35119665 DOI: 10.1007/978-1-0716-1920-9_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
In spite of the fact that women spend 1/3 of their lives in postmenopause, the search for appropriate therapies able to counteract the derangements associated with the menopause still represents a sort of sought after the "Holy Grail."Nowadays, the combination of estrogens and selective estrogen receptor modulators (SERMs), a class of compounds with a mixed agonist/antagonistic activity on the estrogen receptor (ER) in various tissues, represents the most promising approach to improve postmenopausal women's health, by preserving the benefits while avoiding the side effects of estrogen-based therapy.Given their complex mechanisms of action, the evaluation of SERM activity in combination with conjugated estrogens (CE) requires a multifactorial analysis that takes into account the multifaceted and dynamic effects of these compounds in target tissues, even in relation to the physiological/pathological status.To accomplish such a goal, we took advantage of the ERE-Luc model, a reporter mouse that allows the monitoring of ER transcriptional activity in a spatio-temporal dimension. Cluster analyses performed on in vivo/ex vivo bioluminescence (BLI) data and ex vivo luciferase activity enabled to sustain the combination of CE plus bazedoxifene (TSEC, tissue-selective estrogen complex) as a valuable option for the pharmacological treatment of the postmenopause.
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Affiliation(s)
- Sara Della Torre
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
| | - Elisabetta Vegeto
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | - Paolo Ciana
- Department of Health Sciences, University of Milan, Milan, Italy
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23
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Yang I, Lin I, Liang Y, Lin J, Chen T, Chen Z, Kuan C, Chi C, Li C, Wu H, Lin F. Development of di(2‐ethylhexyl) phthalate‐containing thioglycolic acid immobilized chitosan mucoadhesive gel as an alternative hormone therapy for menopausal syndrome. Bioeng Transl Med 2021; 7:e10267. [PMID: 35600649 PMCID: PMC9115706 DOI: 10.1002/btm2.10267] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 10/20/2021] [Accepted: 11/02/2021] [Indexed: 01/25/2023] Open
Abstract
Menopausal syndrome includes the symptoms that most women experience owing to hormone changes after menopause. Although hormone replacement therapy is a common treatment for menopausal syndrome, there are still many side effects and challenges hindering research. In this study, thioglycolic acid (TGA)‐immobilized chitosan mucoadhesive gel was synthesized by a new method of low concentration of 1,4‐butanediol diglycidyl ether (BDDE) would encapsulate di(2‐ethylhexyl) phthalate (DEHP) as an alternative hormone replacement therapy for menopausal syndrome. The efficacies of the DEHP‐containing TGA‐chitosan gel (CT‐D) were confirmed and evaluated by materials characterization and in vitro study. Results showed that CT‐D was not cytotoxic and had better mucoadhesive ability than chitosan. The animal model was constructed 1 month after bilateral ovariectomy in SD rats. CT‐D was administered intravaginally every 3 days. Bodyweight, wet weight of the uterus and vagina, vaginal smears, histology, blood element analysis, and serological analysis was used to assess the ability of the material to relieve menopausal syndrome. The results indicated that the combination of the sustained release of DEHP and mucoadhesive TGA‐immobilized chitosan allows the developed CT‐D to relieve the menopausal syndrome through low concentrations of DEHP, which falls in the safety level of the tolerable daily intake of DEHP.
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Affiliation(s)
- I‐Hsuan Yang
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
| | - I‐En Lin
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
| | - Ya‐Jyun Liang
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
| | - Jhih‐Ni Lin
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
| | - Tzu‐Chien Chen
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
| | - Zhi‐Yu Chen
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
| | - Che‐Yung Kuan
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
- Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan, Miaoli County Taiwan
| | - Chih‐Ying Chi
- Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan, Miaoli County Taiwan
- PhD Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan
| | - Chi‐Han Li
- Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan, Miaoli County Taiwan
- PhD Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan
| | - Hung‐Ming Wu
- Department of Neurology Changhua Christian Hospital Changhua Taiwan
| | - Feng‐Huei Lin
- Department of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University Taipei Taiwan
- Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan, Miaoli County Taiwan
- PhD Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan
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24
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Rozenberg S, Di Pietrantonio V, Vandromme J, Gilles C. Menopausal hormone therapy and breast cancer risk. Best Pract Res Clin Endocrinol Metab 2021; 35:101577. [PMID: 34535397 DOI: 10.1016/j.beem.2021.101577] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
This narrative review analyses the customization of Menopause Hormone Therapy in the context of breast cancer risk in women with premature ovarian insufficiency (POI) and with menopause at a normal age. Women with Idiopathic POI, FMR-1 premutation or Turner syndrome, if left untreated, may have lower breast cancer risk compared to the healthy age-matched female population. These women should be treated with MHT until the age of 50, as the risk of breast cancer is equal to that of normally menstruating women. Carriers of BRCA 1 & 2 mutation after risk-reducing bilateral salpingo-oophorectomy (RRSO), without a personal history of cancer, have an increased breast cancer risk, but may probably be treated with MHT till the age of 50. POI resulting from endometriosis or cancer related treatment is discussed in a separate paper in this issue. In peri- and postmenopausal women with menopausal symptoms and/or risk factors for osteoporosis in need of MHT, the individual breast cancer risk can be evaluated using internet-based calculators. In most women the 5-year-breast cancer risk is low (<3%) and MHT is a safe option. MHT should be prescribed with caution in women who have an intermediate risk (3-6%) and should not be prescribed in those who have a high risk of breast cancer (>6%). Oestrogen-only MHT and oestrogen-progestogen MHT containing micronized progesterone or dydrogesterone are associated with lower breast cancer risk compared to other combined MHT regimens.
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Affiliation(s)
- Serge Rozenberg
- Department of Obstetrics and Gynecology, CHU St Pierre, Laboratoire de Santé Génésique Université Libre de Bruxelles (ULB), Vrije Universiteit Brussel, Brussels, Belgium.
| | - Victoria Di Pietrantonio
- Department of Obstetrics and Gynecology, CHU St Pierre, Laboratoire de Santé Génésique Université Libre de Bruxelles (ULB), Vrije Universiteit Brussel, Brussels, Belgium
| | - Jean Vandromme
- Department of Obstetrics and Gynecology, CHU St Pierre, Laboratoire de Santé Génésique Université Libre de Bruxelles (ULB), Vrije Universiteit Brussel, Brussels, Belgium
| | - Christine Gilles
- Department of Obstetrics and Gynecology, CHU St Pierre, Laboratoire de Santé Génésique Université Libre de Bruxelles (ULB), Vrije Universiteit Brussel, Brussels, Belgium
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25
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Gosset A, Pouillès JM, Trémollieres F. Menopausal hormone therapy for the management of osteoporosis. Best Pract Res Clin Endocrinol Metab 2021; 35:101551. [PMID: 34119418 DOI: 10.1016/j.beem.2021.101551] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Postmenopausal osteoporosis is a frequent clinical condition which affects nearly 1 in 3 women. Estrogen deficiency leads to rapid bone loss which is maximal within the first 2-3 years after the menopause transition and can be prevented by menopause hormone therapy (MHT). Not only, MHT prevents bone loss and the degradation of the bone microarchitecture but it significantly reduces the risk of fracture at all bone sites by 20-40%. It is the only anti-osteoporotic therapy that has a proven efficacy regardless of basal level of risk, even in low-risk women for fracture. Following the publication of the WHI results, use of MHT has considerably declined due to safety concerns which raise the question as to whether it might still be used in the prevention of osteoporosis. Over the last years, subsequent re-analyses of the WHI and further trials have challenged the initial conclusions of the WHI. It is now clearer that the individual benefit-risk balance of MHT is dependent on the individual risk profile in each woman as well as whether estrogen is opposed or unopposed, the type of estrogens and progestogens or doses and routes of administration. It must be also reminded that to date osteoporosis is a chronic disease that cannot be cured. The choice of the 1st treatment option should thus always be made in the context of a more comprehensive long-term strategy. This is particular true in early postmenopausal women found to be at low/moderate risk of fragility fracture over the first 10 years after menopause but who may have a much greater lifetime risk. In the absence of contraindication, use of MHT should be considered as a 1st option for the maintenance of bone health in those women where specific bone active medications are not warranted. Subsequent reassessment of the individual benefit-risk balance of MHT is thereafter recommended, with the possibility of switching to another osteoporosis treatment if the balance is not considered as favourable as at the beginning of the menopause for women still at high risk of fracture.
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Affiliation(s)
- Anna Gosset
- Centre de Ménopause et Maladies Osseuses Métaboliques, Hôpital Paule de Viguier, 330 Avenue de Grande-Bretagne, TSA 70034, 31059, Toulouse, France
| | - Jean-Michel Pouillès
- Centre de Ménopause et Maladies Osseuses Métaboliques, Hôpital Paule de Viguier, 330 Avenue de Grande-Bretagne, TSA 70034, 31059, Toulouse, France
| | - Florence Trémollieres
- Centre de Ménopause et Maladies Osseuses Métaboliques, Hôpital Paule de Viguier, 330 Avenue de Grande-Bretagne, TSA 70034, 31059, Toulouse, France; INSERM U1048-I2MC-Equipe 9, Université Toulouse III Paul Sabatier, 1 Avenue du Professeur Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.
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26
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Dos Santos Cavaleiro RM, da Silva Arouche T, Martins Tanoue PS, Sá Pereira TS, de Carvalho Junior RN, Paranhos Costa FL, de Andrade Filho TS, Dos Santos Borges R, de Jesus Chaves Neto AM. Hormones Nanofiltration in Carbon Nanotubes and Boron Nitride Nanotubes Using Uniform External Electric Field Through Molecular Dynamics. JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY 2021; 21:5499-5509. [PMID: 33980360 DOI: 10.1166/jnn.2021.19467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Hormones are a dangerous group of molecules that can cause harm to humans. This study based on classical molecular dynamics proposes the nanofiltration of wastewater contaminated by hormones from a computer simulation study, in which the water and the hormone were filtered in two single-walled nanotube compositions. The calculations were carried out by changing the intensities of the electric field that acted as a force exerting pressure on the filtration along the nanotube, in the simulation time of 100 ps. The hormones studied were estrone, estradiol, estriol, progesterone, ethinylestradiol, diethylbestrol, and levonorgestrel in carbon nanotubes (CNTs) and boron nitride (BNNTs). The most efficient nanofiltrations were for fields with low intensities in the order of 10-8 au and 10-7 au. The studied nanotubes can be used in membranes for nanofiltration in water treatment plants due to the evanescent field potential caused by the action of the electric field inside. Our data showed that the action of EF in conjunction with the van der Walls forces of the nanotubes is sufficient to generate the attractive potential. Evaluating the transport of water molecules in CNTs and BNNTs, under the influence of the electric field, a sequence of simulations with the same boundary conditions was carried out, seeking to know the percentage of water molecules filtered in the nanotubes.
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Affiliation(s)
| | - Tiago da Silva Arouche
- Laboratory for Preparation and Computing of Nanomaterials (LPCN), Federal University of Pará, 66075-110, Belém, PA, Brazil
| | - Phelipe Seiichi Martins Tanoue
- Laboratory for Preparation and Computing of Nanomaterials (LPCN), Federal University of Pará, 66075-110, Belém, PA, Brazil
| | - Tais Souza Sá Pereira
- Laboratory for Preparation and Computing of Nanomaterials (LPCN), Federal University of Pará, 66075-110, Belém, PA, Brazil
| | | | - Fabio Luiz Paranhos Costa
- Federal University of Goiás, Campus Jataí. Rodovia BR-364, Setor Francisco Antônio, 75801615 - Jataí, GO - Brazil
| | - Tarciso Silva de Andrade Filho
- Federal University of the South and Southeast of Pará, Campus de Marabá. FL 17, QD 04, LT Especial Nova Marabá 68505080 - Maraba, PA - Brazil
| | - Rosivaldo Dos Santos Borges
- Federal University of Pará, Department of Pharmacy. Rua Augusto Correa, SN Pharmaceutical Chemistry Laboratory Guarna 66075-110 - Belem, PA - Brazil
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27
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Liu G, Wang Y, Chen Y, Ren F. Malignant transformation of abdominal wall endometriosis: A systematic review of the epidemiology, diagnosis, treatment, and outcomes. Eur J Obstet Gynecol Reprod Biol 2021; 264:363-367. [PMID: 34391052 DOI: 10.1016/j.ejogrb.2021.08.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/23/2021] [Accepted: 08/04/2021] [Indexed: 02/07/2023]
Abstract
Malignant transformation of abdominal wall endometriosis (AWE) is rare. The clinical characteristics and treatment of malignant transformation of AWE are not well known. Therefore, in this review, we performed a thorough search for malignant transformation of AWE on MEDLINE and Web of Science from their inception to May 2021. In total, the data of 46 patients with malignant transformation of AWE were retrieved, and all the data on these patients were collected. After reviewing and analyzing the clinical parameters, we found that cesarean scar was the most common site of malignant transformation of AWE, and the most common pathological type of malignant transformation of AWE was clear cell cancer, followed by endometrioid adenocarcinoma. The main symptoms of malignant transformation of AWE included an abdominal nodule or mass, and ultrasonography was the first choice for diagnosis. The most widely accepted treatment was surgical resection of local lesions with adjunctive chemotherapy and/or radiotherapy, and the overall survival of patients with malignant transformation of AWE was poor. In conclusion, malignant transformation of AWE is rare, and the prognosis is poor. Thus, improving abdominal surgical technology and avoiding iatrogenic ectopia and implantation of the endometrium are necessary to prevent malignant transformation of AWE.
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Affiliation(s)
- Gang Liu
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Yizi Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Yinghan Chen
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Fang Ren
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
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28
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Protective effect of metformin against ovariectomy induced depressive- and anxiety-like behaviours in rats: role of oxidative stress. Neuroreport 2021; 32:666-671. [PMID: 33913928 DOI: 10.1097/wnr.0000000000001634] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Several studies have shown that low estrogen levels can lead to an increase in the incidence of depression and anxiety during menopause. The hippocampus and prefrontal cortex are parts of the brain involved in depressive- and anxiety-like behaviors. Recent studies have revealed that metformin has neuroprotective effects mainly due to its antioxidant properties. The aim of the present study was to examine the therapeutic potential of metformin in depressive- and anxiety-like behavior as well as oxidative stress in the prefrontal cortex and hippocampus of ovariectomized rats. Young female Wistar Albino rats were distributed into four groups (n:8): control, metformin-administered control, ovariectomized and metformin administered ovariectomized groups. Metformin (25 mg/kg) was administered daily by oral gavage for 2 weeks. Forced swimming test and open field test were performed to evaluate depression- and anxiety-like behaviors, respectively. Following the treatment with metformin, the tissues of the hippocampus and prefrontal cortex were isolated for the measurement of malondialdehyde, reduced glutathione and ascorbic acid contents. Ovariectomy resulted in depressive- and anxiety-like behaviors, and besides, increased content of malondialdehyde in both prefrontal cortex and hippocampus. The levels of ascorbic acid and glutathione were found to be reduced in ovariectomized rats. Metformin treatment significantly decreased depressive behaviour and malondialdehyde content in the prefrontal cortex. Reducing oxidative stress of the prefrontal cortex was suggested as a possible mechanism implicated in the beneficial effects of metformin on ovariectomy-induced depressive-like behaviour. We believe that the therapeutic efficiency of metformin needs to be tested for potential clinical use in surgical menopause or gonadal hormone deficiency women with depression.
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29
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El-Gawad AMA, El-Hassan DGA, Aboul-Enein AM, Abdelgayed SS, Aly SA, Esmat G, Mostafa AA, Bakr MH, Ali RA, Ayoub MA. Anticancer activity of milk fat rich in conjugated linoleic acid against Ehrlich ascites carcinoma cells in female Swiss albino mice. Vet World 2021; 14:696-708. [PMID: 33935416 PMCID: PMC8076465 DOI: 10.14202/vetworld.2021.696-708] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 02/02/2021] [Indexed: 12/15/2022] Open
Abstract
Background and Aim: The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106/0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.
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Affiliation(s)
| | - Diea G Abo El-Hassan
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Ahmed M Aboul-Enein
- Department of Biochemistry, Faculty of Agriculture, Cairo University, Giza, Egypt
| | - Sherein S Abdelgayed
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Salwa A Aly
- Department of Food Hygiene, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Gamal Esmat
- Department of Hepatogastroenterology and Infectious Diseases, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Amr A Mostafa
- Department of Biochemistry, Faculty of Agriculture, Cairo University, Giza, Egypt
| | - Mohamed H Bakr
- Department of Animal Production, Faculty of Agriculture, Cairo University, Giza, Egypt
| | - Rida A Ali
- Department of Animal Production, Faculty of Agriculture, Cairo University, Giza, Egypt
| | - Mahmoud A Ayoub
- Department of Clinical and Chemical Pathology, National Cancer Institute, Cairo University, Giza, Egypt
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30
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Stevenson JC, Rozenberg S, Maffei S, Egarter C, Stute P, Römer T. Progestogens as a component of menopausal hormone therapy: the right molecule makes the difference. Drugs Context 2020; 9:dic-2020-10-1. [PMID: 33312219 PMCID: PMC7716720 DOI: 10.7573/dic.2020-10-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 11/13/2020] [Accepted: 11/14/2020] [Indexed: 12/25/2022] Open
Abstract
Optimizing menopausal hormone therapy (MHT) requires an awareness of the benefits and risks associated with the available treatments. This narrative review, which is based on the proceedings of an Advisory Board meeting and supplemented by relevant articles identified in literature searches, examines the role of progestogens in MHT, with the aim of providing practical recommendations for prescribing physicians. Progestogens are an essential component of MHT in menopausal women with a uterus to prevent endometrial hyperplasia and reduce the risk of cancer associated with using unopposed estrogen. Progestogens include natural progesterone, dydrogesterone (a stereoisomer of progesterone), and a range of synthetic compounds. Structural differences and varying affinities for other steroid receptors (androgen, glucocorticoid, and mineralocorticoid) confer a unique biological and clinical profile to each progestogen that must be considered during treatment selection. MHT, including the progestogen component, should be tailored to each woman, starting with an estrogen and a progestogen that has the safest profile with respect to breast cancer and cardiovascular effects, while addressing patient-specific needs, risk factors, and treatment goals. Micronized progesterone and dydrogesterone appear to be the safest options, with lower associated cardiovascular, thromboembolic, and breast cancer risks compared with other progestogens, and are the first-choice options for use in ‘special situations,’ such as in women with high-density breast tissue, diabetes, obesity, smoking, and risk factors for venous thromboembolism, among others.
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Affiliation(s)
- John C Stevenson
- National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK
| | - Serge Rozenberg
- Department of Obstetrics and Gynecology, CHU St Pierre, Laboratoire de santé génésique Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Silvia Maffei
- Cardiovascular Gynecological Endocrinology Unit, Cardiovascular Endocrinology and Metabolism Department, Italian National Research Council - Regione Toscana 'G. Monasterio Foundation', Pisa, Italy
| | - Christian Egarter
- Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria
| | - Petra Stute
- Department of Obstetrics and Gynecology, University Women's Hospital, Bern, Switzerland
| | - Thomas Römer
- Department of Obstetrics and Gynecology, Evangelisches Klinikum Weyertal gGmbH, Academic Hospital, University of Cologne, Germany
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Rozenberg S, Al-Daghri N, Aubertin-Leheudre M, Brandi ML, Cano A, Collins P, Cooper C, Genazzani AR, Hillard T, Kanis JA, Kaufman JM, Lambrinoudaki I, Laslop A, McCloskey E, Palacios S, Prieto-Alhambra D, Reginster JY, Rizzoli R, Rosano G, Trémollieres F, Harvey NC. Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis? Osteoporos Int 2020; 31:2271-2286. [PMID: 32642851 PMCID: PMC7661391 DOI: 10.1007/s00198-020-05497-8] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 05/04/2020] [Indexed: 12/21/2022]
Abstract
We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.
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Affiliation(s)
- S Rozenberg
- Department of Obstetrics and Gynecology CHU St Pierre, Université Libre de Bruxelles, Vrije Universiteit, Brussels, Belgium
| | - N Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - M Aubertin-Leheudre
- Department of Physical Activity Sciences, Faculty of Sciences, Université du Québec à Montréal, CRIUGM, Montreal, Québec, Canada
| | - M-L Brandi
- Department of Biochemical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
- Unit of Bone and Mineral Diseases, University Hospital of Florence, Florence, Italy
| | - A Cano
- Department of Obstetrics and Gynecology, University of Valencia and INCLIVA Health Research Institute, Valencia, Spain
| | - P Collins
- National Heart and Lung Institute, Imperial College London, London, UK
- Royal Brompton Hospital, Royal Brompton Campus, Sydney Street, London, UK
| | - C Cooper
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, UK
- NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
| | - A R Genazzani
- Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - T Hillard
- Department of Obstetrics & Gynaecology, Poole Hospital NHS Trust, Poole, UK
| | - J A Kanis
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
- Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK
| | - J-M Kaufman
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - I Lambrinoudaki
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - A Laslop
- Scientific Office, Federal Office for Safety in Health Care, Vienna, Austria
| | - E McCloskey
- Centre for Integrated research in Musculoskeletal Ageing, Mellanby Centre for Bone Research, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - S Palacios
- Director of Palacios Institute of Women's Health, Madrid, Spain
| | - D Prieto-Alhambra
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - J-Y Reginster
- WHO Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liege, Belgium
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - R Rizzoli
- Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | | | - F Trémollieres
- Menopause Center, Hôpital Paule de Viguier, University Hospital of Toulouse and INSERM U1048-I2MC-Equipe 9, Toulouse, France
| | - N C Harvey
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, UK.
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Uehara IA, Soldi LR, Silva MJB. Current perspectives of osteoclastogenesis through estrogen modulated immune cell cytokines. Life Sci 2020; 256:117921. [DOI: 10.1016/j.lfs.2020.117921] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/02/2020] [Accepted: 06/04/2020] [Indexed: 12/12/2022]
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Cheng L, Zhu Y, Ke D, Xie D. Oestrogen-activated autophagy has a negative effect on the anti-osteoclastogenic function of oestrogen. Cell Prolif 2020; 53:e12789. [PMID: 32157750 PMCID: PMC7162800 DOI: 10.1111/cpr.12789] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 02/10/2020] [Accepted: 02/16/2020] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES Oestrogen is known to inhibit osteoclastogenesis, and numerous studies have identified it as an autophagic activator. To date, the role of oestrogen in the autophagy of osteoclast precursors (OCPs) during osteoclastogenesis remains unclear. This study aimed to determine the effect of autophagy regulated by the biologically active form of oestrogen (17β-estradiol) on osteoclastogenesis. MATERIALS AND METHODS After treatment with 17β-estradiol in OCPs (from bone marrow-derived macrophages, BMMs) and ovariectomy (OVX) mice, we measured the effect of 17β-estradiol on the autophagy of OCPs in vitro and in vivo. In addition, we studied the role of autophagy in the OCP proliferation, osteoclast differentiation and bone loss regulated by 17β-estradiol using autophagic inhibitor or knock-down of autophagic genes. RESULTS The results showed that direct administration of 17β-estradiol enhanced the autophagic response of OCPs. Interestingly, 17β-estradiol inhibited the stimulatory effect of receptor activator of nuclear factor-κB ligand (RANKL) on the autophagy and osteoclastogenesis of OCPs. Moreover, 17β-estradiol inhibited the downstream signalling of RANKL. Autophagic suppression by pharmacological inhibitors or gene silencing enhanced the inhibitory effect of 17β-estradiol on osteoclastogenesis. In vivo assays showed that the autophagic inhibitor 3-MA not only inhibited the autophagic activity of the OCPs in the trabecular bone of OVX mice but also enhanced the ability of 17β-estradiol to ameliorate bone loss. CONCLUSIONS In conclusion, our study showed that oestrogen directly enhanced the autophagy of OCPs, which inhibited its anti-osteoclastogenic effect. Drugs based on autophagic inhibition may enhance the efficacy of oestrogen on osteoporosis.
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Affiliation(s)
- Liang Cheng
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration DiseasesThe Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina
| | - Yunrong Zhu
- Department of OrthopedicsThe Affiliated Jiangyin Hospital of Medical College of Southeast UniversityJiangyinChina
| | - Dianshan Ke
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration DiseasesThe Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina
| | - Denghui Xie
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration DiseasesThe Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina
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Zhang B, Wang J, Wei Q, Liu Y, Zhang H, Chen X, Xu K. Epigallocatechin-3-O-gallate modulates the diversity of gut microbiota in ovariectomized rats. Food Sci Nutr 2020; 8:1295-1302. [PMID: 32148835 PMCID: PMC7020287 DOI: 10.1002/fsn3.1419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 12/23/2019] [Accepted: 12/27/2019] [Indexed: 01/09/2023] Open
Abstract
Epigallocatechin-3-O-gallate (EGCG) exists as one of the major active components of green tea and has been studied extensively; however, the relationship between EGCG and the changes in the gut microflora of ovariectomized (OVX) rats as a model of menopause women have not yet been studied. Female Wistar rats were fed on a maintenance material diet and underwent either ovariectomy or SHAM surgery. The ovariectomized rats were divided into OVX group with the treatment of placebo or EGCG group which was treated with EGCG by oral gavage. After 8 weeks of treatment, anxiety-like behaviors were assessed using elevated plus maze test (EMP) and open field test (OFT). The serum estradiol concentration was assayed through ELISA. High-throughput V3-V4 16S rDNA sequencing was conducted to assess the microbial diversity in fecal samples collected from all rats. EGCG, at a concentration of 10 mg/kg, caused behavioral changes in rats similar to anxiety. In EPM, OVX rats spent less time in open arms than SHAM group rats and EGCG group rats (F = 16.043, p < .01). In OFT, the total travelled distance and the number of entries for EGCG group were higher compared with OVX group (F = 30.939, H = 13.107, respectively; p < .01). In addition, the distribution and composition of intestinal microflora in rats changed after ovariectomy. EGCG modulated the diversity of gut microbiota in OVX group at the phylum and the genus levels. Our results suggested that the composition of gut microbiota and anxiety in OVX rats were simultaneously affected by EGCG, and therefore, the two conditions might be strongly related, yet the deeper mechanistic links need further exploration.
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Affiliation(s)
- Beilin Zhang
- Department of PhysiologyCollege of Basic Medical SciencesJilin UniversityJilinChina
| | - Jinpeng Wang
- Department of Cardiologythe Second Hospital of Jilin UniversityJilinChina
| | - Qiyan Wei
- College of Chinese Medicinal MaterialsJilin Agricultural UniversityJilinChina
| | - Yi Liu
- Department of Nutrition and Food HygieneSchool of Public HealthJilin UniversityJilinChina
| | - Huiwen Zhang
- Department of Nutrition and Food HygieneSchool of Public HealthJilin UniversityJilinChina
| | - Xiaohui Chen
- Department of Cardiologythe Second Hospital of Jilin UniversityJilinChina
| | - Kun Xu
- Department of Nutrition and Food HygieneSchool of Public HealthJilin UniversityJilinChina
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Valicherla GR, Gupta AP, Hossain Z, Riyazuddin M, Syed AA, Husain A, Lahiri S, Dave KM, Gayen JR. Pancreastatin inhibitor, PSTi8 ameliorates metabolic health by modulating AKT/GSK-3β and PKCλ/ζ/SREBP1c pathways in high fat diet induced insulin resistance in peri-/post-menopausal rats. Peptides 2019; 120:170147. [PMID: 31473204 DOI: 10.1016/j.peptides.2019.170147] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 08/26/2019] [Accepted: 08/28/2019] [Indexed: 01/03/2023]
Abstract
Increase in the prevalence of insulin resistance (IR) in peri-/post-menopause women is mainly due to hormone deficiency and lifestyle. PSTi8 (PEGKGEQEHSQQKEEEEEMAV-amide) is a pancreastatin inhibitor peptide which showed potent antidiabetic activity in genetic and lifestyle induced type 2 diabetic mice. In the present work, we have investigated the antidiabetic activity of PSTi8 in rat models of peri-/post-menopausal IR. 4-vinylcyclohexenediepoxide treated and ovariectomized rats were fed with high fat diet for 12 weeks to develop the peri-/post-menopausal IR. PSTi8 peptide was administered after the development of peri-/post-menopausal IR rats. PSTi8 (1 mg/kg, i.p) improved the glucose homeostasis which is characterized by elevated glycogenesis, enhanced glycolysis and reduced gluconeogenesis. PSTi8 suppressed palmitate- and PST- induced IR in HepG2 cells. PSTi8 treatment enhanced energy expenditure in peri-/post-menopausal IR rats. PSTi8 treatment increased insulin sensitivity in peri-/post-menopausal IR rats, may be mediated by modulating IRS1-2-phosphatidylinositol-3-kinase-AKT-GSK3β and IRS1-2-phosphatidylinositol-3-kinase-PKCλ/ζ-SREBP1c signaling pathways in the liver. PSTi8 can act as a potential therapeutic peptide for the treatment of peri-/post-menopausal IR.
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Affiliation(s)
- Guru R Valicherla
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
| | - Anand P Gupta
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
| | - Zakir Hossain
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
| | - Mohammed Riyazuddin
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
| | - Anees A Syed
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
| | - Athar Husain
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
| | - Shibani Lahiri
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
| | - Kandarp M Dave
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raibarelly, India
| | - Jiaur R Gayen
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
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Attitudes to the prescription of menopause hormone therapy for vasomotor symptoms and osteoporosis for patients of different ages: A survey of gynecologists in Belgium. Maturitas 2019; 128:60-63. [DOI: 10.1016/j.maturitas.2019.07.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 07/18/2019] [Accepted: 07/30/2019] [Indexed: 11/21/2022]
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Fidelis GP, Silva CHF, Nobre LTDB, Medeiros VP, Rocha HAO, Costa LS. Antioxidant Fucoidans Obtained from Tropical Seaweed Protect Pre-Osteoblastic Cells from Hydrogen Peroxide-Induced Damage. Mar Drugs 2019; 17:E506. [PMID: 31466337 PMCID: PMC6780742 DOI: 10.3390/md17090506] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 08/08/2019] [Accepted: 08/15/2019] [Indexed: 12/31/2022] Open
Abstract
Some antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and consequently reduce the deleterious effects of ROS in osteoblasts. Thus, these compounds fight against osteoporosis. Brown seaweeds are a rich source of antioxidant fucose-containing sulfated polysaccharides (fucans and fucoidans). We obtained six fucoidans (FRFs)-F0.3, F0.5, F0.7, F1.0, F1.5, and F2.1-from Dictyota mertensii by proteolytic digestion followed by sequential acetone precipitation. Except for F0.3, all FRFs showed antioxidant activity in different in vitro tests. In pre- osteoblast-like cells (MC3T3-L1) exposed to H2O2-oxidative stress, caspase-3 and caspase-9 were activated, resulting in apoptosis of the cells. We also observed a decrease in superoxide dismutase (SOD) and alkaline phosphatase (ALP) activity. The antioxidant FRFs protected the cells from the oxidative damage caused by H2O2, decreasing intracellular ROS and caspase activation, and increasing SOD activity. The most effective protection against damage was provided by F0.7, F1.5, and F2.1. At 0.5 mg/mL, these FRFs also suppressed the H2O2-mediated inhibition of ALP activity. The data indicated that FRFs F0.7, F1.5, and F2.1 from D. mertensii were antioxidants that protected bone tissue from oxidative stress and could represent possible adjuvants for the treatment of bone fragility through counteracting oxidative phenomena.
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Affiliation(s)
- Gabriel Pereira Fidelis
- Department of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte 59.078-970, Brazil
| | | | | | - Valquíria Pereira Medeiros
- Department of Biochemistry, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-900, Brazil
| | - Hugo Alexandre Oliveira Rocha
- Department of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte 59.078-970, Brazil.
| | - Leandro Silva Costa
- Instituto Federal de Educação, Ciência, e Tecnologia do Rio Grande do Norte (IFRN), Rio Grande do Norte, Canguaretama, Rio Grande do Norte 59.500-000, Brazil
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Zanello M, Borghese G, Manzara F, Degli Esposti E, Moro E, Raimondo D, Abdullahi LO, Arena A, Terzano P, Meriggiola MC, Seracchioli R. Hormonal Replacement Therapy in Menopausal Women with History of Endometriosis: A Review of Literature. ACTA ACUST UNITED AC 2019; 55:medicina55080477. [PMID: 31416164 PMCID: PMC6723930 DOI: 10.3390/medicina55080477] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 08/09/2019] [Accepted: 08/12/2019] [Indexed: 01/25/2023]
Abstract
Hormonal replacement therapy (HRT) is effective in treating the symptoms of menopause. Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity with a tendency towards invasion and infiltration. Being an estrogen-dependent disease, it tends to regress after menopause. Nevertheless, it affects up to 2.2% of postmenopausal women. Conclusive data are not available in the literature on the appropriateness of HRT in women with endometriosis or a past history of the disease. The hypothesis that exogenous estrogen stimulation could reactivate endometriotic foci has been proposed. The aim of this state-of-the-art review was to revise the current literature about endometriosis in perimenopause and menopause and to investigate the possible role of HRT in this setting of patients. An electronic databases search (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) was performed, with the date range of from each database’s inception until May 2019. All of the studies evaluating the impact of different HRT regimens in patients with a history of endometriosis were selected. 45 articles were found: one Cochrane systematic review, one systematic review, five narrative reviews, two clinical trials, two retrospective cohort studies, 34 case reports and case series. Some authors reported an increased risk of malignant transformation of endometriomas after menopause in patients assuming HRT with unopposed estrogen. Low-quality evidence suggests that HRT can be prescribed to symptomatic women with a history of endometriosis, especially in young patients with premature menopause. Continuous or cyclic combined preparations or tibolone are the best choices. HRT improves quality of life in symptomatic post-menopausal women, who should not be denied the replacement therapy only due to their history of endometriosis. Based on low-grade literature evidence, we recommend to prescribe combined HRT schemes; tibolone could be considered.
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Affiliation(s)
- Margherita Zanello
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Giulia Borghese
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy.
| | - Federica Manzara
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Eugenia Degli Esposti
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Elisa Moro
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Diego Raimondo
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Layla Omar Abdullahi
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Alessandro Arena
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Patrizia Terzano
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Maria Cristina Meriggiola
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
| | - Renato Seracchioli
- Gynecology and Human Reproduction Physiopathology, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy
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Watcho P, Guiadem Kamto Kamto B, Defo Deeh PB, Nguelefack TB, Kamanyi A, Kamtchouing P. The aqueous and methanol extracts of Bambusa vulgaris (Poaceae) improve calcium and phosphorus levels, and bone microstructure in ovariectomized model of osteoporosis. J Basic Clin Physiol Pharmacol 2019; 30:jbcpp-2018-0157. [PMID: 30951500 DOI: 10.1515/jbcpp-2018-0157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 01/23/2019] [Indexed: 06/09/2023]
Abstract
Background Osteoporosis represents the most common metabolic bone disease. Bambusa vulgaris (Poaceae) is a plant with potential antiosteoporotic effects, due to its phytoestrogenic, antioxidative, and anti-inflammatory properties. This study was undertaken to evaluate the effects of aqueous and methanol extracts of B. vulgaris on osteoporosis in rats. Methods Adult female Wistar rats were randomly divided into normal (n = 6) and ovariectomized (n = 42) groups. Twelve weeks after ovariectomy, animals were treated for 4 weeks as follows: distilled water (10 mL/kg, per os (p.o.)), 17β-estradiol (10 μg/kg, intraperitoneal (i.p.)), soya oil (1 mL/kg, i.p.), aqueous or methanol extract of B. vulgaris (55 or 110 mg/kg, p.o.). All rats were weighed daily and sacrificed on day 29. Plasma was collected, and the uterus and femur were dissected out, weighed, and used for biochemical and histological measurements. Results In the untreated ovariectomized females, a non-significant (p > 0.05) increase in body weight and a significant decrease (p < 0.001) in the uterine and bone weights were recorded. Ovariectomy also significantly (p < 0.001) lowered the bone calcium and phosphorus concentrations, and deteriorated the microarchitecture of the femur. Interestingly, B. vulgaris extracts significantly (p < 0.001) improved the bone calcium concentration and femur microarchitecture (increase in trabecular bone density, reorganization of the trabecular network, and increase in bone marrow) with estrogenic-like effects compared to 17β-estradiol. Conclusion These results suggest that B. vulgaris is a potential therapeutic drug for the treatment of osteoporosis. The present findings further justify the ethno-medicinal claims of B. vulgaris.
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Affiliation(s)
- Pierre Watcho
- Department of Animal Biology, Faculty of Science, Animal Physiology and Phytopharmacology Laboratory, University of Dschang, P.O. BOX 67, Dschang, Cameroon
| | - Bernadette Guiadem Kamto Kamto
- Department of Animal Biology, Faculty of Science, Animal Physiology and Phytopharmacology Laboratory, University of Dschang, Dschang, Cameroon
| | - Patrick Brice Defo Deeh
- Department of Animal Biology, Faculty of Science, Animal Physiology and Phytopharmacology Laboratory, University of Dschang, Dschang, Cameroon
| | - Telesphore Benoit Nguelefack
- Department of Animal Biology, Faculty of Science, Animal Physiology and Phytopharmacology Laboratory, University of Dschang, Dschang, Cameroon
| | - Albert Kamanyi
- Department of Animal Biology, Faculty of Science, Animal Physiology and Phytopharmacology Laboratory, University of Dschang, Dschang, Cameroon
| | - Pierre Kamtchouing
- Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
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Saad MA, El-Sahar AE, Sayed RH, Elbaz EM, Helmy HS, Senousy MA. Venlafaxine Mitigates Depressive-Like Behavior in Ovariectomized Rats by Activating the EPO/EPOR/JAK2 Signaling Pathway and Increasing the Serum Estradiol Level. Neurotherapeutics 2019; 16:404-415. [PMID: 30361931 PMCID: PMC6554373 DOI: 10.1007/s13311-018-00680-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Reduced estradiol levels are associated with depression in women during the transition to and after menopause. A considerable number of studies focusing on the theme of treating depression through the activation of erythropoietin (EPO)-induced signaling pathways have been published. Venlafaxine is an approved antidepressant drug that inhibits both serotonin and norepinephrine transporters. The aim of the present study was to investigate the effects of venlafaxine on the depressive-like behaviors and serum estradiol levels in female rats following ovariectomy (OVX) and the possible roles of EPO-induced signaling pathways. Venlafaxine (10 mg/kg/day) was orally administered to OVX rats over a period of 4 weeks using two different treatment regimens: either starting 24 h or 2 weeks after OVX. Venlafaxine showed a superior efficacy in inducing antidepressant-like effects after an acute treatment (24 h post-OVX) than after the delayed treatment (2 weeks post-OVX) and was characterized by a decreased immobility time in the forced swimming test. In parallel, venlafaxine induced EPO and EPO receptor mRNA expression and increased levels of phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 5, and phospho-extracellular signal-regulated kinase 1/2 in the hippocampus of OVX rats. Meanwhile, rats exhibited a marked reduction in the hippocampal Bax/Bcl2 ratio, caspase-3 activity, and tumor necrosis factor alpha levels after venlafaxine treatment. Venlafaxine also increased the hippocampal brain-derived neurotrophic factor and serum estradiol levels. Based on these findings, venlafaxine exerts a neuroprotective effect on OVX rats that is at least partially attributed to the activation of EPO/EPOR/JAK2 signaling pathways, anti-apoptotic activities, anti-inflammatory activities, and neurotrophic activities, as well as an increase in serum estradiol level. Graphical Abstract ᅟ.
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Affiliation(s)
- Muhammed A Saad
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Ayman E El-Sahar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Rabab H Sayed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
| | - Eman M Elbaz
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Hebatullah S Helmy
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Mahmoud A Senousy
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Li N, Li J, Hao J, Zhang M, Yin J, Geng J, Wu T, Lyv X. Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway. Food Funct 2019; 10:3430-3438. [DOI: 10.1039/c9fo00639g] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
With aging, there is an increasing risk for women to develop perimenopause syndrome, which is harmful to women's physical and mental health.
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Affiliation(s)
- Na Li
- State Key Laboratory of Food Nutrition and Safety
- Tianjin University of Science & Technology
- Tianjin 300457
- China
| | - Jing Li
- State Key Laboratory of Food Nutrition and Safety
- Tianjin University of Science & Technology
- Tianjin 300457
- China
| | - Junyu Hao
- State Key Laboratory of Food Nutrition and Safety
- Tianjin University of Science & Technology
- Tianjin 300457
- China
| | - Min Zhang
- State Key Laboratory of Food Nutrition and Safety
- Tianjin University of Science & Technology
- Tianjin 300457
- China
| | - Jinjin Yin
- State Key Laboratory of Food Nutrition and Safety
- Tianjin University of Science & Technology
- Tianjin 300457
- China
| | - Jieting Geng
- Department of Food Science and Technology
- Tokyo University of Marine Science and Technology
- Tokyo 108-8477
- Japan
| | - Tao Wu
- State Key Laboratory of Food Nutrition and Safety
- Tianjin University of Science & Technology
- Tianjin 300457
- China
- Beijing Advanced Innovation Center for Food Nutrition and Human Health
| | - Xiaoling Lyv
- State Key Laboratory of Food Nutrition and Safety
- Tianjin University of Science & Technology
- Tianjin 300457
- China
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Lapid K, Lim A, Berglund ED, Lu Y. Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance. Diabetes Metab Syndr Obes 2019; 12:1419-1436. [PMID: 31616172 PMCID: PMC6699149 DOI: 10.2147/dmso.s190752] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Accepted: 02/22/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Low estrogen states, exemplified by postmenopausal women, are associated with increased adiposity and metabolic dysfunction. We recently reported a paradox, in which a conditional estrogen receptor-alpha (ERα) mutant mouse shows a hyper-metabolic phenotype with enhanced brown/beige cell formation ("browning/beiging"). HYPOTHESIS These observations led us to consider that although systemic deficiency of estrogen or ERα in mice results in obesity and glucose intolerance at room temperature, cold exposure might induce enhanced browning/beiging and improve glucose metabolism. METHODS AND RESULTS Remarkably, studying cold-exposure in mouse models of inhibited estrogen signaling - ERαKO mice, ovariectomy, and treatment with the ERα antagonist Fulvestrant - supported this notion. ERα/estrogen-deficient mice demonstrated enhanced cold-induced beiging, reduced adiposity and improved glucose tolerance. Fulvestrant was also effective in diet-induced obesity settings. Mechanistically, ERα inhibition sensitized cell-autonomous beige cell differentiation and stimulation, including β3-adrenoreceptor-dependent adipocyte beiging. CONCLUSION Taken together, our findings highlight a therapeutic potential for obese/diabetic postmenopausal patients; cold exposure is therefore predicted to metabolically benefit those patients.
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Affiliation(s)
- Kfir Lapid
- Department of Developmental Biology
- Division of Endocrinology, Department of Internal Medicine
- Correspondence: Kfir Lapid Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX75390-9133, USATel +1 214 648 6804Fax +1 214 648 8917Email
| | - Ajin Lim
- Department of Developmental Biology
| | - Eric D Berglund
- Advanced Imaging Research Center
- Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Yue Lu
- Division of Endocrinology, Department of Internal Medicine
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Fu W, Gao XP, Zhang S, Dai YP, Zou WJ, Yue LM. 17β-Estradiol Inhibits PCSK9-Mediated LDLR Degradation Through GPER/PLC Activation in HepG2 Cells. Front Endocrinol (Lausanne) 2019; 10:930. [PMID: 32082252 PMCID: PMC7002320 DOI: 10.3389/fendo.2019.00930] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 12/20/2019] [Indexed: 12/22/2022] Open
Abstract
Plasma levels of PCSK9 are significantly higher in postmenopausal women. Pharmacologically increased estrogen levels have been shown to lower PCSK9 and LDL-C levels in animals and humans. The action of estrogen suggests that it has the ability to prevent PCSK9-mediated LDLR degradation in liver cells. However, little is known about how estrogen alters PCSK9-mediated LDLR degradation. Here, we report that 17β-estradiol (βE2) reduces PCSK9-mediated LDLR degradation by a mechanism that involves activation of the G protein-coupled estrogen receptor (GPER). In cultured HepG2 cells, βE2 prevented the internalization of PCSK9, which subsequently lead to PCSK9-mediated LDLR degradation. The altered LDLR levels also resulted in an increase in LDL uptake that was not observed in the absence of PCSK9. In addition, we showed that clathrin was rapidly increased in the presence of PCSK9, and this increase was blocked by βE2 incubation, suggesting rapid recruitment of clathrin in HepG2 cells. PLCγ activation and intracellular Ca2+ release were both increased due to the rapid effect of estrogen. By using a GPER antagonist G15, we demonstrated that the GPER mediates the action of estrogen. Together, the data from this in vitro study demonstrate that estrogen can regulate LDLR levels mainly through GPER activation, which prevents PCSK9-dependent LDLR degradation in HepG2 cells.
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Affiliation(s)
- Wei Fu
- Department of Physiology, West China School of Basic Medical and Forensic Medicine, Sichuan University, Chengdu, China
| | - Xiao-Ping Gao
- College of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Sheng Zhang
- Department of Physiology, West China School of Basic Medical and Forensic Medicine, Sichuan University, Chengdu, China
| | - Yan-Ping Dai
- College of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wen-Jun Zou
- College of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li-Min Yue
- Department of Physiology, West China School of Basic Medical and Forensic Medicine, Sichuan University, Chengdu, China
- *Correspondence: Li-Min Yue
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Khan MM. Translational Significance of Selective Estrogen Receptor Modulators in Psychiatric Disorders. Int J Endocrinol 2018; 2018:9516592. [PMID: 30402099 PMCID: PMC6196929 DOI: 10.1155/2018/9516592] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/10/2018] [Accepted: 09/02/2018] [Indexed: 12/11/2022] Open
Abstract
Accumulating data from various clinical trial studies suggests that adjuvant therapy with ovarian hormones (estrogens) could be effective in reducing cognitive deficit and psychopathological symptoms in women with psychiatric disorders. However, estrogen therapy poses serious limitations and health issues including feminization in men and increased risks of thromboembolism, hot flashes, breast hyperplasia, and endometrium hyperplasia when used for longer duration in older women (aged ≥ 60 years) or in women who have genetic predispositions. On the other hand, selective estrogen receptor modulators (SERMs), which may (or may not) carry some risks of hot flashes, thromboembolism, breast hyperplasia, and endometrial hyperplasia, are generally devoid of feminization effect. In clinical trial studies, adjuvant therapy with tamoxifen, a triphenylethylene class of SERM, has been found to reduce the frequency of manic episodes in patients with bipolar disorder, whereas addition of raloxifene, a benzothiophene class of SERM, to regular doses of antipsychotic drugs has been found to reduce cognitive deficit and psychological symptoms in men and women with schizophrenia, including women with treatment refractory psychosis. These outcomes together with potent neurocognitive, neuroprotective, and cardiometabolic properties suggest that SERMs could be the potential targets for designing effective and safer therapies for psychiatric disorders.
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Affiliation(s)
- Mohammad M. Khan
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Zawia, P.O. Box 16418, Az-Zawiyah, Libya
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Park JY, Yun H, Jo J, Baek JY, Lee SC, Choi YJ, Shim JS, Choi HJ, Lee S, Kang KS. Beneficial effects of Cirsium japonicum var. maackii on menopausal symptoms in ovariectomized rats. Food Funct 2018; 9:2480-2489. [PMID: 29632938 DOI: 10.1039/c7fo01258f] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In women, menopause refers to a series of physiological and mental symptoms of distress that result from a decrease in 17β-estradiol. In addition to the loss of fertility, the symptoms include facial flushing, depression, osteoporosis, sexual dysfunction, and genitourinary atrophy. Cirsium japonicum var. maackii is a perennial herbaceous species found in the mountains and fields of Korea, China, and Japan. The medicinal uses of C. japonicum include antioxidant, antidiabetic, antitumor, antifungal, and anti-inflammatory activities. We investigated the effect of C. japonicum extract in a rat model of menopause that exhibited rapid estrogen decline induced by ovariectomy (OVX rats). The rats were treated with C. japonicum extract for 10 weeks and the following parameters were measured: food intake, feed efficiency, body weight, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, liver weight, 17β-estradiol, uterus weight, AST, ALT, bone mineral density (BMD), bone alkaline phosphatase, calcitonin, and osteocalcin. In OVX rats, the administration of 50 and 100 mg kg-1C. japonicum extract significantly decreased body weight, total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol and significantly increased 17β-estradiol and BMD. During the light/dark box test, the C. japonicum treatment group (100 mg kg-1) spent more time in the light chamber than in the dark area, which was reflective of their diurnal nature. Using a molecular docking simulation, we predicted the plausible binding mode of the active compounds of C. japonicum with the ligand binding domain of estrogen receptor (ER)-α and ER-β. These results showed that C. japonicum extract can treat the symptoms before and after the menopause.
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Affiliation(s)
- Jun Yeon Park
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
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Brusselaers N, Tamimi RM, Konings P, Rosner B, Adami HO, Lagergren J. Different menopausal hormone regimens and risk of breast cancer. Ann Oncol 2018; 29:1771-1776. [PMID: 29917061 DOI: 10.1093/annonc/mdy212] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND There are considerable knowledge gaps concerning different estrogen and progestin formulations, regimens, and modes of administration of menopausal hormone therapy (HT) and the risk of breast cancer. Our objective was to assess the different treatment options for menopausal HT and the risk of breast cancer. PATIENTS AND METHODS This Swedish prospective nationwide cohort study included all women who received ≥1 HT prescription during the study period 2005-2012 (290 186 ever-users), group-level matched (1 : 3) to 870 165 never-users; respectively, 6376 (2.2%) and 18 754 (2.2%) developed breast cancer. HT, ascertained from the Swedish Prescribed Drug Register, was subdivided by estrogen and progestogen formulation types, regimens (continuous versus sequential) and modes of administration (oral versus transdermal). The risk of invasive breast cancer was presented as adjusted odds ratios (OR) and 95% confidence intervals. RESULTS Current use of estrogen-only therapy was associated with a slight excess breast cancer risk [odds ratio (OR) = 1.08 (1.02-1.14)]. The risk for current estrogen plus progestogen therapy was higher [OR = 1.77 (1.69-1.85)] and increased with higher age at initiation [OR = 3.59 (3.30-3.91) in women 70+ years]. In contrast, past use was associated with reduced breast cancer risk. Current continuous estrogen/progestin use was associated with higher risk [OR = 2.18 (1.99-2.40) for progesterone-derived; OR = 2.66 (2.49-2.84) for testosterone-derived] than sequential use [OR = 1.37 (0.97-1.92) for progesterone-derived; OR = 1.12 (0.96-1.30) for testosterone-derived]. The OR for current use was 1.12 (1.04-1.20) for estradiol, 0.76 (0.69-0.84) for estriol, 4.47 (2.67-7.48) for conjugated estrogens, and 1.68 (1.51-1.87) for tibolone. Oral and cutaneous HT showed similar associations. CONCLUSION Different HT regimens have profoundly different effects on breast cancer risk. Because of registry limitations some confounders could not be assessed. This knowledge may guide clinical decision-making when HT is considered.
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Affiliation(s)
- N Brusselaers
- Department of Microbiology, Centre for Translational Microbiome Research, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Stockholm, Sweden.
| | - R M Tamimi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, USA
| | - P Konings
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, USA
| | - B Rosner
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, USA
| | - H-O Adami
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - J Lagergren
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Division of Cancer Studies, King's College London, London, UK
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Stevens VL, Wang Y, Carter BD, Gaudet MM, Gapstur SM. Serum metabolomic profiles associated with postmenopausal hormone use. Metabolomics 2018; 14:97. [PMID: 30830410 DOI: 10.1007/s11306-018-1393-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 07/02/2018] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Postmenopausal hormone use is linked to several health outcomes and the risk associated with some may differ depending on whether estrogen is used alone or in combination with progestin. OBJECTIVE Metabolomic analyses of postmenopausal hormone use and differences between hormone regimes was done to identify metabolites associated with each type of hormone treatment. METHODS Untargeted metabolomics analysis was done on serum from 1336 women enrolled in the Cancer Prevention II Nutrition Cohort. Levels of 781 named metabolites were compared between 667 nonusers with 332 estrogen-only and with 337 estrogen plus progestin users using linear regression. Metabolite levels were also compared between estrogen-only and estrogen plus progestin users. RESULTS Compared to nonusers, 276 metabolites were statistically significantly (P < 6.40 × 10- 5) associated with estrogen-only use and 222 were associated with estrogen plus progestin use. The metabolites associated with both types of hormones included numerous lipids, acyl carnitines, and amino acids as well as the thyroid hormone thyroxine and the oncometabolite fumarate. The 65 metabolites that differed significantly between estrogen-only and estrogen plus progestin users included 19 steroids and 12 lipids that contained the bioactive fatty acid arachidonic acid. CONCLUSIONS These findings suggest that postmenopausal hormone use influences metabolic pathways linked to a variety of cellular processes, including the regulation of metabolism and stress responses, energy production, and inflammation. The differential association of numerous lipids which influence cellular signaling suggests that differences in signal transduction may contribute to the disparate risks for some diseases between estrogen-only and estrogen plus progestin users.
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Affiliation(s)
- Victoria L Stevens
- Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St, NW, Atlanta, GA, 30329, USA.
| | - Ying Wang
- Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St, NW, Atlanta, GA, 30329, USA
| | - Brian D Carter
- Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St, NW, Atlanta, GA, 30329, USA
| | - Mia M Gaudet
- Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St, NW, Atlanta, GA, 30329, USA
| | - Susan M Gapstur
- Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St, NW, Atlanta, GA, 30329, USA
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Bourque M, Morissette M, Di Paolo T. Repurposing sex steroids and related drugs as potential treatment for Parkinson's disease. Neuropharmacology 2018; 147:37-54. [PMID: 29649433 DOI: 10.1016/j.neuropharm.2018.04.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 03/27/2018] [Accepted: 04/05/2018] [Indexed: 01/19/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder for which a greater prevalence and incidence is described in men. This suggests a protective effect of sex hormones in the brain. Therefore, steroids and drugs to treat endocrine conditions could have additional application for PD. Here, we review the protective effect of sex hormones, particularly estrogens, progesterone, androgens and dehydroepiandrosterone, in animal models of PD and also in human studies. Data also support that drugs affecting estrogen neurotransmission such as selective estrogen receptor modulators or affecting steroid metabolism with 5α-reductase inhibitors could be repositioned for treatment of PD. Sex steroids are also modulator of neurotransmission, thus they could repurposed to treat PD motor symptoms and to modulate the response to PD medication. No drug is yet available to limit PD progression. PD is a complex disease implicating multiple pathological processes and a therapeutic strategy using drugs with several mechanisms of action, such as sex steroids and endocrine drugs are interesting repositioning options for symptomatic treatment and disease-modifying activity for PD. This article is part of the Special Issue entitled 'Drug Repurposing: old molecules, new ways to fast track drug discovery and development for CNS disorders'.
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Affiliation(s)
- Mélanie Bourque
- Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, G1V 4G2, Canada; Faculty of Pharmacy, Université Laval, Quebec City, G1K 7P4, Canada
| | - Marc Morissette
- Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, G1V 4G2, Canada
| | - Thérèse Di Paolo
- Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, G1V 4G2, Canada; Faculty of Pharmacy, Université Laval, Quebec City, G1K 7P4, Canada.
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Souza LS, Rochette NF, Pedrosa DF, Magnago RPL, Filho TBF, Vieira FLH, Fin IDCF, Eis SR, Graceli JB, Rangel LBA, Silva IV. Role of APOE Gene in Bone Mineral Density and Incidence of Bone Fractures in Brazilian Postmenopausal Women. J Clin Densitom 2018; 21:227-235. [PMID: 28784276 DOI: 10.1016/j.jocd.2017.03.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 03/20/2017] [Indexed: 12/23/2022]
Abstract
Osteoporosis is one of the major diseases that affects mostly postmenopausal women. Despite being a multifactorial disease, some genes have been shown to play an important role in osteoporosis. Bone mineral density (BMD) is still largely used to diagnose it, although many other biomarkers are used to better follow the disease onset. It has been shown that the apolipoprotein E (APOE) gene could be a biomarker for risk of fractures as well as to predict lower BMD in patients with osteoporosis. The human APOE gene encodes 3 protein isoforms called ApoE2, ApoE3, and ApoE4, resulting in 4 possible genotypes, because they are a product of a single nucleotide polymorphism found in this gene. So far, the APOE4 allele has been associated with low BMD in postmenopausal women and to incidence of bone breaking in older women. This study aimed to investigate the role of ApoE isoforms in a cohort of 413 postmenopausal Brazilian women. These patients were randomly recruited, clinically examined, and subjected to dual-energy X-ray absorptiometry to measure their BMD. Patients were further grouped as normal BMD (T-score < 0.5) or low BMD (T-score > 1.0, osteopenic or osteoporotic). Patients with osteopenia or osteoporosis were further genotyped for APOE alleles as well as tested for many serum bone turnover biomarkers. Our data showed that presence of the APOE3 allele was associated with both higher BMDs and higher serum concentrations of osteocalcin and alkaline phosphatase, biomarkers for bone formation. On the other hand, the APOE2 and APOE4 alleles were associated with lower BMD as well as higher levels of serum C-terminus collagen peptide and urinary deoxipyridinolines, biomarkers for bone resorption. However, these effects on lower BMD and bone resorption biomarkers observed in either APOE2 or APOE4 alleles were eliminated when patients' genotype carried the APOE3 allele. Codominance of the APOE3 allele was also associated with lesser cases of bone fractures in these patients within a 5-year follow-up. In conclusion, our data show that APOE4 may be associated with lower bone formation as well as increased risk of osteoporosis and bone fractures, whereas APOE3 seems to decrease lowering BMD in postmenopausal women, and its presence seemed to lower the incidence of bone breaking in patients with osteoporosis.
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Affiliation(s)
- Leticia S Souza
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Neuza Felix Rochette
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Diego França Pedrosa
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Rafaella P Lopes Magnago
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Teodiano B Freire Filho
- Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Laboratory of Artificial Intelligence, Electrical Engineering Department, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Fernando Luiz H Vieira
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Department of Physiological Sciences, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Irani do Carmo F Fin
- Centro de Diagnóstico e Pesquisa em Osteoporose do Espírito Santo (CEDOES), Vitória, Espírito Santo, Brazil
| | - Sergio R Eis
- Centro de Diagnóstico e Pesquisa em Osteoporose do Espírito Santo (CEDOES), Vitória, Espírito Santo, Brazil
| | - Jones B Graceli
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Ciências Fisiológicas, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Leticia B A Rangel
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Laboratory of Cellular and Molecular Biology of Cancer, Department of Pharmaceutical Sciences, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Ian V Silva
- Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
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Monteiro NE, Queirós LD, Lopes DB, Pedro AO, Macedo GA. Impact of microbiota on the use and effects of isoflavones in the relief of climacteric symptoms in menopausal women – A review. J Funct Foods 2018. [DOI: 10.1016/j.jff.2017.12.043] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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