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1
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Guo D, Tang B, Luo P, Zhang J, Deng L, Fu S, Shen Z, Li Q, Xie Z, Hang N, Fan H, Wang L. A real-world pharmacovigilance study and pharmacological analysis of sulfasalazine based on the FDA adverse event reporting system (FAERS) database. Expert Opin Drug Saf 2025:1-9. [PMID: 40222949 DOI: 10.1080/14740338.2025.2488241] [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: 05/01/2024] [Revised: 10/26/2024] [Accepted: 03/05/2025] [Indexed: 04/15/2025]
Abstract
OBJECTIVE The purpose of this study was to use the FDA Adverse Event Reporting System (FAERS) to detect and identify adverse events (AEs) related to sulfasalazine to provide a reference for clinical use. METHODS Four algorithms (ROR, PRR, BCPNN and EBGM) were used to detect sulfasalazine-correlated AE signals in real data to calculate the signals associated with sulfasalazine-related AEs. RESULTS During the study period, FAERS was used to extract a total of 91,509 sulfasalazine-related (SASP-related) adverse event reports. In total, 6830 sulfasalazine adverse event signals were found, involving 23 organ systems. The analysis revealed several common adverse reactions; the most common were dizziness, malaise, asthenia, decreased appetite, rash, and anemia, and these adverse reactions are listed on the warning label for sulfasalazine. It is worth noting that in our study, in the preferred term (PT), we also found some reactions that were not mentioned on the warning label, such as blurred vision and cardiac failure. CONCLUSION This study revealed potential new AEs resulting from sulfasalazine, and further studies are needed to confirm these new AEs.
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Affiliation(s)
- Dandan Guo
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Bufu Tang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peng Luo
- The Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jian Zhang
- The Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Lvdan Deng
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Sentao Fu
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Zhijun Shen
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Qing Li
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Zhao Xie
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Na Hang
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Hongjie Fan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Wang
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, PR China
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Tancer S, Wallace BI. Advances in the Medical Treatment of Rheumatoid Arthritis. Hand Clin 2025; 41:11-23. [PMID: 39521584 DOI: 10.1016/j.hcl.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Rheumatoid arthritis is a common, chronic autoimmune disease. Its clinical presentation includes both articular and extra-articular manifestations. The past few decades have seen significant developments in our understanding of RA pathogenesis, leading to the development of effective novel targeted treatment options. This article reviews the clinical presentation, pathogenesis, and treatment of RA, along with specific treatment considerations related to reproductive health, vaccination, and the perioperative period.
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Affiliation(s)
- Stephanie Tancer
- Cleveland Clinic Orthopedic and Rheumatologic Institute, 1730 West 25th Street, Cleveland, OH 44113, USA
| | - Beth I Wallace
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Section of Medicine, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
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Yessirkepov M, Kocyigit BF, Zhakipbekov K, Adilbekov E, Sultanbekov K, Akaltun MS. Uncovering the link between inflammatory rheumatic diseases and male reproductive health: a perspective on male infertility and sexual dysfunction. Rheumatol Int 2024; 44:1621-1636. [PMID: 38693253 PMCID: PMC11344082 DOI: 10.1007/s00296-024-05602-8] [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: 02/22/2024] [Accepted: 04/22/2024] [Indexed: 05/03/2024]
Abstract
Inflammatory rheumatic diseases (IRDs) refer to a range of persistent disorders that have a major influence on several physiological systems. Although there is much evidence connecting IRDs to sexual dysfunction and fertility problems, research specifically focusing on male infertility in relation to these diseases is sparse. This review addresses the complicated connection between IRDs and male infertility, emphasising the physiological, psychological, and pharmacological aspects that influence reproductive health outcomes in men with rheumatic conditions. We explore the effects of IRDs and their treatments on many facets of male reproductive well-being, encompassing sexual functionality, semen characteristics, and hormonal balance. Additionally, we present a comprehensive analysis of the present knowledge on the impact of several categories of anti-rheumatic drugs on male reproductive function. Although there is an increasing awareness of the need of addressing reproductive concerns in individuals IRDs, there is a noticeable lack of research especially dedicated to male infertility. Moving forward, more comprehensive research is needed to determine the prevalence, risk factors, and mechanisms driving reproductive difficulties in males with IRDs. We can better assist the reproductive health requirements of male IRD patients by expanding our understanding of male infertility in the setting of rheumatic disorders and implementing holistic methods to care.
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Affiliation(s)
- Marlen Yessirkepov
- Department of Biology and Biochemistry, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Burhan Fatih Kocyigit
- Department of Physical Medicine and Rehabilitation, University of Health Sciences, Adana City Research and Training Hospital, Adana, Türkiye, Turkey
| | - Kairat Zhakipbekov
- Department of Organization and Management and Economics of Pharmacy and Clinical Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | | | - Kassymkhan Sultanbekov
- Department Social Health Insurance and Public Health, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Mazlum Serdar Akaltun
- Faculty of Medicine, Department of Physical Medicine and Rehabilitaton, Gaziantep University, Gaziantep, Türkiye, Turkey.
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4
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Wushouer X, Aximujiang K, Kadeer N, Aihemaiti A, Zhong L, Yunusi K. Effect of huankuile on colon injury in rats with ulcerative colitis by reducing TNF-α and MMP9. Eur J Med Res 2024; 29:102. [PMID: 38321559 PMCID: PMC10845565 DOI: 10.1186/s40001-024-01695-w] [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: 10/19/2022] [Accepted: 01/24/2024] [Indexed: 02/08/2024] Open
Abstract
OBJECTIVE To explore the mechanism of huankuile (HKL) in colon injury repair in rats with ulcerative colitis (UC). METHODS Fifty SPF Wistar male rats were divided randomly into a normal group, a negative control group, an HKL intervention group ('HKL group') and a 5-aminosalicylic acid intervention group ('5-ASA group'). After 14 days of intervention with corresponding drugs, pathological scores were obtained using the results of immunohistochemical staining; morphological changes were observed by hematoxylin-eosin staining, and the mRNA expression levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9) and interleukin-13 (IL-13) were detected by real-time quantitative PCR. RESULTS After the successful construction of the rat model, it was compared with the rats in the normal group. In the negative group, it was found that the expression of TNF-α and MMP9 was significantly increased in the colonic mucosal epithelia of the rats, the pathological score was significantly increased (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were increased (P < 0.05). After treatment with HKL, the colonic morphology of the rats returned to normal, the expression of TNF-α and MMP9 in the colonic mucosal epithelium of the rats returned to normal, the pathological score grade was significantly reduced (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were reduced; these results were largely consistent with those of the normal group, with no statistically significant difference. CONCLUSION HKL effectively improved the general symptoms and tissue injury in UC rats, and the therapeutic effect was better than that of 5-ASA group. Ulcerative colitis in rats increased the expression of TNF-α, MMP9 and IL-13. HKL repaired UC-induced colonic injury in rats by decreasing the expression of TNF-α, MMP9 and IL-13.
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Affiliation(s)
- Xilinguli Wushouer
- Department of Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
- Xinjiang key laboratory of Molecular Biology for endemic diseases, Urumqi , 830054, China
| | - Kasimujiang Aximujiang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Nafeisha Kadeer
- Department of Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Abulaiti Aihemaiti
- The Functional Center, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Li Zhong
- The Functional Center, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Kurexi Yunusi
- UygurMedical College, Xinjiang Medical University, Urumqi, 830017, China.
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Alhamam A, Garabed LR, Julian S, Flannigan R. The association of medications and supplements with human male reproductive health: a systematic review. Fertil Steril 2023; 120:1112-1137. [PMID: 37898470 DOI: 10.1016/j.fertnstert.2023.10.021] [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: 09/07/2023] [Revised: 10/20/2023] [Accepted: 10/23/2023] [Indexed: 10/30/2023]
Abstract
Some medications used to treat comorbidities and conditions in reproductive-aged individuals could have a negative impact on fertility. This may occur through hormonal disruption, toxicity to germ cells and spermatozoa, functional impact on the sperm, teratogenicity potential, or ejaculatory abnormalities. Having knowledge of these potential interactions between medications and reproductive potential is important for clinicians to be aware of and guide the patient, along with their treating clinicians, to reproductively favorable alternatives when available. This review aims to summarize the state of the literature regarding medication interactions with human male reproduction using the Anatomical Therapeutic Chemical Classification System of medications.
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Affiliation(s)
- Abdullah Alhamam
- Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Urology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Laurianne Rita Garabed
- Division of Urology, Department of Surgery, University of Montreal, Montreal, Quebec, Canada
| | - Sania Julian
- Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Ryan Flannigan
- Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Urology, Weill Cornell Medicine, New York, New York.
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Gubatan J, Barber GE, Nielsen OH, Juhl CB, Maxwell C, Eisenberg ML, Streett SE. Paternal Medications in Inflammatory Bowel Disease and Male Fertility and Reproductive Outcomes: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2023; 21:2222-2238. [PMID: 35870769 DOI: 10.1016/j.cgh.2022.07.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 07/04/2022] [Accepted: 07/07/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes (early pregnancy loss [EPL], preterm birth [PB], congenital malformations [CM]). METHODS We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios (ORs) of outcomes were pooled and analyzed using a random effects model. RESULTS Ten studies reporting semen parameters (268 patients with IBD) and 16 studies reporting adverse pregnancy outcomes (over 25,000 patients with IBD) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared with nonexposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to nonexposed patients (5%). Biologic use was not associated with risk of EPL (OR, 1.26; I2 = 0%; P = .12), PB (OR, 1.10; I2 = 0%; P = .17), or CM (OR, 1.03; I2 = 0%; P = .69). Thiopurine use was not associated with risk of EPL (OR, 1.31; I2 = 19%; P = .17), PB (OR, 1.05; I2 = 0%; P = .20), or CM (OR, 1.07; I2 = 7%; P = .34). Methotrexate use was not associated with risk of PB (OR, 1.06; I2 = 0%; P = .62) or CM (OR, 1.03; I2 = 0%; P = .81). CONCLUSIONS Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.
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Affiliation(s)
- John Gubatan
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
| | - Grant E Barber
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Ole Haagen Nielsen
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Carsten Bogh Juhl
- Department of Sports Science and Biomechanics, University of Southern Denmark, Odense, Denmark; Department of Physiotherapy and Occupational Therapy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Cynthia Maxwell
- Department of Obstetrics & Gynaecology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Michael L Eisenberg
- Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California; Department of Urology, Stanford University School of Medicine, Stanford, California
| | - Sarah E Streett
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
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7
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Cronin SJF, Andrews NA, Latremoliere A. Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy. Front Pharmacol 2023; 14:1173599. [PMID: 37251335 PMCID: PMC10213231 DOI: 10.3389/fphar.2023.1173599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 05/02/2023] [Indexed: 05/31/2023] Open
Abstract
The development of novel analgesics for chronic pain in the last 2 decades has proven virtually intractable, typically failing due to lack of efficacy and dose-limiting side effects. Identified through unbiased gene expression profiling experiments in rats and confirmed by human genome-wide association studies, the role of excessive tetrahydrobiopterin (BH4) in chronic pain has been validated by numerous clinical and preclinical studies. BH4 is an essential cofactor for aromatic amino acid hydroxylases, nitric oxide synthases, and alkylglycerol monooxygenase so a lack of BH4 leads to a range of symptoms in the periphery and central nervous system (CNS). An ideal therapeutic goal therefore would be to block excessive BH4 production, while preventing potential BH4 rundown. In this review, we make the case that sepiapterin reductase (SPR) inhibition restricted to the periphery (i.e., excluded from the spinal cord and brain), is an efficacious and safe target to alleviate chronic pain. First, we describe how different cell types that engage in BH4 overproduction and contribute to pain hypersensitivity, are themselves restricted to peripheral tissues and show their blockade is sufficient to alleviate pain. We discuss the likely safety profile of peripherally restricted SPR inhibition based on human genetic data, the biochemical alternate routes of BH4 production in various tissues and species, and the potential pitfalls to predictive translation when using rodents. Finally, we propose and discuss possible formulation and molecular strategies to achieve peripherally restricted, potent SPR inhibition to treat not only chronic pain but other conditions where excessive BH4 has been demonstrated to be pathological.
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Affiliation(s)
| | - Nick A. Andrews
- The Salk Institute for Biological Studies, La Jolla, CA, United States
| | - Alban Latremoliere
- Departments of Neurosurgery and Neuroscience, Johns Hopkins School of Medicine, Neurosurgery Pain Research Institute, Baltimore, MD, United States
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8
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Sharma A, Kumar A, Agarwal A. Diffuse Idiopathic Skeletal Hyperostosis in a Young Male. Eur J Rheumatol 2023; 10:84-85. [PMID: 37470385 PMCID: PMC10544329 DOI: 10.5152/eurjrheum.2023.22072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 05/04/2023] [Indexed: 07/21/2023] Open
Affiliation(s)
- Ashish Sharma
- Department of Rheumatology, Rheumatology Clinic, New Delhi, India
| | - Ashok Kumar
- Department of Rheumatology, Fortis Flt. Lt. Rajan Dhall Hospital, New Delhi, India
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9
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Perez-Garcia LF, Dolhain RJEM, Vorstenbosch S, Bramer W, van Puijenbroek E, Hazes JMW, Te Winkel B. The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review. Hum Reprod Update 2021; 26:961-1001. [PMID: 32743663 PMCID: PMC7600290 DOI: 10.1093/humupd/dmaa022] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/17/2020] [Accepted: 05/01/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment. OBJECTIVE AND RATIONALE The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes. SEARCH METHODS A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data. OUTCOMES A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported. WIDER IMPLICATIONS Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods.
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Affiliation(s)
- L F Perez-Garcia
- Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - R J E M Dolhain
- Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - S Vorstenbosch
- Netherlands Pharmacovigilance Centre Lareb, 5237 MH 's-Hertogenbosch, The Netherlands
| | - W Bramer
- Medical Library, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - E van Puijenbroek
- Netherlands Pharmacovigilance Centre Lareb, 5237 MH 's-Hertogenbosch, The Netherlands.,Groningen Research Institute of Pharmacy, PharmacoTherapy, Epidemiology and Economics, University of Groningen, 9712 CP Groningen, The Netherlands
| | - J M W Hazes
- Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - B Te Winkel
- Netherlands Pharmacovigilance Centre Lareb, 5237 MH 's-Hertogenbosch, The Netherlands
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10
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Hoffmann M, Kant TA, Emig R, Rausch JSE, Newe M, Schubert M, Künzel K, Winter L, Klapproth E, Peyronnet R, Ravens U, El-Armouche A, Künzel SR. Repurposing mesalazine against cardiac fibrosis in vitro. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2021; 394:533-543. [PMID: 33064167 PMCID: PMC7892689 DOI: 10.1007/s00210-020-01998-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 10/08/2020] [Indexed: 12/11/2022]
Abstract
Cardiovascular diseases are exacerbated and driven by cardiac fibrosis. TGFβ induces fibroblast activation and differentiation into myofibroblasts that secrete excessive extracellular matrix proteins leading to stiffening of the heart, concomitant cardiac dysfunction, and arrhythmias. However, effective pharmacotherapy for preventing or reversing cardiac fibrosis is presently unavailable. Therefore, drug repurposing could be a cost- and time-saving approach to discover antifibrotic interventions. The aim of this study was to investigate the antifibrotic potential of mesalazine in a cardiac fibroblast stress model. TGFβ was used to induce a profibrotic phenotype in a human cardiac fibroblast cell line. After induction, cells were treated with mesalazine or solvent control. Fibroblast proliferation, key fibrosis protein expression, extracellular collagen deposition, and mechanical properties were subsequently determined. In response to TGFβ treatment, fibroblasts underwent a profound phenoconversion towards myofibroblasts, determined by the expression of fibrillary αSMA. Mesalazine reduced differentiation nearly by half and diminished fibroblast proliferation by a third. Additionally, TGFβ led to increased cell stiffness and adhesion, which were reversed by mesalazine treatment. Collagen 1 expression and deposition-key drivers of fibrosis-were significantly increased upon TGFβ stimulation and reduced to control levels by mesalazine. SMAD2/3 and ERK1/2 phosphorylation, along with reduced nuclear NFκB translocation, were identified as potential modes of action. The current study provides experimental pre-clinical evidence for antifibrotic effects of mesalazine in an in vitro model of cardiac fibrosis. Furthermore, it sheds light on possible mechanisms of action and suggests further investigation in experimental and clinical settings.
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Affiliation(s)
- Maximilian Hoffmann
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Theresa A Kant
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Ramona Emig
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg, Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
- CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany
- Faculty of Biology, University of Freiburg, Freiburg, Germany
| | - Johanna S E Rausch
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Manja Newe
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Mario Schubert
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Karolina Künzel
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Luise Winter
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Erik Klapproth
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Rémi Peyronnet
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg, Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Ursula Ravens
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg, Freiburg, Germany
| | - Ali El-Armouche
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany
| | - Stephan R Künzel
- Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fiedlerstraße 42, 01309, Dresden, Germany.
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11
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Finelli R, Leisegang K, Finocchi F, De Masi S, Agarwal A, Damiani G. The impact of autoimmune systemic inflammation and associated medications on male reproductive health in patients with chronic rheumatological, dermatological, and gastroenterological diseases: A systematic review. Am J Reprod Immunol 2021; 85:e13389. [PMID: 33420722 DOI: 10.1111/aji.13389] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/04/2021] [Indexed: 01/13/2023] Open
Abstract
Autoimmune disorders currently affect 5%-8% of the global population, characterized by an aberrant chronic inflammatory response to self-antigens. The aim of this study was to systematically review the current available evidence investigating the impact of systemic autoimmune diseases and associated immunosuppressive treatment on fertility parameters of adult men. Clinical trials, observational studies, and case reports written in English and reporting semen analysis, evaluation of seminal oxidative stress, and/or sperm DNA fragmentation in patients affected by psoriasis and psoriatic arthritis, celiac disease, inflammatory bowel diseases, systemic lupus erythematosus, ankylosing spondylitis, hidradenitis suppurativa, uveitis, dermatomyositis, and rheumatoid arthritis were collected by searching on PubMed, EMBASE, OVID, Scopus, and Cochrane Library databases, with no limit of time. The study quality and the extent of bias in design, methods, and outcome assessment were evaluated by applying the Joanna Briggs Institute Critical Appraisal tools. Evidence suggested that various autoimmune diseases or relevant medications can adversely affect male fertility parameters and that patients may benefit of counseling and sperm cryopreservation. Clinical trials further investigating any adverse effect of autoimmunity and related thereby on male infertility are warranted, to develop appropriate guidelines for males diagnosed and treated for autoimmune disorders.
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Affiliation(s)
- Renata Finelli
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Kristian Leisegang
- School of Natural Medicine, University of the Western Cape, Cape Town, South Africa
| | - Federica Finocchi
- Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy
| | | | - Ashok Agarwal
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Giovanni Damiani
- Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.,Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
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12
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Bermas BL. Paternal safety of anti-rheumatic medications. Best Pract Res Clin Obstet Gynaecol 2020; 64:77-84. [DOI: 10.1016/j.bpobgyn.2019.09.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 09/12/2019] [Indexed: 12/18/2022]
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13
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New changes in pregnancy and lactation labelling: Review of dermatologic drugs. Int J Womens Dermatol 2019; 5:216-226. [PMID: 31700976 PMCID: PMC6831768 DOI: 10.1016/j.ijwd.2019.05.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 04/15/2019] [Accepted: 05/02/2019] [Indexed: 12/24/2022] Open
Abstract
Background The U.S. Food and Drug Administration has published new pregnancy and lactation labelling rules that set standards on the presentation of information with regard to drug usage during pregnancy and breastfeeding, as well as the effects on fertility. These guidelines became effective June 30, 2015, and classified the risks of using prescription drugs during pregnancy in three detailed subsections: Pregnancy, Lactation, and Females and Males of Reproductive Potential. These sections describe the risks within a real-world context of caring for these patients. Objective In this study, we reclassified and categorized drugs and treatments commonly used in dermatology according to these new guidelines. Methods We performed a search of the medical literature about the use of relevant prescription drugs during pregnancy and breastfeeding and their effect on fertility. The search included prospective and retrospective studies, review articles from PubMed-indexed journals (from inception to November 2018), U.S. Food and Drug Administration records, pregnancy exposure registries, relevant information and studies provided in drug labeling by companies, and updated pharmacologic texts and guidelines up to 2018. Results Topical immunomodulators, systemic immunomodulators (including biologics), systemic antipruritic agents, antimicrobials, as well as acne, hair, and cosmetic agents were included. We have made best attempts to review and consolidate existing and new data and include them in our guide. Conclusion This new narrative format facilitates prescribing by considering a variety of factors. One previously overlooked aspect was the impact on the reproductive potential of both male and female patients. Rather than depending on overly simplistic letter risk categories, dermatologists will now need to make prescribing decisions based on each patient and the information provided, which will allow for better decision making and patient care.
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14
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Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence. Semin Arthritis Rheum 2019; 48:911-920. [DOI: 10.1016/j.semarthrit.2018.07.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 05/18/2018] [Accepted: 07/23/2018] [Indexed: 12/31/2022]
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15
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Park YE, Kim TO. Sexual Dysfunction and Fertility Problems in Men with Inflammatory Bowel Disease. World J Mens Health 2019; 38:285-297. [PMID: 30929327 PMCID: PMC7308231 DOI: 10.5534/wjmh.190007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 01/29/2019] [Accepted: 02/10/2019] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is usually diagnosed in young individuals. Crohn's disease and ulcerative colitis are the 2 principal forms of IBD. Patients with IBD demonstrate varying degrees of disease activity and sometimes need to undergo bowel surgery such as proctocolectomy with ileal pouch-anal anastomosis that involves removal of the entire colon and rectum with consequent sexual dysfunction. Several studies have shown that sulfasalazine, affects male fertility. Additionally, many men with IBD are unable to control their smoking, drinking, and eating habits, which can cause worsening of disease activity and fertility. Therefore, infertility and sexual dysfunction are important issues in young patients diagnosed with IBD because they are related to optimal management of the disease and patients' quality of life. Only a few studies have reported sexual dysfunction and infertility in men with IBD. Therefore, this study reviewed the current literature describing male sexual dysfunction scales and evaluated the causes of sexual dysfunction and infertility in men with IBD.
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Affiliation(s)
- Yong Eun Park
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Tae Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
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16
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Osawe SO, Farombi EO. Quercetin and rutin ameliorates sulphasalazine-induced spermiotoxicity, alterations in reproductive hormones and steroidogenic enzyme imbalance in rats. Andrologia 2018. [PMID: 29512831 DOI: 10.1111/and.12981] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Certain dietary flavonoids exhibit protective potentials against drug-induced male reproductive toxicities. We investigated the protective effects of quercetin and rutin on sulphasalazine-induced alterations in steroidogenic enzyme activity, hormone profile and spermiotoxicity in rats. Sulphasalazine (SASP, 600 mg/kg bw) was administered alone or in combination with quercetin (20 mg/kg bw) or rutin (10 mg/kg bw) for 14 days. SASP treatment significantly increased relative weights of the epididymis and seminal vesicles. Also, testicular and epididymal sperm numbers (TSN, ESN), motility, daily sperm production (DSP) and acrosome reaction (AR) significantly decreased. SASP altered plasma testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels while testicular cholesterol levels, 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) activities were decreased. Elevated malondialdehyde levels and concomitant decrease in reduced glutathione, glutathione-S-transferase, peroxidase and superoxide dismutase activities were evident in testis and epididymis of SASP-treated rats. Quercetin or rutin co-treatment with SASP significantly reversed organ weights, preserved sperm integrity, restored plasma hormone levels and increased cholesterol levels, 3β-HSD and 17β-HSD activities in testis. Both flavonoids also prevented oxidative stress in testis and epididymis of SASP-treated rats. Quercetin and rutin protect against the negative effects of SASP treatment on reproductive capacity in male rats.
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Affiliation(s)
- S O Osawe
- Molecular Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - E O Farombi
- Molecular Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
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17
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Abstract
There has been considerable literature on sexual issues in women with inflammatory bowel disease (IBD), but relatively little attention has been paid to these aspects in men. To review the available literature and to provide the best management of sexual and reproductive issues in male patients with IBD. The scientific literature on sexual and reproductive issues in men with IBD was reviewed. Several factors, including surgical and medication treatments, disease activity, lifestyle, and psychological factors, may play a role in the development of infertility and sexual dysfunction and may negatively impact pregnancy outcomes. Proctocolectomy with ileal pouch-anal anastomosis increases the risk of erectile and ejaculatory dysfunction by up to 26%. A treatment with sildenafil can be effective. Sperm banking should be advised to young men with IBD before surgery. Both sulfasalazine and methotrexate may be responsible for reversible sexual dysfunction and infertility. Furthermore, sulfasalazine should be switched to mesalazine at least 4 months before conception because of a higher risk of congenital malformations in pregnancies fathered by men treated with this drug. Psychotropic drugs, frequently used in IBD, may cause sexual dysfunction up to 80%. Last but not the least, voluntary childlessness occurs frequently, mainly because of concerns about medication safety in pregnancy and fear of transmitting disease. Accurate counseling, and where necessary, psychological support can decrease any misperceptions and fears. Close collaboration between the gastroenterologist and the patient is recommended for the best management of these relevant, neglected aspects in men with IBD.
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18
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Ding J, Shang X, Zhang Z, Jing H, Shao J, Fei Q, Rayburn ER, Li H. FDA-approved medications that impair human spermatogenesis. Oncotarget 2018; 8:10714-10725. [PMID: 27801671 PMCID: PMC5354694 DOI: 10.18632/oncotarget.12956] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 10/17/2016] [Indexed: 01/14/2023] Open
Abstract
We herein provide an overview of the single-ingredient U.S. Food and Drug Administration (FDA)-approved drugs that affect human spermatogenesis, potentially resulting in a negative impact on male fertility. To provide this information, we performed an in-depth search of DailyMed, the official website for FDA-approved drug labels. Not surprisingly, hormone-based agents were found to be the drugs most likely to affect human spermatogenesis. The next category of drugs most likely to have effects on spermatogenesis was the antineoplastic agents. Interestingly, the DailyMed labels indicated that several anti-inflammatory drugs affect spermatogenesis, which is not supported by the peer-reviewed literature. Overall, there were a total of 65 labels for drugs of various classes that showed that they have the potential to affect human sperm production and maturation. We identified several drugs indicated to be spermatotoxic in the drug labels that were not reported in the peer-reviewed literature. However, the details about the effects of these drugs on human spermatogenesis are largely lacking, the mechanisms are often unknown, and the clinical impact of many of the findings is currently unclear. Therefore, additional work is needed at both the basic research level and during clinical trials and post-marketing surveillance to fill the gaps in the current knowledge. The present findings will be of interest to physicians and pharmacists, researchers, and those involved in drug development and health care policy.
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Affiliation(s)
- Jiayi Ding
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Xuejun Shang
- Department of Andrology, Jinling Hospital/Nanjing General Hospital Affiliated with Nanjing University School of Medicine, Nanjing, China
| | - Zhanhu Zhang
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Hua Jing
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Jun Shao
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Qianqian Fei
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | | | - Haibo Li
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
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19
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Population Based Paternity Rate and Partner Birth Outcomes Among Utah Men With Inflammatory Bowel Disease. Am J Gastroenterol 2017; 112:1722-1727. [PMID: 28972596 DOI: 10.1038/ajg.2017.279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 07/01/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Crohn's disease (CD) and ulcerative colitis (UC) impact an estimated 350,000 reproductive age men in the United States. The reproductive consequences are largely unknown. The objective of this study was to evaluate the effects of CD and UC on reproductive outcomes. METHODS From the Utah Population Database, we identified a cohort of male patients with CD (1,245) and UC (1,368). Male-sibling controls were identified, and birth outcome data from offspring were obtained. Analyses for CD and UC were completed separately. RESULTS Among UC patients (473) with at least one male sibling (1,020), 66% had offspring, which was not different compared with siblings (61%, P=0.16). Birth outcomes were not different between UC patients and male siblings: congenital malformations (UC 6% vs. 6%, P=0.99), perinatal complications (UC 35% vs. 31%, P=0.23), mean birth weight (UC 3,347 vs. 3,357 g, P=0.53), mean length of gestation (UC 39.0 vs. 39.1 weeks, P=0.54). Among CD patients (421) with at least one male sibling (833), 58% had offspring, which did not differ compared with siblings (57%, P=0.77). Similarly, there were no differences in partner birth outcomes: congenital malformations (CD 7% vs. 6%, P=0.27), perinatal complications (CD 35% vs. 32%, P=0.12), mean birth weight (CD 3,276 vs. 3,324 g, P=0.13), or mean length of gestation (38.8 vs. 39 weeks, P=0.24). CONCLUSIONS We found no differences in paternity rate or female partner birth outcomes in Utah men with UC or CD compared with male-sibling controls. UC and CD do not appear to affect the reproductive outcomes of men in Utah.
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20
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Saberi A, Salarkia E, Safi Z, Sepehri G. Effects of Subacute Administration of Co-Trimoxazole and Folic Acid on Ovarian Tissue in Adult Female Rats. IRANIAN JOURNAL OF MEDICAL SCIENCES 2017; 42:561-568. [PMID: 29184264 PMCID: PMC5684377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Previous studies have reported the antifertility activities of sulfonamides. This study was designed to evaluate the effects of co-trimoxazole and its co-administration with folic acid on ovarian tissue in female rats. METHODS A total of 54 rats were randomly divided into 9 groups (n=6). Group I served as the control and group II (vehicle) received saline. Other groups, III to IX, received co-trimoxazole (30, 60, and 120 mg/kg; i.p.), folic acid (1 mg/kg; i.p.) or their combination for 14 days, respectively. The oocytes were obtained from each group at the end of the 14th days and scored for maturational status as germinal vesicle (GV), metaphase I (MI), or metaphase II (MII). The number of primordial follicle (PrF), primary follicle (PF), and secondary follicle in formalin-fixed ovaries were counted under light microscopy. The data were analyzed by one-way ANOVA followed by post-hoc Dunnet test using SPSS statistical software (version 17.0). Results were considered statistically significant at P<0.05. RESULTS Co-trimoxazole (60 and 120 mg/kg) treatment for 14 days caused a significant decrease in the number of GV (P=0.02, P<0.001), MI and MII (P=0.03, P<0.001), a significant increase in structural abnormalities, including PrF, PF and secondary follicle (P<0.001) as well as congestion, inflammation and necrosis of ovarian tissue compared to the vehicle group. Folic acid co-administration with co-trimoxazole reversed partially all these parameters compared to the co-trimoxazole group (P<0.001). CONCLUSION The data showed the adverse effects of co-trimoxazole on the ovarian maturational status and tissue structure which was reversed partially by folic acid co-administration in rats.
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Affiliation(s)
- Arezoo Saberi
- Kerman Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Ehsan Salarkia
- Kerman Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Zohreh Safi
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Gholamreza Sepehri
- Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran,Correspondence: Gholamreza Sepehri, PhD; Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran Tel\Fax: +98 34 33257581
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21
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Zheng H, Chen M, Li Y, Wang Y, Wei L, Liao Z, Wang M, Ma F, Liao Q, Xie Z. Modulation of Gut Microbiome Composition and Function in Experimental Colitis Treated with Sulfasalazine. Front Microbiol 2017; 8:1703. [PMID: 28936203 PMCID: PMC5594074 DOI: 10.3389/fmicb.2017.01703] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 08/23/2017] [Indexed: 12/18/2022] Open
Abstract
Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing. The study found that SASP treatment could not only restore the TNBS-induced gut dysbiosis, which was proved by the increasing amount of SCFAs-producing bacteria and lactic acid-producing bacteria as well as the decreasing amount of Proteobacteria, but also modulate the dysregulated function of the TNBS-induced colitis to resemble that of the control group, including an increased capacity for basic metabolism (carbohydrate metabolism, citrate cycle) and a decrease in the oxidative stress (riboflavin, sulfur, cysteine) as well as bacterial pathogenesis (cell motility and secretion, bacterial motility proteins, flagellar assembly). Moreover, a higher proportion of Mycoplasma was observed in the SASP group, which may associate with infertility. In all, the study provides insight into specific microbial clades and pathways linked with SASP treatment to elaborate the mechanism for treatment of IBD.
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Affiliation(s)
- Haihui Zheng
- School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou, China
| | - Mingyi Chen
- School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou, China
| | - Yuan Li
- School of Chinese Materia Medica, Guangzhou University of Chinese MedicineGuangzhou, China
| | | | - Lin Wei
- School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou, China
| | - Ziqiong Liao
- School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou, China
| | - Mengxia Wang
- School of Chinese Materia Medica, Guangzhou University of Chinese MedicineGuangzhou, China
| | - Fangli Ma
- Infinitus (China) Company Ltd.Guangzhou, China
| | - Qiongfeng Liao
- School of Chinese Materia Medica, Guangzhou University of Chinese MedicineGuangzhou, China
| | - Zhiyong Xie
- School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou, China
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22
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Semet M, Paci M, Saïas-Magnan J, Metzler-Guillemain C, Boissier R, Lejeune H, Perrin J. The impact of drugs on male fertility: a review. Andrology 2017. [PMID: 28622464 DOI: 10.1111/andr.12366] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Beside cytotoxic drugs, other drugs can impact men's fertility through various mechanisms. Via the modification of the hypothalamic-pituitary-gonadal axis hormones or by non-hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed.
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Affiliation(s)
- M Semet
- Centre clinico-biologique d'Assistance Médicale à la Procréation - CECOS, Pole Femmes-Parents-Enfants, AP-HM La Conception, Marseille, France
| | - M Paci
- Centre clinico-biologique d'Assistance Médicale à la Procréation - CECOS, Pole Femmes-Parents-Enfants, AP-HM La Conception, Marseille, France.,Aix Marseille Univ, INSERM, GMGF UMR_S 910, Marseille, France
| | - J Saïas-Magnan
- Centre clinico-biologique d'Assistance Médicale à la Procréation - CECOS, Pole Femmes-Parents-Enfants, AP-HM La Conception, Marseille, France
| | - C Metzler-Guillemain
- Centre clinico-biologique d'Assistance Médicale à la Procréation - CECOS, Pole Femmes-Parents-Enfants, AP-HM La Conception, Marseille, France.,Aix Marseille Univ, INSERM, GMGF UMR_S 910, Marseille, France
| | - R Boissier
- Aix-Marseille University, Marseille, France.,Department of Urology and Renal Transplantation, APHM, Conception University Hospital, Marseille, France
| | - H Lejeune
- Service de Médecine de la Reproduction, Hôpital Femme Mère, Enfant, CHU de Lyon, Bron, France
| | - J Perrin
- Centre clinico-biologique d'Assistance Médicale à la Procréation - CECOS, Pole Femmes-Parents-Enfants, AP-HM La Conception, Marseille, France.,Aix Marseille Univ, Univ Avignon, CNRS, IRD, IMBE, Marseille, France
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23
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McClelland TJ, Penfold R, Kluzek S, Nagra NS. A large chronic pericardial effusion in an ultramarathon runner with anti-CCP positive rheumatoid arthritis. BMJ Case Rep 2017; 2017:bcr-2017-219350. [PMID: 28611162 DOI: 10.1136/bcr-2017-219350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Pericardial effusions arise as an extra-articular manifestation of rheumatoid arthritis (RA). Pericardial effusions are often asymptomatic, particularly in the early phase, but patients are at risk of cardiac tamponade as the effusion progresses. We discuss the case of a 40-year-old male ultramarathon runner with RA who presented with mild pleuritic chest pain and exertional dyspnoea after a recent long-haul flight. Despite a relative tachycardia, his observations were otherwise unremarkable. His blood tests revealed a C-reactive protein (CRP) of 86 mg/L and an anti-cyclic citrullinated peptide (anti-CCP) titre of 360 units/mL. He was initially diagnosed with a pulmonary embolism; however, a large pericardial effusion was found incidentally on CT pulmonary angiogram with over 1500 mL subsequently drained. The patient's symptoms resolved and CRP normalised 2 weeks later. This unique case illustrates that physically fit patients may physiologically compensate for large pericardial effusions and that arthritic symptoms do not correlate with the severity of extra-articular features in RA.
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Affiliation(s)
| | - Rose Penfold
- Botnar Research Centre (NDORMS), University of Oxford, Oxford, UK
| | - Stefan Kluzek
- Botnar Research Centre (NDORMS), University of Oxford, Oxford, UK
| | - Navraj S Nagra
- Botnar Research Centre (NDORMS), University of Oxford, Oxford, UK
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24
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Yamamoto-Furusho J, Bosques-Padilla F, Daffra P, De Paula J, Etchevers J, Galiano M, Ibañez P, Juliao F, Kotze P, Marroquín de la Garza J, Monreal Robles R, Rocha J, Steinwurz F, Vázquez-Frías R, Veitia G, Zaltman C. Special situations in inflammatory bowel disease: First Latin American consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) (Second part). REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2017. [DOI: 10.1016/j.rgmxen.2016.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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25
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Yamamoto-Furusho JK, Bosques-Padilla F, Daffra P, De Paula JA, Etchevers J, Galiano MT, Ibañez P, Juliao F, Kotze PG, Marroquín de la Garza JM, Monreal Robles R, Rocha JL, Steinwurz F, Vázquez-Frías R, Veitia G, Zaltman C. Special situations in inflammatory bowel disease: First Latin American consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) (Second part). REVISTA DE GASTROENTEROLOGIA DE MEXICO 2017; 82:134-155. [PMID: 28318706 DOI: 10.1016/j.rgmx.2016.07.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 07/18/2016] [Accepted: 07/21/2016] [Indexed: 12/15/2022]
Abstract
This is the first Latin American Consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) regarding special situations in patients with inflammatory bowel disease (IBD). The aim of this consensus is to raise awareness in the medical community in all Latin American countries with respect to pregnancy, vaccinations, infections, neoplasms, including colorectal cancer, and pediatric issues in patients with IBD.
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Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
| | - F Bosques-Padilla
- Servicio de Gastroenterología, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, México; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, México
| | - P Daffra
- Servicio de Gastroenterología, Hospital Italiano, Buenos Aires, Argentina
| | - J A De Paula
- Servicio de Gastroenterología, Hospital Italiano, Buenos Aires, Argentina
| | - J Etchevers
- Servicio de Gastroenterología, Hospital Italiano, Buenos Aires, Argentina
| | - M T Galiano
- Clínica de Enfermedad Inflamatoria Intestinal, Clínica Marly, Bogotá, Colombia
| | - P Ibañez
- Programa de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - F Juliao
- Clínica de Enfermedad Inflamatoria Intestinal, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - P G Kotze
- Hospital Universitario Cajuru, Universidad Católica del Paraná (PUCPR), Curitiba, Brasil
| | - J M Marroquín de la Garza
- Servicio de Gastroenterología, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, México; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, México
| | - R Monreal Robles
- Servicio de Gastroenterología, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, México; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, México
| | - J L Rocha
- Grupo Académico y de Investigación en Crohn y Colitis Ulcerosa Crónica Idiopática de México, Ciudad de México, México
| | - F Steinwurz
- Hospital Israelita Albert Einstein, São Paulo, Brasil
| | - R Vázquez-Frías
- Departamento de Gastroenterología Pediátrica, Hospital Infantil de México Federico Gómez, Ciudad de México, México
| | - G Veitia
- Servicio de Gastroenterología, Hospital Vargas, Caracas, Venezuela
| | - C Zaltman
- Servicio de Gastroenterología, Hospital Clementino Fraga Filho, Departamento de Medicina Interna, Universidad Federal do Rio de Janeiro (UFRJ), Río de Janeiro, Brasil
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Mohammadifard M, Mottaghipisheh J. The effects of ethanolic herbal extracts and CuO nanoparticles on catalase, glutathione peroxidase and malondialdehyde in male diabetic rats. Biologia (Bratisl) 2017. [DOI: 10.1515/biolog-2017-0031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Choi CH, Moon W, Kim YS, Kim ES, Lee BI, Jung Y, Yoon YS, Lee H, Park DI, Han DS. [Second Korean Guideline for the Management of Ulcerative Colitis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2017; 69:1-28. [PMID: 28135789 DOI: 10.4166/kjg.2017.69.1.1] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2025]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases established the first Korean guideline for the management of UC in 2012. This is an update of the first guideline. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations.
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Affiliation(s)
- Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Bo In Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yunho Jung
- Division of Gastroenterology, Department of Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea
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Choi CH, Moon W, Kim YS, Kim ES, Lee BI, Jung Y, Yoon YS, Lee H, Park DI, Han DS, IBD Study Group of the Korean Association for the Study of Intestinal Diseases. Second Korean guidelines for the management of ulcerative colitis. Intest Res 2017; 15:7-37. [PMID: 28239313 PMCID: PMC5323310 DOI: 10.5217/ir.2017.15.1.7] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 01/10/2017] [Accepted: 01/11/2017] [Indexed: 12/12/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the IBD study group of the Korean Association for the Study of Intestinal Diseases established the first Korean guidelines for the management of UC in 2012. This is an update of the first guidelines. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations.
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Affiliation(s)
- Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Bo-In Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yunho Jung
- Division of Gastroenterology, Department of Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
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Immunosuppressants and Male Reproduction. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1034:179-210. [PMID: 29256132 DOI: 10.1007/978-3-319-69535-8_12] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Prolonged use of immunosuppressant medications is occasionally seen in infertile men with chronic inflammatory conditions; autoimmune disorders; or an organ or hematopoietic stem cell transplant. Chronic inflammation impacts negatively on male reproductive endpoints, so immunosuppressant therapy can produce improvements. Corticosteroids have been used to treat antisperm antibodies and even as an empirical treatment for male infertility in general. Trials of these methods have provided mixed results on semen quality and fertility, with improvement, no change and negative effects reported by different investigators. In a substantial number of observational studies, patients on long-term therapy with prednisone for chronic inflammatory disease, testosterone levels were lower compared to untreated controls, though randomized controlled trials have not been conducted. Similarly decreases in testosterone have been reported in men receiving corticosteroids to minimize transplant rejection; however, most were treated with multiple immunosuppressive medications that may have contributed to this effect. A large number of trials of healthy men treated with corticosteroids have shown some disruption in reproductive hormone levels, but other studies reported no effect. Studies in monkeys, rats (at human equivalent dose), cattle, sheep, and horses have shown endocrine disruption, including low testosterone with dexamethasone treatment. Of the cytostatic immunosuppressives, which have high potential for cellular damage, cyclophosphamide has received the most attention, sometimes lowering sperm counts significantly. Methotrexate may decrease sperm numbers in humans and has significant negative impacts in rodents. Other chemotherapeutic drugs used as immunosuppressants are likely to impact negatively on male fertility endpoints, but few data have been collected. The TNF-α Inhibitors have also received little experimental attention. There is some evidence that the immunophilin modulators: cyclosporine, sirolimus, and everolimus cause endocrine disruption and semen quality impairment. As we review in this chapter, results in experimental species are concerning, and well-designed studies are lacking for the effects of these medications on reproductive endpoints in men.
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Cimpoca BA, Nedelea F, Furtuna M, Peltecu G, Panaitescu AM. Managing Crohn's Disease during Pregnancy. MAEDICA 2016; 11:221-226. [PMID: 28694857 PMCID: PMC5486164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Crohn's disease (CD) is a chronic infl ammatory bowel disease with onset during reproductive age. Advancement in medical therapies and treatment strategies have made pregnancy following a diagnosis of CD a viable and safe option for more women with this disease. In this review we discuss the evidence based management of Crohn's disease during pregnancy.
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Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications. Gastroenterol Clin North Am 2016; 45:285-301. [PMID: 27261899 DOI: 10.1016/j.gtc.2016.02.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
For many women with inflammatory bowel disease (IBD), the illness coincides with their childbearing years. IBD increases the risk of pregnancy complications and adverse pregnancy outcomes. The multidisciplinary care team should emphasize the importance of medication adherence to achieve preconception disease control and maintain corticosteroid-free remission throughout pregnancy. Medication adjustments to reduce fetal exposure may be considered on an individualized basis in quiescent disease; however, any benefits of such adjustments remain theoretic and there is risk of worsening disease activity. Mode of delivery is determined by obstetric indications, except for women with active perianal disease who should consider cesarean delivery.
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FERTILIDAD Y EMBARAZO EN PACIENTES CON ENFERMEDADES INFLAMATORIAS INTESTINALES. REVISTA MÉDICA CLÍNICA LAS CONDES 2015. [DOI: 10.1016/j.rmclc.2015.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Sands K, Jansen R, Zaslau S, Greenwald D. Review article: the safety of therapeutic drugs in male inflammatory bowel disease patients wishing to conceive. Aliment Pharmacol Ther 2015; 41:821-34. [PMID: 25752753 DOI: 10.1111/apt.13142] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Revised: 04/27/2013] [Accepted: 02/05/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Many therapeutic drugs are used by patients with inflammatory bowel disease, often around the time of conception. The pregnancy outcomes of males and females exposed to these therapeutics needs to be examined and this information is necessary to counsel patients appropriately. AIM To review the literature describing male infertility and inflammatory bowel disease to educate practitioners of the impact of inflammatory bowel disease on male reproduction and the impact of therapeutics on pregnancy outcomes. METHODS We performed a PubMed search using the search terms 'male infertility,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'ciprofloxacin AND infertility,' 'metronidazole AND infertility,' 'sulfasalazine AND infertility,' 'azathioprine AND infertility,' 'methotrexate AND infertility,' 'ciclosporin AND infertility,' 'corticosteroids AND infertility,' 'infliximab AND male fertility,' 'infliximab AND infertility,' 'infliximab AND foetus,' 'infliximab AND paternal exposure' and 'infliximab AND sperm.' References from selected papers were reviewed and used if relevant. RESULTS Over half of male patients with IBD have some degree of infertility, compared to 8-17% of the general population. Semen parameters including total count, motility and morphology may be adversely affected by therapeutics. IBD medications in males do not increase foetal risk with the possible exception of azathioprine and mercaptopurine; however, increased foetal risk is seen in other drugs if taken by female patients. CONCLUSIONS It is recognised that male infertility is often impacted with therapeutic drugs used to treat inflammatory bowel disease; however, the effects of the paternal drug exposure at the time of conception and exposure in utero should be considered to counsel patients appropriately.
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Affiliation(s)
- K Sands
- EW Sparrow Hospital Urology Residency, Michigan State University College of Osteopathic Medicine, Lansing, MI, USA
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Schulze H, Esters P, Dignass A. Review article: the management of Crohn's disease and ulcerative colitis during pregnancy and lactation. Aliment Pharmacol Ther 2014; 40:991-1008. [PMID: 25200000 DOI: 10.1111/apt.12949] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2014] [Revised: 02/24/2014] [Accepted: 08/14/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) commonly affect young patients in the reproductive phase of their lives. The chronic and relapsing nature of IBD and the potential need for medical or surgical interventions raise concerns about family planning issues. AIM To review the current knowledge on IBD management in pregnant and nursing IBD patients. METHODS A PubMed literature search was performed using the search terms 'reproduction' and 'inflammatory bowel disease' and using the headers and main subjects of each section of this article as search terms. RESULTS Male and female fertility are not impaired in the majority of IBD patients. In IBD patients with quiescent disease pregnancy outcomes are not impaired in comparison to the general population, however, an increased incidence of pregnancy complications is observed in active IBD patients. As methotrexate (MTX) has been demonstrated to be teratogenic, the use of MTX is contraindicated in patients, who wish to conceive, throughout pregnancy and when nursing. However, normal pregnancies following MTX treatment at conception and later have been reported. Most of the other currently approved IBD medications are not associated with adverse pregnancy outcomes and may be used to maintain quiescent disease or to induce a rapid remission in patients with flares and active disease. Breast-feeding in IBD patients is possible and recommended. CONCLUSIONS The overall outcome of pregnancies in IBD patients is favourable and not different to healthy controls, thus patients with IBD should not be discouraged from having children.
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Affiliation(s)
- H Schulze
- Department of Medicine I - Gastroenterology, Hepatology, Oncology and Nutrition, Agaplesion Markus Hospital, Goethe University, Frankfurt, Germany
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Shin T, Kobori Y, Suzuki K, Iwahata T, Yagi H, Soh S, Arai G, Okada H. Inflammatory bowel disease in subfertile men and the effect of mesalazine on fertility. Syst Biol Reprod Med 2014; 60:373-6. [PMID: 25144125 DOI: 10.3109/19396368.2014.952391] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This study aimed to examine the effect of mesalazine on fertility. In this retrospective analysis of 1,225 male subfertile patients, we reviewed the cases of inflammatory bowel disease (IBD) in the medical records and evaluated the prevalence of the disease in our reproduction center. Specifically, we examined IBD patients who ceased mesalazine during male infertility treatment, and compared the seminogram of these patients before and after discontinuation of mesalazine. We also analyzed pregnancy outcome after discontinuation. The prevalence rate of Crohn's disease and ulcerative colitis in our male infertile patients was 163 per 100,000 men and 490 per 100,000 men, respectively. Seven patients had taken mesalazine and six of them subsequently stopped the medication. The mean values of sperm concentration, sperm motility, percentage of normal formed sperm, semen volume, and total motile sperm count taken before discontinuation increased after discontinuation of mesalazine. Among these parameters, the sperm motility and total motile sperm count were significantly improved (p < 0.05) after discontinuation. Of the six patients who stopped the drug, four achieved pregnancy with their partners, with two of the four men showing significant improvement not only in the percentage of normal shaped sperm but also sperm motility and total motile sperm count. This study provides further insight into the rarely investigated relationship between male fertility and mesalazine.
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Affiliation(s)
- Takeshi Shin
- Department of Urology, Dokkyo Medical University Koshigaya Hospital , Koshigaya , Japan
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Palomba S, Sereni G, Falbo A, Beltrami M, Lombardini S, Boni MC, Fornaciari G, Sassatelli R, La Sala GB. Inflammatory bowel diseases and human reproduction: a comprehensive evidence-based review. World J Gastroenterol 2014; 20:7123-36. [PMID: 24966584 PMCID: PMC4064059 DOI: 10.3748/wjg.v20.i23.7123] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 02/13/2014] [Accepted: 02/26/2014] [Indexed: 02/06/2023] Open
Abstract
To evaluate the effects of inflammatory bowel diseases (IBDs) on human reproduction, we reviewed the current literature using a systematic search for published studies (articles and/or abstracts) without limits for English language. We searched on Medline (through PubMed), the Institute for Scientific Information, the Web of Science and the websites for the registration of controlled trials (http://controlled-trials.com/). Bibliographies of retrieved articles, books, expert opinion review articles and reviewed bibliographies from subject experts were manually searched. Titles and abstracts were screened initially, and potential relevant articles were identified and reviewed. Whenever possible, data were analyzed by comparing IBD patients vs healthy controls, and patients with active IBDs vs those with disease in remission. The effects of IBDs on female fertility, fertility in infertile couples, pregnancy and male infertility were examined separately. Patients with IBDs in remission have normal fertility. At the moment, there is no established guideline for the preservation of fertility in women with IBD undergoing surgery. Further data are needed regarding guidelines for the management of these patients. Data regarding IBDs and infertility are currently completely lacking. Considering the prevalence of intestinal pathology in young adults of childbearing age, this field is of great scientific and clinical interest, opening up important future perspectives. Another important and as yet unexplored point is the response to treatments for infertility in patients with IBDs. In particular, the question is whether the reproductive outcomes (clinical and biological) can be influenced by the IBD of one of the partners. The goals for successful reproductive outcomes in IBD population are correct counseling and disease remission. IBDs significantly affect several reproductive aspects of human (female, male, couple) reproduction. Further data are needed to develop guidelines for the clinical management of subjects of reproductive age with IBDs.
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Ramonda R, Foresta C, Ortolan A, Bertoldo A, Oliviero F, Lorenzin M, Pizzol D, Punzi L, Garolla A. Influence of tumor necrosis factor α inhibitors on testicular function and semen in spondyloarthritis patients. Fertil Steril 2013; 101:359-65. [PMID: 24332378 DOI: 10.1016/j.fertnstert.2013.10.048] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Revised: 10/27/2013] [Accepted: 10/29/2013] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To evaluate sperm parameters and sexual hormones in young males affected with spondyloarthritis (SpA) before and after 1 year of anti-tumor necrosis factor (TNF) α treatment. DESIGN Prospective case-control study. SETTING Rheumatology and human reproduction pathology units at a university hospital. PATIENTS Ten SpA outpatients attending the rheumatology clinic; 20 healthy control subjects attending the unit of human reproduction pathology within an infertility prevention program. INTERVENTIONS At baseline and after a 12-month treatment, disease activity was assessed and an andrologic evaluation made. MAIN OUTCOME MEASURE(S) Rheumatologists assessed anamnestic, clinical, functional, and biomarker data. Andrologists evaluated semen analysis, fluorescence in situ hybridization for chromosomes X, Y, 13, 18, and 21, FSH, LH, and T plasma levels, and testicular color Doppler ultrasound. RESULTS At baseline, SpA patients showed reduced sperm motility, higher plasma LH and FSH, and lower T levels compared with control subjects; a significant correlation between disease activity and sperm quality was found. After treatment, a statistically significant decrease in sperm aneuploidies and normal hormone levels were observed. CONCLUSIONS Although inflammation in SpA appears to be related to impaired testicular function, anti-TNF-α agents seem to be safe on testicular function and fertility.
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Affiliation(s)
- Roberta Ramonda
- Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - Carlo Foresta
- Unit of Human Reproduction Pathology, Department of Molecular Medicine, University of Padua, Padua, Italy
| | - Augusta Ortolan
- Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - Alessandro Bertoldo
- Unit of Human Reproduction Pathology, Department of Molecular Medicine, University of Padua, Padua, Italy
| | - Francesca Oliviero
- Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | | | - Damiano Pizzol
- Unit of Human Reproduction Pathology, Department of Molecular Medicine, University of Padua, Padua, Italy
| | - Leonardo Punzi
- Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - Andrea Garolla
- Unit of Human Reproduction Pathology, Department of Molecular Medicine, University of Padua, Padua, Italy.
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Yarur A, Kane SV. Update on pregnancy and breastfeeding in the era of biologics. Dig Liver Dis 2013; 45:787-794. [PMID: 23474350 DOI: 10.1016/j.dld.2013.02.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2013] [Accepted: 02/01/2013] [Indexed: 12/11/2022]
Abstract
Inflammatory bowel diseases are chronic conditions that frequently affect patients during their childbearing years. Considering the characteristics of disease and the medications used to treat it, several issues arise in the care of these patients when they attempt or achieve conception. We review the most current evidence concerning fertility and pregnancy outcomes in patients with inflammatory bowel diseases. With the exception of those women who undergo pelvic surgery, patients with inflammatory bowel diseases have no decreased fertility. Sulfasalazine decreases fertility in men. When looking at obstetrical outcomes, active disease at conception is associated with an increased risk of preterm delivery and low birth weight. While most medications used to treat inflammatory bowel diseases are low risk, some precautions need to be taken and the risk-to-benefit ratio needs to be considered on an individualized basis. In general, aminosalicylates and thiopurines should be continued, but methotrexate is contraindicated. Anti-tumour necrosis factor agents are considered safe to continue but full monoclonal antibodies do cross the placenta. As a general rule, the it is important to counsel women that conception is optimal when disease is in remission, as adverse obstetrical outcomes are directly associated with disease activity. Clinicians need to educate patients before, during and after conception, emphasizing treatment compliance.
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Affiliation(s)
- Andres Yarur
- Department of Medicine, University of Florida, USA
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Tavernier N, Fumery M, Peyrin-Biroulet L, Colombel JF, Gower-Rousseau C. Systematic review: fertility in non-surgically treated inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38:847-53. [PMID: 24004045 DOI: 10.1111/apt.12478] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2013] [Revised: 08/12/2013] [Accepted: 08/17/2013] [Indexed: 12/28/2022]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) typically affect young patients during the reproductive years, and reproductive issues are of key concern to them. AIM To evaluate the impact of IBD on fertility in both women and men with IBD who had no history of surgical treatment for IBD. METHODS We searched MEDLINE, Cochrane Library, EMBASE and international conference abstracts and included all controlled observational studies that evaluated fertility in Crohn's disease (CD) and/or ulcerative colitis (UC) in women and/or men. RESULTS Eleven studies matching our criteria were included. In women with CD, there was a 17-44% reduction in fertility as compared with controls. Reduction in fertility was linked to voluntary childlessness, while there was no evidence of physiological causes of infertility. Most studies did not find any reduction in fertility in women with UC as compared with controls. In men with CD, there was an 18-50% reduction in fertility as compared with controls with no difference in reproductive capacity. There was no evidence of reduced fertility in men with UC. CONCLUSIONS The infertility observed in both women and men with CD is due to voluntary childlessness as opposed to involuntary infertility. This voluntary childlessness is often based on incorrect beliefs about the impact of the disease on fertility and pregnancy outcomes. Our results reinforce the need to increase awareness among male and female patients that IBD does not itself lead to reduced fertility.
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Affiliation(s)
- N Tavernier
- Department of Hepato-Gastroenterology, University Lille Nord de France, CHRU Lille, Lille, France
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Mortimer D, Barratt CLR, Björndahl L, de Jager C, Jequier AM, Muller CH. What should it take to describe a substance or product as 'sperm-safe'. Hum Reprod Update 2013; 19 Suppl 1:i1-45. [PMID: 23552271 DOI: 10.1093/humupd/dmt008] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Male reproductive potential continues to be adversely affected by many environmental, industrial and pharmaceutical toxins. Pre-emptive testing for reproductive toxicological (side-)effects remains limited, or even non-existent. Many products that come into direct contact with spermatozoa lack adequate testing for the absence of adverse effects, and numerous products that are intended for exposure to spermatozoa have only a general assumption of safety based on the absence of evidence of actual harm. Such assumptions can have unfortunate adverse impacts on at-risk individuals (e.g. couples who are trying to conceive), illustrating a clear need for appropriate up-front testing to establish actual 'sperm safety'. METHODS After compiling a list of general areas within the review's scope, relevant literature and other information was obtained from the authors' personal professional libraries and archives, and supplemented as necessary using PubMed and Google searches. Review by co-authors identified and eliminated errors of omission or bias. RESULTS This review provides an overview of the broad range of substances, materials and products that can affect male fertility, especially through sperm fertilizing ability, along with a discussion of practical methods and bioassays for their evaluation. It is concluded that products can only be claimed to be 'sperm-safe' after performing objective, properly designed experimental studies; extrapolation from supposed predicate products or other assumptions cannot be trusted. CONCLUSIONS We call for adopting the precautionary principle, especially when exposure to a product might affect not only a couple's fertility potential but also the health of resulting offspring and perhaps future generations.
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Affiliation(s)
- David Mortimer
- Oozoa Biomedical Inc., Caulfeild Village, West Vancouver, BC, Canada.
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Ng SW, Mahadevan U. Management of inflammatory bowel disease in pregnancy. Expert Rev Clin Immunol 2013; 9:161-73; quiz 174. [PMID: 23390947 DOI: 10.1586/eci.12.103] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The management of inflammatory bowel disease (IBD) in women who are pregnant or contemplating pregnancy requires special considerations. Although many of the medications in IBD treatment are generally low risk, this is not the case for all agents, and substitution of medications or adjustments in dosage or dose timing may be needed. Furthermore, while women with IBD who have not had prior pelvic surgery are as likely to conceive as non-IBD counterparts, there is evidence to suggest that pregnancy outcomes may be worse in women with IBD, particularly if they have active disease during conception or pregnancy. Therefore, a thoughtful discussion between the patient and her healthcare team is critical to ensure awareness of the possible risks of pregnancy to the mother and her infant and how these risks can be minimized with a coordinated effort in counseling, monitoring and medication adherence.
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Affiliation(s)
- Susie W Ng
- Department of Gastroenterology, University of California, San Francisco, CA 94122, USA
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Vermeire S, Carbonnel F, Coulie PG, Geenen V, Hazes JMW, Masson PL, De Keyser F, Louis E. Management of inflammatory bowel disease in pregnancy. J Crohns Colitis 2012; 6:811-23. [PMID: 22595185 DOI: 10.1016/j.crohns.2012.04.009] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Revised: 04/13/2012] [Accepted: 04/13/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) is a chronic disease affecting mainly young people in their reproductive years. IBD therefore has a major impact on patients' family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety considerations. This article aims to provide a framework for clinical decision making in IBD based on review of the literature on pregnancy-related topics. METHODS Medline searches with search terms 'IBD', 'Crohn's disease' or 'ulcerative colitis' in combination with keywords for the topics fertility, pregnancy, congenital abnormalities and drugs names of drugs used for treatment of IBD. RESULTS IBD patients have normal fertility, except for women after ileal pouch-anal anastomosis (IPAA) and men under sulfasalazine treatment. Achieving and maintaining disease remission is a key factor for successful pregnancy outcomes in this population, as active disease at conception carries an increased risk of preterm delivery and low birth weight. Clinicians should discuss the need for drug therapy to maintain remission with their patients in order to ensure therapy compliance. Most IBD drugs are compatible with pregnancy, except for methotrexate and thalidomide. If possible, anti-TNF therapy should be stopped by the end of the second trimester and the choice of delivery route should be discussed with the patient. CONCLUSIONS Disease control prior to conception and throughout pregnancy is the cornerstone of successful pregnancy management in IBD patients.
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Affiliation(s)
- Séverine Vermeire
- Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
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Fréour T, Miossec C, Bach-Ngohou K, Dejoie T, Flamant M, Maillard O, Denis MG, Barriere P, Bruley des Varannes S, Bourreille A, Masson D. Ovarian reserve in young women of reproductive age with Crohn's disease. Inflamm Bowel Dis 2012; 18:1515-22. [PMID: 21936034 DOI: 10.1002/ibd.21872] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Accepted: 08/02/2011] [Indexed: 12/20/2022]
Abstract
BACKGROUND Crohn's disease (CD) mainly affects young adults of reproductive age. Whereas a large amount of data is available concerning pregnancy in young CD women, no study has been conducted on their ovarian reserve status. This study aimed to investigate the potential effect of CD on ovarian reserve in young women in remission, as reflected by serum anti-Müllerian hormone (AMH). METHODS This retrospective case-control study was conducted in the University Hospital of Nantes, France. Serum levels of AMH were retrospectively measured in 50 women with CD in remission and in 163 control women with normal ovarian reserve, matched by age. RESULTS No statistical difference was found between mean serum AMH levels in CD and control women. Serum AMH levels remained comparable between CD and control women <30 years, but they were significantly lower in CD women ≥ 30 years compared to the control group. Furthermore, the negative correlation between age and AMH level tended to be more pronounced in CD than control women. Multivariate analysis of CD patients' clinical and demographic characteristics showed that serum AMH level was influenced by disease location, with a colonic location of the disease being independently associated with a high risk of altered ovarian reserve. CONCLUSIONS Women with CD do not have severe ovarian reserve alterations compared to a control population. However, age ≥ 30 years and a colonic location of the disease could be associated with an accelerated loss of follicles. These data could encourage gastroenterologists to inform CD women of the risk of delaying childbirth.
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Affiliation(s)
- Thomas Fréour
- Department of Human Reproduction, University Hospital of Nantes, Nantes, France.
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Choi CH, Kim YH, Kim YS, Ye BD, Lee KM, Lee BI, Jung SA, Kim WH, Lee H. [Guidelines for the management of ulcerative colitis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2012; 59:118-40. [PMID: 22387836 DOI: 10.4166/kjg.2012.59.2.118] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The quality of life can decreases significantly during exacerbations of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies are currently used for the management of UC. However, many challenging issues exist and sometimes these lead to differences in practice between clinicians. Therefore, Inflammatory Bowel Diseases (IBD) Study Group of Korean Association for the Study of Intestinal Diseases (KASID) set out the Korean guidelines for the management of UC. These guidelines are made by the adaptation using several foreign guidelines and encompass treatment of active colitis, maintenance of remission and indication for surgery in UC. The specific recommendations are presented with the quality of evidence. These are the first Korean treatment guidelines for UC and will be revised with new evidences on treatment of UC.
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Affiliation(s)
- Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Korea
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Navaneethan U, Shen B. Pros and cons of medical management of ulcerative colitis. Clin Colon Rectal Surg 2012; 23:227-38. [PMID: 22131893 DOI: 10.1055/s-0030-1268249] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffuse mucosal inflammation limited to the colon and rectum. Although a complete medical cure may not be possible, UC can be treated with medications that induce and maintain remission. The medical management of this disease continues to evolve with a goal to avoid colectomy and ultimately alter the natural history of UC. Emergence of antitumor necrosis factor-α (TNF-α) agents has expanded the medical armamentarium. 5-Aminosalicylates continue to be used in mild to moderate UC and corticosteroids are mainly used for induction of remission with immunomodulators (6-mercaptopurine/azathiopurine/methotrexate) being applied as steroid-sparing agents for maintenance therapy. Infliximab has been approved by the U.S. Food and Drug Administration and used in the treatment of moderate to severe UC; nevertheless, its use may be associated with significant adverse effects and have a negative impact on the postoperative course should the patients undergo restorative proctocolectomy. In addition, there is always a concern about patients' compliance to medical therapy, cost of medications, and risk for UC-associated dysplasia. The authors discuss the pros and cons of medications used in the treatment of UC.
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Affiliation(s)
- Udayakumar Navaneethan
- Center for Inflammatory Bowel Disease, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio. USA
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Spezielle Arzneimitteltherapie in der Schwangerschaft. ARZNEIMITTEL IN SCHWANGERSCHAFT UND STILLZEIT 2012. [PMCID: PMC7271212 DOI: 10.1016/b978-3-437-21203-1.10002-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Linares V, Alonso V, Domingo JL. Oxidative stress as a mechanism underlying sulfasalazine-induced toxicity. Expert Opin Drug Saf 2011; 10:253-63. [PMID: 21219240 DOI: 10.1517/14740338.2011.529898] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease (CD) and rheumatoid arthritis (RA). A high incidence of side effects limits therapy with this drug. Getting a wider knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care, minimizing toxicity and inappropriate use. AREAS COVERED This paper gives an overview of recent research about SASP and its main adverse effects, highlighting the mechanisms underlying them. To give an overview and comment on the data available so far on this topic, relevant literature was identified using a PubMed search of articles published up to December 2009. Search terms included: 'sulfasalazine', 'oxidative stress, 'renal effects', 'hepatotoxicity' and 'male fertility'. Original papers were reviewed and relevant citations from these articles were also considered. EXPERT OPINION Although SASP and 5-aminosalicylic acid also scavenge ROS, which may account for some of their anti-inflammatory properties, the reaction with ROS may also generate toxic free radicals; hence, the ability of other antioxidants to suppress the toxicity of SASP in vivo. Further investigations, particularly about SASP mechanism, are still needed.
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Affiliation(s)
- Victoria Linares
- Physiology Unit, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia, Spain
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Garrido E, Van Domselaar M, Morales S, López-Sanromán A. Enfermedad inflamatoria intestinal y gestación. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33:517-29. [DOI: 10.1016/j.gastrohep.2009.11.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Accepted: 11/01/2009] [Indexed: 12/23/2022]
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Krtolica A, Giritharan G. Use of Human Embryonic Stem Cell-based Models for Male Reproductive Toxicity Screening. Syst Biol Reprod Med 2010; 56:213-21. [DOI: 10.3109/19396368.2010.486470] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Sato A, Naganuma M, Asakura K, Nishiwaki Y, Yajima T, Hisamatsu T, Iwao Y, Takebayashi T, Watanabe M, Hibi T. Conception outcomes and opinions about pregnancy for men with inflammatory bowel disease. J Crohns Colitis 2010; 4:183-8. [PMID: 21122503 DOI: 10.1016/j.crohns.2009.10.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2009] [Revised: 10/08/2009] [Accepted: 10/22/2009] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel disease (IBD) who want to have children are anxious to receive medical treatment. The consensus regarding pregnancy has not been surveyed for male IBD patients. The present study was investigated opinions among male IBD patients about pregnancy, conception and neonatal outcomes for partners. METHODS Subjects comprised 364 of 386 patients enrolled (94.3%). Subjects received a questionnaire regarding their opinions and thoughts about pregnancy. The course of partner's conceptions and presence of neonatal malformations was also surveyed. RESULTS The rate of live births for partners of male IBD patients was 91.6% (219/239). Most patients with CD (29/33; 88%) had their children after surgery had been performed. The rate of expressing hopes to have a child tended to be higher for patients with UC (93/128; 73%) than for patients with CD (61/97; 63%; p=0.21). Furthermore, the rate of hesitation was significantly higher in CD patients (34/107; 32%) than in UC patients (38/188; 20%; p=0.03).Patients considered that safety of medication (51%) and maintenance of remission (41%) was more important than receiving no treatment for IBD (19%) when planning to conceive. Mesalamine and infliximab were more favorable at conception than sulfasalazine and immunomodulators. CONCLUSIONS This is the first report to survey the thinking of male IBD patients regarding pregnancy. Most male IBD patients considered "maintaining remission" as important at conception. Our study provides important information for IBD patients and for the treating physician when planning to conceive.
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Affiliation(s)
- Asaka Sato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Japan
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