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Goad J, Rajkovic A. Uterine fibroids at single-cell resolution: unveiling cellular heterogeneity to improve understanding of pathogenesis and guide future therapies. Am J Obstet Gynecol 2025; 232:S124-S134. [PMID: 40253076 DOI: 10.1016/j.ajog.2024.08.037] [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: 10/18/2023] [Revised: 07/16/2024] [Accepted: 08/16/2024] [Indexed: 04/21/2025]
Abstract
Uterine leiomyomas or fibroids are benign tumors of the myometrium that affect approximately 70% of reproductive-age women. Fibroids continue to be the leading cause of hysterectomy, resulting in substantial healthcare costs. Genetic complexity and lack of cellular and molecular understanding of fibroids have posed considerable challenges to developing noninvasive treatment options. Over the years, research efforts have intensified to unravel the genetic and cellular diversities within fibroids to deepen our understanding of their origins and progression. Studies using immunostaining and flow cytometry have revealed cellular heterogeneity within these tumors. A correlation has been observed between genetic mutations in fibroids and their size, which is influenced by cellular composition, proliferation rates, and extracellular matrix accumulation. Fibroids with mediator complex subunit 12 (MED12) mutation are composed of smooth muscle cells and fibroblasts equally. In contrast, the fibroids with high-mobility group AT-hook 2 (HMGA2) translocation are 90% composed of smooth muscle cells. More recently, single-cell RNA sequencing in the myometrium and MED12 mutation carrying fibroids has identified further heterogeneity in smooth muscle cells and fibroblast cells, identifying 3 different smooth muscle cell populations and fibroblast cell populations. Although both myometrium and fibroids have similar cellular composition, these cells differs in their transcriptomic profile and have specialized roles, underscoring the complex cellular landscape contributing to fibroid pathogenesis. Furthermore, not all smooth muscle cells in MED12-mutant fibroid carry the MED12 mutation, suggesting that MED12-mutant fibroids might not be monoclonal in nature. This review describes the intricacies of fibroid biology revealed by single-cell RNA sequencing. These advances have identified new cellular targets for potential therapies, provided insights into treatment resistance, and laid the groundwork for more personalized approaches to fibroid management. As we continue to unravel the cellular and molecular complexity of fibroids, we anticipate that this knowledge will translate into more effective and less invasive treatments, ultimately improving outcomes for the millions of women affected by this condition.
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Affiliation(s)
- Jyoti Goad
- Department of Pathology, University of California San Francisco, San Francisco, CA
| | - Aleksandar Rajkovic
- Department of Pathology, University of California San Francisco, San Francisco, CA; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA.
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Neblett MF, Ducharme MT, Meridew JA, Haak AJ, Girard S, Tschumperlin DJ, Stewart EA. Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model. Reprod Sci 2025; 32:417-427. [PMID: 39738934 DOI: 10.1007/s43032-024-01775-6] [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: 09/10/2024] [Accepted: 12/17/2024] [Indexed: 01/02/2025]
Abstract
Uterine leiomyomas are common noncancerous hormonally-dependent neoplasms comprised of uterine smooth-muscle cells and fibroblasts. Despite their significant impact on morbidity, effective non-hormonal medical treatments are lacking. In vitro studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway as a promising target in leiomyoma cells. Our objective was to evaluate the efficacy of AZD1480, a JAK 1/2 inhibitor, in treating uterine leiomyomas using a patient-derived xenograft murine model. Ovariectomized immunodeficient mice received an estrogen and progesterone pellet and were subsequently implanted with human leiomyoma tissue surgically resected from premenopausal women not on hormonal medication. Mice were divided into treatment (n = 6) and vehicle control (n = 6) groups receiving either 50 mg/kg of AZD1480 or vehicle via oral gavage for 5 days/week for 28 days. Our results demonstrate a significant AZD1480-mediated reduction in both xenograft volume (59.5% vs. 0.3%; treated vs. control, p < .0001) and weight (56.0% vs. 31.2%; p = 0.03) compared to controls. Moreover, xenografts from the treated group exhibited a significant decrease in cell density(p = 0.01). Levels of pSTAT3-positive cells (4.1% vs. 10.3%), Ki67-positive cells (4.1% vs. 6.5%), and fibrillar collagen (19.8% vs. 29.5%) declined but did not reach statistical significance, whereas AZD1480 treatment significantly reduced blood vessel formation in the xenografts (20.1 vs 45.6 per FOV; p = 0.01). These findings suggest JAK inhibition as a potential treatment for uterine leiomyomas by targeting angiogenesis. However, further studies are warranted to explore alternative JAK inhibitors, examine downstream effects, optimize dosing, and establish clinical efficacy and safety.
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Affiliation(s)
- Michael F Neblett
- Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA
- Mayo Clinic Alix School of Medicine, Rochester, MN, USA
| | | | - Jeffrey A Meridew
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
| | - Andrew J Haak
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
| | - Sylvie Girard
- Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA
- Mayo Clinic Alix School of Medicine, Rochester, MN, USA
- Department of Immunology, Mayo Clinic, Rochester, MN, USA
| | - Daniel J Tschumperlin
- Mayo Clinic Alix School of Medicine, Rochester, MN, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
| | - Elizabeth A Stewart
- Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA.
- Mayo Clinic Alix School of Medicine, Rochester, MN, USA.
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
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Ogunsina K, O’Brien KM, White AJ, Chang CJ, Gaston SA, Jackson CL, Sandler DP. Hair Straightener Use in Relation to Prevalent and Incident Fibroids in the Sister Study with a Focus on Black Women. ENVIRONMENTAL HEALTH PERSPECTIVES 2025; 133:17004. [PMID: 39808082 PMCID: PMC11730732 DOI: 10.1289/ehp14493] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 10/08/2024] [Accepted: 12/16/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Uterine fibroids disproportionately affect Black women, and exposure to chemicals from hair relaxers or straighteners ("straighteners") may contribute to fibroid development. OBJECTIVES We examined the association between straightener use and prevalent young-onset uterine fibroids (diagnosed before age 36 y), as well as incident fibroids (diagnosed age 36-60 y), with a focus on Black women. We also examined differences in associations across birth cohorts as proxies for formulation changes. METHODS Data from 4,162 Black women in the Sister Study, a prospective cohort of women 35-74 y of age (enrolled 2003-2009), were analyzed. We used logistic regression to estimate odds ratios (ORs) for the association of straightener use at 10-13 y of age and self-reported young-onset fibroids. We used Cox regression to assess hazard ratios (HRs) for straightener use (age 10-13 y and in 12 months before enrollment) and incident fibroids among 779 premenopausal Black women. Similar analyses were conducted in 40,782 non-Hispanic White women. RESULTS Over 70% of Black women used straighteners. In comparison with no use, any [OR = 1.15 ; 95% confidence interval (CI): 0.96, 1.36] and frequent use (OR = 1.18 ; 95% CI: 0.99, 1.42) of straighteners at 10-13 y of age were associated with young-onset fibroids. This association was most apparent among those born between 1928 and 1945 (OR = 1.78 ; 95% CI: 1.15, 2.74) and 1965-1974 (OR = 1.64 ; 95% CI: 0.82, 3.29). Fibroid incidence from 36 to 60 y of age was modestly associated with use of straighteners at 10-13 y of age [hazard ratio ( HR ) = 1.14 ; 95% CI: 0.81, 1.63] and in the 12 months prior to enrollment (HR = 1.32 ; 95% CI: 0.88, 2.00). Among non-Hispanic White women, straightener use at 10-13 y of age was similarly associated with young-onset fibroids (OR = 1.23 ; 95% CI: 1.03, 1.47) despite lower use (≤ 5 % ) of straighteners. Sensitivity analyses indicated a potential for bias due to fibroid misclassification, with an overestimation of the effect likely if nulliparous women or women from households with lower education reported their fibroid status less accurately. DISCUSSION Hair straightener use may be positively associated with fibroid risk. https://doi.org/10.1289/EHP14493.
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Affiliation(s)
- Kemi Ogunsina
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
| | - Katie M. O’Brien
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
| | - Alexandra J. White
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
| | - Che-Jung Chang
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
| | - Symielle A. Gaston
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
| | - Chandra L. Jackson
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
- Intramural Research Program, National Institute on Minority Health and Health Disparities, Bethesda, Maryland, USA
| | - Dale P. Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
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Keizer AL, Semmler A, Kok HS, van Kesteren PJM, Huirne JAF, Hehenkamp WJK. Modifiable prognostic factors in uterine fibroid development: a systematic review of literature. J OBSTET GYNAECOL 2024; 44:2288225. [PMID: 38102975 DOI: 10.1080/01443615.2023.2288225] [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: 01/26/2023] [Accepted: 11/20/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND Many risk factors in uterine fibroid development have been identified, but women and their physicians are less aware of the influence of lifestyle on uterine fibroid development. The objective of this systematic review is to investigate and summarize modifiable prognostic factors associated with uterine fibroid development. METHODS Pubmed and Embase were searched for relevant articles according to PRISMA guidelines. References from included articles were screened and when relevant also included. Human in vivo studies on modifiable factors in fibroid development were included. Studies on non-modifiable factors and treatment, in vitro studies and animal studies were excluded. 607 articles were screened and 33 articles were included. Two independent investigators collected data from the report. RESULTS The strongest risk factor for fibroid development was a high BMI, while the strongest protective factors were a high fruit and vegetable intake and high vitamin D intake. CONCLUSION More high-quality studies are necessary to better understand the impact of the abovementioned factors as well as the role they play in the growth of already existing fibroids.
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Affiliation(s)
- Alieke L Keizer
- Department of Obstetrics and Gynaecology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
| | - Annika Semmler
- Department of Obstetrics and Gynaecology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
| | - Helen S Kok
- Department of Obstetrics and Gynaecology, Alrijne Ziekenhuis location Leiden, Leiden, The Netherlands
| | - Paul J M van Kesteren
- OLVG Location East, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands
| | - Judith A F Huirne
- Department of Obstetrics and Gynaecology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
- Department of Obstetrics and Gynaecology, University of Amsterdam, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
| | - Wouter J K Hehenkamp
- Department of Obstetrics and Gynaecology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
- Department of Obstetrics and Gynaecology, University of Amsterdam, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
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Stewart EA, Laughlin-Tommaso SK. Uterine Fibroids. N Engl J Med 2024; 391:1721-1733. [PMID: 39504521 DOI: 10.1056/nejmcp2309623] [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: 11/08/2024]
Affiliation(s)
- Elizabeth A Stewart
- From the Divisions of Reproductive Endocrinology (E.A.S.) and Gynecology (S.K.L.-T.), Department of Obstetrics and Gynecology, the Department of Physiology and Biomedical Engineering (E.A.S.), the Division of Endocrinology, Department of Medicine (E.A.S.), the Department of Surgery (E.A.S., S.K.L.-T.), and the Women's Health Research Center (E.A.S., S.K.L.-T.), Mayo Clinic, and the Mayo Clinic College of Medicine and Science (E.A.S., S.K.L.-T.) - both in Rochester, MN
| | - Shannon K Laughlin-Tommaso
- From the Divisions of Reproductive Endocrinology (E.A.S.) and Gynecology (S.K.L.-T.), Department of Obstetrics and Gynecology, the Department of Physiology and Biomedical Engineering (E.A.S.), the Division of Endocrinology, Department of Medicine (E.A.S.), the Department of Surgery (E.A.S., S.K.L.-T.), and the Women's Health Research Center (E.A.S., S.K.L.-T.), Mayo Clinic, and the Mayo Clinic College of Medicine and Science (E.A.S., S.K.L.-T.) - both in Rochester, MN
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Yousofzai BS, Alami M, Sheela SK, Subhan M, Bibi R, Ali A, Dhakecha MD, Zafar T, Vasudevan L, Shafique Ur Rehman M. Mifepristone's Efficacy for Symptomatic Relief and Size Reduction in Uterine Fibroids: A 2023 Prospective Observational Study at Rabia Balkhi Hospital, Afghanistan. Cureus 2024; 16:e73432. [PMID: 39664156 PMCID: PMC11633070 DOI: 10.7759/cureus.73432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2024] [Indexed: 12/13/2024] Open
Abstract
Background Uterine fibroids (leiomyomas) are common benign tumors, affecting 70-80% of women by age 50, and can cause symptoms such as heavy bleeding, pelvic pain, and pressure, significantly impacting the quality of life. In severe cases, fibroids may lead to infertility or miscarriage, making their management a key healthcare challenge. Traditional treatments, including hysterectomy, may not be suitable for women wishing to preserve fertility or avoid surgery. Mifepristone, an antiprogestogen, has shown promise as a non-invasive alternative by blocking progesterone, which promotes fibroid growth. It has been proven to reduce fibroid size and alleviate symptoms, offering a valuable option for women seeking alternatives to invasive procedures. Objective This study aimed to evaluate the efficacy of mifepristone in providing symptomatic relief and reducing fibroid size in patients with uterine fibroids at Rabia Balkhi Hospital, Kabul, Afghanistan, in 2023. Methodology A descriptive, prospective study was conducted from January to June 2023, enrolling 20 women with symptomatic uterine fibroids. The inclusion criteria were women aged 30-55 years with clinically diagnosed fibroids causing symptoms such as heavy bleeding or pelvic pain. Exclusion criteria included pregnancy, active infections, or other uterine pathologies. Patients were treated with 25 mg of mifepristone daily for three months. Follow-up assessments were conducted at one, two, and three months to monitor clinical outcomes, including changes in bleeding, fibroid size (measured by ultrasound), and hemoglobin levels. Results Twenty patients (6.25%) with symptomatic fibroids were treated with mifepristone. The majority of cases were in patients aged 46-55 years (50%). Treatment led to a reduction in bleeding in 78% of patients, a decrease in fibroid size in 42.6%, and a reduction in menorrhagia in 44%, evidenced by fewer daily sanitary products used. Hemoglobin levels improved in 33.5% of patients, with an average post-treatment level of 11.8 ± 1.4 g/dL. Statistical significance was set at p < 0.05, supporting mifepristone's efficacy in managing symptomatic fibroids and enhancing patient quality of life. Conclusion Our study concludes that mifepristone at 25 mg is an effective and accessible treatment for fibroids, the same as other published evidence. It offers a practical and economical alternative to surgery, reducing bleeding, inhibiting fibroid growth, and decreasing fibroid size. These findings have significant public health implications, reassuring patients and healthcare providers about the accessibility of effective fibroid treatment.
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Affiliation(s)
| | - Malalai Alami
- Obstetrics and Gynaecology, Rabia Balkhi Hospital (RBH) National Hospital, Kabul, AFG
| | | | - Muhammad Subhan
- Medicine, Jinnah Hospital Lahore, Allama Iqbal Medical College, Lahore, PAK
| | - Ruqiya Bibi
- Medicine, Allama Iqbal Medical College Lahore, Pakistan, Lahore, PAK
| | - Ashik Ali
- Paediatrics and Child Health, SRM Medical College, Chennai, IND
| | | | - Tooba Zafar
- Internal Medicine, Sheikh Zayed Medical College, Rahim Yar Khan, PAK
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Echague C, Malik M, Driggers P, Catherino WH. Coenzyme Q-10 reduced the aberrant production of extracellular matrix proteins in uterine leiomyomas through transforming growth factor beta 3. F&S SCIENCE 2024; 5:342-351. [PMID: 39004304 DOI: 10.1016/j.xfss.2024.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 07/09/2024] [Accepted: 07/09/2024] [Indexed: 07/16/2024]
Abstract
OBJECTIVE To evaluate the impact of coenzyme Q-10 (CoQ-10) on the dysregulated synthesis of extracellular matrix proteins mediated by transforming growth factor beta 3 (TGF-β3) in uterine leiomyomas. DESIGN Laboratory study. SETTING University. PATIENTS None. INTERVENTIONS Treatment of immortalized uterine myometrial and leiomyoma cells to TGF-β3 and CoQ-10. MAIN OUTCOME MEASURES The protein concentrations of collagen 1A1 (COL1A1), collagen 3A1 (COL3A1), collagen 11A1 (COL11A1), and fibronectin (FN1) were assessed through western blot analysis after treatment of immortalized uterine myometrial and leiomyoma cells with both transforming growth factor beta (TGF-β) 3 and concentrations of CoQ-10 at 10, 50, and 100 μM concurrently for 24 hours. RESULTS Immortalized uterine leiomyoma and myometrial cells exposed to TGF-β3 for 24 hours demonstrated a significant up-regulation of COL1A1, COL3A1, COL11A1, and FN1 compared with untreated cells. In leiomyoma cells, concurrent treatment with CoQ-10 over the same timeframe revealed a dose-dependent decrease in these protein concentrations compared with those in cells treated with TGF-β3 alone. At the highest concentration of 100 μM of CoQ-10, significant decreases in the amounts of COL1A1 (0.59 ± 0.10-fold), COL3A1 (0.46 ± 0.09-fold), COL11A1 (0.53 ± 0.09-fold), and FN1 (0.56 ± 0.09-fold) were observed. Similarly, myometrial cells exposed to both TGF-β3 and CoQ-10 demonstrated a dose-responsive decline in the amount of extracellular matrix protein compared with cells exposed to TGF-β3 alone. Significant reductions in the amounts of COL1A1 (0.75 ± 0.03-fold), COL3A1 (0.48 ± 0.06-fold), COL11A1 (0.38 ± 0.06), and FN1 (0.69 ± 0.04-fold) were appreciated at 100-μM CoQ-10. CONCLUSION Coenzyme Q-10 mitigated the aberrant production of key biomarkers of the extracellular matrix mediated by TGF-β3 in uterine leiomyomas. Our findings highlight a promising nonhormonal compound that can counteract the fibroproliferative process inherent to leiomyomas.
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Affiliation(s)
- Charlene Echague
- Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Program in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Minnie Malik
- Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Paul Driggers
- Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - William H Catherino
- Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Program in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
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Harmon QE, Patchel S, Denslow S, Wegienka G, Baird DD. Body Mass Index and Uterine Fibroid Development: A Prospective Study. J Clin Endocrinol Metab 2024; 109:e2016-e2023. [PMID: 38298165 PMCID: PMC11479715 DOI: 10.1210/clinem/dgae036] [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] [Received: 09/26/2023] [Revised: 01/04/2024] [Accepted: 01/18/2024] [Indexed: 02/02/2024]
Abstract
OBJECTIVE Fibroids are hormonally dependent uterine tumors. The literature on adiposity and fibroid prevalence is inconsistent. Previous work usually combined all those with a body mass index (BMI) ≥30 kg/m2 into a single category and relied on clinically diagnosed fibroids, which misclassifies the many women with undiagnosed fibroids. We used a prospective cohort design with periodic ultrasound screening to investigate associations between repeated measures of BMI and fibroid incidence and growth assessed at each follow-up ultrasound. METHODS The Study of Environment, Lifestyle & Fibroids followed 1693 Black/African American women, ages 23 to 35 years from Detroit, Michigan, with ultrasound every 20 months for 5 years. Measured height and repeated weight measures were used to calculate BMI. Fibroid incidence was modeled using Cox models among those who were fibroid free at the enrollment ultrasound. Fibroid growth was estimated for individual fibroids matched across visits as the difference in log-volume between visits and was modeled using linear mixed models. All models used time-varying BMI and adjusted for time-varying covariates. RESULTS Compared with BMI <25 kg/m2, those with BMI 30 to <35 kg/m2 had increased fibroid incidence (adjusted hazard ratio, 1.37; 95% CI, 0.96-1.94), those with BMI ≥40 kg/m2 had reduced incidence (adjusted hazard ratio, 0.61; 95% CI, 0.41-0.90). Fibroid growth had mostly small magnitude associations with BMI. CONCLUSION BMI has a nonlinear association with fibroid incidence, which could be driven by effects of BMI on inflammation and reproductive hormones. More detailed measures of visceral and subcutaneous adiposity and their effects on hormones, DNA damage, and cell death are needed.
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Affiliation(s)
- Quaker E Harmon
- Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
| | - Stacy Patchel
- Westat, Public Health Practice, Durham, NC 27713, USA
| | - Sheri Denslow
- Social & Scientific Systems Inc., a DLH Holdings Company, Durham, NC 27703, USA
| | - Ganesa Wegienka
- Department of Public Health Sciences, Henry Ford Health, Detroit, MI 48202, USA
| | - Donna D Baird
- Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
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Drukker K, Medved M, Harmath CB, Giger ML, Madueke-Laveaux OS. Radiomics and quantitative multi-parametric MRI for predicting uterine fibroid growth. J Med Imaging (Bellingham) 2024; 11:054501. [PMID: 39280239 PMCID: PMC11391479 DOI: 10.1117/1.jmi.11.5.054501] [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: 05/29/2024] [Revised: 08/21/2024] [Accepted: 08/21/2024] [Indexed: 09/18/2024] Open
Abstract
Significance Uterine fibroids (UFs) can pose a serious health risk to women. UFs are benign tumors that vary in clinical presentation from asymptomatic to causing debilitating symptoms. UF management is limited by our inability to predict UF growth rate and future morbidity. Aim We aim to develop a predictive model to identify UFs with increased growth rates and possible resultant morbidity. Approach We retrospectively analyzed 44 expertly outlined UFs from 20 patients who underwent two multi-parametric MR imaging exams as part of a prospective study over an average of 16 months. We identified 44 initial features by extracting quantitative magnetic resonance imaging (MRI) features plus morphological and textural radiomics features from DCE, T2, and apparent diffusion coefficient sequences. Principal component analysis reduced dimensionality, with the smallest number of components explaining over 97.5% of the variance selected. Employing a leave-one-fibroid-out scheme, a linear discriminant analysis classifier utilized these components to output a growth risk score. Results The classifier incorporated the first three principal components and achieved an area under the receiver operating characteristic curve of 0.80 (95% confidence interval [0.69; 0.91]), effectively distinguishing UFs growing faster than the median growth rate of 0.93 cm 3 / year / fibroid from slower-growing ones within the cohort. Time-to-event analysis, dividing the cohort based on the median growth risk score, yielded a hazard ratio of 0.33 [0.15; 0.76], demonstrating potential clinical utility. Conclusion We developed a promising predictive model utilizing quantitative MRI features and principal component analysis to identify UFs with increased growth rates. Furthermore, the model's discrimination ability supports its potential clinical utility in developing tailored patient and fibroid-specific management once validated on a larger cohort.
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Affiliation(s)
- Karen Drukker
- University of Chicago, Department of Radiology, Chicago, Illinois, United States
| | - Milica Medved
- University of Chicago, Department of Radiology, Chicago, Illinois, United States
| | - Carla B Harmath
- University of Chicago, Department of Radiology, Chicago, Illinois, United States
| | - Maryellen L Giger
- University of Chicago, Department of Radiology, Chicago, Illinois, United States
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Chandrakumar DL, Aref-Adib M, Odejinmi F. Advancing women's health: The imperative for public health screening of uterine fibroids for personalized care. Eur J Obstet Gynecol Reprod Biol 2024; 299:266-271. [PMID: 38917750 DOI: 10.1016/j.ejogrb.2024.06.014] [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: 04/16/2024] [Revised: 06/02/2024] [Accepted: 06/08/2024] [Indexed: 06/27/2024]
Abstract
Uterine fibroids represent the most prevalent genital tract tumours among women, with a disproportionately higher impact on ethnic minority groups, notably black women. These hormonally dependent monoclonal tumours, characterized by excessive extracellular matrix and influenced by genetic, epigenetic, and lifestyle factors, significantly affect women's quality of life and pose substantial economic burdens on healthcare systems. Recent advances in early detection and minimally invasive treatment options have shifted management paradigms towards personalized care, yet challenges in early diagnosis, education and access to treatment persist. This review synthesizes current knowledge on uterine fibroids, highlighting the impact of fibroids on women's health, risk factors, principles of screening, diagnostic tools, and treatment modalities. It emphasizes the importance of early screening and individualized management strategies in improving patient outcomes and reducing healthcare costs. The article also discusses the socio-economic and health disparities affecting the disease burden, underscoring the need for improved patient education, clinician training, and public health strategies to enhance fibroid management. This review proposes a pathway to not only ameliorate the quality of life for women with fibroids, but also to advance global women's health equity.
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Affiliation(s)
| | | | - Funlayo Odejinmi
- Whipps Cross University Hospital, Whipps Cross Road, London E11 1NR, UK
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11
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Dolmans MM, Petraglia F, Catherino WH, Donnez J. Pathogenesis of uterine fibroids: current understanding and future directions. Fertil Steril 2024; 122:6-11. [PMID: 38453042 DOI: 10.1016/j.fertnstert.2024.02.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 02/29/2024] [Indexed: 03/09/2024]
Abstract
Fibroids are benign uterine tumors characterized by the proliferation of uterine smooth muscle cells, embedded in an abundant extracellular matrix. Their prevalence is estimated to be >50% in women aged >45 years. Fibroids represent a considerable health burden. It is time to acquire a deeper mechanistic understanding of uterine fibroid-related etiology and pathogenesis, which may help pinpoint new strategies and an individualized approach. There is a need to gather prospective data and conduct studies to compare alternative approaches and assess long-term outcomes with respect to quality of life, recurrence of symptoms (bleeding and bulk symptoms), fertility, and even complications The goal of this review was to evaluate the widely accepted pathogenesis and identify risks factors and future directions for clinical and basic research into fibroids.
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Affiliation(s)
- Marie-Madeleine Dolmans
- Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCL), Brussels, Belgium; Gynecology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
| | - Felice Petraglia
- Obstetrics and Gynecology, Department of Maternal-Infancy, Careggi University Hospital Florence, Florence, Italy; Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
| | - William H Catherino
- Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Jacques Donnez
- Université Catholique de Louvain, Brussels, Belgium; Society for Research into Infertility (SRI), Brussels, Belgium
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George JW, Cancino RA, Griffin Miller JL, Qiu F, Lin Q, Rowley MJ, Chennathukuzhi VM, Davis JS. Characterization of m6A Modifiers and RNA Modifications in Uterine Fibroids. Endocrinology 2024; 165:bqae074. [PMID: 38946397 PMCID: PMC11222979 DOI: 10.1210/endocr/bqae074] [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] [Received: 09/02/2023] [Revised: 06/07/2024] [Accepted: 06/20/2024] [Indexed: 07/02/2024]
Abstract
Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA sequencing (RNA-seq) data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by ultra-high performance liquid chromatography-mass spectrometry identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic subtype. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression, and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort.
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Affiliation(s)
- Jitu W George
- Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Veterans Affairs Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA
| | - Rosa A Cancino
- Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Jennifer L Griffin Miller
- Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Fang Qiu
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Qishan Lin
- RNA Epitranscriptomics and Proteomics Resource, Department of Chemistry, University at Albany, Albany, NY 12222, USA
| | - M Jordan Rowley
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Varghese M Chennathukuzhi
- Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - John S Davis
- Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Veterans Affairs Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA
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Medved M, Harmath CB, Siblini H, Giurcanu M, Kulkarni K, Hellman KM, Madueke-Laveaux OS. Multiparametric quantitative magnetic resonance imaging of uterine fibroids for prediction of growth rate-a pilot study. Quant Imaging Med Surg 2024; 14:4362-4375. [PMID: 39022288 PMCID: PMC11250352 DOI: 10.21037/qims-23-1663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 04/11/2024] [Indexed: 07/20/2024]
Abstract
Background Uterine fibroid (UF) growth rate and future morbidity cannot be predicted. This can lead to sub-optimal clinical management, with women being lost to follow-up and later presenting with severe disease that may require hospitalization, transfusions, and urgent surgical interventions. Multi-parametric quantitative magnetic resonance imaging (MRI) could provide a biomarker to predict growth rate facilitating better-informed disease management and better clinical outcomes. We assessed the ability of putative quantitative and qualitative MRI predictive factors to predict UF growth rate. Methods Twenty women with UFs were recruited and completed baseline and follow-up MRI exams, 1-2.5 years apart. The subjects filled out symptom severity and health-related quality of life questionnaires at each visit. A standard clinical pelvic MRI non-contrast exam was performed at each visit, followed by a contrast-enhanced multi-parametric quantitative MRI (mp-qMRI) exam with T2, T2*, and apparent diffusion coefficient (ADC) mapping and dynamic contrast-enhanced MRI. Up to 3 largest fibroids were identified and outlined on the T2-weighted sequence. Fibroid morphology and enhancement patterns were qualitatively assessed on dynamic contrast-enhanced MRI. The UFs' volumes and average T2, T2*, and ADC values were calculated. Pearson correlation coefficients were calculated between UF growth rate and T2, T2*, ADC, and baseline volume. Multiple logistic regression and receiver operating characteristic (ROC) analysis were performed to predict fast-growing UFs using combinations of up to 2 significant predictors. A significance level of alpha =0.05 was used. Results Forty-four fibroids in 20 women had growth rate measurement available, and 36 fibroids in 16 women had follow-up quantitative MRI available. The distribution of fibroid growth rate was skewed, with approximately 20% of the fibroids exhibiting fast growth (>10 cc/year). However, there were no significant changes in median baseline and follow-up values of symptom severity and health-related quality of life scores. There was no change in average T2, T2*, and ADC at follow-up exams and there was a moderate to strong correlation to the fibroid growth rate in baseline volume and average T2 and ADC in slow-growing fibroids (<10 cc/year). A multiple logistic regression to identify fast growing UFs (>10 cc/year) achieved an area under the curve (AUC) of 0.80 with specificity of 69% at 100% sensitivity. Conclusions The mp-qMRI parameters T2, ADC, and UF volume obtained at the time of initial fibroid diagnosis may be able to predict UF growth rate. Mp-qMRI could be integrated into the management of UFs, for individualized care and improved clinical outcomes.
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Affiliation(s)
- Milica Medved
- Department of Radiology, The University of Chicago, Chicago, IL, USA
| | - Carla B. Harmath
- Department of Radiology, The University of Chicago, Chicago, IL, USA
| | - Hiba Siblini
- Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL, USA
| | - Mihai Giurcanu
- Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA
| | - Kirti Kulkarni
- Department of Radiology, The University of Chicago, Chicago, IL, USA
| | - Kevin M. Hellman
- Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL, USA
- Department of Obstetrics and Gynecology, Northshore University Health System, Chicago, IL, USA
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Wang Y, Zhao Y, Shi C, Li J, Huang X. Development and Validation of a Nomogram to Predict the Risk of Special Uterine Leiomyoma Pathological Types or Leiomyosarcoma in Postmenopausal Women: A Retrospective Study. Risk Manag Healthc Policy 2024; 17:1669-1685. [PMID: 38919406 PMCID: PMC11198023 DOI: 10.2147/rmhp.s461773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 06/10/2024] [Indexed: 06/27/2024] Open
Abstract
Purpose The aim of this study was to investigate the risk factors of postmenopausal special uterine leiomyoma pathological types or leiomyosarcoma and to develop a nomogram for clinical risk assessment, ultimately to reduce unnecessary surgical interventions and corresponding economic expenses. Methods A total of 707 patients with complete information were enrolled from 1 August 2012 to 1 August 2022. Univariate and multivariate logistic regression models were used to analyse the association between variables and special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. A nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients was developed and validated by bootstrap resampling. The calibration curve was used to assess the accuracy of the model and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were compared with the clinical experience model. Results The increasing trend after menopause, the diameter of the largest uterine fibroid, serum carcinoembryonic antigen 125 concentration, Serum neutrophil to lymphocyte ratio, and Serum phosphorus ion concentration were independent risk factors for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. We developed a user-friendly nomogram which showed good diagnostic performance (AUC=0.724). The model was consistent and the calibration curve of our cohort was close to the ideal diagonal line. DCA indicated that the model has potential value for clinical application. Furthermore, our model was superior to the previous clinical experience model in terms of ROC and DCA. Conclusion We have developed a prediction nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. This nomogram could serve as an important warning signal and evaluation method for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients.
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Affiliation(s)
- Yaping Wang
- Zhejiang University, Womens Hospital, Sch Med, Department Obstet & Gynecol, Hangzhou, Zhejiang, People’s Republic of China
| | - Yiyi Zhao
- Zhejiang University, Womens Hospital, Sch Med, Department Obstet & Gynecol, Hangzhou, Zhejiang, People’s Republic of China
| | - Chaolu Shi
- Cixi maternity&health Care Hospital, Department Obstet & Gynecol Ningbo, Ningbo, Zhejiang, People’s Republic of China
| | - Juanqing Li
- Zhejiang University, Womens Hospital, Sch Med, Department Obstet & Gynecol, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Xiufeng Huang
- Zhejiang University, Womens Hospital, Sch Med, Department Obstet & Gynecol, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
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15
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Kiesler ZG, Hunter MI, Balboula AZ, Patterson AL. Periostin's role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma. Arch Gynecol Obstet 2024; 309:1825-1831. [PMID: 38441600 DOI: 10.1007/s00404-024-07435-z] [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: 10/02/2023] [Accepted: 02/14/2024] [Indexed: 04/16/2024]
Abstract
Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-β, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-β-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.
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Affiliation(s)
- Zahra G Kiesler
- Division of Animal Sciences, University of Missouri, Columbia, MO, 65211, USA
| | - Mark I Hunter
- Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO, 65211, USA
| | - Ahmed Z Balboula
- Division of Animal Sciences, University of Missouri, Columbia, MO, 65211, USA
| | - Amanda L Patterson
- Division of Animal Sciences, University of Missouri, Columbia, MO, 65211, USA.
- Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO, 65211, USA.
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16
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Baker C, Indir P, Handy K, Jones J. Symptomatic Calcified Uterine Fibroids Refractory to Repeat Uterine Artery Embolization: A Case Report. Cureus 2024; 16:e61081. [PMID: 38919206 PMCID: PMC11197667 DOI: 10.7759/cureus.61081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2024] [Indexed: 06/27/2024] Open
Abstract
Uterine leiomyomas, also known as uterine fibroids, are a commonly encountered condition with a diverse clinical presentation. Uterine fibroids are benign, smooth muscle tumors of the uterus arising from a single myometrial cell. The presentation can vary from asymptomatic incidental findings to causing a wide array of gynecological symptoms, including abnormal uterine bleeding, infertility, chronic pelvic pain, and bulk-related symptoms. There are several management approaches depending on the patient's clinical manifestations and goals. This is a unique case of a patient with symptomatic calcified uterine fibroids refractory to medical management and two uterine artery embolizations presenting with persistent abnormal uterine bleeding and chronic pelvic pain. Preservation of the uterus was desired, so an open myomectomy was subsequently performed. The patient was asymptomatic at two weeks follow-up, and further follow-up was unable to be obtained. When considering interventions for symptomatic uterine fibroids, it is essential to consider the patient's preference for uterine-sparing methods and desire to preserve fertility. It is necessary that all modes of treatment and their potential future implications be discussed so that patients can make well-informed decisions regarding all aspects of their care. Further studies are needed comparing the outcomes of uterine-sparing interventions for symptomatic uterine fibroids so that the best possible shared decision-making can take place.
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Affiliation(s)
- Christopher Baker
- Osteopathic Medicine, Philadelphia College of Osteopathic Medicine, Moultrie, USA
| | - Pooja Indir
- Family Medicine, Piedmont Columbus Midtown, Columbus, USA
| | - Kendall Handy
- Obstetrics and Gynecology, Piedmont Columbus Midtown, Columbus, USA
| | - Jefferson Jones
- Obstetrics and Gynecology, Piedmont Columbus Midtown, Columbus, USA
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Langton CR, Harmon QE, Baird DD. Family History and Uterine Fibroid Development in Black and African American Women. JAMA Netw Open 2024; 7:e244185. [PMID: 38568693 PMCID: PMC10993075 DOI: 10.1001/jamanetworkopen.2024.4185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 01/22/2024] [Indexed: 04/05/2024] Open
Abstract
Importance Uterine fibroids are an understudied condition, with earlier onset in Black than White women. Prior studies of the importance of family history on fibroid development are limited by reliance on hospital-based participant selection, poorly defined measures of family history, and nonsystematic fibroid assessment. Objective To examine whether family history is a risk factor for fibroid development using prospective ultrasonography data to identify incident fibroids and measure fibroid growth and standardized methods to ascertain family history. Design, Setting, and Participants This prospective community cohort of Black and African American women from the Detroit, Michigan, area was conducted from January 1, 2010, to December 31, 2018, using 4 standardized ultrasonographic examinations during 5 years to detect fibroids 0.5 cm or larger in diameter and measure fibroid growth. Data analysis was performed between May 2022 and January 2024. Exposures Maternal fibroid history data were gathered directly from participants' mothers when possible (1425/1628 [88%]), and 2 exposure variables were created: maternal history of fibroids (diagnosed vs not diagnosed) and age at maternal fibroid diagnosis (20-29, 30-39, or ≥40 years vs not diagnosed). Main Outcomes and Measures Fibroid incidence was assessed using multivariable Cox proportional hazards regression models; fibroid growth was calculated as change in log-volume per 18 months for fibroids matched at successive ultrasonograms. Results A total of 1610 self-identified Black and/or African American women aged 23 to 35 years (mean [SD] age, 29.2 [3.4] years) with no prior clinical diagnosis of fibroids at enrollment were available for analysis. Of 1187 fibroid-free participants at enrollment, 442 (37%) had mothers who were diagnosed with fibroids. Compared with participants without a maternal history of fibroids, those reporting maternal history had an adjusted hazard ratio (AHR) of 1.21 (95% CI, 0.96-1.52). Risk was strongest in those whose mothers were diagnosed at a younger age (20-29 years: AHR, 1.56; 95% CI, 1.11-2.21; 30-39 years: AHR, 1.03; 95% CI, 0.71-1.49; ≥40 years: AHR, 1.11; 95% CI, 0.81-1.52; P = .053 for trend). Fibroid growth rates were higher when mothers were diagnosed with fibroids vs not diagnosed (8.0% increased growth; 95% CI, -1.2% to 18.0%). Conclusions and Relevance In this prospective cohort study, results supported maternal history of fibroids as a risk factor for incident fibroids, especially when mothers were diagnosed at a younger age. Maternal history was also associated with increased fibroid growth. Asking patients about their family history of fibroids could encourage patient self-advocacy and inform care.
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Affiliation(s)
- Christine R. Langton
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
| | - Quaker E. Harmon
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
| | - Donna D. Baird
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
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Tang NH, Fang CL, Hu WH, Tian L, Lin C, Hu HQ, Shi QL, Xu F. Age-stratified risk factors of re-intervention for uterine fibroids treated with high-intensity focused ultrasound. Int J Gynaecol Obstet 2024; 164:1212-1219. [PMID: 37953647 DOI: 10.1002/ijgo.15217] [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: 04/01/2023] [Revised: 07/17/2023] [Accepted: 10/17/2023] [Indexed: 11/14/2023]
Abstract
OBJECTIVE To estimate the rate and risk factors of re-intervention for patients with uterine fibroids (UFs) undergoing high-intensity focused ultrasound (HIFU) at different age distributions. METHOD A retrospective cohort study was conducted in Nanchong Central Hospital, recruiting a total of 672 patients with UFs undergoing HIFU from June 2017 to December 2019. Using univariate and multivariate logistic regression, risk factors for re-intervention were assessed. RESULTS Among 401 patients with UFs who completed the follow-up visits (median 47 months, range 34-61), 50 (12.46%) patients underwent re-intervention (such as high-intensity focused ultrasound, uterine artery embolization, myomectomy and hysterectomy). In the different age distributions, the re-intervention rate was 17.5% (34/194) in patients aged <45 years and 7.7% (16/207) in those aged ≥45 years. Regarding the younger patient group (aged <45 years), hypo- or iso-intensive fibroids in T2-weighted magnetic resonance imaging (T2WI) intensity may elevate the risk of re-intervention for UFs (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.37-6.62; P = 0.007). Among the older patient group (aged ≥45 years), preoperative anemic patients had an increased risk of re-intervention compared with those without anemia (OR 3.30, 95% CI 1.01-10.37; P = 0.041). CONCLUSION The re-intervention rate of HIFU decreased with increasing age. Among those aged <45 years, T2WI intensity was the independent risk factor for re-intervention, and among those aged ≥45 years, preoperative anemic status may be related to re-intervention outcome.
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Affiliation(s)
- Neng-Huan Tang
- State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People's Republic of China
- Department of Obstetrics and Gynecology, Affiliated Nanchong Central Hospital of North Sichuan Medical University, Nanchong, People's Republic of China
| | - Chun-Ling Fang
- Department of Obstetrics and Gynecology, Affiliated Nanchong Central Hospital of North Sichuan Medical University, Nanchong, People's Republic of China
| | - Wen-Hao Hu
- State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People's Republic of China
| | - Ling Tian
- Department of Obstetrics and Gynecology, Affiliated Nanchong Central Hospital of North Sichuan Medical University, Nanchong, People's Republic of China
| | - Chuan Lin
- Department of Obstetrics and Gynecology, Affiliated Nanchong Central Hospital of North Sichuan Medical University, Nanchong, People's Republic of China
| | - Hui-Quan Hu
- Department of Obstetrics and Gynecology, Affiliated Nanchong Central Hospital of North Sichuan Medical University, Nanchong, People's Republic of China
| | - Qiu-Ling Shi
- State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People's Republic of China
- School of Public Health and Management, Chongqing Medical University, Chongqing, People's Republic of China
| | - Fan Xu
- State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People's Republic of China
- Department of Obstetrics and Gynecology, Affiliated Nanchong Central Hospital of North Sichuan Medical University, Nanchong, People's Republic of China
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Coyne K, Purdy MP, Bews KA, Habermann EB, Khan Z. Risk of hysterectomy at the time of myomectomy: an underestimated surgical risk. Fertil Steril 2024; 121:107-116. [PMID: 37777107 DOI: 10.1016/j.fertnstert.2023.09.017] [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: 07/21/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/02/2023]
Abstract
OBJECTIVE To evaluate the risk of hysterectomy at the time of myomectomy and the associated 30-day postoperative morbidity. DESIGN Cohort study. PATIENTS Patients who underwent myomectomies identified from the American College of Surgeons' National Surgical Quality Improvement Program from 2010 to 2021. INTERVENTION Unplanned hysterectomy at the time of a myomectomy procedure. MAIN OUTCOME MEASURES The Current Procedural Terminology codes were used to identify myomectomies performed with or without concurrent hysterectomy. Preoperative characteristics and morbidity outcomes were obtained. The univariate analysis was performed using the chi-square and Fisher exact tests, as appropriate. Multivariate logistic regression reported risk factors for individuals who underwent hysterectomy at the time of myomectomy. P values of <.05 were considered statistically significant. RESULTS A total of 13,213 individuals underwent myomectomy, and 399 (3.0%) had a hysterectomy performed during myomectomy. Concurrent hysterectomy was most frequently performed with the laparoscopic approach (7.1%), followed by the abdominal (3.2%) and hysteroscopic (1.9%) approaches. Age ≥43 years, obesity class II and higher, American Society of Anesthesiologists (ASA) class greater than II, tobacco use, longer operative time (>85 minutes), and laparoscopic approach were associated with a significantly increased risk of hysterectomy. When adjusting for age, body mass index, race, ASA class, case type, surgical approach, operative time, preoperative transfusion, preoperative hematocrit, and high fibroid burden, an increased odds of hysterectomy was noted for white race, longer operative time, ASA class III or higher, obesity, laparoscopic approach, and low fibroid burden. Patients who underwent concurrent hysterectomy had a longer median length of hospital stay (2 vs. 1 day), longer median operative time (161 vs. 126 minutes), increased intraoperative/postoperative blood transfusions (14.5% vs. 9.0%), and higher rates of organ/space surgical site infections (1.5% vs. 0.5%) and return to surgery (2.0% vs. 0.7%) than those who did not (P<.05). The risk of a major complication within 30 days of myomectomy increased in patients who underwent concurrent hysterectomy after adjusting for relevant confounders (adjusted odds ratio, 2.4; 95% confidence interval, 1.8-3.2). CONCLUSION The risk of hysterectomy during a myomectomy is higher than previously reported. The patient age of ≥43 years, obesity, white race, ASA class III or higher, longer operative time, and laparoscopic approach were associated with higher odds of hysterectomy. Identification of patients with these risk factors can aid in patient counseling and surgical planning, which may help reduce the unexpectedly high rates of hysterectomy at planned myomectomy.
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Affiliation(s)
- Kathryn Coyne
- Division of Reproductive Endocrinology and Infertility, University Hospitals, Cleveland, Ohio.
| | | | - Katherine A Bews
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Surgical Outcomes Program, Mayo Clinic, Rochester, Minnesota
| | - Elizabeth B Habermann
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Surgical Outcomes Program, Mayo Clinic, Rochester, Minnesota
| | - Zaraq Khan
- Division of Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, Minnesota; Division of Minimally Invasive Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota
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Adebamowo CA, Adebamowo SN. Population-based study of the reproductive risk factors for transvaginal ultrasound diagnosed uterine fibroids in Nigerian women. Sci Rep 2023; 13:18926. [PMID: 37919335 PMCID: PMC10622570 DOI: 10.1038/s41598-023-44703-5] [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: 05/10/2023] [Accepted: 10/11/2023] [Indexed: 11/04/2023] Open
Abstract
There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74-0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24-0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35-0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27-0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01-1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.
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Affiliation(s)
- Clement A Adebamowo
- Department of Epidemiology and Public Health, and the Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, 660 West Redwood Street, Baltimore, MD, 21201, USA.
- Center for Bioethics and Research, Ibadan, Nigeria.
- Institute of Human Virology Nigeria, Abuja, Nigeria.
| | - Sally N Adebamowo
- Department of Epidemiology and Public Health, and the Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, 660 West Redwood Street, Baltimore, MD, 21201, USA
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Warwar R, Zupan AM, Nietupski C, Manzanares M, Hurley EG, Schutte SC. Uterine fibroid cell cytoskeletal organization is affected by altered G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase signaling. F&S SCIENCE 2023; 4:327-338. [PMID: 37797815 DOI: 10.1016/j.xfss.2023.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 09/05/2023] [Accepted: 09/26/2023] [Indexed: 10/07/2023]
Abstract
OBJECTIVE To determine whether cyclic strain affects fibroid cell cytoskeletal organization, proliferation, and collagen synthesis differently than myometrial cells. DESIGN A basic science study using primary cultures of patient-matched myometrial and fibroid cells. SETTING Academic laboratory. PATIENT(S) Premenopausal women undergoing myomectomy or hysterectomy for the treatment of symptomatic uterine fibroids. INTERVENTION(S) Application of uniaxial strain patterns mimicking periovulation, menses, or dysmenorrhea using the Flexcell tension system or static control. Secondarily, inhibition of G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase. MAIN OUTCOME MEASURE(S) Cell alignment, cell number, and collagen content. RESULT(S) Menses-strained cells demonstrated the most variation in cell alignment, cell proliferation, and procollagen content between myometrial and fibroid cells. Procollagen content decreased in myometrial cells with increasing strain amplitude and decreasing frequency. G protein-coupled estrogen receptor-1 inhibition decreases cellular alignment in the presence of strain. CONCLUSION(S) Mechanotransduction affecting cytoskeletal arrangement through the G protein-coupled estrogen receptor-1-phosphatidylinositol 3-kinase pathway is altered in fibroid cells. These results highlight the importance of incorporating mechanical stimulation into the in vitro study of fibroid pathology.
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Affiliation(s)
- Rachel Warwar
- Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Andreja Moset Zupan
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio
| | - Carolyn Nietupski
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio
| | - Maricela Manzanares
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio
| | - Emily G Hurley
- Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Stacey C Schutte
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio.
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22
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Liu L, Xiao YH, Zhou XH. Effects of humanized nursing care on negative emotions and complications in patients undergoing hysteromyoma surgery. World J Clin Cases 2023; 11:6763-6773. [PMID: 37901016 PMCID: PMC10600858 DOI: 10.12998/wjcc.v11.i28.6763] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/13/2023] [Accepted: 08/29/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND Uterine fibroids, are prevalent benign tumors affecting women of reproductive age. However, surgical treatment is often necessary for symptomatic hysteromyoma cases. This study examines the impact of humanized nursing care on reducing negative emotions and postoperative complications in patients receiving hysteromyoma surgery. AIM To investigate the impact of humanized nursing care on patients undergoing hysteromyoma surgery. METHODS Among patients who underwent hysteromyoma surgery at the Fudan University Affiliated Obstetrics and Gynecology Hospital, 200 were randomly assigned to either the control group (n = 100) or the humanized nursing care group (n = 100). The control group received traditional nursing care, while the humanized nursing care group received a comprehensive care plan encompassing psychological support, pain management, and tailored rehabilitation programs. In addition, anxiety and depression levels were assessed using the hospital anxiety and depression scale preoperatively and postoperatively. Postoperative complications were evaluated during follow-up assessments and compared between both groups. RESULTS The humanized nursing care group demonstrated a significant decrease in anxiety and depression levels compared to the control group (P < 0.05). The rate of postoperative complications, including infection, bleeding, and deep venous thrombosis, was also markedly lower in the humanized nursing care group (P < 0.05). CONCLUSION Humanized nursing care can effectively alleviate negative emotions and reduce the incidence of postoperative complications in patients undergoing hysteromyoma surgery. This approach should be considered a crucial component of perioperative care for these patients. Further research may be needed to explore additional benefits and long-term outcomes of implementing humanized nursing care in this population.
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Affiliation(s)
- Li Liu
- Operating Room, Fudan University Affiliated Obstetrics and Gynecology Hospital, Shanghai 200092, China
| | - Ya-Hong Xiao
- Operating Room, Cardiovascular Hospital of The Second Affiliated Hospital of Hainan Medical College, Haikou 571199, Hainan Province, China
| | - Xue-Hua Zhou
- Department of Nursing, Chongzuo People's Hospital, Chongzuo 532200, Guangxi Zhuang Autonomous Region, China
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23
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Gracia M, Rius M, Carmona F. Clinical relevance of uterine fibroids: Epidemiology, risk and protective factors, and pathophysiology. Med Clin (Barc) 2023; 161 Suppl 1:S1-S4. [PMID: 37923508 DOI: 10.1016/j.medcli.2023.06.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 06/07/2023] [Accepted: 06/27/2023] [Indexed: 11/07/2023]
Affiliation(s)
- Meritxell Gracia
- Departamento de Ginecología. Institut Clínic de Ginecologia, Obstetrícia i Neonatologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Facultad de Medicina, Universidad de Barcelona, Barcelona, España.
| | - Mariona Rius
- Departamento de Ginecología. Institut Clínic de Ginecologia, Obstetrícia i Neonatologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Facultad de Medicina, Universidad de Barcelona, Barcelona, España
| | - Francisco Carmona
- Departamento de Ginecología. Institut Clínic de Ginecologia, Obstetrícia i Neonatologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Facultad de Medicina, Universidad de Barcelona, Barcelona, España
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24
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Sim-Ifere O, Aref-Adib M, Odejinmi F. Oral gonadotrophin-releasing hormone (GnRH) antagonists: the continuing search for the ideal nonsurgical therapy of uterine fibroids with a cautionary tale. Curr Opin Obstet Gynecol 2023; 35:460-465. [PMID: 37560806 DOI: 10.1097/gco.0000000000000907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/11/2023]
Abstract
PURPOSE OF REVIEW Uterine fibroids are very common with a prevalence of over 70%. They present a significant economic and psychological burden. A variety of nonsurgical treatments exist for its management encompassing hormonal and nonhormonal methods. Gonadotrophin-releasing hormone (GnRH) antagonists are a novel treatment for uterine fibroids. They cause a rapid reduction in endogenous GnRH, leading to a dose-dependent reduction in levels of oestradiol and progesterone, thus reduction in bleeding. The addition of hormones, estrogen, and progesterone, known as add-back therapy, helps curb the menopausal side effects. As such, they pose a potential long-term nonsurgical therapy for management of symptomatic fibroids. RECENT FINDINGS There are various uses of GnRH antagonists and the results from the clinical trials are promising. Caution needs to be taken when new treatment options are introduced with audit and data collection tools in place to assess effectiveness as well as any side effects. SUMMARY This article highlights the uses of GnRH antagonists in practice and reflects on previous novel treatments for fibroids with a focus on Ulipristal acetate. It states the importance of using audit tools and multiinstitutional databases to prevent and allow early discovery of issues such as those that encumbered Ulipristal.
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Affiliation(s)
| | | | - Funlayo Odejinmi
- Whipps cross university hospital Barts Health NHS Trust, London, UK
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25
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Zuberi A, Huang Y, Dotts AJ, Wei H, Coon JS, Liu S, Iizuka T, Wu O, Sotos O, Saini P, Chakravarti D, Boyer TG, Dai Y, Bulun SE, Yin P. MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas. JCI Insight 2023; 8:e171305. [PMID: 37607000 PMCID: PMC10561729 DOI: 10.1172/jci.insight.171305] [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: 04/13/2023] [Accepted: 08/15/2023] [Indexed: 08/23/2023] Open
Abstract
Uterine leiomyomas cause heavy menstrual bleeding, anemia, and pregnancy loss in millions of women worldwide. Driver mutations in the transcriptional mediator complex subunit 12 (MED12) gene in uterine myometrial cells initiate 70% of leiomyomas that grow in a progesterone-dependent manner. We showed a distinct chromatin occupancy landscape of MED12 in mutant MED12 (mut-MED12) versus WT-MED12 leiomyomas. Integration of cistromic and transcriptomics data identified tryptophan 2,3-dioxygenase (TDO2) as the top mut-MED12 target gene that was significantly upregulated in mut-MED12 leiomyomas when compared with adjacent myometrium and WT-MED12 leiomyomas. TDO2 catalyzes the conversion of tryptophan to kynurenine, an aryl hydrocarbon receptor (AHR) ligand that we confirmed to be significantly elevated in mut-MED12 leiomyomas. Treatment of primary mut-MED12 leiomyoma cells with tryptophan or kynurenine stimulated AHR nuclear translocation, increased proliferation, inhibited apoptosis, and induced AHR-target gene expression, whereas blocking the TDO2/kynurenine/AHR pathway by siRNA or pharmacological treatment abolished these effects. Progesterone receptors regulated the expression of AHR and its target genes. In vivo, TDO2 expression positively correlated with the expression of genes crucial for leiomyoma growth. In summary, activation of the TDO2/kynurenine/AHR pathway selectively in mut-MED12 leiomyomas promoted tumor growth and may inform the future development of targeted treatments and precision medicine.
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Affiliation(s)
- Azna Zuberi
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Yongchao Huang
- Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Ariel J. Dotts
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Helen Wei
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - John S. Coon
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Shimeng Liu
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Takashi Iizuka
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Olivia Wu
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Olivia Sotos
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Priyanka Saini
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Debabrata Chakravarti
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Thomas G. Boyer
- Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Yang Dai
- Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Serdar E. Bulun
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Ping Yin
- Division of Reproductive Science in Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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26
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Nowak M, Bartosik W, Witana W, Nowak K, Wilkusz J. Rapidly growing uterine myoma - should we be afraid of it? PRZEGLAD MENOPAUZALNY = MENOPAUSE REVIEW 2023; 22:161-164. [PMID: 37829270 PMCID: PMC10566336 DOI: 10.5114/pm.2023.131497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 03/11/2023] [Indexed: 10/14/2023]
Abstract
During a year, myomas may undergo radical changes in their dimensions - from decreasing by 90% to growing by 200%. On average, myomas of the uterus increase in volume by 20-30% annually in the premenopausal period. On the other hand, myomas regress spontaneously in about 20% of women. After menopause uterine fibroids stabilize or regress. Every new or growing lesion of the uterus after menopause has to be diagnosed. There is no general definition of fast growing uterine myoma. The presence of fast growing uterine myoma, regardless of its definition, is associated with some clinical issues: it may become symptomatic (pain, bleeding, bulk symptoms), may be responsible for infertility, and a malignant process (leiomyosarcoma) may be present. Regardless of common belief, the risk of sarcoma is not related to the size of the uterus or its fast enlargement. The prevalence of sarcoma in myomas is 0.26%, and in rapidly growing myomas is 0.27%. Treatment should be individualized, selected for the age of the woman and her expectations (preservation of fertility, uterus), symptoms, size and localization of the myomas. The methods of surgical treatment of unsuspected "rapidly growing myomas" are the same as those of common uterine fibroids. Minimally invasive surgery is optimal, but a decision has to be made after evaluation of the risk factors of sarcoma.
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Affiliation(s)
- Marek Nowak
- Department of Operative Gynecology and Gynecologic Oncology of Polish Mother’s Memorial Hospital – Research Institute, Łódź, Poland
- Department of Operative and Endoscopic Gynecology, Medical University of Łódź, Łódź, Poland
| | - Wojciech Bartosik
- Department of Operative Gynecology and Gynecologic Oncology of Polish Mother’s Memorial Hospital – Research Institute, Łódź, Poland
| | - Weronika Witana
- Department of Operative Gynecology and Gynecologic Oncology of Polish Mother’s Memorial Hospital – Research Institute, Łódź, Poland
| | - Krzysztof Nowak
- Department of Operative Gynecology and Gynecologic Oncology of Polish Mother’s Memorial Hospital – Research Institute, Łódź, Poland
| | - Julia Wilkusz
- Students’ Scientific Association, Medical University of Łódź, Łódź, Poland
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George JW, Cancino RA, Miller JLG, Qiu F, Lin Q, Rowley MJ, Chennathukuzhi VM, Davis JS. Characterization of m 6A modifiers and RNA modifications in uterine fibroids. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.07.552278. [PMID: 37609293 PMCID: PMC10441280 DOI: 10.1101/2023.08.07.552278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
Uterine leiomyoma or fibroids are the most common prevalent noncancerous tumors of the uterine muscle layer. Common symptoms associated with fibroids include pelvic pain, heavy menstrual bleeding, anemia, and pelvic pressure. These tumors are a leading cause of gynecological care but lack long-term therapy as the origin and development of fibroids are not well understood. Several next-generation sequencing technologies have been performed to identify the underlying genetic and epigenetic basis of fibroids. However, there remains a systemic gap in our understanding of molecular and biological process that define uterine fibroids. Recent epitranscriptomics studies have unraveled RNA modifications that are associated with all forms of RNA and are thought to influence both normal physiological functions and the progression of diseases. We quantified RNA expression profiles by analyzing publicly available RNA-seq data for 15 known epigenetic mediators to identify their expression profile in uterine fibroids compared to myometrium. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key m6A modifiers in fibroids and their matched myometrium. In concordance with our RNA expression profiles, no significant differences were observed in these proteins in uterine fibroids compared to myometrium. To determine abundance of RNA modifications, mRNA and small RNA from fibroids and matched myometrium were analyzed by UHPLC MS/MS. In addition to the prevalent N6-methyladenosine (m6A), we identified 11 other known modifiers but did not identify any aberrant expression in fibroids. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic sub-type. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and varied patient cohort.
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Affiliation(s)
- Jitu W. George
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Veterans Affairs Nebraska Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA
| | - Rosa A. Cancino
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Jennifer L. Griffin Miller
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Fang Qiu
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA
| | - Qishan Lin
- RNA Epitranscriptomics and Proteomics Resource, Department of Chemistry, University at Albany, Albany, NY, United States
| | - M Jordan Rowley
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska
| | - Varghese M. Chennathukuzhi
- Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - John S. Davis
- Olson Center for Women’s Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Veterans Affairs Nebraska Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA
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28
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Wesselink AK, Wegienka G, Coleman CM, Geller RJ, Harmon QE, Upson K, Lovett SM, Claus Henn B, Marsh EE, Noel NL, Baird DD, Wise LA. A prospective ultrasound study of cigarette smoking and uterine leiomyomata incidence and growth. Am J Obstet Gynecol 2023; 229:151.e1-151.e8. [PMID: 37148957 PMCID: PMC10524545 DOI: 10.1016/j.ajog.2023.04.041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 04/12/2023] [Accepted: 04/29/2023] [Indexed: 05/08/2023]
Abstract
BACKGROUND Uterine leiomyomata (fibroids) are common, benign neoplasms that contribute substantially to gynecologic morbidity. Some existing epidemiologic studies indicate that cigarette smoking is associated with lower uterine leiomyomata risk. However, no prospective studies have systematically screened an entire study population for uterine leiomyomata using transvaginal ultrasound or evaluated the association between cigarette smoking and uterine leiomyomata growth. OBJECTIVE This study aimed to examine the association between cigarette smoking and uterine leiomyomata incidence and growth in a prospective ultrasound study. STUDY DESIGN We enrolled 1693 residents from the Detroit metropolitan area into the Study of Environment, Lifestyle, and Fibroids during 2010 to 2012. Eligible participants were aged 23 to 34 years, had an intact uterus but no previous diagnosis of uterine leiomyomata, and self-identified as Black or African American. We invited participants to complete a baseline visit and 4 follow-up visits over approximately 10 years. At each visit, we used transvaginal ultrasound to assess uterine leiomyomata incidence and growth. Participants provided extensive self-reported data throughout follow-up including exposures to active and passive cigarette smoking in adulthood. We excluded participants who did not return for any follow-up visits (n=76; 4%). We fit Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals for the association between time-varying smoking history and incidence rates of uterine leiomyomata. We fit linear mixed models to estimate the percentage difference and 95% confidence intervals for the association between smoking history and uterine leiomyomata growth. We adjusted for sociodemographic, lifestyle, and reproductive factors. We interpreted our results based on magnitude and precision rather than binary significance testing. RESULTS Among 1252 participants without ultrasound evidence of uterine leiomyomata at baseline, uterine leiomyomata were detected in 394 participants (31%) during follow-up. Current cigarette smoking was associated with a lower uterine leiomyomata incidence rate (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Associations were stronger among participants who had smoked for longer durations (≥15 years vs never: hazard ratio, 0.49; 95% confidence interval, 0.25-0.95). The hazard ratio for former smokers was 0.78 (95% confidence interval, 0.50-1.20). Among never smokers, the hazard ratio for current passive smoke exposure was 0.84 (95% confidence interval, 0.65-1.07). Uterine leiomyomata growth was not appreciably associated with current (percent difference, -3%; 95% confidence interval, -13% to 8%) or former (percent difference, -9%; 95% confidence interval, -22% to 6%) smoking. CONCLUSION We provide evidence from a prospective ultrasound study that cigarette smoking is associated with lower uterine leiomyomata incidence.
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Affiliation(s)
- Amelia K Wesselink
- Department of Epidemiology, Boston University School of Public Health, Boston, MA.
| | - Ganesa Wegienka
- Department for Public Health Sciences, Henry Ford Health, Detroit, MI
| | - Chad M Coleman
- Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | - Ruth J Geller
- Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | - Quaker E Harmon
- Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
| | - Kristen Upson
- Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI
| | - Sharonda M Lovett
- Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | - Birgit Claus Henn
- Department of Environmental Health, Boston University School of Public Health, Boston, MA
| | - Erica E Marsh
- Department of Obstetrics & Gynecology, University of Michigan Medical School, Ann Arbor, MI
| | - Nyia L Noel
- Department of Obstetrics & Gynecology, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, MA
| | - Donna D Baird
- Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
| | - Lauren A Wise
- Department of Epidemiology, Boston University School of Public Health, Boston, MA
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29
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Qu Y, Chen L, Guo S, Liu Y, Wu H. Genetic liability to multiple factors and uterine leiomyoma risk: a Mendelian randomization study. Front Endocrinol (Lausanne) 2023; 14:1133260. [PMID: 37576957 PMCID: PMC10415162 DOI: 10.3389/fendo.2023.1133260] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 06/06/2023] [Indexed: 08/15/2023] Open
Abstract
Background and objective Uterine leiomyoma is the most common benign tumor in females of reproductive age. However, its causes have never been fully understood. The objective of our study was to analyze the causal association between various factors and uterine leiomyoma using Mendelian randomization (MR). Methods Genetic variables associated with risk factors were obtained from genome-wide association studies. Summary-level statistical data for uterine leiomyoma were obtained from FinnGen and the UK Biobank (UKB) consortium. We used inverse variance weighted, MR-Egger, and weighted median methods in univariate analysis. Multivariable MR analysis was used to identify independent risk factors. A fixed-effect model meta-analysis was used to combine the results of the FinnGen and UKB data. Results In the FinnGen data, higher genetically predicted age at natural menopause, systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting insulin were associated with an increased risk of uterine leiomyoma, while higher age at menarche was associated with a reduced risk of uterine leiomyoma. Multivariable MR analysis of SBP and DBP showed that higher DBP might be an independent risk factor of uterine leiomyoma. In the UKB data, the results for age at natural menopause, SBP, DBP, and age at menarche were replicated. The result of the meta-analysis suggested that uterine leiomyoma could also be affected by polycystic ovary syndrome (PCOS), endometriosis, and 2-hour glucose level. Conclusion Our MR study confirmed that earlier menstrual age, hypertension, obesity, and elevated 2-hour glucose post-challenge were risk factors for uterine leiomyoma, and the causal relationship between smoking and uterine leiomyoma was ruled out. In addition, later age of menopause and endometriosis were found to increase the risk of uterine leiomyoma, while PCOS was found to decrease the risk.
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Affiliation(s)
- Yangming Qu
- Department of Neonatology, the First Hospital of Jilin University, Changchun, Jilin, China
| | - Lanlan Chen
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun, Jilin, China
| | - Shijie Guo
- Department of Neonatology, the First Hospital of Jilin University, Changchun, Jilin, China
| | - Ying Liu
- Department of Neonatology, the First Hospital of Jilin University, Changchun, Jilin, China
| | - Hui Wu
- Department of Neonatology, the First Hospital of Jilin University, Changchun, Jilin, China
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Adebamowo CA, Morhason-Bello IO, Adebamowo SN. Validation of self-report of uterine fibroid diagnosis using a transvaginal ultrasound scan. Sci Rep 2023; 13:9091. [PMID: 37277479 DOI: 10.1038/s41598-023-36313-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 05/31/2023] [Indexed: 06/07/2023] Open
Abstract
Self-report of uterine fibroids (UF) has been used for epidemiologic research in different environments. Given the dearth of studies on the epidemiology of UF in Sub-Saharan Africa (SSA), it is valuable to evaluate its performance as a potential tool for much needed research on this common neoplasm in SSA women. We conducted a cross-sectional study of self-report of UF compared with transvaginal ultrasound diagnosis (TVUS) among 486 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria. We used log-binomial regression models to compute the classification, sensitivity, specificity, and predictive values of self-report compared to TVUS, adjusted for significant covariates. The prevalence of UF on TVUS was 45.1% (219/486) compared to 5.4% (26/486) based on self-report of abdominal ultrasound scan and 7.2% (35/486) based on report of healthcare practitioner's diagnosis. Self-report correctly classified 39.5% of the women compared to TVUS in multivariable adjusted models. The multivariable adjusted sensitivity of self-report of healthcare worker diagnosis was 38.8%, specificity was 74.5%, positive predictive value (PPV) was 55.6%, and negative predictive value (NPV) was 59.8%. For self-reported abdominal ultrasound diagnosis, the multivariable adjusted sensitivity was 40.6%, specificity was 75.3%, PPV was 57.4%, and NPV was 60.6%. Self-report significantly underestimates the prevalence of UF and is not accurate enough for epidemiological research on UF. Future studies of UF should use population-based designs and more accurate diagnostic tools such as TVUS.
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Affiliation(s)
- Clement A Adebamowo
- Department of Epidemiology and Public Health, School of Medicine, University of Maryland, 660 West Redwood Street, Baltimore, MD, 21201, USA.
- Greenebaum Comprehensive Cancer Center, School of Medicine, University of Maryland, Baltimore, MD, USA.
- Center for Bioethics and Research, Ibadan, Nigeria.
- Institute of Human Virology Nigeria, Abuja, Nigeria.
| | - Imran O Morhason-Bello
- Department of Obstetrics and Gynecology, Faculty of Clinical Sciences, and the Institute of Advanced Medical Research and Training College of Medicine University of Ibadan, Ibadan, Nigeria
| | - Sally N Adebamowo
- Department of Epidemiology and Public Health, School of Medicine, University of Maryland, 660 West Redwood Street, Baltimore, MD, 21201, USA
- Greenebaum Comprehensive Cancer Center, School of Medicine, University of Maryland, Baltimore, MD, USA
- Center for Bioethics and Research, Ibadan, Nigeria
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Yin K, Whitaker L, Hojo E, McLenachan S, Walker J, McKillop G, Stubbs C, Priest L, Cruz M, Roberts N, Critchley H. Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB). Hum Reprod Open 2023; 2023:hoad021. [PMID: 37304815 PMCID: PMC10247393 DOI: 10.1093/hropen/hoad021] [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: 11/21/2022] [Revised: 03/28/2023] [Indexed: 06/13/2023] Open
Abstract
STUDY QUESTION Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)? SUMMARY ANSWER Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids. WHAT IS KNOWN ALREADY SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids. STUDY DESIGN SIZE DURATION In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology. PARTICIPANTS/MATERIALS SETTING METHODS A cohort of 19 women aged 38-52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI). MAIN RESULTS AND THE ROLE OF CHANCE Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (P = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (P = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (P = 0.17). LIMITATIONS REASONS FOR CAUTION The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected. WIDER IMPLICATIONS OF THE FINDINGS The imaging protocol that we have developed represents a generic paradigm for measuring the volume of the uterus and uterine fibroids that can be readily incorporated in future studies of medical treatments of HMB. In the present study, SPRM-UPA failed to produce a significant reduction in the volume of the uterus or the total volume of fibroids (which were present in approximately half of the patients) after either two or three 12-week courses of treatment. This finding represents a new insight in respect of the management of HMB using treatment strategies that target hormone-dependence. STUDY FUNDING/COMPETING INTERESTS The UPA Versus Conventional Management of HMB (UCON) trial was funded by the EME Programme (Medical Research Council (MRC) and National Institutes of Health Research (NIHR)) (12/206/52). The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care.Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. H.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (All paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., and Myovant Sciences GmbH. H.C. has received royalties from UpToDate for an article on abnormal uterine bleeding. L.W. has received grant funding from Roche Diagnostics (Paid to Institution). All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER The study reported here is an embedded mechanism of action study (no comparator) within the UCON clinical trial (registration ISRCTN: 20426843).
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Affiliation(s)
- K Yin
- Edinburgh Imaging Facility QMRI, University of Edinburgh, Edinburgh, UK
| | - L Whitaker
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
| | - E Hojo
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
| | - S McLenachan
- Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK
| | - J Walker
- Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK
| | - G McKillop
- Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK
| | - C Stubbs
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - L Priest
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - M Cruz
- Departamento de Matemáticas Estadística y Computación, University of Cantabria, Santander, Spain
| | - N Roberts
- Edinburgh Imaging Facility QMRI, University of Edinburgh, Edinburgh, UK
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
| | - H Critchley
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
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Knipprath-Mészáros AM, Tozzi A, Butenschön A, Reina H, Schoetzau A, Montavon C, Heinzelmann-Schwarz V, Manegold-Brauer G. High negative prediction for the Basel sarcoma score: Sonographic assessment of features suspicious of uterine sarcoma. Gynecol Oncol 2023; 174:182-189. [PMID: 37210928 DOI: 10.1016/j.ygyno.2023.05.005] [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: 12/18/2022] [Revised: 04/23/2023] [Accepted: 05/09/2023] [Indexed: 05/23/2023]
Abstract
INTRODUCTION In the management of uterine myomas, laparoscopic surgery with morcellation enables a minimal invasive procedure. Cases of unsuspected uterine sarcoma dissemination have been reported and led to regulative restrictions. To help to distinguish preoperatively myomas from sarcomas, we assessed the value of six sonographic criteria (Basel Sarcoma Score, BSS) in a prospective outpatient cohort of consecutive patients with uterine masses. MATERIAL AND METHODS We prospectively evaluated all patients presenting with myoma-like masses planned for surgery with standardized ultrasound examination. BSS including the following criteria was investigated: rapid growth in past three months, high blood flow, atypical growth, irregular lining, central necrosis and oval solitary lesion. For each criterion, a score 0/1 was given. BSS (0-6) equals the sum of all given scores. Histological diagnosis was used as reference. RESULTS Among 545 patients, 522 had the final diagnosis of myoma, 16 had peritoneal masses with sarcomatous components (PMSC), and seven had other malignancies. Median BSS for PMSC was 2.5 (range: 0-4) vs 0 for myomas (range: 0-3). The most common sonographic criteria leading to a false positive score in myomas were rapid growth in past three months and high blood flow. For the detection of sarcomatous masses with BSS threshold of >1, sensitivity was 93.8%, specificity 97.9%, and positive predictive value (PPV) and negative predictive value (NPV) were 57.7% and 99.8%, respectively (AUC 0.95). CONCLUSION BSS can help distinguishing between myomas and sarcomatous masses, with high NPV. Caution is required when >1 criterion is present. As a simple tool, it could easily be integrated into routine myoma sonographic examination and help develop standardized assessment of uterine masses for better preoperative triage.
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Affiliation(s)
| | - Alessandra Tozzi
- Department of Gynecologic Ultrasound and Prenatal Diagnostics, Women's Hospital, University Hospital Basel, Basel, Switzerland
| | - Annkathrin Butenschön
- Department of Gynecologic Ultrasound and Prenatal Diagnostics, Women's Hospital, University Hospital Basel, Basel, Switzerland
| | - Hubertina Reina
- Department of Gynecologic Ultrasound and Prenatal Diagnostics, Women's Hospital, University Hospital Basel, Basel, Switzerland
| | - Andreas Schoetzau
- Ovarian Cancer Research, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Céline Montavon
- Gynecological Cancer Center, Women's Hospital, University Hospital Basel, Basel, Switzerland
| | - Viola Heinzelmann-Schwarz
- Gynecological Cancer Center, Women's Hospital, University Hospital Basel, Basel, Switzerland; Ovarian Cancer Research, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Gwendolin Manegold-Brauer
- Department of Gynecologic Ultrasound and Prenatal Diagnostics, Women's Hospital, University Hospital Basel, Basel, Switzerland.
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Adebamowo CA, Adebamowo SN. Population-based study of the reproductive risk factors for Transvaginal Ultrasound diagnosed Uterine Fibroids in Nigerian women. RESEARCH SQUARE 2023:rs.3.rs-2917100. [PMID: 37292609 PMCID: PMC10246270 DOI: 10.21203/rs.3.rs-2917100/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Objective There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. Design We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. Results In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74-0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24-0.73, p-value = 0.02), history of any type of abortion (OR = 0.53, 95%CI = 0.35-0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27-0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01-1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Conclusion Our study confirms the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.
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Langton CR, Gerety M, Harmon QE, Baird DD. Keloids, hypertrophic scars, and uterine fibroid development: a prospective ultrasound study of Black and African American women. F&S SCIENCE 2023; 4:172-180. [PMID: 37028513 PMCID: PMC10200770 DOI: 10.1016/j.xfss.2023.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/29/2023] [Accepted: 03/29/2023] [Indexed: 04/09/2023]
Abstract
OBJECTIVE To examine the association between keloids, hypertrophic scars, and uterine fibroid incidence as well as growth. Both keloids and fibroids are fibroproliferative conditions that have been reported to be more prevalent among Blacks than Whites, and they share similar fibrotic tissue structures, including extracellular matrix composition, gene expression, and protein profiles. We hypothesized that women with a history of keloids would have greater uterine fibroid development. DESIGN A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds to detect and measure fibroids ≥0.5 cm in diameter, assess the history of keloid and hypertrophic scars, and update covariates. SETTING Detroit, Michigan area. PATIENTS A total of 1,610 self-identified Black and/or African American women aged 23-35 years at enrollment without a previous clinical diagnosis of fibroids. EXPOSURE(S) Keloids (raised scars that grow beyond the margins of the original injury) and hypertrophic scars (raised scars that stay within the bounds of the original injury). Because of the difficulties in distinguishing keloids and hypertrophic scars, we separately examined the history of keloids and the history of either keloids or hypertrophic scars (any abnormal scarring) and their associations with fibroid incidence and growth. MAIN OUTCOME MEASURE(S) Fibroid incidence (new fibroid after a fibroid-free ultrasound at enrollment) was assessed using Cox proportional-hazards regression. Fibroid growth was assessed using linear mixed models. The estimates for the change in log volume per 18 months were converted to the estimated percentage difference in volume for scarring vs. no-scarring. Both incidence and growth models were adjusted for time-varying demographic, reproductive, and anthropometric factors. RESULT(S) Of the 1,230 fibroid-free participants, 199 (16%) reported ever having keloids, 578 (47%) reported keloids or hypertrophic scars, and 293 (24%) developed incident fibroids. Neither keloids (adjusted hazard ratio = 1.04; 95% confidence interval: 0.77, 1.40) nor any abnormal scarring (adjusted hazard ratio = 1.10; 95% confidence interval: 0.88, 1.38) were associated with fibroid incidence. Fibroid growth differed little by scarring status. CONCLUSION(S) Despite molecular similarities, self-reported keloid and hypertrophic scars did not show an association with fibroid development. Future research may benefit from the examination of dermatologist-confirmed keloids or hypertrophic scars; however, our data suggest little shared susceptibility for these 2 types of fibrotic conditions.
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Affiliation(s)
- Christine R Langton
- Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
| | - Meghan Gerety
- Department of Statistics, University of Virginia, Charlottesville, Virginia
| | - Quaker E Harmon
- Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
| | - Donna D Baird
- Women's Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
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Seidel V, Wernecke KD, Bellingkrodt AL, Armbrust R, David M. Sonographic Monitoring of Growth of Uterine Myomas in Untreated Women and Respective Influence Factors. Geburtshilfe Frauenheilkd 2023; 83:446-452. [PMID: 37034415 PMCID: PMC10076097 DOI: 10.1055/a-1996-2980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 12/01/2022] [Indexed: 04/11/2023] Open
Abstract
Research Question What are the growth patterns of uterine myomas in untreated premenopausal women? Which factors influence the growth rate of uterine myomas in premenopausal women? Method All premenopausal women who presented to the outpatient myoma consultation clinic between January 2005 and March 2022 at least twice were screened. Exclusion criteria were hormonal therapy, pregnancy, and postmenopausal status. Results A total of 189 patients were included in our study which focused on the respective largest uterine myoma of each woman. An ideal linear growth over time was assumed. Most myomas (82%) increased in size. The mean annual growth of these myomas was 68.42 cm 3 . The most important prognostic factor for growth was the initial size of the myoma. The absolute annual growth of myomas measuring > 50 cm 3 at first presentation was higher compared to smaller myomas (p < 0.001). The relative annual growth rate was highest for myomas measuring between 20 and 50 cm 3 at the initial presentation (p = 0.003). The relative annual growth rate in women older than 40 years was significantly lower than that in women below the age of 40 years (p = 0.003). Conclusion Overall, it is difficult to make an individual prognosis about the growth pattern of a uterine myoma in a specific patient. It should be noted especially in asymptomatic patients that spontaneous regression of myoma size can also occur in premenopausal women.
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Affiliation(s)
- Vera Seidel
- Obstetrics, Charité – Universitätsmedizin Berlin, Berlin, Germany
- Klinik für Gynäkologie, Charité Campus Virchow-Klinikum, Berlin, Germany
| | - Klaus Dieter Wernecke
- Institut für Biometrie und Klinische Epidemiologie, Charité Universitätsmedizin Berlin, Berlin, Germany
- SOSTANA GmbH, Berlin, Germany
| | | | - Robert Armbrust
- Klinik für Gynäkologie, Charité Campus Virchow-Klinikum, Berlin, Germany
| | - Matthias David
- Klinik für Gynäkologie, Charité Campus Virchow-Klinikum, Berlin, Germany
- Correspondence/Korrespondenzadresse Prof. Matthias David Charité Campus Virchow-KlinikumKlinik für GynäkologieAugustenburger
Platz 113353 BerlinGermany
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Tal MG, Keidar R, Magnazi G, Henn O, Kim JH, Chudnoff SG, Stepp KJ. Pressure-Induced Fibroid Ischemia: First-In-Human Experience with a Novel Device for Laparoscopic Treatment of Symptomatic Uterine Fibroids. Reprod Sci 2023; 30:1366-1375. [PMID: 35941511 PMCID: PMC9360636 DOI: 10.1007/s43032-022-01033-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 07/04/2022] [Indexed: 11/29/2022]
Abstract
The purpose of this study was to assess the feasibility of use of a novel uterine fibroid treatment device hypothesized to cause fibroid infarction by increasing intra-tumoral pressure. Between August 2019 and January 2020, 21 uterine fibroids were treated in 16 symptomatic pre-menopausal black women. Pelvic magnetic resonance imaging was performed before the procedure, a day after the procedure and at 1, 3, 6, and 12 months. The subjects were also followed for clinical outcomes and quality of life up to 12 months at a single investigational site. At 3 months, the mean reduction in the fibroid volume was 36.3% (P = .002). Incremental reduction in volume peaked at the end of the follow-up, at the 12-month mark (60.4%; P = .008). There were no procedures in which the users failed to perform laparoscopic pressure suturing of fibroids with the pressure-induced fibroid ischemia device. Improvement in the quality of life was evident in the Health-Related Quality of Life total, Energy/Mood, Control, and Sexual Function domains of the Uterine Fibroid Symptom and Quality of Life questionnaire at 3 months post-procedure. Unanticipated risks were not identified. Serious adverse events were not identified. The initial clinical assessment of the pressure-induced fibroid ischemia device supports feasibility of the approach and does not reveal serious safety concerns. Trial is currently being registered retrospectively (This was a feasibility study and therefore registration was not mandatory).
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Affiliation(s)
- Michael G Tal
- Division of Interventional Radiology, Hadassah Medical Center, Jerusalem, Israel.
| | - Ran Keidar
- Department of Obstetrics and Gynecology, E. Wolfson Medical Center, Holon, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | | | - Ohad Henn
- Empress Medical Ltd., Tel Aviv, Israel
| | - Jin Hee Kim
- Department of Obstetrics & Gynecology, Columbia University, New York, NY, USA
| | - Scott G Chudnoff
- Obstetrics and Gynecology, Maimonides Medical Center, New York, NY, USA
| | - Kevin J Stepp
- Atrium Health Women's Care Urogynecology and Pelvic Surgery, Atrium Health, Charlotte, NC, USA
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Yang Q, Al-Hendy A. Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids. Int J Mol Sci 2023; 24:5778. [PMID: 36982852 PMCID: PMC10051203 DOI: 10.3390/ijms24065778] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 02/22/2023] [Accepted: 03/08/2023] [Indexed: 03/30/2023] Open
Abstract
Uterine fibroids (UFs), also known as leiomyomas, are benign tumors of the myometrium affecting over 70% of women worldwide, particularly women of color. Although benign, UFs are associated with significant morbidity; they are the primary indication for hysterectomy and a major source of gynecologic and reproductive dysfunction, ranging from menorrhagia and pelvic pain to infertility, recurrent miscarriage, and preterm labor. So far, the molecular mechanisms underlying the pathogenesis of UFs are still quite limited. A knowledge gap needs to be filled to help develop novel strategies that will ultimately facilitate the development of therapies and improve UF patient outcomes. Excessive ECM accumulation and aberrant remodeling are crucial for fibrotic diseases and excessive ECM deposition is the central characteristics of UFs. This review summarizes the recent progress of ascertaining the biological functions and regulatory mechanisms in UFs, from the perspective of factors regulating ECM production, ECM-mediated signaling, and pharmacological drugs targeting ECM accumulation. In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of the extracellular matrix in the pathogenesis of UFs and in applications. Comprehensive and deeper insights into ECM-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with this common tumor.
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Affiliation(s)
- Qiwei Yang
- Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA;
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Pulmonary Embolism after Liposuction Totally by Tumescent Local Anesthesia in a Patient with Large Uterine Fibroids. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2023; 11:e4876. [PMID: 36923713 PMCID: PMC10010803 DOI: 10.1097/gox.0000000000004876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/31/2023] [Indexed: 03/16/2023]
Abstract
A fatal pulmonary embolism occurred in a 43-year-old black woman after tumescent liposuction totally by local anesthesia. An autopsy revealed large uterine fibroids, peri-uterine vascular thrombi, and a large saddle pulmonary embolism. Large uterine fibroids are a risk factor for postsurgical venous thromboembolism. Fatal outcomes after tumescent liposuction totally by local anesthesia are exceedingly rare.
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Sefah N, Ndebele S, Prince L, Korasare E, Agbleke M, Nkansah A, Thompson H, Al-Hendy A, Agbleke AA. Uterine fibroids - Causes, impact, treatment, and lens to the African perspective. Front Pharmacol 2023; 13:1045783. [PMID: 36703761 PMCID: PMC9871264 DOI: 10.3389/fphar.2022.1045783] [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: 09/16/2022] [Accepted: 12/12/2022] [Indexed: 01/12/2023] Open
Abstract
Leiomyomas, or uterine fibroids as they are commonly known, are mostly seen in women of reproductive age. However, they can go undetected in most women, and approximately 25% of women show clinical symptoms. Although fibroids are a global burden impacting 80% of premenopausal women, they are more prevalent among Black women than among women of other races. Based on clinical diagnosis, the estimated cumulative incidence of fibroids in women ≤50 years old is significantly higher for black (>80%) versus white women (∼70%). The cause of leiomyomas is not clearly known, but studies have shown evidence of factors that drive the development or exacerbation of the disease. Evidence has linked risk factors such as lifestyle, age, environment, family history of uterine fibroids, and vitamin D deficiencies to an increased risk of uterine fibroids, which impact women of African descent at higher rates. Treatments may be invasive, such as hysterectomy and myomectomy, or non-invasive, such as hormonal or non-hormonal therapies. These treatments are costly and tend to burden women who have the disease. Sub-Saharan Africa is known to have the largest population of black women, yet the majority of uterine fibroid studies do not include populations from the continent. Furthermore, the prevalence of the disease on the continent is not well determined. To effectively treat the disease, its drivers need to be understood, especially with regard to racial preferences. This paper aims to review the existing literature and build a case for conducting future research on African women.
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Langton CR, Harmon QE, Upson K, Baird DD. Soy-Based Infant Formula Feeding and Uterine Fibroid Development in a Prospective Ultrasound Study of Black/African-American Women. ENVIRONMENTAL HEALTH PERSPECTIVES 2023; 131:17006. [PMID: 36696103 PMCID: PMC9875846 DOI: 10.1289/ehp11089] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 11/14/2022] [Accepted: 12/19/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND Uterine fibroids are highly prevalent, benign tumors. They are the leading indication for hysterectomy, and Black women are disproportionally burdened. Soy-based infant formula contains phytoestrogens, and exposure during sensitive developmental windows may adversely affect the developing uterus; early phytoestrogen treatment in rodent studies led to detrimental uterine effects, including increased fibroid risk in Eker rats. Limited epidemiological studies also have suggested increased fibroid development with soy formula infant feeding. OBJECTIVE The goal of this study was to examine the association between soy formula feeding in infancy and fibroid development in adulthood. METHODS We evaluated this association among 1,610 Black/African-American women age 23-35 y in the Study of Environment, Lifestyle & Fibroids (SELF). Soy formula feeding data was gathered directly from the participants' mothers (89%). A standardized ultrasound examination was conducted during 4 clinic visits over 5 y to detect fibroids ≥0.5cm in diameter. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between soy formula feeding and incident fibroids adjusted for early-life and adult factors. Fibroid growth was calculated as change in log-volume for fibroids matched at successive visits. RESULTS Of 1,121 fibroid-free participants at baseline, 150 (13%) were ever fed soy formula as infants, and 269 (24%) developed incident fibroids. We did not observe an association between ever being fed soy formula and incident fibroid risk (HR=1.08; 95% CI: 0.75, 1.54). However, participants fed soy formula within 2 months of birth and for >6 months (n=53) had an elevated risk of fibroid incidence in comparison with those never fed soy formula (HR=1.56; 95% CI: 0.92, 2.65). Fibroid growth rates did not differ. DISCUSSION Adding support to limited human data, this prospective fibroid study found that soy-based formula feeding during infancy was associated with a suggestive increase in risk of ultrasound-identified incident fibroids in adulthood. https://doi.org/10.1289/EHP11089.
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Affiliation(s)
- Christine R. Langton
- Women’s Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
| | - Quaker E. Harmon
- Women’s Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
| | - Kristen Upson
- Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Donna D. Baird
- Women’s Health Group, Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
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Derico SQ, Hicklin K, Davis LB, Brooks KC. Data-driven analyses to quantify information seeking behaviour for women with uterine fibroids. Health Syst (Basingstoke) 2022; 13:73-96. [PMID: 38800604 PMCID: PMC11123465 DOI: 10.1080/20476965.2022.2150570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2022] [Indexed: 12/24/2022] Open
Abstract
Uterine fibroids (UF) are noncancerous growths of the uterus and impact the livelihood of over 26 million women in the United States. Although UF may not have accompanying symptoms, for some women their presence leads to surgical treatment, which can be a difficult decision-making process. Web-scraping of online media is used to identify information-seeking behavior of women searching for UF treatment options. We synthesize the data to describe trends in UF treatment, including the identification of gaps between the information individuals are seeking (demand) and information that is publicly available as a resource (supply), which contributes to this study's creation of the term "information desert." We perform statistical analysis to understand information-seeking behavior, determine the gap between information supply and information demand, and determine the correlation between a doctor's treatment recommendation and a patient's treatment decision as a function of age, symptoms, and knowledge obtained about specific types of treatment.
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Affiliation(s)
- Saleigh Q. Derico
- Department of Industrial and Systems Engineering, North Carolina A&T State University, Greensboro, NC
| | - Karen Hicklin
- Department of Industrial and Systems Engineering, University of Florida,Gainesville, FL
| | - Lauren B. Davis
- Department of Industrial and Systems Engineering, University of Florida,Gainesville, FL
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Harmon QE, Patchel SA, Denslow S, LaPorte F, Cooper T, Wise LA, Wegienka G, Baird DD. Vitamin D and uterine fibroid growth, incidence, and loss: a prospective ultrasound study. Fertil Steril 2022; 118:1127-1136. [PMID: 36150919 PMCID: PMC9771933 DOI: 10.1016/j.fertnstert.2022.08.851] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/17/2022] [Accepted: 08/18/2022] [Indexed: 01/13/2023]
Abstract
OBJECTIVE Fibroid treatments that have few side-effects and can preserve fertility are a clinical priority. We studied the association between serum vitamin D and uterine fibroid growth, incidence, and loss. DESIGN A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds, measure 25-hydroxyvitamin D (25(OH)D), and update covariates. SETTING Detroit, Michigan area. PATIENTS Self-identified African American or Black women aged 23-35 at enrollment without previous clinical diagnosis of fibroids. INTERVENTION(S) Serum 25(OH)D measured using immunoassay or liquid chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURE(S) The primary outcomes were fibroid growth, as measured by change in log volume per 18 months, and fibroid incidence (first detection of fibroid in previously fibroid-free uterus). Adjusted growth estimates from linear mixed models were converted to estimated difference in volume for high vs. low 25(OH)D. Incidence differences were estimated as hazard ratios from age-specific Cox regression. A secondary outcome fibroid loss (reduction in fibroid number between visits), was modeled using Poisson regression. Covariates (reproductive and hormonal variables, demographics, body mass index, current smoking) and 25(OH)D were modeled as time-varying factors. RESULT(S) At enrollment among 1,610 participants with ≥1 follow-up ultrasound, mean age was 29.2 years, 73% had deficient vitamin D (<20ng/mL), and only 7% had sufficient vitamin D (≥30ng/mL). Serum 25(OH)D ≥20ng/mL compared with <20ng/mL was associated with an estimated 9.7% reduction in fibroid growth (95% confidence interval [CI]: -17.3%, -1.3%), similar to the minimally adjusted estimate -8.4% (95% CI: -16.4, 0.3). Serum 25(OH)D ≥30ng/mL compared with <30ng/mL was associated with an imprecise 22% reduction in incidence (adjusted hazard ratio=0.78; 95% CI: 0.47, 1.30), similar to the unadjusted estimate of 0.84 (95% CI: 0.51, 1.39). The >30ng/mL group also had a 32% increase in fibroid loss (adjusted risk ratio=1.32; 95% CI: 0.95, 1.83). CONCLUSION(S) Our data support the hypothesis that high concentrations of vitamin D decrease fibroid development but are limited by the few participants with serum 25(OH)D ≥30ng/mL. Interventional trials that raise and maintain 25(OH)D concentrations >30ng/mL and then prospectively monitor fibroid development are needed to further assess supplemental vitamin D efficacy and determine optimal treatment protocols.
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Affiliation(s)
- Quaker E Harmon
- Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina.
| | - Stacy A Patchel
- Public Health and Epidemiology Practice at Westat, Durham, North Carolina
| | - Sheri Denslow
- Social & Scientific Systems, Inc., a DLH Holdings company, Durham, North Carolina
| | - Frankie LaPorte
- Social & Scientific Systems, Inc., a DLH Holdings company, Durham, North Carolina
| | - Tracy Cooper
- Division of Ultrasound, Department of Diagnostic Radiology, Henry Ford Health, Detroit, Michigan
| | - Lauren A Wise
- Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts
| | - Ganesa Wegienka
- Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan
| | - Donna D Baird
- Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina
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Lasmar RB, Lasmar BP, Moawad NS. HYSTEROSCOPIC MYOMECTOMY. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1627. [PMID: 36422166 PMCID: PMC9692806 DOI: 10.3390/medicina58111627] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 10/31/2022] [Accepted: 11/04/2022] [Indexed: 08/13/2023]
Abstract
Leiomyomas are the most common pelvic tumors. Submucosal fibroids are a common cause of abnormal bleeding and infertility. Hysteroscopic myomectomy is the definitive management of symptomatic submucosal fibroids, with high efficacy and safety. Several techniques have been introduced over time and will be covered in depth in this manuscript. Advances in optics, fluid management, electrosurgery, smaller diameter scopes, and tissue removal systems, along with improved training have contributed to improving the safety and efficiency of hysteroscopic myomectomy.
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Affiliation(s)
- Ricardo Bassil Lasmar
- Department of Surgery and Specialized, Faculty of Medicine, Universidade Federal Fluminense, UFF, Niterói 24020-141, RJ, Brazil
| | - Bernardo Portugal Lasmar
- University of the Maternal-Infant Department of the Faculty of Medicine, Universidade Federal Fluminense, UFF, Niterói 24020-141, RJ, Brazil
- Estácio de Sá University, São João de Meriti 25550-100, RJ, Brazil
- Gynecological Endoscopy, Hospital Central Aristarcho Pessoa HCAP–CBMERJ, Rio de Janeiro 20261-243, RJ, Brazil
| | - Nash S. Moawad
- Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics & Gynecology, P.O. Box 100294, Gainesville, FL 32610, USA
- UF Health COEMIG, P.O. Box 100294, Gainesville, FL 32610, USA
- University of Florida College of Medicine, P.O. Box 100294, Gainesville, FL 32610, USA
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Disi ES. Sciatica in Early Pregnancy With Coexisting Uterine Leiomyoma and Tarlov Cyst: A Case Report. Cureus 2022; 14:e27855. [PMID: 35968245 PMCID: PMC9366029 DOI: 10.7759/cureus.27855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2022] [Indexed: 11/05/2022] Open
Abstract
Uterine fibroids are common, especially among women of African descent. Several women with fibroids are asymptomatic, which may contribute to underestimating its prevalence. Symptomatic uterine fibroids present with menstrual problems, anemia, infertility, miscarriages, an enlarged abdomen, pressure symptoms involving the bladder and bowels (such as frequent urination or constipation), and sometimes coital-related problems. This case report describes a 25-year-old African American woman with uterine fibroids who suffered from lower back pain radiating to the left lower extremity, along with paresthesias and weakness of the left leg. She was diagnosed with lumbar radiculopathy, early pregnancy, and an incidental finding of a Tarlov cyst. As the pregnancy progressed, the sciatic pain ceased within the first trimester. Sciatic pain can result from a sudden increase in the uterus size caused by an early pregnancy coexisting with large fibroids. The sciatic pain may not remain throughout the pregnancy as the growing uterus with large fibroids may be displaced from the site of nerve compression.
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Zanolli NC, Bishop KC, Kuller JA, Price TM, Harris BS. Fibroids and Fertility: A Comparison of Myomectomy and Uterine Artery Embolization on Fertility and Reproductive Outcomes. Obstet Gynecol Surv 2022; 77:485-494. [DOI: 10.1097/ogx.0000000000001052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Response to letter to the editor. Menopause 2022; 29:999-1000. [PMID: 35905472 DOI: 10.1097/gme.0000000000002044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Letter to the Editor. Menopause 2022; 29:999. [PMID: 35905471 DOI: 10.1097/gme.0000000000002043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Moawad NS, Palin H. Hysteroscopic Myomectomy. Obstet Gynecol Clin North Am 2022; 49:329-353. [DOI: 10.1016/j.ogc.2022.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Zaritsky E, Le A, Tucker LY, Ojo A, Weintraub MR, Raine-Bennett T. Minimally invasive myomectomy: practice trends and differences between Black and non-Black women within a large integrated healthcare system. Am J Obstet Gynecol 2022; 226:826.e1-826.e11. [PMID: 35101407 DOI: 10.1016/j.ajog.2022.01.022] [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: 08/12/2021] [Revised: 12/13/2021] [Accepted: 01/24/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND Although multiple professional organizations encourage minimally invasive surgical approaches whenever feasible, nationally, fewer than half of myomectomies are performed via minimally invasive routes. Black women are less likely than their non-Black counterparts to have minimally invasive surgery. OBJECTIVE This study aimed to assess the trends in surgical approach among women who underwent minimally invasive myomectomies for uterine leiomyomas within a large integrated healthcare system as initiatives were implemented to encourage minimally invasive surgery, particularly evaluating differences in the proportion of minimally invasive surgery performed in Black vs non-Black women. STUDY DESIGN We conducted a retrospective cohort study of women, aged ≥18 years, who underwent a myomectomy for a uterine leiomyoma within Kaiser Permanente Northern California between 2009 and 2019. Generalized estimating equations and Cochran-Armitage testing were used to assess myomectomy incidence and linear trend in the proportions of myomectomy by surgical route-abdominal myomectomy and minimally invasive myomectomy. Multivariable logistic regression analyses were used to assess the associations between surgical route and (1) race and ethnicity and (2) complications, controlling for patient demographic, clinical, and surgical characteristics. RESULTS A total of 4033 adult women underwent a myomectomy during the study period. Myomectomy incidence doubled from 0.12 (95% confidence interval, 0.12-0.13) per 1000 women in 2009 to 0.25 (95% confidence interval, 0.24-0.25) per 1000 women in 2019 (P<.001). During the 11-year study period, the proportion of minimally invasive myomectomy increased from 6.0% to 89.5% (a 15-fold increase). The proportion of minimally invasive myomectomy in Black women remained lower than in non-Black women (54.5% vs 64.7%; P<.001). Black women undergoing myomectomy were younger (36.4±5.6 vs 37.4±5.8 years; P<.001), had a higher mean fibroid weight (436.0±505.0 vs 324.7±346.1 g; P<.001), and had a higher mean body mass index (30.8±7.3 vs 26.6±5.9 kg/m2; P<.001) than their non-Black counterparts. In addition to patient race, surgery performed between 2016 and 2019 compared with surgery performed between 2009 and 2012 and higher surgeon volume compared with low surgeon volume were associated with an increased proportion of minimally invasive myomectomy (adjusted relative risks, 12.58 [95% confidence interval, 9.96-15.90] and 6.63 [95% confidence interval, 5.35-8.21], respectively). Black race and fibroid weight of >500 g each independently conferred lower rates of minimally invasive myomectomy. In addition, there was an interaction between race and fibroid weight such that Black women with a fibroid weight of ≤500 g or >500 g were both less likely to have minimally invasive myomectomy than non-Black women with a fibroid weight of ≤500 g (adjusted relative risks, 0.74 [95% confidence interval, 0.58-0.95] and 0.26 [95% confidence interval, 0.18-0.36], respectively). Operative, perioperative, and medical complications were low during the 11-year study period. In regression analyses, after controlling for race, age, fibroid weight, parity, low-income residence, body mass index, surgeon volume, and year of myomectomy, the risk of complications was not markedly different comparing abdominal myomectomy with minimally invasive myomectomy. Similar results were found comparing laparoscopic minimally invasive myomectomy with robotic-assisted minimally invasive myomectomy except for women who underwent laparoscopic minimally invasive myomectomy had a lower risk of experiencing any medical complications than those who underwent robotic-assisted minimally invasive myomectomy (adjusted relative risk, 0.27; 95% confidence interval, 0.09-0.83; P=.02). CONCLUSION Within an integrated healthcare delivery system, although initiatives to encourage minimally invasive surgery were associated with a marked increase in the proportion of minimally invasive myomectomy, Black women continued to be less likely to undergo minimally invasive myomectomy than their non-Black counterparts. Race and fibroid weight alone did not explain the disparities in minimally invasive myomectomy.
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Review of uterine fibroids: imaging of typical and atypical features, variants, and mimics with emphasis on workup and FIGO classification. Abdom Radiol (NY) 2022; 47:2468-2485. [PMID: 35554629 DOI: 10.1007/s00261-022-03545-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/23/2022] [Accepted: 04/26/2022] [Indexed: 12/28/2022]
Abstract
Uterine fibroids are the most common gynecologic neoplasm. Although non-degenerated fibroids are easily identifiable on imaging, degenerated fibroids, fibroid variants, and fibroids with unusual growth patterns can constitute a diagnostic dilemma. Identification of these abnormal morphologic features can alter the diagnosis of presumed uterine fibroids and hence change management plans. This article reviews the typical and atypical radiologic imaging features of uterine fibroids, with an emphasis on the pitfalls, mimics, and radiologically identifiable features that can alter clinical management plans.
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