Family History and Uterine Fibroid Development in Black and African American Women.

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.

Hypertension, Cardiovascular Risk Factors, and Uterine Fibroid Diagnosis in Midlife.

Importance: Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. Objective: To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. Design, Setting, and Participants: The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Exposures: Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Main Outcomes and Measures: Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Results: Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Conclusions and Relevance: Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.

Incidence and health care burden of uterine fibroids among female service members in the active component of the U.S. Armed Forces, 2011-2022.

Uterine fibroids are the most common benign tumors of the uterus among women of reproductive age, disproportionally affecting non-Hispanic Black women compared to other races and ethnicities. This report is an update of a 2011 MSMR report that examined uterine fibroids among female active component service members in the U.S. Armed Forces from 2001 to 2010. Incident uterine fibroids were identified for this report from inpatient and outpatient medical encounter data from 2011 to 2022. Health care burden was estimated utilizing uterine fibroid-related inpatient and outpatient diagnostic and procedure codes. Crude incidence rates and incidence rate ratios were calculated to compare rate differences between subpopulations. A total of 16,046 new uterine fibroid cases were identified, with an incidence rate of 63.5 cases per 10,000 person-years (95% confidence interval: 62.5-64.5). The highest incidence rates were observed among service women 40 years and older, non-Hispanic Black women, and those who served in the Army. Health care burden analysis showed that, even with increases in medical encounters and individuals affected, the numbers of hospital bed days declined over time. The decline in uterine fibroid-related hospital bed days could be attributed to early diagnoses and minimally-invasive treatments. Continued promotion of uterine fibroid awareness can potentially help further reduce uterine fibroid-related impacts on military readiness.

Laparoscopic continuous seromuscular circumsuture for myomectomy: a real-world, retrospective, East-Asian cohort study.

OBJECTIVE: This study aimed to introduce a novel laparoscopic haemostasis for myomectomy and investigate the independent risk factors for uterine fibroid recurrence. DESIGN: A retrospective cohort study. SETTING: Following strengthening the reporting of observational studies in epidemiology (STROBE) criteria, a retrospective study of prospectively collected available data of the consecutive patients who underwent the myomectomy in the department of obstetrics and gynaecology of the single centre between February 2018 and December 2020. PARTICIPANTS: 177 patients who underwent laparoscopic myomectomy resection were enrolled in the present cohort study. MATERIALS AND METHODS: Patients were classified into two groups according to their different methods of haemostasis in laparoscopic surgery. Recurrence-free survival was compared between the groups during an average follow-up of nearly 2 years. RESULTS: Of the 177 patients from 672 consecutive patients in the retrospective cohort, laparoscopic circular suture and baseball suture were carried out in 102 (57.6%) and 75 (42.4%) patients, respectively. The total amount of blood lost during surgery varied significantly (37.6 vs 99.5 mL) (p<0.001). Univariable analyses identified that age ≥40 years, position at intramural myoma, multiple fibroids and largest fibroid volume ≥50 mm3 (HR 2.222, 95% CI 1.376 to 3.977, p=0.039; HR 3.625, 95% CI 1.526 to 6.985, p=0.003; HR 3.139, 95% CI 1.651 to 5.968, p<0.001; HR 2.328, 95% CI 0.869 to 3.244, p=0.040, respectively) are independent risk factor of the recurrence of uterine fibroids. The formula of the nomogram prediction model was established as the practical clinical tool. CONCLUSION: The laparoscopic continuous seromuscular circumsuture for myomectomy can effectively reduce the amount of surgical bleeding and accelerate the perioperative recovery for surgical safety. The main factors affecting the recurrence of uterine fibroids were age, location, number and volume of uterine fibroids. The nomogram can more straightforwardly assist clinicians to determine the risk of recurrence after laparoscopic myomectomy.

Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System.

OBJECTIVE: To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system. METHODS: We studied a cohort of 10,324 patients aged 18-50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009-2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan-Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics. RESULTS: Median follow-up was 3.8 years (interquartile range 1.8-7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients. CONCLUSION: Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.

Dietary intake is associated with the prevalence of uterine leiomyoma in Korean women: A retrospective cohort study.

OBJECTIVE: Uterine leiomyoma (UL), the most prevalent benign gynecologic tumor among reproductive-aged women, lacks sufficient research on the potential association between dietary intake and its occurrence in Korean women. Addressing this research gap, this study aims to evaluate the potential link between dietary intake and the prevalence of UL in Korean women. METHODS: In this cross-sectional study, a cohort of 672 women, aged 23 to 73, were enrolled, with 383 (57%) being premenopausal. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and UL presence was determined through ultrasonography. The analysis focused exclusively on items within ten categories, including vegetables/fruit, vegetables, fruits, red meat, processed meat, poultry, fish, dairy product, milk, and alcohol. Multiple logistic regression models were employed to explore the relationship between dietary intake and the prevalence of UL, calculating odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for confounding factors. RESULTS: Within the total cohort, 220 (32.7%) women were diagnosed with UL. High intakes of fish and poultry showed an association with higher UL prevalence. Odds ratios (95% CIs) for the upper quartiles compared to the lower quartiles were 1.68 (1.01-2.81; p trend = 0.05) for fish intake and 1.87 (1.11-3.17; p trend = 0.06) for poultry intake. Conversely, an inverse relationship emerged between dairy product intake and UL prevalence, with an odds ratio of 0.58 (95% CI 0.35-0.96; p trend = 0.05). Stratifying the analysis by menopausal status revealed a parallel pattern, with heightened UL prevalence with fish intake and reduced prevalence with dairy product intake. However, the link between poultry intake and UL prevalence was primarily observed among postmenopausal women. Among premenopausal women, elevated vegetable intake was linked to a decreased UL prevalence (OR 0.45, 95% CI 0.21-0.97 for top vs. bottom quartiles; p trend = 0.01). CONCLUSION: We found that high consumption of fish and poultry, coupled with low intake of dairy products, correlated with an elevated prevalence of UL. Furthermore, vegetable intake exhibited an inverse relationship with UL prevalence, particularly among premenopausal women.

Uterine Fibroid Prevalence in a Predominantly Black, Chicago-Based Cohort.

(1) Objectives: To investigate the effect of individual-level, neighborhood, and environmental variables on uterine fibroid (UF) prevalence in a Chicago-based cohort. (2) Methods: Data from the Chicago Multiethnic Prevention and Surveillance Study (COMPASS) were analyzed. Individual-level variables were obtained from questionnaires, neighborhood variables from the Chicago Health Atlas, and environmental variables from NASA satellite ambient air exposure levels. The Shapiro-Wilk test, logistic regression models, and Spearman's correlations were used to evaluate the association of variables to UF diagnosis. (3) Results: We analyzed 602 participants (mean age: 50.3 ± 12.3) who responded to a question about UF diagnosis. More Black than White participants had a UF diagnosis (OR, 1.32; 95% CI, 0.62-2.79). We observed non-significant trends between individual-level and neighborhood variables and UF diagnosis. Ambient air pollutants, PM2.5, and DSLPM were protective against UF diagnosis (OR 0.20, CI: 0.04-0.97: OR 0.33, CI: 0.13-0.87). (4) Conclusions: Associations observed within a sample in a specific geographic area may not be generalizable and must be interpreted cautiously.

Pregnancy Outcomes After Laparoscopic Radiofrequency Ablation of Uterine Leiomyomas Compared With Myomectomy.

OBJECTIVE: To compare pregnancy outcomes after laparoscopic radiofrequency ablation and myomectomy. METHODS: The ULTRA (Uterine Leiomyoma Treatment With Radiofrequency Ablation) study is an ongoing multicenter prospective cohort study with longitudinal follow-up up to 5 years comparing outcomes of radiofrequency ablation with myomectomy in premenopausal women older than age 21 years with symptomatic uterine leiomyomas. Participants were queried every 6 months after surgery to assess the incidence of pregnancy and pregnancy outcomes. RESULTS: Among 539 women enrolled in ULTRA, a total of 37 participants (mean age at first pregnancy 35.0±4.7 years) conceived 43 times as of March 2023 (22 radiofrequency ablation, 21 myomectomy). The average length of follow-up time after all procedures was 2.5±1.0 years. The baseline miscarriage rate in the study population was 33.3%. In participants who underwent radiofrequency ablation, 9 of 22 pregnancies (40.9%, 95% CI, 20.3-61.5%) ended in first-trimester miscarriage, 11 resulted in live births (50.0%, 95% CI, 29.1-70.9%), one resulted fetal death at 30 weeks of gestation, and one resulted in uterine rupture during miscarriage treatment with misoprostol 10 weeks after radiofrequency ablation. Among the live births in the radiofrequency ablation group, 45.5% were by vaginal delivery. In the myomectomy group, 9 of 21 pregnancies (42.9%, 95% CI, 21.7-64.0%) ended in first-trimester miscarriage and 12 resulted in live births (57.1%, 95% CI, 36.0-78.3%). There were no significant differences in the likelihood of live birth or miscarriage between the study groups. CONCLUSION: Full-term pregnancy and vaginal delivery are achievable after radiofrequency ablation of leiomyomas. However, in this interim analysis, the miscarriage rate in both radiofrequency ablation and myomectomy groups was higher than expected for women in this age group. Long-term data collection in the ongoing ULTRA study aims to further understand pregnancy outcomes after radiofrequency ablation compared with myomectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT0210094.

Genetic contribution of reproductive traits to risk of uterine leiomyomata: a large-scale, genome-wide, cross-trait analysis.

BACKGROUND: Although phenotypic associations between female reproductive characteristics and uterine leiomyomata have long been observed in epidemiologic investigations, the shared genetic architecture underlying these complex phenotypes remains unclear. OBJECTIVE: We aimed to investigate the shared genetic basis, pleiotropic effects, and potential causal relationships underlying reproductive traits (age at menarche, age at natural menopause, and age at first birth) and uterine leiomyomata. STUDY DESIGN: With the use of large-scale, genome-wide association studies conducted among women of European ancestry for age at menarche (n=329,345), age at natural menopause (n=201,323), age at first birth (n=418,758), and uterine leiomyomata (ncases/ncontrols=35,474/267,505), we performed a comprehensive, genome-wide, cross-trait analysis to examine systematically the common genetic influences between reproductive traits and uterine leiomyomata. RESULTS: Significant global genetic correlations were identified between uterine leiomyomata and age at menarche (rg, -0.17; P=3.65×10-10), age at natural menopause (rg, 0.23; P=3.26×10-07), and age at first birth (rg, -0.16; P=1.96×10-06). Thirteen genomic regions were further revealed as contributing significant local correlations (P<.05/2353) to age at natural menopause and uterine leiomyomata. A cross-trait meta-analysis identified 23 shared loci, 3 of which were novel. A transcriptome-wide association study found 15 shared genes that target tissues of the digestive, exo- or endocrine, nervous, and cardiovascular systems. Mendelian randomization suggested causal relationships between a genetically predicted older age at menarche (odds ratio, 0.88; 95% confidence interval, 0.85-0.92; P=1.50×10-10) or older age at first birth (odds ratio, 0.95; 95% confidence interval, 0.90-0.99; P=.02) and a reduced risk for uterine leiomyomata and between a genetically predicted older age at natural menopause and an increased risk for uterine leiomyomata (odds ratio, 1.08; 95% confidence interval, 1.06-1.09; P=2.30×10-27). No causal association in the reverse direction was found. CONCLUSION: Our work highlights that there are substantial shared genetic influences and putative causal links that underlie reproductive traits and uterine leiomyomata. The findings suggest that early identification of female reproductive risk factors may facilitate the initiation of strategies to modify potential uterine leiomyomata risk.

Association of Fibroids, Endometriosis, and Gynecologic Surgeries with Breast Cancer Incidence and Hormone Receptor Subtypes.

BACKGROUND: Fibroids and endometriosis are sex hormone-mediated and exhibit cancer-like behavior. Breast cancer may be more common in women who have had these conditions, but the literature is conflicting and does not always address factors like hysterectomy/oophorectomy status, race/ethnicity, menopause, and hormone receptor subtypes. METHODS: Data are from the Sister Study, a cohort of 50,884 U.S. women enrolled in 2003 to 2009 and followed through 2020. Cox proportional hazards models with time-varying exposures and covariates assessed the relationship of fibroids or endometriosis with breast cancer. Logistic regression examined the association with estrogen receptor (ER) status among cases. RESULTS: Fibroids (19,932 cases) were positively associated with breast cancer [fully adjusted HR: 1.07; 95% confidence interval (CI): 1.01-1.14], notably among Black participants (HR: 1.34; 95% CI: 1.07-1.69) and women who had a hysterectomy (HR: 1.18; 95% CI: 1.05-1.31). Endometriosis (3,970 cases) was not associated with breast cancer (HR: 0.99; 95% CI: 0.91-1.08). Among 4,419 breast cancer cases, fibroids were positively associated with ER+ subtypes (OR: 1.34; 95% CI: 1.10-1.65), while endometriosis was negatively associated with ER+ subtypes (OR: 0.78; 95% CI: 0.61-1.01). CONCLUSIONS: We observed a modest positive association between fibroids and breast cancer, particularly ER+ breast cancer. No relationship with endometriosis and breast cancer incidence was found. IMPACT: Fibroids, even in those with a family history of breast cancer, might modify breast cancer risk stratification tools. Future studies should further assess this link and interrogate shared risk factors.

Uterine leiomyomata claim rate estimates and demographic characteristics by county. Florida, 2010-2019.

To describe the demographic characteristics and estimate the uterine leiomyomata claim rates (ULCRs) by women 18 years and older in Florida, we conducted a cross-sectional analysis of the 2010-2019 administrative claims for uterine leiomyomata and associated study variables (age, race, ethnicity, county of residence, anatomic site, length of stay, and additional diagnoses). ULCR ratios were estimated by race and ethnicity, using ULCR for non-Hispanic White women as the reference group. We identified 232,475 claims, most of which were among non-Hispanic White women in their forties. The overall ULCR estimate [95 percent CI] was 284.8 [284.21, 285.39] per 100,000 women 18 years and older, with a small, nonsignificant trend to increase over time (R2 = .310; p = .094). Black, Hispanic, and other women of color presented with higher ULCR ratios (4.84, 1.87, and 1.58, respectively). Urban counties had significantly higher ULCRs than suburban and rural counties. While non-Hispanic White women had the highest frequency of ULCRs, women of color-especially Black women-presented with significantly higher ULCR ratios. The epidemiologic profile of uterine leiomyomata in terms of age, race, ethnicity, and geographic location points to unmet healthcare needs among specific demographic and geographic groups of women in Florida.

The Role of Nutrition in Pathogenesis of Uterine Fibroids.

Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs for the health care system and the substantial impact on women's quality of life, they are a significant public health concern. Previous literature on the impact of diet on the occurrence, growth and symptoms of fibroids is limited. Recently, many papers have been written on this topic. A scoping review of PubMed and Cochrane databases was performed using the following keywords: uterine fibroids, antioxidants, diet, diet, vegetarian, vegetables, fruits, meat and soy foods, dairy products, tea, vitamin D, vitamin C, ascorbic acid. Preliminary research has shown a beneficial effect of vegetable and fruit consumption on the occurrence of fibroids. A relationship between hypovitaminosis D and an increased risk of fibroids has also been demonstrated. Studies on epigallocatechin gallate showed its apoptosis-promoting and antifibrinolytic effect in fibroid cells. Initial results are promising, but further randomized trials are needed to draw firm conclusions about the effects of diet and nutrients on uterine fibroids.

Population-based study of the reproductive risk factors for transvaginal ultrasound diagnosed uterine fibroids in Nigerian women.

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.

Relationship between myomectomy and risk of osteoporosis or fracture: A population-based cohort study.

Myomectomy, a surgery to remove multiple leiomyomas from the uterus, is a treatment option for uterine fibroids (UF) in premenopausal patients. Osteoporosis and bone fractures are known to be strongly associated with menopausal status or hormonal changes. However, no studies have discussed the association between myomectomy and osteoporosis or fractures. This study investigated the risk of osteoporosis or fractures (vertebrae, hip, and others) in Korean patients who had undergone myomectomy without bilateral oophorectomy. We used data from the 10-year claims database of the Korean National Health Insurance from January 2009 to December 2020. Data for patients who had undergone myomectomy without oophorectomy (n = 211,969) and the control group (n = 450,124) who were randomly selected from the database were extracted. The incidence and hazard ratios (HRs) of osteoporosis or fracture between the myomectomy patients and the control group were calculated. A Cox proportional hazards model was used to analyze hazard ratios and 95% confidence intervals (CI). Subgroup analyses were performed based on age. The adjusted hazard ratios for osteoporosis and total fractures were 0.934 (95% CI: 0.916-0.954, P<0.001) and 0.919 (95% CI: 0.896-0.941, P<0.001), respectively, in the myomectomy group. The adjusted hazard ratios according to fracture site were 0.857 (95% CI: 0.799-0.92, P<0.001) for vertebral fractures, 0.706 (95% CI: 0.48-1.037, P = 0.076) for hip fractures, and 0.919 (95% CI: 0.896-0.943, P<0.001) for other fractures. In conclusion, patients who have undergone myomectomy might have a decreased risk of osteoporosis or fractures.

Genetic liability to multiple factors and uterine leiomyoma risk: a Mendelian randomization study.

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.

Risk of uterine leiomyomata with menstrual and reproductive factors in premenopausal women: Korea nurses' health study.

BACKGROUND: Uterine leiomyomata (UL) are benign smooth muscle tumors that may cause significant morbidity in women of reproductive age. This study aimed to investigate the relationship of menstrual and reproductive factors with the risk of UL in premenopausal women. METHODS: This prospective study included 7,360 premenopausal women aged 22-48 years who were part of the Korea Nurses' Health Study. Information on the menstrual cycle and reproductive history was assessed between 2014 and 2016, and self-reported cases of UL were obtained through 2021. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 32,072 person-years of follow-up, 447 incident cases of UL were reported. After adjusting for other risk factors, women with late age at menarche had a lower incidence of UL (≥ 16 vs. 12-13 years: HR 0.68; 95% CI 0.47-0.99; p for trend = 0.026). The risk of UL was inversely associated with current menstrual cycle length (≥ 40 or too irregular to estimate vs. 26-31 days: HR 0.40; 95% CI 0.24-0.66) and cycle length at ages 18-22 years (HR 0.45; 95% CI 0.31-0.67; p for trend < 0.001, each). Parous women had lower risk of UL than nulliparous women (HR 0.40; 95% CI 0.30-0.53) and women who were aged 29-30 years at first birth had a lower risk of UL than those who were aged ≤ 28 years at first birth (HR 0.58; 95% CI 0.34-0.98). There was no significant association of the number of births or breastfeeding with the risk of UL among parous women. Neither a history of infertility nor oral contraceptive use was associated with the risk of UL. CONCLUSIONS: Our results suggest that age at menarche, menstrual cycle length, parity, and age at first birth are inversely associated with the risk of UL in premenopausal Korean women. Future studies are warranted to confirm the long-term effects of menstrual and reproductive factors on women's health.

Beta blockers reduce uterine fibroid incidence in hypertensive women.

OBJECTIVE: Is prior beta blocker (BB) use associated with reduced odds of the clinical incidence of leiomyomas? WHAT IS KNOWN ALREADY: In-vitro and in-vivo evidence has supported the role of beta receptor blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association. STUDY DESIGN, SIZE, DURATION: A nested case-control study was conducted in a population of women aged 18-65 with arterial hypertension (n = 699,966). Cases (n = 18,918) with a leiomyoma diagnosis were matched to controls (n = 681,048) with no such diagnosis at a 1:36 ratio by age and region of origin within the United States. PARTICIPANTS/MATERIALS, SETTING, METHODS: This population was assembled from the Truven Health MarketScan® Research Database, which includes health insurance claims from January 1st, 2012 to December 31st, 2017. Prior use of BB wasdetermined fromoutpatient drug claims and leiomyoma development was indicated by a first-time diagnosis code. We conducted a conditional logistic regression to determine the odds of uterine fibroid development in women with prior use of BB compared to women with no such history. We then conducted subset analyses, stratifying the women by age group and by type of BB. RESULTS: Women on a BB experienced 15% reduced odds of developing clinically recognized leiomyoma compared to non-users (OR 0.85, 95% CI 0.76-0.94). This association was significant for the 30-39 age group (OR 0.61, 95% CI 0.40-0.93) but no other age group. Of the BBs, propranolol (OR 0.58, 95% CI 0.36-95) demonstrated a significant association with reduced leiomyoma incidence and metoprolol (OR 0.82, 95% CI 0.70-0.97) was associated with lower uterine fibroid incidence after adjustment for comorbidities. CONCLUSIONS: Hypertensive women with prior BB use experienced reduced odds of developing clinically recognized leiomyoma compared to non-users. A key predisposing risk factor for uterine leiomyoma is elevated blood pressure. Thus, the results of this analysis may have clinical relevance to women with hypertension, as the use of this drug may introduce a dual benefit of managing hypertension as well as curbing an increased risk of leiomyomas.

A prospective ultrasound study of cigarette smoking and uterine leiomyomata incidence and growth.

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.