Menopausal Hormone Therapy, an Ever-Present Topic: A Pilot Survey about Women's Experience and Medical Doctors' Approach.

Background and Objective: Menopause can be associated with many clinical manifestations: vasomotor symptoms, urogenital problems, and additional psychological disturbances, such as anxiety, mood changes, and sleep alterations. The prolonged lack of hormones also increases the risk of long-term consequences. Hormone Replacement Treatment (HRT) in menopause consists of the administration of estrogen, alone or associated to progesterone, to relieve these uncomfortable disturbances and to prevent the onset of other pathologic conditions. The aim of this study is to examine the prevalence of HRT use in a sample of menopausal women and their experience with menopause and HRT. This study also investigates the knowledge of general practitioners (GPs) and gynecologists about HRT and its prescription. Materials and Methods: We conducted a cross-sectional population survey on 126 women of 50-59 years in an industrial city in the North of Italy, Vercelli (Novara), in Eastern Piedmont. We also presented a questionnaire on the topic to 54 medical doctors (GPs and gynecologists) of the same area. Results: The prevalence of HRT use in our sample was 11.9%. In total, a good percentage of the users affirmed to be satisfied with HRT. Additionally, a minority of women reported being ideally against the use of replacement hormones, were advised against using HRT by doctors, and did not use it because of the fear of side effects. We found a positive association between patient education, health care attitude, and HRT usage. A significant number of women knew about HRT from the media, and most of them were not informed by a health professional. Despite this, the interviewed doctors considered their knowledge about HRT as 'good' and would recommend HRT: only 5.6% would not prescribe it. Conclusions: Our results highlight the need for information about HRT among patients and health professionals, along with the need for more effective communication, evaluation, and suggestion of treatment.

Menopause hormone therapy prescribing in ambulatory care visits among midlife and older U.S. women from 2018 to 2019.

The rates of prescription for menopause hormone therapy have been low in the U.S. since the 2002 Women's Health Initiative study, but no recent studies have assessed the prescribing of hormone therapy in the U.S. Using the National Ambulatory Medical Care Survey data from 2018 to 2019, we found that hormone therapy was prescribed in 3.8 % of U.S. visits by midlife and older women, with 60 % of these visits including estradiol-only prescriptions. Older age and Hispanic/Latina ethnicity were associated with decreased odds of prescribing, while White race and depression were associated with increased odds, indicating possible disparities in menopause care.

Association between menopausal hormone therapy and the risk of gastric cancer: A Korean nationwide population-based cohort study.

OBJECTIVE: Gastric cancer (GC) is more common in men than women, but also more common among postmenopausal than premenopausal women. The protective effect of reproductive hormones against GC remains unclear. Therefore, we evaluated the association between menopausal hormone therapy (MHT) and the risk of GC in women. METHODS: We investigated the national cohort data of women aged over 40 years who underwent health checkups by the Korean National Health Insurance Service in 2009. After excluding individuals with missing data and those previously diagnosed with cancer, 1,354,621 postmenopausal women were included and divided into groups according to their MHT history. We followed the study population until 2018 and analyzed the hazard ratios (HR) with 95 % confidence intervals (CIs) for the incidence rate of GC in a multivariate adjusted model. RESULTS: The number of women with and without a history of MHT was 214,723 (15.9 %) and 1,139,898 (84.1 %), respectively. During the mean 8.32 ± 0.8 years of follow-up, a total of 12,496 GC cases developed in the study population (10,962 MHT non-users; 1534 MHT users). In the adjusted model, MHT was associated with a 12 % decrease in the development of GC relative to non-use of MHT (HR 0.88; 95 % CI 0.83-0.93). Exposure to MHT for >2 years was linked to a reduction in GC risk, particularly when initiated before the age of 50, giving a 45 % risk reduction. CONCLUSIONS: According to our large-scale prospective national cohort study, exogenous MHT is associated with a decreased risk of GC in postmenopausal women.

Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses.

Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value<0.001), BSML rs1544410 (OR=1.078; 95 %CI (1.024, 1.153); P-value=0.004), and Fokl rs2228570 (OR=1.123; 95 % CI (1.089, 1.157); P-value<0.001), which were significantly associated with increasing risk of ovarian cancer. Among the other factors, coffee intake (OR=1.106; 95 % CI (1.009, 1.211); P-value=0.030), hormone therapy (RR=1.057; 95 % CI (1.030, 1.400); P-value<0.001), hysterectomy (OR=0.863; 95 % CI (0.745, 0.999); P-value=0.049), and breast feeding (OR=0.719, 95 % CI (0.679, 0.762) and P-value<0.001) were mostly reported in studies. Among nutritional factors, coffee, egg, and fat intake significantly increase the risk of ovarian cancer. Estrogen, estrogen-progesterone, and overall hormone therapies also are related to the higher incidence of ovarian cancer. Some diseases, such as diabetes, endometriosis, and polycystic ovarian syndrome, as well as several genetic polymorphisms, cause a significant increase in ovarian cancer occurrence. Moreover, other factors, for instance, obesity, overweight, smoking, and perineal talc use, significantly increase the risk of ovarian cancer.

Parity, menopausal hormone therapy, and risk of ovarian granulosa cell tumor - A population-based case-control study.

OBJECTIVE: Adult-type ovarian granulosa cell tumors (AGCTs) are hormonally active neoplasms with limited epidemiological data available. We evaluated the effect of parity and postmenopausal hormone therapy (HT) use on the risk of AGCT in a population-based case-control setting. METHODS: We identified all women diagnosed with AGCT during 1994-2015 (n = 505) from the Finnish Cancer Registry. For each case, five controls matched for age were selected from the National Population Registry, which also provided data on parity and ages at deliveries. Information on postmenopausal HT by different regimens (estradiol-only, sequential estrogen-progestin and continuous estrogen-progestin) was obtained from nationwide Prescription Register. The association between parity, ages at deliveries, HT use, and AGCT incidence was evaluated by odds ratios (ORs) using a conditional logistic regression model and stratified by age at index date (<55 years or ≥ 55 years). RESULTS: Parity and age at first or last delivery had no significant effect on AGCT risk. Systemic postmenopausal HT had been used by 20.4% of women who were later diagnosed with AGCT. The risk for subsequent AGCT was significantly decreased among users of estradiol-only therapy for at least five years (OR 0.28; 95% confidence interval 0.08-0.94) and continuous estradiol-progestin therapy for 6 months to 5 years (0.23; 0.08-0.71). CONCLUSIONS: Unlike in epithelial ovarian cancer, AGCT development is not clearly associated with parity, and users of postmenopausal HT do not seem to carry an excess risk for AGCT formation.

Menopausal hormone therapy and women's health: An umbrella review.

BACKGROUND: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). CONCLUSIONS: MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

Prevalence and trends in urinary incontinence among women in the United States, 2005-2018.

BACKGROUND: Women are disproportionately affected by urinary incontinence compared with men. Urinary incontinence results in physical and psychological adverse consequences and impaired quality of life and contributes to significant societal and economic burden. Previous studies reported high urinary incontinence burden in the United States. However, the current prevalence and recent trends in urinary incontinence and its subtypes among US women have not been described. In addition, correlates of urinary incontinence among US women have not been systematically evaluated in the contemporary population. OBJECTIVE: The purpose of this study was to determine the prevalence and trends in urinary incontinence among adult women in the United States from 2005 to 2018. In addition, this study aimed to investigate the relationship of urinary incontinence subtypes with several sociodemographic, lifestyle, health-related, and gynecologic factors. STUDY DESIGN: We used data from the National Health and Nutrition Examination Survey, a nationally representative series of surveys that was designed to evaluate the health status of the US population. Data on urinary incontinence from 7 consecutive 2-year cycles (2005-2006 to 2017-2018) were used for this study. A total of 19,791 participants aged ≥20 years were included. Weighted prevalence estimates and 95% confidence intervals were calculated in each study cycle for stress, urgency, and mixed urinary incontinence. Multivariate-adjusted weighted logistic regression was used to investigate the temporal trends in urinary incontinence, in addition to determining the association between urinary incontinence subtypes with several participants' factors. RESULTS: In the 2017-2018 cycle, stress urinary incontinence was the most prevalent subtype (45.9%; 95% confidence interval, 42.1-49.7), followed by urgency urinary incontinence (31.1%; 95% confidence interval, 28.6-33.6) and mixed urinary incontinence (18.1%; 95% confidence interval, 15.7-20.5). The prevalence rates of urgency and mixed urinary incontinence were higher in women aged 60 years and older (urgency, 49.5% [95% confidence interval, 43.9-55.2]; mixed, 31.4% [95% confidence interval, 26.2-36.6]) than in those aged 40 to 59 years (urgency, 27.9% [95% confidence interval, 23.6-32.1]; mixed, 15.9% [95% confidence interval, 12.9-19.0]) and those aged 20 to 39 years (urgency, 17.6% [95% confidence interval, 13.8-21.5]; mixed, 8.3% [95% confidence interval, 5.4-11.3]). The overall prevalence of stress and mixed urinary incontinence was stable throughout 2005 to 2018 (both Ptrend=.3), with increases in mixed urinary incontinence among women aged 60 years and older (P=.001). The prevalence of urgency urinary incontinence significantly increased, particularly among women aged 60 years and older (both P=.002). Age, obesity, smoking, comorbidities, and postmenopausal hormone therapy were associated with higher prevalence of all types of urinary incontinence. Black women were less likely to report stress urinary incontinence but more likely to report urgency urinary incontinence. CONCLUSION: Although the estimated overall prevalence of stress and mixed urinary incontinence remained stable from 2005 to 2018, the prevalence of urgency and mixed urinary incontinence significantly increased among women aged 60 years and older. All subtypes of urinary incontinence were higher among women with obesity and comorbidities, those who used postmenopausal hormone therapy, and those who smoke.

Association of Premenopausal Bilateral Oophorectomy With Restless Legs Syndrome.

Importance: Restless legs syndrome is a common neurologic disorder that is more prevalent in women than in men, and it has been suggested that female hormones may be involved in the disorder's pathophysiology. Objective: To determine whether women who underwent premenopausal bilateral oophorectomy were at increased risk of restless legs syndrome. Design, Setting, and Participants: This cohort study was performed using data from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2 for a population in Olmsted County, Minnesota. There were 1653 women who underwent premenopausal bilateral oophorectomy before the age of 50 years for a benign indication between 1988 and 2007 and 1653 age-matched women (of same age plus or minus 1 year) in a reference group. Follow-up was conducted until the end of the study period (ie, December 31, 2014). Data were analyzed from January to July 2020. Exposures: Undergoing bilateral oophorectomy, as shown in medical record documentation. Main Outcomes and Measures: Diagnosis of restless legs syndrome, as defined using Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria, was recorded. Results: Among 3306 women, the median (interquartile range) age at baseline was 44.0 (40.0-47.0) years. Women who underwent bilateral oophorectomy, compared with women who did not undergo this procedure, had a greater number of chronic conditions at the index date (eg, 300 women [18.1%] vs 171 women [10.3%] with ≥3 chronic conditions; overall P < .001), were more likely to have obesity (576 women [34.8%] vs 442 women [27.1%]; overall P < .001), and were more likely to have a history of anemia of any type (573 women [34.7%] vs 225 women [13.6%]; P < .001), iron deficiency anemia (347 women [21.0%] vs 135 women [8.2%]; P < .001), and restless legs syndrome before the index date (32 women [1.9%] vs 14 women [0.8%]; P = .008). Women who underwent bilateral oophorectomy prior to natural menopause had a higher risk of restless legs syndrome after the index date compared with women in the reference group (120 diagnoses vs 74 diagnoses), with an adjusted hazard ratio (HR) of 1.44 (95% CI, 1.08-1.92; P = .01). After stratification by indication for the bilateral oophorectomy, there was an increased risk of restless legs syndrome among women without a benign ovarian condition (HR, 1.52; 95% CI, 1.03-2.25; P = .04) but not among women with a benign condition (HR, 1.25; 95% CI, 0.80-1.96; P = .34). Treatment with estrogen therapy through the age of 46 years in women who underwent bilateral oophorectomy at younger ages was not associated with a difference in risk. Conclusions and Relevance: This cohort study found that risk of restless legs syndrome was increased among women who underwent bilateral oophorectomy prior to menopause, especially those without a benign ovarian indication.

Association of Female Reproductive Factors With Incidence of Fracture Among Postmenopausal Women in Korea.

Importance: Although estrogen level is positively associated with bone mineral density, there are limited data on the risk of fractures after menopause. Objective: To investigate whether female reproductive factors are associated with fractures among postmenopausal women. Design, Setting, and Participants: This population-based retrospective cohort study used data from the Korean National Health Insurance Service database on 1 272 115 postmenopausal women without previous fracture who underwent both cardiovascular and breast and/or cervical cancer screening from January 1 to December 31, 2009. Outcome data were obtained through December 31, 2018. Exposures: Information was obtained about reproductive factors (age at menarche, age at menopause, parity, breastfeeding, and exogenous hormone use) by self-administered questionnaire. Main Outcomes and Measures: Incidence of any fractures and site-specific fractures (vertebral, hip, and others). Results: Among the 1 272 115 participants, mean (SD) age was 61.0 (8.1) years. Compared with earlier age at menarche (≤12 years), later age at menarche (≥17 years) was associated with a higher risk of any fracture (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.17-1.31) and vertebral fracture (aHR, 1.42; 95% CI, 1.28-1.58). Compared with earlier age at menopause (<40 years), later age at menopause (≥55 years) was associated with a lower risk of any fracture (aHR, 0.89; 95% CI, 0.86-0.93), vertebral fracture (aHR, 0.77; 95% CI, 0.73-0.81), and hip fracture (aHR, 0.88; 95% CI, 0.78-1.00). Longer reproductive span (≥40 years) was associated with lower risk of fractures compared with shorter reproductive span (<30 years) (any fracture: aHR, 0.86; 95% CI, 0.84-0.88; vertebral fracture: aHR, 0.73; 95% CI, 0.71-0.76; and hip fracture: aHR, 0.87; 95% CI, 0.80-0.95). Parous women had a lower risk of any fracture than nulliparous women (aHR, 0.96; 95% CI, 0.92-0.99). Although breastfeeding for 12 months or longer was associated with a higher risk of any fractures (aHR, 1.05; 95% CI, 1.03-1.08) and vertebral fractures (aHR, 1.22; 95% CI, 1.17-1.27), it was associated with a lower risk of hip fracture (aHR, 0.84; 95% CI, 0.76-0.93). Hormone therapy for 5 years or longer was associated with lower risk of any factures (aHR, 0.85; 95% CI, 0.83-0.88), while use of oral contraceptives for 1 year or longer was associated with a higher risk of any fractures (aHR, 1.03; 95% CI, 1.01-1.05). Conclusions and Relevance: The findings of this cohort study suggest that female reproductive factors are independent risk factors for fracture, with a higher risk associated with shorter lifetime endogenous estrogen exposure. Interventions to reduce fracture risk may be needed for women at high risk, including those without osteoporosis.

Associations of Endometriosis and Hormone Therapy With Risk of Hyperlipidemia.

Using claims data from the universal health insurance program of Taiwan, we conducted a retrospective cohort study to investigate whether endometriosis and hormone therapy are associated with the risk of developing hyperlipidemia. We selected 9,155 women aged 20-55 years with endometriosis diagnosed during the period 2000-2013 and 212,641 women without endometriosis with a median follow-up time of 7 years. Among patients with endometriosis, 86% of cases were identified on the basis of diagnosis codes with an ultrasound claim, and 14% were defined by diagnostic laparoscopy or surgical treatments. In a Cox proportional hazards model, the adjusted hazard ratio was 1.30 (95% confidence interval (CI): 1.19, 1.41) for all women, 1.04 (95% CI: 0.81, 1.32) for women under 35 years of age, 1.17 (95% CI: 1.03, 1.32) for women aged 35-44 years, and 1.34 (95% CI: 1.18, 1.52) for women aged 45-54 years. Hysterectomy and/or bilateral oophorectomy accounted for 46.9% of the association between endometriosis and hyperlipidemia, and hormone therapy accounted for 21.6%. Among women with endometriosis, the marginal structural model approach adjusting for time-varying hysterectomy/bilateral oophorectomy showed no association between use of hormone medications and risk of hyperlipidemia. We concluded that women with endometriosis are at increased risk of hyperlipidemia; use of hormone therapy by these women was not independently associated with the development of hyperlipidemia.

The Menopause Transition: Signs, Symptoms, and Management Options.

CONTEXT: Menopause, the permanent cessation of menses, reflects oocyte depletion and loss of gonadal steroids. It is preceded by a transition state, the perimenopause, which is characterized by the gradual loss of oocytes, altered responsiveness to gonadal steroid feedback, wide hormonal fluctuations, and irregular menstrual patterns. The goal of this mini-review is to discuss the basic pathophysiology of the menopausal transition and the hormonal and nonhormonal management of clinicopathology attributed to it. EVIDENCE ACQUISITION: A Medline search of epidemiologic, population-based studies, and studies of reproductive physiology was conducted. A total of 758 publications were screened. EVIDENCE SYNTHESIS: The reproductive hormonal milieu of the menopausal transition precipitates bothersome vasomotor symptoms, mood disruption, temporary cognitive dysfunction, genitourinary symptoms, and other disease processes that reduce the quality of life of affected women. The endocrine tumult of the menopause transition also exposes racial and socioeconomic disparities in the onset, severity, and frequency of symptoms. Hormone therapy (HT) treatment can be effective for perimenopausal symptoms but its use has been stymied by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years. CONCLUSIONS: The menopause transition is a disruptive process that can last for over a decade and causes symptoms in a majority of women. It is important for clinicians to recognize early signs and symptoms of the transition and be prepared to offer treatment to mitigate these symptoms. Many safe and effective options, including HT, are available.

Randomized Trial Evaluation of the Benefits and Risks of Menopausal Hormone Therapy Among Women 50-59 Years of Age.

The health benefits and risks of menopausal hormone therapy among women aged 50-59 years are examined in the Women's Health Initiative randomized, placebo-controlled trials using long-term follow-up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy postmenopausal women aged 50-79 years at 40 US clinical centers during 1993-1998, including 10,739 post-hysterectomy participants in a trial of conjugated equine estrogens and 16,608 participants with a uterus in the trial of these estrogens plus medroxyprogesterone acetate. Over a (median) 18-year follow-up period (1993-2016), risk for a global index (defined as the earliest of coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and all-cause mortality) was reduced with conjugated equine estrogens with a hazard ratio of 0.82 (95% confidence interval: 0.71, 0.95), and with nominally significant reductions for coronary heart disease, breast cancer, hip fracture, and all-cause mortality. Corresponding global index hazard ratio estimates of 1.06 (95% confidence interval: 0.95, 1.19) were nonsignificant for combined estrogens plus progestin, but increased breast cancer risk and reduced endometrial cancer risk were observed. These results, among women 50-59 years of age, substantially agree with the worldwide observational literature, with the exception of breast cancer for estrogens alone.

Association of tibolone and dementia risk: a cohort study using Korean claims data.

OBJECTIVE: Few studies have examined whether tibolone (TIB), a type of hormone replacement therapy widely used in Asia and Europe, affects dementia risk in postmenopausal women. Our study aims to investigate the association of TIB and dementia risk in Korean women aged 50-80 years. METHODS: A population-based longitudinal study was conducted using the Korean National Health Insurance Service claims database merged with national health examination data from 2002 to 2015. Among 13,110 participants, exposure to TIB was determined using the standardized defined daily dose (DDD) system from 2003 to 2007. Starting from 2007, participants were followed up for overall dementia, Alzheimer's disease (AD) and vascular dementia (VD) until 2015. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of dementia according to TIB use. RESULTS: TIB use was not significantly associated with the risk of total dementia (aHR = 1.040; 95% CI = 0.734-1.472; p = .827), AD (aHR = 0.949; 95% CI = 0.652-1.381; p = .785) and VD (aHR = 1.245; 95% CI = 0.631-2.457; p = .528). CONCLUSIONS: Our results suggest that TIB use does not have a significant association with dementia risk. Further randomized controlled trials are necessary to elucidate the role of exogenous hormones in the development of dementia.

Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival.

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival. CONCLUSIONS: Pre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism.

A retrospective multicenter study of bone mineral density in adolescents and adults with Turner syndrome in Japan.

Osteoporosis is one of the clinical features of women with Turner syndrome (TS). The reasons for low bone mineral density (BMD) and increased bone fragility are multifactorial, including estrogen deficiency, X-chromosome abnormalities, and environmental factors. Few, large-scale studies on bone mineral density in either adolescents or adults with TS have been done in Japan. The goal of the present study was to investigate spinal BMD in women with TS, assess its relationship with clinical parameters, especially estrogen replacement therapy, and investigate its longitudinal changes. The spinal BMD and clinical data of 149 Japanese women with TS aged 15 to 49 years who were followed at the four participating hospitals were retrospectively analyzed. The BMD Z-scores of the women with TS ranged from -5.30 to +1.89. Women with TS aged 15-39 years had lower BMD than healthy Japanese women (p < 0.01) while women with spontaneous menstruation had a significantly higher BMD Z-score than those without spontaneous menstruation (-0.73 ± 1.11 vs. -1.67 ± 1.18, p < 0.01). In women without spontaneous menstruation, BMD Z-scores correlated with the duration of their estrogen therapy (r = 0.167, p < 0.01). Women aged 15-39 years with TS had low BMD, which was associated with primary amenorrhea and short estrogen replacement therapy duration.

Doppler ultrasonography of the ophthalmic artery in perimenopausal and postmenopausal women: a new approach.

BACKGROUND: The vascular endothelium has specific estrogen receptors and the impact of hormone therapy (HT) on circulation is associated with cardiovascular protection in perimenopause and postmenopause. Blood vessels can be assessed by ultrasound Doppler velocimetry, and more specifically the study of the ophthalmic artery (OA) can be used for brain vessel assessment; more recently, it is a possible method for cardiovascular risk assessment. METHODS: A cross-sectional study involved perimenopausal and postmenopausal women divided into three groups: 60 non-HT users (control group), 23 users of estrogen therapy (ET group), and 23 users of estrogen-progesterone therapy (EPT group). Doppler velocimetry of the OA was performed with analysis of the resistance index (RI), pulsatility index (PI), systolic peak velocity (P1), second systolic peak velocity (P2), peak velocity ratio (PVR), final diastolic velocity (FDV), and ratio between means of systolic and diastolic velocity (SDR). RESULTS: There was no significant difference between the groups in Doppler velocimetry indices of the OA: RI (p = 0.94), PI (p = 0.85), P1 (p = 0.81), P2 (p = 0.53), PVR (p = 0.41), FDV (p = 0.76), and SDR (p = 0.84). We observed a positive correlation of the SDR with age only in the control group (r = 0.34, p = 0.01). CONCLUSIONS: There is a positive correlation between the SDR and age in the control group. Therefore, this new index is a promising instrument in the non-invasive assessment of cardiovascular risk.

Development and validation of a prediction model for incident hand osteoarthritis in the HUNT study.

OBJECTIVE: To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women. DESIGN: We included 17,153 men and 18,682 women from a population-based cohort, aged 35-70 years at baseline (1995-1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995-2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting. RESULTS: The model for men showed modest discriminatory ability (AUC = 0.67, 95% CI 0.62-0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC = 0.62, 95% CI 0.59-0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC = 0.62, 95% CI 0.57-0.65). CONCLUSION: We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability.

Skin Cancer and Skin Cancer Risk Factors in Sexual and Gender Minorities.

Sexual and gender minorities have unique risk factors that may increase their risk of developing skin cancer. In particular, sexual minority men report a higher prevalence of skin cancer (including both keratinocytes carcinomas and melanoma), higher rates of indoor tanning, and overall poorer sun protection behaviors. Sexual and gender minorities also have high rates of alcohol and tobacco use, and infection with human immunodeficiency virus and human papillomavirus, which may increase overall risk of developing skin cancer in these populations. In this review, we discuss the evidence surrounding skin cancer and associated risk factors among sexual and gender minorities.

Physical Activity, Hormone Therapy Use, and Stroke Risk among Women in the California Teachers Study Cohort.

BACKGROUND: Postmenopausal hormone therapy (HT) increases the risk of stroke. Here we evaluate whether leisure time physical activity (LTPA) can change stroke risk in women using HT, leveraging data from the California Teachers Study. METHODS: Female California educators without a prior history of stroke (n = 118,294) were followed from 1995 through 2015 for stroke end points. Based on statewide hospitalization data, 4,437 women had ischemic (n = 3,162; International Classification of Diseases [ICD]-9 433, 434, 436) or hemorrhagic (n = 1,275; ICD-9 430-432, excluding 432.1) stroke. LTPA and HT use were evaluated at 2 time points (baseline [1995-1996] and 10-year follow-up [2005-2006]). LTPA was assessed using American Heart Association (AHA) recommendations (>150 min/week moderate or >75 min/week strenuous physical activity). Using multivariable Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% CIs for the associations between HT use and concurrent LTPA with incident stroke. RESULTS: Compared to women who never used HT, stroke risk was highest among women who were current HT users and did not meet AHA recommendations for LTPA at the time of their HT use: HRbaseline 1.28 (95% CI 1.13-1.44); HR10-year follow-up 1.17 (95% CI 0.91-1.50). Based on the baseline questionnaire, current HT users who met AHA recommendations for LTPA in 1995-1996 still had elevated stroke risk in the 20-year follow-up (HR 1.22, 95% CI 1.08-1.37). However, among current HT users who met AHA recommendations for LTPA at the 2005-2006 follow-up questionnaire, stroke risk was not elevated (HR 1.01, 95% CI 0.80-1.29). Evaluation of the 2 time points in concert further demonstrated that meeting AHA recommendations for LTPA at the most recent follow-up time point was required to reduce HT-related stroke risk. CONCLUSION: Concurrent physical activity may attenuate the short-term increase in risk of stroke risk associated with HT use.

Hormonal therapy in menopausal transition: implications for improvement of health-related quality of life.

The study aim was to assess scores of the Menopause Rating Scale (MRS) among women who use and desire to use hormonal therapy (HT), as well as to evaluate factors contributing to HT use and desire to use HT among women in menopausal transition. A total of 513 mid-aged women participated in the study. Data were collected using socio-demographic questionnaire, MRS and Beck Depression Inventory. The prevalence of current HT use was 9.7%, while 4.5% of women who did not use HT expressed a desire to start using HT. The MRS cutoff score for HT use was 10.5 and 11.5 among those who desire to use HT. Living in the central city districts, having lower body mass index, younger age at menopause, more gynecological illnesses, and worse MRS were associated with HT use. Living in the central city districts, having fewer births, more gynecological and chronic illnesses and having more depressive symptoms were associated with the desire to use HT. Mid-aged women who perceive their quality of life as poor due to climacteric symptoms should be advised to consider HT to improve their health status and everyday functioning.