Genitourinary symptoms and sexual function in women with primary ovarian insufficiency.

OBJECTIVE: There are limited studies on urogenital symptoms in women who experience menopause before the age of 40 years due to primary ovarian insufficiency (POI) or bilateral oophorectomy (surgical POI). This study aimed to compare the urogenital symptoms, including sexuality, of women with POI to those without the condition. METHODS: This cross-sectional study conducted was in seven Latin American countries, in which postmenopausal women (with POI and non-POI) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS) and the six-item Female Sexual Function Index (FSFI-6). The association of premature menopause with more urogenital symptoms and lower sexual function was evaluated with logistic regression analysis. RESULTS: Women with POI experience more urogenital symptoms (MRS urogenital score: 3.54 ± 3.16 vs. 3.15 ± 2.89, p < 0.05) and have lower sexual function (total FSFI-6 score: 13.71 ± 7.55 vs. 14.77 ± 7.57 p < 0.05) than women who experience menopause at a normal age range. There were no significant differences in symptoms when comparing women based on the type of POI (idiopathic or surgical). After adjusting for covariates, our logistic regression model determined that POI is associated with more urogenital symptoms (odds ratio [OR]: 1.38, 95% confidence interval [CI] 1.06-1.80) and lower sexual function (OR: 1.67, 95% CI 1.25-2.25). CONCLUSION: POI, whether idiopathic or secondary to bilateral oophorectomy, is associated with symptoms that affect vaginal and sexual health.

Peculiarities of local immunity in dry eye disease on the background of hormonal dysfunction.

OBJECTIVE: Aim: to determine the state of local immunity in DED on the background of hormonal dysfunction. PATIENTS AND METHODS: Materials and Methods: Of 32 women, 17 patients with diagnosed SM and 15 women of the control group were examined. The Ocular Surface Disease Index and the state of local immunity were defined by determining Ig As in lacrimal fluid (LF) by radial immunodiffusion in Mancini agar. RESULTS: Results: During the OSDI questionnaire, a mild degree of DED was detected in 21 (65.6%) women, and an average degree was observed in 11 (34.4%) patients with SM. On average, OSDI was 34.54 ±2.01. As a result of studies of the state of local immunity in patients with SM, a tendency to increase Ig As was noted, compared with the control group. An increase in Ig As in the lacrimal fluid in patients with SM to 0.34 ±0.09 g/l was found, compared with the control group (0.24 ±0.03 g/l). CONCLUSION: Conclusions: Using the OSDI questionnaire, the presence of DED was detected in women with SM, mainly mild and moderate degree. The obtained results of the state of local immunity indicate in favor of a nonspecific inflammatory process, accompanied by a decrease in local immune protection and leading to further changes in the ocular surface.

Age at menopause and all-cause and cause-specific dementia: a prospective analysis of the UK Biobank cohort.

STUDY QUESTION: Are there associations between natural or surgical menopause and incident dementia by age at menopause? SUMMARY ANSWER: Compared to age at menopause of 46-50 years, earlier natural menopause (≤40 and 41-45 years) was related to higher risk of all-cause dementia, while a U-shape relationship was observed between age at surgical menopause and risk of dementia. WHAT IS KNOWN ALREADY: Menopause marks the end of female reproductive period. Age at menopause reflects the length of exposure to endogenous estrogen. Evidence on the association between age at natural, surgical menopause, and risk of dementia has been inconsistent. STUDY DESIGN, SIZE, DURATION: A population-based cohort study involving 160 080 women who participated in the UK Biobank study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with no dementia at baseline, and had no missing data on key exposure variables and covariates were included. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs on the association of categorical menopause age with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). Restricted cubic splines were used to model the non-linear relationship between continuous age at natural, surgical menopause, and risk of dementia. In addition, we analyzed the interaction effect of ever-used menopausal hormone therapy (MHT) at baseline, income level, leisure activities, and age at menopause on risk of dementia. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with age at menopause of 46-50 years, women with earlier natural menopause younger than 40 years (1.36, 1.01-1.83) and 41-45 years (1.19, 1.03-1.39) had a higher risk of all-cause dementia, while late natural menopause >55 years was linked to lower risk of dementia (0.83, 0.71-0.98). Compared to natural menopause, surgical menopause was associated with 10% higher risk of dementia (1.10, 0.98-1.24). A U-shape relationship was observed between surgical menopause and risk of dementia. Women with surgical menopause before age 40 years (1.94, 1.38-2.73) and after age 55 years (1.65, 1.21-2.24) were both linked to increased risk of all-cause dementia. Women with early natural menopause without ever taking MHT at baseline had an increased risk of AD. Also, in each categorized age at the menopause level, higher income level or higher number of leisure activities was linked to a lowers risk of dementia. LIMITATIONS, REASONS FOR CAUTION: Menopausal age was based on women's self-report, which might cause recall bias. WIDER IMPLICATION OF THE FINDINGS: Women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures to delay the development of dementia. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Start-up Foundation for Scientific Research in Shandong University (202099000066), Science Fund Program for Excellent Young Scholars of Shandong Provence (Overseas) (2022HWYQ-030), and the National Natural Science Foundation of China (82273702). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Concurrent uterine surgery and uptake of hormone therapy in patients undergoing bilateral salpingo-oophorectomy for risk-reducing or therapeutic indications.

OBJECTIVE: This study aimed to analyze factors associated with concurrent uterine surgery in patients undergoing bilateral salpingo-oophorectomy (BSO) for risk reducing or therapeutic purposes. Additionally, trends in surgical choice and uptake of post-operative hormone therapy (HT) were examined. METHODS: A 10-year retrospective study was conducted on patients who underwent risk-reducing or therapeutic BSO at one institution. Multinomial regression analysis of patient and case characteristics was performed evaluating associations with surgery type (BSO, BSO and hysterectomy, or BSO and endometrial sampling). Trends in surgery type and uptake of HT post operatively are described. RESULTS: Among the study sample of 643 patients, 140 (22%) patients underwent therapeutic BSO for a history of hormone receptor (HR) positive breast cancer, while the remainder underwent risk-reducing BSO due to a pathogenic variant and/or family history. Pathogenic variants included BRCA1 (141, 40%) BRCA2 (173, 49%), and Lynch syndrome genes (15, 4%). Regression analysis revealed significant associations between concurrent hysterectomy and Black race (RR = 3.55, CI = 1.51-8.38, p = 0.004), history of HR positive breast cancer (RR = 1.88, CI = 1.03-3.42, p = 0.04), and surgeon (Surgeon 1, RR = 2.43, CI = 1.36-4.35, p = 0.003). Among eligible patients under age 51, 36% initiated HT. Over the study period, concurrent hysterectomy rates declined while endometrial sampling increased. CONCLUSIONS: Rates of hysterectomy declined over the study period and slightly more than one-third of eligible patients utilized post-operative HT. Further research on concurrent uterine surgery is needed to establish standardized treatment recommendations in the risk-reducing and therapeutic BSO population. Additionally, education regarding the benefits of postoperative HT in eligible patients is warranted.

Sexual functioning more than 15 years after premenopausal risk-reducing salpingo-oophorectomy.

BACKGROUND: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure 1 to 3 years after a premenopausal oophorectomy. However, the long-term effects of premenopausal oophorectomy on sexual functioning are unknown. OBJECTIVE: This study aimed to study long-term sexual functioning in women at increased familial risk of breast or ovarian cancer who underwent a risk-reducing salpingo-oophorectomy either before the age of 46 years (premenopausal group) or after the age of 54 years (postmenopausal group). Subgroup analyses were performed in the premenopausal group, comparing early (before the age of 41 years) and later (at ages 41-45 years) premenopausal risk-reducing salpingo-oophorectomy. STUDY DESIGN: Between 2018 and 2021, 817 women with a high familial risk of breast or ovarian cancer from an ongoing cohort study were invited to participate in our study. Because of a large difference in age in the study between the premenopausal and postmenopausal salpingo-oophorectomy groups, we restricted the comparison of sexual functioning between the groups to 368 women who were 60 to 70 years old at completion of the questionnaire (226 in the premenopausal group and 142 in the postmenopausal group). In 496 women with a premenopausal risk-reducing salpingo-oophorectomy, we compared the sexual functioning between women in the early premenopausal group (n=151) and women in the later premenopausal group (n=345). Differences between groups were analyzed using multiple regression analyses, adjusting for current age, breast cancer history, use of hormone replacement therapy, body mass index, chronic medication use (yes or no), and body image. RESULTS: Mean times since risk-reducing salpingo-oophorectomy were 20.6 years in the premenopausal group and 10.6 years in the postmenopausal group (P<.001). The mean age at questionnaire completion was 62.7 years in the premenopausal group, compared with 67.0 years in the postmenopausal group (P<.001). Compared with 48.9% of women in the postmenopausal group, 47.4% of women in the premenopausal group were still sexually active (P=.80). Current sexual pleasure scores were the same for women in the premenopausal group and women in the postmenopausal group (mean pleasure score, 8.6; P=.99). However, women in the premenopausal group more often reported substantial discomfort than women in the postmenopausal group (35.6% vs 20.9%; P=.04). After adjusting for confounders, premenopausal risk-reducing salpingo-oophorectomy was associated with substantially more discomfort during sexual intercourse than postmenopausal risk-reducing salpingo-oophorectomy (odds ratio, 3.1; 95% confidence interval, 1.04-9.4). Moreover, after premenopausal risk-reducing salpingo-oophorectomy, more severe complaints of vaginal dryness were observed (odds ratio, 2.6; 95% confidence interval, 1.4-4.7). Women with a risk-reducing salpingo-oophorectomy before the age of 41 years reported similar pleasure and discomfort scores as women with a risk-reducing salpingo-oophorectomy between ages 41 and 45 years. CONCLUSION: More than 15 years after premenopausal risk-reducing salpingo-oophorectomy, the proportion of sexually active women was comparable with the proportion of sexually active women with a postmenopausal risk-reducing salpingo-oophorectomy. However, after a premenopausal risk-reducing salpingo-oophorectomy, women experienced more vaginal dryness and more often had substantial sexual discomfort during sexual intercourse. This did not lead to less pleasure with sexual activity.

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Subjective cognitive changes following premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Women at high risk of ovarian cancer are commonly advised to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) prior to natural menopause. Cognitive symptoms during natural menopause transition are frequently reported; however, very few studies have examined cognitive changes following surgical menopause. To address this gap, we explored the cognitive experiences of women within 24 months post BSO. METHODS: This observational cross-sectional sub-study is part of a larger project, the Early Menopause and Cognition Study (EM-COG). We investigated perceived cognitive experiences in Australian women (n = 16) who underwent risk-reducing BSO using qualitative interviews. Thematic analysis was undertaken to identify key themes. RESULTS: Fifteen out of 16 participants (93.75%) reported changes to cognition within 24 months post BSO. The key cognitive symptoms reported were brain fog, memory and retrieval difficulties, slower processing speed as well as attention difficulties. Five participants (31.3%) experienced negative mood symptoms post BSO. CONCLUSION: Findings from this study suggest that women experience subjective cognitive changes within 24 months post BSO. This period could be a vulnerable time for women's cognitive health. While these findings need to be confirmed by a large prospective study, our research indicates that psychoeducation and awareness will be helpful in managing cognitive symptoms after surgical menopause.

Real-world practice of estrogen therapy after surgery for endometrial cancer: a descriptive study using a Japanese claims database.

BACKGROUND: Estrogen therapy (ET) plays a key role in maintaining the post-surgical quality of life of patients with endometrial cancer. This study investigated the reality of the use of ET after endometrial cancer surgery in Japan. METHODS: Using a healthcare database in Japan, patients who underwent surgery for endometrial cancer between the ages of 40 and 59 years from January 2006 to March 2021 were included. The cumulative prescriptions of ET after endometrial cancer surgeries in patients who had received chemotherapy or radiation therapy (adj-group) and those who did not (non-adj-group) was estimated using the Kaplan-Meier method. RESULTS: Of the 1475 patients, 115 received ET, among whom transdermal estradiol was initiated in 100 (87.0%) individuals. The cumulative proportions of ET prescription 24 months after surgery [95% confidence intervals (CIs)] were 0.088 [0.072, 0.11] in the non-adj-group and 0.058 [0.040, 0.084] in the adj-group. The cumulative proportion [95% CI] of women who received ET at 24 months after surgeries decreased with increasing age, ranging from 0.29 [0.21, 0.38] in the 40‒44 years old to 0.009 [0.002, 0.034] in the 55‒59 years old women in the non-adj-group and from 0.17 [0.094, 0.31] in the 40‒44 years old to 0 in the 55‒59 years old women in the adj-group. CONCLUSION: The present study shows that ET after endometrial cancer surgery may be underused, even in women who underwent surgery between 40 and 44 years of age and without adjuvant therapy.

Behavioral Despair Is Blocked by the Flavonoid Chrysin (5,7-Dihydroxyflavone) in a Rat Model of Surgical Menopause.

Women have a high susceptibility to the negative effects of stress. Hormonal changes experienced throughout their reproductive life partially contribute to a higher incidence of anxiety and depression symptoms, particularly, during natural or surgical menopause. In preclinical research, the flavonoid chrysin (5,7-dihydroxyflavone) exerts anxiolytic- and anti-despair-like effects; however, it is unknown whether chrysin exerts a protective effect against the behavioral changes produced by acute stress on locomotor activity and behavioral despair in rats at 12-weeks post-ovariectomy. Ovariectomized female Wistar rats were assigned to eight groups: vehicle group (10% DMSO), three groups with chrysin and three groups with the same dose of allopregnanolone (0.5, 1, and 2 mg/kg), and one group with diazepam (2 mg/kg). The treatments were administered for seven consecutive days and the effects were evaluated in the locomotor activity and swimming tests. Chrysin (2 mg/kg) increased the latency to first immobility and decreased the total immobility time in the swimming test as the reference drugs allopregnanolone and diazepam (2 mg/kg); while locomotor activity prevented the behavioral changes produced by swimming. In conclusion, chrysin exerts a protective effect against the behavioral changes induced by acute stress, similarly to the neurosteroid allopregnanolone and the benzodiazepine diazepam in rats subjected to a surgical menopause model.

Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: cohort study of UK Biobank participants.

STUDY QUESTION: What is the association between menopausal hormone therapy (MHT) and cause-specific mortality? SUMMARY ANSWER: Self-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes. WHAT IS KNOWN ALREADY: Evidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality. STUDY DESIGN, SIZE, DURATION: Cohort study (the UK Biobank), 178 379 women, recruited in 2006-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74). LIMITATIONS, REASONS FOR CAUTION: Self-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT. WIDER IMPLICATIONS OF THE FINDINGS: The current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation. STUDY FUNDING/COMPETING INTEREST(S): This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

What happens after menopause? (WHAM): A prospective controlled study of symptom profiles up to 12 months after pre-menopausal risk-reducing salpingo-oophorectomy.

OBJECTIVE: Understanding how symptoms cluster after premenopausal risk-reducing salpingo-oophorectomy (RRSO) can inform patient expectations but information is lacking. We aimed to identify symptom profiles after RRSO, changes over time, and the effect of hormone therapy (HT). METHOD: Participants were premenopausal women from a longitudinal controlled study (What Happens After Menopause? (WHAM)). Menopausal symptoms were prospectively measured in three groups: pre-menopausal comparisons who retained their ovaries (n = 99), RRSO HT users (n = 57) and RRSO non-HT users (n = 38). Symptoms (hot flashes, night sweats, low desire, vaginal dryness, poor sleep, anxiety/depression) were measured at baseline (pre-surgery) and at 3, 6 and 12 months using standardised questionnaires. Latent transition analysis was used to identify symptom profiles post-RRSO, and the probability of changing profiles over time. RESULTS: Three symptom profiles were identified: Most Symptoms (81-87% non-HT; 36-41% HT; 7-9% comparisons), Few Symptoms (7-13% non-HT; 36-42% HT; 77-80% comparisons), and Sexual Symptoms (0-10% non-HT; 17-27% HT; 14-15% comparisons). Most of the non-HT group reported Most Symptoms at 3 months with only a 2% chance of improvement by 12 months. The HT group were split between profiles at 3 months with a 5-13% chance of improvement by 6 months (14% chance of worsening), and a 12-32% chance of improvement by 12 months (4-25% chance of worsening). CONCLUSIONS: Symptoms cluster into distinct profiles after premenopausal RRSO. Most non-HT users are highly symptomatic with little chance of improvement by 12 months. In contrast, two-thirds of HT users have fewer symptoms and a much higher chance of improvement. These findings can inform patient decision-making and expectations.

Hormone replacement in premenopausal women treated with bilateral oophorectomy for ovarian cancer - a nationwide population-based study.

OBJECTIVE: To study the extent of hormone replacement therapy (HRT) dispensing in premenopausal women after being treated with bilateral salpingo-oophorectomy (BSOE) for ovarian cancer (OC). METHODS: Nationwide population- and register-based cohort study including women 18-50 years old, registered in The Swedish Quality Register for Gynecological Cancer (SQRGC), where BSOE was performed due to epithelial (EOC) and non-epithelial ovarian cancers (NEOC) or borderline ovarian tumor (BOT) between 2008 and 2014. Data on HRT dispensing was obtained from the National Prescribed Drug Register analyzed at semi-annual intervals from surgery until end of follow-up December 2015, including a logistic regression analysis. RESULTS: A cohort of 664 women were identified with OC, whereas 396 women had an EOC, 61 a NEOC and 207 a BOT. At surgery 49% of the women were ≤44 years. HRT dispensed to the total cohort varied between 32% and 41% the first five years after surgery. During follow-up at first 0.5-1 year 51% of the women <40 years were dispensed HRT compared to 25% of women ≥40 years. Of women with EOC, 21% dispensed HRT at first 0.5-1 year. In the multivariable regression analysis; age <40 (OR6.17, p < 0.001) and age 40-44 (OR2.95, p < 0.001) as well as BOT histology (OR3.84, p < 0.001) were found significant variables for dispensing of HRT. CONCLUSION: A majority of premenopausal women undergoing BSOE for OC did not use HRT postoperatively. Our study shows that there is a need to address HRT use after OC treatment in young women to prevent from morbidity and a poorer quality of life.

Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy: A national retrospective cohort study of women in England.

OBJECTIVE: To examine the associations between adverse childhood experiences (ACE) and the risk of hysterectomy and bilateral oophorectomy in a national sample of women in England. DESIGN: Retrospective cohort study. SETTING: A stratified random sample of households across England. POPULATION: 2648 women aged ≥55 years in 2007 from the English Longitudinal Study of Ageing (ELSA) were included in the bilateral oophorectomy analyses and 2622 in the hysterectomy analyses. METHODS: Logistic and multinomial logistic regression analyses of the associations between categories of the ACE summary score (0, 1, 2, ≥3 ACE), eight individual ACE, and hysterectomy and bilateral oophorectomy. RESULTS: 615 women had undergone hysterectomy and 259 women bilateral oophorectomy. We found graded associations between the summary ACE score and risk of hysterectomy and bilateral oophorectomy. In the fully adjusted model, compared with women with no ACE, those with ≥3 ACE had double the odds of hysterectomy (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.30-3.11) and more than double the odds of bilateral oophorectomy (OR 2.61, 95% CI 1.54-4.42). The exclusion of women with cancer history made the associations stronger, especially in women who underwent hysterectomy at age <40 years or bilateral oophorectomy at age ≤44 years. Several individual ACE were positively associated with both outcomes. CONCLUSIONS: ACE are associated with increased risk of hysterectomy and bilateral oophorectomy. Individual-level covariates did not explain these associations. Our findings highlight the importance of a life course approach to understanding surgical menopause and add to our knowledge of the societal and public health impact of ACE. TWEETABLE ABSTRACT: Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy in a national sample of women in England.

Menopausal hormonal therapy in surgically menopausal women with underlying endometriosis.

OBJECTIVE: This study aimed to investigate the relationship between menopausal hormone therapy (MHT) and endometriosis recurrence in women who underwent hysterectomy with bilateral salpingo-oophorectomy to treat endometriosis. METHOD: This retrospective cohort study included 330 women who underwent definitive surgery to treat endometriosis during 1996-2012. Follow-up data until December 2018 were analyzed. Patients were grouped as MHT non-users (non-MHT, n = 43), estrogen-only therapy (ET, n = 230), estrogen-progestogen therapy (EPT, n = 39) and tibolone (n = 18). RESULTS: The mean age at surgery was 41.5 ± 5.3 years. The overall median follow-up duration was 6.0 years (interquartile range [IQR]: 3.0-10.4), and the median duration of MHT use was 66.0 months (IQR: 36.0-116.3). The overall recurrence rate was 3.0% (95% confidence interval: 1.5-5.5) and there was no significant difference in recurrence among the study groups. Disease recurrence resolved after MHT discontinuation, or change in MHT type and/or dose. CONCLUSIONS: No significant association between MHT use and endometriosis recurrence was found in this study. The endometriosis recurrence rate was non-significantly different between ET and EPT. Recurrent endometriosis can be successfully treated without invasive measures. No study patients had malignant transformation after a median follow-up of 6 years. Our findings suggest that any of the three evaluated MHT regimens can be used in surgically menopausal Thai women with underlying endometriosis.

Impact of Global Consensus Statement on compliance with hormonal therapy for surgical menopause.

OBJECTIVE: Initiation of and compliance with menopausal hormonal therapy (MHT) have been dropping due to the 2002 Women's Health Initiative (WHI) publication. We evaluated the change in practice of MHT for surgical menopause after implementing the 2013 'Global Consensus Statement on MHT' to our institutional guideline. METHODS: A retrospective study was conducted in surgically menopausal women newly registering at the Siriraj Menopause Clinic in a university hospital, Thailand, from 1995 to 2013. The patients were categorized into four groups according to periods of MHT initiation: 1995-1998 (control), 2000-2003 (WHI affected), 2005-2008 (post WHI) and 2010-2013 (Global Consensus Statement affected). Their 3-year compliance with MHT was compared using forward stepwise regression analysis. RESULTS: There were 288, 156, 107 and 104 cases in the 1995-1998, 2000-2003, 2005-2008 and 2010-2013 groups. Their mean age at surgery was 42.8 ± 4.7 years. After the first, second and third years, overall compliance was 82.4%, 70.9% and 61.2%, respectively. The 3-year compliance drastically dropped in the 2000-2003 group, and then improved to control level in the 2010-2013 group (51.9% vs. 77.9%, p = 0.035). CONCLUSION: The initiation of MHT continuously dropped during 2000-2013; however, compliance with MHT initiated during 2010-2013 improved after implementing the 2013 'Global Consensus Statement on MHT' to our institutional guideline. Each institute should have a strategy to encourage the initiation of and compliance with MHT for surgical menopause to achieve long-term health benefits.

Is there any difference in hearing function between surgical and natural menopause?

This study was designed to examine cochlear function in surgical postmenopausal women and natural menopause. Three groups, each including 20 patients, were formed: surgical menopause (SM), natural menopause (NM), and healthy controls who had not yet gone through menopause. Conventional audiometry (0.125-8 kHz), ultra-high frequency audiometry (10-16 kHz), and otoacoustic emission (OAE) tests were used in the evaluation of the patients. Almost all the hearing thresholds were significantly poorer in the menopause groups than in the control group (p < .05). However, the amplitudes of the healthy controls were higher in transient evoked otoacoustic emissions (TEOAEs), especially in many frequencies of distortion product otoacoustic emissions (DPOAEs) (p < .05). In the SM group, all the frequencies between 0.125 and 10 kHz for the right ear, and 1, 2, 6 and 8 kHz air-conduction hearing thresholds for the left ear were significantly poorer compared to the NM group (p < .05). There was also a significant decrease in the 4, 6, and 8 kHz DPOAE amplitudes of the SM group compared to the NM group (p < .05). This study showed that postmenopausal women, in particular those with SM had significantly poorer hearing thresholds and lower OAE amplitudes. Menopause may be a potential risk factor for the development of hearing loss in women.

Effect of rosuvastatin on spatial learning, memory, and anxiety-like behaviour in ovariectomized rats.

The effect of rosuvastatin (Ros) on cognitive function and anxiety-like behaviour in ovariectomized rats were evaluated. Eighteen female Wistar rats (218-310 g, 6-8 months old) were allocated into sham (n = 6), ovariectomy (Ovx, n = 6) or Ovx + Ros (up to eighth week n = 6, then n = 4) groups. Ros was administered at 20 mg/kg/day by oral gavage for 12 weeks. Behavioural tests were performed at 4, 8 and 12 weeks following Ovx. At 12 weeks, Ovx group had significantly longer escape latency than the sham group at the first day of the four-day training period of the Morris Water Maze test (p < .01). In the Elevated Plus Maze test, Ovx group spent significantly more time in the closed arms than the sham group (p < .01), and this anxiety-like behavioural effect of Ovx was prevented by 12-weeks Ros treatment (p < .05). In conclusion, Ros prevents memory deficit and anxiety-like behaviour in the ovariectomized rats, a model for human surgical menopause. Impact StatementWhat is already known on this subject? Reduced levels of oestrogen in surgical postmenopausal period has been linked to an increased risk of cognitive dysfunction. Although statins have been shown to improve cognitive function in experimental and clinical studies, there are limited studies evaluating the effect of statins on the cognitive decline and anxiety-like behaviour associated with surgical menopause.What do the results of this study add? Rosuvastatin, a long-acting statin, prevents learning and memory deficit and anxiety-like behaviour in the ovariectomized rat model.What are the implications of these findings for future clinical practice and/or future clinical research? These findings will form the basis for further experimental and clinical research on the effects of statins on cognitive functions and anxiety-like behaviour in the surgical menopause.

The relevance of the endocrine condition in microglia morphology and dendrite complexity of doublecortin-associated neurons in young adult and middle-aged female rats exposed to acute stress.

Menopause, natural or surgical, might facilitate the onset of psychiatric pathologies. Some reports suggest that their severity could increase if the decline of ovarian hormones occurs abruptly and before natural endocrine senescence. Therefore, we compared the effects of ovariectomy on microglia's morphological alterations, the complexity of newborn neurons, and the animal's ability to cope with stress. Young adult (3 months) and middle-aged (15 months) female Wistar rats were subjected to an ovariectomy (OVX) or were sham-operated. After 3 weeks, animals were assigned to one of the following independent groups: (1) young adult OVX + no stress; (2) young adult sham + no stress; (3) young adult OVX + stress; (4) young adult sham + stress; (5) middle-aged OVX + no stress; (6) middle-aged sham + no stress; (7) middle-aged OVX + stress; (8) middle-aged sham + stress. Acute stress was induced by forced swimming test (FST) exposure. Immobility behavior was scored during FST and 30 min after; animals were euthanized, their brains collected and prepared for immunohistochemical detection of Iba-1 to analyze morphological alterations in microglia, and doublecortin (DCX) detection to evaluate the dendrite complexity of newborn neurons. OVX increased immobility behavior, induced microglia morphological alterations, and reduced dendrite complexity of newborn neurons in young adult rats. FST further increased this effect. In middle-aged rats, the main effects were related to the aging process without OVX or stress exposure. In conclusion, surgical menopause favors in young adult rats, but not in middle-aged, the vulnerability to develop immobility behavior, retracted morphology of microglial cells, and decreased dendrite complexity of newborn neurons.

Loss of bone density and bone strength following premenopausal risk-reducing bilateral salpingo-oophorectomy: a prospective controlled study (WHAM Study).

Prophylactic oophorectomy is recommended for women at high risk for ovarian cancer, but the associated impact on bone health is of clinical concern. This prospective, controlled study demonstrated substantial loss of bone density and bone strength following surgical menopause. Postoperative hormone therapy alleviated, but not fully prevented, spinal bone loss. INTRODUCTION: This prospective study investigated bone health in women following premenopausal oophorectomy. METHODS: Dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and pQCT-based finite element analysis (pQCT-FEA) were used to assess bone health between systemic hormone therapy (HT) users and non-users after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared with premenopausal controls over 24-month follow-up. RESULTS: Mean age was 42.4 ± 2.6 years (n = 30) for the surgery group and 40.2 ± 6.3 years for controls (n = 42), and baseline bone measures were similar between groups. Compromised bone variables were observed at 24 months after RRBSO, among which areal bone mineral density (aBMD) at the lumbar spine, tibial volumetric cortical density (Crt vBMD), and tibial bending stiffness (kbend) had decreased by 4.7%, 1.0%, and 12.1%, respectively (all p < 0.01). In non-HT users, significant losses in lumbar spine (5.8%), total hip (5.2%), femoral neck (6.0%) aBMD, tibial Crt vBMD (2.3%), and kbend (14.8%) were observed at 24 months (all p < 0.01). HT prevented losses in kbend, tibial Crt vBMD, and aBMD, except for modest 2.3% loss at the lumbar spine (p = 0.01). CONCLUSION: This prospective, controlled study of bone health following RRBSO or premenopausal oophorectomy demonstrated substantial loss of bone density and bone strength following RRBSO. HT prevented loss of bone density and bone stiffness, although there was still a modest decrease in lumbar spine aBMD in HT users. These findings may inform decision-making about RRBSO and clinical management following premenopausal oophorectomy.

What happens after menopause? (WHAM): A prospective controlled study of sleep quality up to 12 months after premenopausal risk-reducing salpingo-oophorectomy.

OBJECTIVE: Sleep difficulties impair function and increase the risk of depression at menopause and premenopausal oophorectomy may further worsen sleep. However, prospective data are limited, and it remains uncertain whether Hormone Therapy (HT) improves sleep. This prospective observational study measured sleep quality before and up to 12 months after risk-reducing salpingo-oophorectomy (RRSO) compared to a similar age comparison group who retained their ovaries. METHODS: Ninety-five premenopausal women undergoing RRSO and 99 comparisons were evaluated over a 12-month period using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Almost half reported poor sleep quality at baseline. Overall sleep quality was not affected by RRSO until 12 months (p = 0.007). However, sleep disturbance increased by 3 months and remained significantly elevated at 12 months (p < 0.001). Trajectory analysis demonstrated that 41% had increased sleep disturbance after RRSO which persisted in 17.9%. Risk factors for sleep disturbance included severe vasomotor symptoms, obesity and smoking. Around 60% initiated HT after RRSO. Sleep quality was significantly better in HT users vs non users (p = 0.020) but HT did not restore sleep quality to baseline levels. CONCLUSIONS: Overall sleep quality is not affected by RRSO, but new onset sleep disturbance is common, particularly in those with severe vasomotor symptoms. Clinicians should be alert to new-onset sleep disturbance and the potential for HT to improve sleep quality.