Natural Menopause Research Articles

Identifying potential causal effects of age at menopause: a Mendelian randomization phenome-wide association study

Age at natural menopause (ANM) is associated with a range of health-related traits, including bone health, female reproductive cancers, and cardiometabolic health. Our objective was to conduct a Mendelian randomization phenome-wide association study (MR-pheWAS) of ANM. We conducted a hypothesis-free analysis of the genetic risk score (GRS) for ANM with 18,961 health-related traits among 181,279 women in UK Biobank. We also stratified the GRS according to the involvement of SNPs in DNA damage response. We sought to replicate our findings in independent cohorts. We conducted a negative control MR-pheWAS among men. Among women, we identified potential effects of ANM on 221 traits (1.17% of all traits) at a false discovery rate (P value ≤ 5.83 × 10–4), and 91 (0.48%) potential effects when using Bonferroni threshold (P value ≤ 2.64 × 10–6). Our findings included 55 traits directly related to ANM (e.g. hormone replacement therapy, gynaecological conditions and menstrual conditions), and liver function, kidney function, lung function, blood-cell composition, breast cancer and bone and cardiometabolic health. Replication analyses confirmed that younger ANM was associated with HbA1c (adjusted mean difference 0.003 mmol/mol; 95% CI 0.001, 0.006 per year decrease in ANM), breast cancer (adjusted OR 0.96; 95% CI 0.95, 0.98), and bone-mineral density (adjusted mean difference − 0.05; 95% CI − 0.07, − 0.03 for lumbar spine). In men, 30 traits were associated with the GRS at a false discovery rate (P value ≤ 5.49 × 10–6), and 11 potential effects when using Bonferroni threshold (P value ≤ 2.75 × 10–6). In conclusion, our results suggest that younger ANM has potential causal effects on a range of health-related traits.

News and Views

Menopause refers to a non-pathological condition, wherein there is cessation of menstruation for atleast one year.The age of natural menopause in india is 46.2 ± 4.9 years.[1] Research studies show that in urban cities like pondicherry, more than one‑third of the postmenopausal women are having a poor quality of life.[2] There is impaired urogenital, vasomotor and cognitive symptoms, caused due to decreased estrogen levels in the body. This estrogen deficient state puts post-menopausal women at a higher risk of cardiovascular events.[3] Also, sympathovagal imbalance is observed in post-menopausal women with  increased sympathetic activity and reduced parasympathetic activity which adds to the cardiovascular risk.[4] Heart rate variability is a sensitive measure of sympathovagal imbalance.[4] It is found that there is a decline in heart rate variability in post menopausal women.[5] Recent study shows that postmenopausal state also offers higher risk of developing metabolic syndrome with an increased level of insulin resistance.[6] This can also be indicated by deranged lipid profile in them, such as higher triglyceride and total cholestrol.[7] With a myriad of symptoms to deal with, there are fewer treatment alternatives for post-menopausal women.

Alu hypomethylation in naturally and surgically postmenopausal women; a cross-sectional study.

Menopause, which may accelerate the hallmarks of the natural aging process, represents a point in time characterized by the permanent cessation of menstruation following the loss of ovarian estrogen production. Unlike natural menopause, which is characterized by a gradual decrease in estrogen production, when both ovaries are removed before the natural age of menopause, the onset of estrogen deprivation is abrupt. Further, a decrease in genome methylation frequently occurs in aging cells, and the major interspersed repetitive DNA elements in humans are Alu elements. In blood cells, Alu demethylation starts at an age of approximately 40 years, and increases with age. Here, we explored the Alu methylation levels corresponding to age-matched pre-menopausal, naturally postmenopausal, and surgically postmenopausal women aged 45–55 years (n = 60 in each group). Our results indicated that the body mass index (BMI), time-since-menopause, and Alu methylation levels corresponding to the three groups were significantly different. However, no correlations between Alu methylation level and BMI, time-since-menopause, or age were observed. Additionally, the Alu methylation level corresponding to the natural post-menopause group was significantly lower those corresponding to the pre-menopausal (p = 0.001) and surgical post-menopausal (p = 0.037) groups. In conclusion, Alu hypomethylation occurs in naturally postmenopausal women, implying that when women reach the age of natural menopause, the cell aging process may progress significantly with genome hypomethylation. These findings, notwithstanding, further studies are necessary to clarify whether bilateral oophorectomy before the age of menopause affects the cell aging process to a greater extent than natural menopause, and whether estrogen therapy or other interventions can delay cell aging in this regard.

Self-reported menstrual cycle length during reproductive years in relation to menopausal symptoms at midlife in Project Viva.

The aim of this study was to investigate the extent to which self-reported menstrual cycle length during reproductive years is associated with menopausal symptoms and age at natural menopause at midlife. This analysis includes 634 women who enrolled in Project Viva during pregnancy (1999-2002) and completed the midlife visit approximately 18 years later. Women self-reported menstrual cycle length at enrollment (early pregnancy) and at midlife reported total and specific menopausal symptoms using the Menopause Rating Scale as well as age at natural menopause. We used linear and regression models to evaluate associations of cycle length with total and specific menopausal symptoms. We also applied a time-to-event Cox proportional hazards model to investigate the relationship between menstrual cycle length and onset of natural menopause. We adjusted models for age at midlife visit, prepregnancy body mass index, race/ethnicity, education, and parity. At enrollment (median age, 33.3 years), 90 (14%) women reported having short (≤25 days) and 39 (6%) reported long (≥35 days) menstrual cycles. Compared with women with a normal menstrual cycle length of 26 to 34 days, women whose cycles were short had a higher total Menopause Rating Scale at midlife ( β = 2.05; 95% confidence interval [CI], 0.73-3.38). Specifically, women with short menstrual cycles during their reproductive years had higher odds of midlife sleep problems (odds ratio [OR], 1.92; 95% CI, 1.10-3.37), heart discomfort (OR, 1.68; 95% CI, 1.03-2.73), and depressive symptoms (OR, 1.85; 95% CI, 1.16-2.96). In addition, compared with women with a normal cycle length of 26 to 34 days, women reporting short cycles had an earlier onset of natural menopause (hazard ratio, 1.67; 95% CI, 1.11-2.51). Compared with women with normal menstrual cycle length, those with short menstrual cycles during their reproductive years had a higher frequency of total and certain menopausal symptoms at midlife and reached menopause earlier.

Recapitulating human ovarian aging using random walks.

Mechanism(s) that control whether individual human primordial ovarian follicles (PFs) remain dormant, or begin to grow, are all but unknown. One of our groups has recently shown that activation of the Integrated Stress Response (ISR) pathway can slow follicular granulosa cell proliferation by activating cell cycle checkpoints. Those data suggest that the ISR is active and fluctuates according to local conditions in dormant PFs. Because cell cycle entry of (pre)granulosa cells is required for PF growth activation (PFGA), we propose that rare ISR checkpoint resolution allows individual PFs to begin to grow. Fluctuating ISR activity within individual PFs can be described by a random process. In this article, we model ISR activity of individual PFs by one-dimensional random walks (RWs) and monitor the rate at which simulated checkpoint resolution and thus PFGA threshold crossing occurs. We show that the simultaneous recapitulation of (i) the loss of PFs over time within simulated subjects, and (ii) the timing of PF depletion in populations of simulated subjects equivalent to the distribution of the human age of natural menopause can be produced using this approach. In the RW model, the probability that individual PFs grow is influenced by regionally fluctuating conditions, that over time manifests in the known pattern of PFGA. Considered at the level of the ovary, randomness appears to be a key, purposeful feature of human ovarian aging.

Cardiovascular health in the menopause transition: a longitudinal study of up to 3892 women with up to four repeated measures of risk factors

BackgroundWomen experience adverse changes in cardiovascular health in mid-life; whether the menopausal transition influences these remains strongly debated. The aim of this study was to examine associations of reproductive age (time since final menstrual period (FMP)) with change in carotid intima media thickness (CIMT) and cardiovascular risk factors and determine the role of chronological and reproductive age.MethodsWe used data from 1702 women from a pregnancy-based UK cohort who had up to four repeat cardiovascular health measures between mean age 51 (SD = 4.0) and 56 (SD = 3.6) years and experienced a natural menopause. Multilevel models were used to assess the relationship between cardiovascular measures and time since FMP (reproductive age), whilst adjusting for the underlying effects of chronological age and confounders (socioeconomic factors, body mass index, smoking, alcohol, parity, age at menarche). In addition, we looked at the relationship between cardiovascular measures by chronological age according to menopausal stages (pre-menopause, peri-menopause and post-menopause) using information from women who had and had not experienced menopause (N = 3892).ResultsThere was no strong evidence that reproductive age was associated with CIMT (difference in mean 0.8 μm/year, 95% CI − 0.4, 2.1), whereas there was a strong positive association of chronological age (7.6 μm/year, 95% CI 6.3, 8.9). Consistent with this, we found weaker linear associations of reproductive compared with chronological age for atherosclerotic risk factors, such as with systolic blood pressure (− 0.1 mmHg/year, 95% CI − 0.3, 0.1, and 0.4 mmHg/year, 95% CI 0.2, 0.5, respectively) and non-HDL-cholesterol (0.02 mmol/l/year, 95% CI 0.005, 0.03, and 0.06, 95% CI 0.04, 0.07, respectively). In contrast, associations with fat mass (0.06 kg/m2/year, 95% CI 0.03, 0.10, and 0 kg/m2/year, 95% CI − 0.04, 0.04, respectively) and C-reactive protein (0.01, 95% CI 0.001, 0.02, and 0.01, 95% CI − 0.001, 0.02 natural logged mg/l/year, respectively) were stronger for reproductive compared with chronological age. Both reproductive and chronological age were (weakly) positively associated with glucose (0.002, 95% CI 0.0001, 0.003, and 0.002, 95% CI 0.0001, 0.003 natural logged mmol/l/year, respectively).ConclusionsOur results suggest that going through the menopausal transition does not further increase women’s risk of atherosclerosis (measured by CIMT) beyond effects of ageing. Menopausal transition may, in additional to ageing, modestly increase adiposity and glucose levels and therefore a possible associated diabetes risk.

Hot flash: experiencing menopause in medicine.

KEY POINTS Menopause occurs at a formative time in a physician’s career, with Canadian data showing that age at natural menopause is generally between the ages of 45 and 55 years.[1][1] Menopause is a life stage during which physicians may expect to increase work productivity, seek academic

Hyaluronic Acid: A Valid Therapeutic Option for Early Management of Genitourinary Syndrome of Menopause in Cancer Survivors?

Genitourinary syndrome of menopause (GSM) is a chronic condition affecting a large number of women, with a major impact on their urogenital health and sexual function. It occurs at midlife because estrogen levels decline with menopause enhancing aging-related changes of the functional anatomy of the urogenital system. Unfortunately, GSM may occur early in the lifespan of women or be exacerbated following anticancer treatments, such as chemotherapy, ionizing radiation, or surgical removal of reproductive organs. Symptoms of GSM are often under-reported by women, under-estimated and under-diagnosed by health care providers (HCPs), and subsequently under-treated, despite their profound negative impact on the quality of life. The mainstay of vaginal treatments is local estrogen therapy (LET) ensuring an effective management of moderate to severe symptomatic GSM. However, LET is generally contraindicated in women with a history of hormone receptor positive cancer, due to the fear of increased recurrence or possible interference with endocrine adjuvant therapies. Among non-hormonal treatments, hyaluronic acid-based moisturizers have shown promising clinical results both in healthy women and in cancer patients or survivors. Its strong water-binding properties provide lubricating and moisturizing effects, which contribute to maintaining a proper level of hydration and viscoelasticity in several body parts, including the urinary tract and genital tissues. Hyaluronic acid-based moisturizers are effective, safe, and well tolerated; therefore, they may represent a valid option for the early management of GSM-associated symptoms in every woman with a history of cancer who is unable or unwilling to undergo hormone-based therapies. Hence, the aim of this review was to provide an overview of GSM etiology and treatment in women with natural or iatrogenic menopause, with a focus on the use of hyaluronic acid as a prophylactic treatment in the context of an integrated management protocol for cancer patients.

Mediating effects of sleep duration on the association between natural menopause and stroke risk among Chinese women.

BackgroundSleep disturbance is commonly reported by menopausal women. Stroke risk and poor stroke outcomes in women have usually been attributed to menopause. This study aimed to investigate the mediating effect of sleep duration on relationship between menopause and risk of stroke in natural menopause women.Materials and methodsA cross-sectional study was performed, and participants were recruited through a multistage, stratified, probability proportional to size sampling method in this research. The stroke risk was measured using the risk assessment form for high-risk stroke population. The average sleep duration was calculated by adding up night sleep and afternoon nap duration. Multivariate regression analysis was conducted to identify the association between menopause, sleep duration, and stroke risk. The direct and indirect effects of menopause on stroke risk were analyzed by using the sleep duration in a mediation framework.ResultsPerimenopause, menopause, average sleep duration, and night sleep duration were significantly associated with stroke risk (P < 0.001), after adjusting for covariates. Perimenopause and menopause were significantly related to average sleep duration (P < 0.001) and night sleep duration (P < 0.001). The average sleep duration (ab = 0.016, 95% CI: 0.003, 0.030; ab = −0.048, 95% CI: −0.070, −0.027) partially mediated the relationship between menopause and stroke risk. And night sleep duration (ab = 0.024, 95% CI: 0.009, 0.040; ab = −0.054, 95% CI: −0.077, −0.033) played a major mediating role, in which night sleep duration of ≤5 h mediated the link between both perimenopause (ab = 0.707, 95% CI: 0.392, 1.021) and menopause (ab = −0.787, 95% CI: −1.096, −0.478) and stroke risk; both night sleep duration of >8–9 h (ab = 0.079, 95% CI: 0.010, 0.193) and >9 h (ab = 0.379, 95% CI: 0.086, 0.712) had mediating effects on perimenopause and stroke risk.ConclusionA significant relationship between menopause and stroke risk factors among natural menopausal status was found in this study. The average sleep duration, especially night sleep duration, partially mediated the association between menopause and stroke risk, which is a novel insight to the progression of stroke risk in Women. Suitable prevention methods and interventions for sleep in menopausal women may reduce the risk of stroke.

Optical coherence tomography evaluation of vaginal epithelial thickness during CO2 laser treatment: A pilot study.

Genitourinary syndrome of menopause (GSM) negatively affects more than half of postmenopausal women. Energy-based therapy has been explored as a minimally invasive treatment for GSM; however, its mechanism of action and efficacy is controversial. Here, we report on a pilot imaging study conducted on a small group of menopause patients undergoing laser treatment. Intravaginal optical coherence tomography (OCT) endoscope was used to quantitatively monitor the changes in the vaginal epithelial thickness (VET) during fractional-pixel CO2 laser treatment. Eleven patients with natural menopause and one surgically induced menopause patient were recruited in this clinical study. Following the laser treatment, 6 out of 11 natural menopause patient showed increase in both proximal and distal VET, while two natural menopause patient showed increase in VET in only one side of vaginal tract. Furthermore, the patient group that showed increased VET had thinner baseline VET compared to the patients that showed decrease in VET after laser treatment. These results demonstrate the potential utility of intravaginal OCT endoscope in evaluating the vaginal tissue integrity and tailoring vaginal laser treatment on a per-person basis, with the potential to monitor other treatment procedures.

Prediction of severe post-castration syndrome in women after surgical menopause

Objectives: prediction of severe post-castration syndrome (PCS) in women after surgical menopause.Materials and methods. The study included 67 surgically menopausal women aged 45–55 years who underwent surgical hysterectomy with or without appendages (the main group) and 30 naturally menopausal women (the comparison group). The method of constructing and analyzing multifactorial mathematical models was used to identify risk factors associated with the development of severe PCS in women after surgical menopause and assess its impact on the severity of PCS. 12 clinical and morphological factors were considered in the analysis. The severity of the PCS in women after surgical menopause was evaluated one month after surgery and symptoms of climacteric syndrome in women with natural menopause were assessed according to the modified Kupperman index.Results. Surgical menopause significantly increases the risk of severe PCS in comparison with natural menopause, when climacteric syndrome develops (p &lt; 0.001). The risk of severe PCS increases with the removal of the uterine appendages, inflammatory changes in the uterine appendages, the ovarian cyst (p &lt; 0.001), and uterine fibroids (p = 0.04). Three factor signs remain after selecting a set of independent signs in a multifactorial model for predicting the risk of severe PCS: removal of the uterine appendages (p &lt; 0.001), inflammatory changes in the uterine appendages (p = 0.006), ovarian cyst (p = 0.082). Based on these factor signs, we can accurately predict the risk of severe PCS (AUC = 0.951, 95% CI 0.89–0.98).Conclusions. Women with surgical menopause after the uterine appendages removal, with inflammatory changes in the uterine appendages, and ovarian cysts are at risk for the development of severe PCS and therefore it is advisable for them to include in the complex treatment of PCS medicines which reduce inflammatory changes in the uterine appendages and restore immunological reactivity.

Dietary lactose and galactose intakes are associated with a later onset of natural menopause among women in a Japanese community.

Galactose and its metabolites, primarily derived from lactose, may have toxic effects on the ovary. We aimed to prospectively examine the associations of galactose and lactose intakes with the onset of natural menopause. The data of a population-based cohort study in a Japanese community (the Takayama study) initiated in 1992 were analysed, with follow-up data collected in 2002. Among the participants of the Takayama study, premenopausal women (n 3115) aged 35-56 years at baseline were included in this study. Dietary intake, including lactose and galactose was assessed only at baseline using a FFQ. The menopausal status and age at menopause were determined based on the participants' self-reports, and natural menopause was defined as the absence of menstruation for 12 months or more. Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95 % CI. A total of 1790 women experienced natural menopause within the 10-year follow-up. Lactose and galactose intakes were associated with a later onset of natural menopause after adjusting for potential confounding factors and the HR (95 % CI) for the highest v. lowest quartile were 0·80 (0·69, 0·92) (P-trend = 0·001) in lactose and 0·86 (0·74, 1·00) in galactose (P-trend = 0·036), respectively. High intakes of lactose and galactose were associated with a later onset of natural menopause. Despite the presumed ovotoxicity effects, lactose and galactose intakes at usual levels may not be deleterious to the ovarian aging process among Japanese community-dwelling women.

Early natural menopause is associated with poor lung health and increased mortality among female smokers

Early natural menopause has been regarded as a biomarker of reproductive and somatic aging. Cigarette smoking is the most harmful factor for lung health and also an established risk factor for early menopause. Understanding the effect of early menopause on health outcomes in middle-aged and older female smokers is important to develop preventive strategies. This study aimed to examine the associations of early menopause with multiple lung health and aging biomarkers, lung cancer risk, and all-cause and cause-specific mortality in postmenopausal women who were moderate or heavy smokers. This study was conducted on postmenopausal women with natural (n=1038) or surgical (n=628) menopause from the Pittsburgh Lung Screening Study. The Pittsburgh Lung Screening Study is a community-based research cohort of current and former smokers, screened with low-dose computed tomography and followed up for lung cancer. Early menopause was defined as occurring before 45 years of age. The analyses were stratified by menopause types because of the different biological and medical causes of natural and surgical menopause. Statistical methods included linear model, generalized linear model, linear mixed-effects model, and time-to-event analysis. The average age of the 1666 female smokers was 59.4±6.7 years, with 1519 (91.2%) of the population as non-Hispanic Whites and 1064 (63.9%) of the population as current smokers at baseline. Overall, 646 (39%) women reported early menopause, including 198 (19.1%) women with natural menopause and 448 (71.3%) women with surgical menopause (P<.001). Demographic variables did not differ between early and nonearly menopause groups, regardless of menopause type. Significant associations were identified between early natural menopause and higher risk of wheezing (odds ratio, 1.65; P<.01), chronic bronchitis (odds ratio, 1.73; P<.01), and radiographic emphysema (odds ratio, 1.70; P<.001) and lower baseline lung spirometry in an obstructive pattern (-104.8 mL/s for forced expiratory volume in the first second with P<.01,-78.6 mL for forced vital capacity with P=.04, and-2.1% for forced expiratory volume in the first second-to-forced vital capacity ratio with P=.01). In addition, early natural menopause was associated with a more rapid decline of forced expiratory volume in the first second-to-forced vital capacity ratio (-0.16% per year; P=.01) and incident airway obstruction (odds ratio, 2.02; P=.04). Furthermore, women early natural menopause had a 40% increased risk of death (P=.023), which was mainly driven by respiratory diseases (hazard ratio, 2.32; P<.001). Mediation analyses further identified that more than 33.3% of the magnitude of the associations between early natural menopause and all-cause and respiratory mortality were explained by baseline forced expiratory volume in the first second. Additional analyses in women with natural menopause identified that the associations between continuous smoking and subsequent lung cancer risk and cancer mortality were moderated by early menopause status, and females with early natural menopause who continued smoking had the worst outcomes (hazard ratio, >4.6; P<.001). This study did not find associations reported above in female smokers with surgical menopause. Early natural menopause was found to be a risk factor for malignant and nonmalignant lung diseases and mortality in middle-aged and older female smokers. These findings have strong public health relevance as preventive strategies, including smoking cessation and chest computed tomography screening, should target this population (ie, female smokers with early natural menopause) to improve their postmenopausal health and well-being.

Associations of hypertensive disorders of pregnancy and gestational diabetes mellitus with menopausal symptoms at midlife in Project Viva.

The aim of this study was to evaluate the associations of a lifetime history of hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) with menopausal symptoms in midlife. This was a secondary analysis of women participating in Project Viva, an ongoing cohort enrolled during pregnancy. The exposure was lifetime history of HDP or GDM assessed for the index pregnancy by review of outpatient and hospital medical records and for all other pregnancies by interview or questionnaire at study entry (1999-2002) and the midlife visit (2017-2021). The primary outcome was the Menopause Rating Scale (MRS) applied at the midlife study visit. We used linear or logistic regression models adjusted for covariates such as baseline age, race/ethnicity, education, married/cohabiting, household income, baseline parity, age at menarche, and body mass index at midlife. Of the 676 included participants, 120 (18%) had a history of HDP, and 47 (7%) had a history of GDM. The mean (SD) age was 52 (3.9) years at the midlife visit, and 48% of the participants had experienced menopause. There were no consistent differences in total, domain-specific, or individual symptoms in women with a history of HDP or GDM. A history of HDP and/or GDM was not associated with age at the onset of natural menopause. Our findings do not support an association of a history of HDP or GDM with the severity of menopausal symptoms or age at the onset of natural menopause. Larger studies of women with a history of these pregnancy complications are needed to clarify their association with menopausal symptoms.

Reproductive factors and cognitive impairment in natural menopausal women: A cross-sectional study.

IntroductionLittle information on rural older women in northern China has been reported, apart from three studies in southern and eastern China in the past decade. This study aims to evaluate the relationships between reproductive factors and the risk of cognitive impairment, including mild cognitive impairment (MCI) and dementia, in Chinese women with natural menopause.MethodsThe cross-sectional study was conducted in 112 community primary healthcare centers in rural northern China between April 2019 and January 2020. A total of 4,275 women aged ≥65 years who had natural menopause were included. Reproductive factors as well as the reproductive period (= age at menopause − age at menarche) were recorded. The relationships between reproductive factors and cognitive impairment were evaluated by correlation and logistic regression analysis.ResultsOverall, 28.6% and 11.4% of women were diagnosed with MCI or dementia, respectively. In natural menopause women, the age at menopause (adjusted r = 0.070, p < 0.001), reproductive period (adjusted r = 0.053, p = 0.001), and number of pregnancies (adjusted r = −0.042, p = 0.007) and parities (adjusted r = −0.068, p < 0.001) were correlated with Mini-Mental State Examination (Chinese version) scores, and with similar findings concerning MCI and dementia with Lewy bodies (DLB). Greater age at menopause and a long reproductive period significantly decreased the risk of MCI and Alzheimer’s disease (AD), and more parities significantly increased the risks of MCI (odds ratio (OR) = 1.111, 95% confidence interval (CI): 1.039–1.187, p = 0.002), dementia (OR = 1.162, 95% CI: 1.061–1.271, p = 0.001), particular AD (OR = 1.131, 95% CI: 1.010–1.266, p = 0.032), DLB (OR = 1.238, 95% CI: 1.003–1.528, p = 0.047), and vascular dementia (VaD) (OR = 1.288, 95% CI: 1.080–1.536, p = 0.005).ConclusionsThe prevalence rates of MCI and dementia were 28.6% and 11.4% in older women. Greater age at menarche, young age at menopause, shorter reproductive period, and larger numbers of pregnancies/parities were correlated with poor cognition and significantly increased the risks of MCI and dementia, particularly AD, DLB, and VaD.

Hormone replacement therapy counseling at prophylactic bilateral salpingo-oophorectomy in high-risk patients (354)

<b>Objectives:</b> Women at high risk for ovarian cancer are advised to undergo bilateral salpingo-oophorectomy (RRSO) prior to natural menopause. Hormone replacement therapy (HRT) mitigates the negative effects of surgical menopause. We sought to understand how high-risk women are counseled about HRT and use patterns of HRT after RRSO. <b>Methods:</b> We performed a chart review of women seen at a high-risk clinic between 2000-2018 who underwent RRSO. Reviewing patient age, surgical details, pathology, documented HRT counseling, and whether HRT was recommended. We then surveyed by mail, online, and by phone all women alive and meeting study criteria (no surgery for ovarian malignancy, surgery not just for ovarian suppression for breast cancer) to determine what they recalled regarding counseling, use of HRT, cancer diagnoses, and depression (PHQ9), anxiety (GAD7), and cancer worry (CWS) scores. Chi-square test and t-test compared categorical and continuous variables, respectively. Logistic regression examined associations between age, history of cancer, surgeries, and reports of HRT discussions and recommendations. <b>Results:</b> A total of 150 women met the survey criteria, with a 60.1% response rate. The median age at the survey was 57.5 years (range: 37-86). RRSO median age was 46 (range: 27-74). Those surveyed included 76 <i>BRCA',</i> 50 <i>BRCA2,</i> 3 <i>BRCA1</i> and <i>BRCA2</i> mutation carriers, and 22 participants with other mutations or strong family histories. Responders and non-responders were alike in RRSO age and mutation status. About 44.4% of respondents recalled discussion about HRT; eight reported recommendations for HRT, 21 against, and 11 other guidance. Among the respondents, 51.5% reported undergoing hysterectomy; 17 (18.9%) respondents took HRT after surgery (64.7% estrogen alone). Five patients stopped HRT, three because a doctor advised, one because she was afraid, and one because she felt she no longer needed it. HRT recommendations were not associated with mastectomy (prophylactic or otherwise), hysterectomy, or cancer history. Younger age at RRSO was associated with receiving HRT counseling (RRSO age 43 if discussed vs 50 not discussed, p<0.01), but not with recommendations about HRT (RRSO age 41 if recommended vs 44 not recommended, p=0.06). RRSO age remained significant in predicting discussion, though other surgeries and cancer history did not. Starting or continuing HRT after RRSO was not indicative of depression or anxiety scores, but those taking HRT after RRSO had higher CWS (CWS > 10 in 82.4% with HRT vs 52.9% without, p=0.03). Eighteen (43.9%) respondents did not remember receiving counseling documented in the chart, while 15 (37.5%) remembered counseling that was not documented. <b>Conclusions:</b> A majority of patients undergoing RRSO did not receive HRT counseling, and nearly 44% did not remember documented HRT counseling. Surgeries and diagnoses that would impact HRT use were not correlated with recommendations. Younger age was correlated with discussion but not a recommendation for HRT. Before RRSO, we propose discussing HRT regardless of the recommendation for or against the use and providing written summaries to which patients and future healthcare providers can refer.

Risk Prediction Models of Natural Menopause Onset: A Systematic Review.

Predicting the onset of menopause is important for family planning and to ensure prompt intervention in women at risk of developing menopause-related diseases. We aimed to summarize risk prediction models of natural menopause onset and their performance. Five bibliographic databases were searched up to March 2022. We included prospective studies on perimenopausal women or women in menopausal transition that reported either a univariable or multivariable model for risk prediction of natural menopause onset. Two authors independently extracted data according to the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist. Risk of bias was assessed using a prediction model risk of bias assessment tool (PROBAST). Of 8132 references identified, we included 14 articles based on 8 unique studies comprising 9588 women (mainly Caucasian) and 3289 natural menopause events. All included studies used onset of natural menopause (ONM) as outcome, while 4 studies also predicted early ONM. Overall, there were 180 risk prediction models investigated, with age, anti-Müllerian hormone, and follicle-stimulating hormone being the most investigated predictors. Estimated C-statistic for the prediction models ranged from 0.62 to 0.95. Although all studies were rated at high risk of bias mainly due to the methodological concerns related to the statistical analysis, their applicability was satisfactory. Predictive performance and generalizability of current prediction models on ONM is limited given that these models were generated from studies at high risk of bias and from specific populations/ethnicities. Although in certain settings such models may be useful, efforts to improve their performance are needed as use becomes more widespread.

Vasomotor symptoms, cardiovascular risk factors, and cardiovascular disease risk among Chinese postmenopausal women in Hong Kong

ABSTRACT Vasomotor symptoms are frequently reported by postmenopausal women and linked with unfavorable changes in cardiovascular risk factors, suggesting a likely association with cardiovascular disease (CVD) risk. This study aimed to investigate the characteristics of and associations between vasomotor symptoms, cardiovascular risk factors, and CVD risk among Chinese postmenopausal women. From March 2018 to August 2019, a convenience sample of 288 postmenopausal women who experienced natural menopause for ≥12 months were recruited from district centers of women associations in Hong Kong. We assessed vasomotor symptoms, cardiovascular risk factors, and CVD risk using questionnaires, anthropometric measures, and laboratory testing of fasting blood samples. Data were analyzed using bivariate correlation analyses and linear regression analyses. Over half of the participants experienced vasomotor symptoms (50.3 percent), and 23.3 percent had a high 10-year CVD risk. After adjusting for sociodemographic and clinical variables, flashing (β = 0.270, P = .002) and sweating (β = > −0.206, P = .018) were significantly associated with low-density lipoprotein cholesterol and flashing (β = 0.229, P = .007) were significantly associated with total cholesterol. No statistically significant association was observed between vasomotor symptoms and CVD risk. Vasomotor symptoms were common and associated with several cardiovascular risk factors in Chinese postmenopausal women.

Research on risk factors of ischemic cerebrovascular disease in postmenopausal women based on the social-ecological model

ObjectiveBased on the social-ecological model, this study aimed to comprehensively explore factors affecting the risk of ischemic cerebrovascular disease (ICVD) in postmenopausal women to provide theoretical bases for further prevention and intervention for postmenopausal women.MethodsPostmenopausal women who underwent medical examinations in one health-checkup agency in Tianjin from May 2015 to October 2015 were enrolled in this study. The ICVD 10-year Risk Assesment Form developed by the research team of the National "Tenth Five-Year Plan" research project was used to assess the factors affecting the risk of ICVD. Based on the social-ecological model, multiple types of scales, including physical activities, depression, Type D personality, social supports, and environment score, were used to comprehensively explore the factors associated with ICVD in postmenopausal women.Results300 valid questionnaires were obtained, with an effective rate of 92.0%. The subjects aged 44–74 years, with the average age of 62.06 ± 7.09 years. Among them, 58.67% of the subjects only obtained high-school diploma, 32.67% obtained college or university diploma, 90.33% were retirees, 95.33% were married, 92.33% experienced the natural menopause, 93.33% lived in urban or suburban areas, and 1.00% had a history of breast cancer. Multivariate logistic regression analysis suggested that monthly income (¥), parity, exposure to second-hand or third-hand smoke, easy access to healthy food, physical activities, depression, Type D personality, social support and environmental factors were associated with the risk of ICVD in postmenopausal women (P < 0.05). Among them, easy access to healthy food (OR = 0.242), social support (OR = 0.861) and environmental factors (OR = 0.866) were protective factors from ICVD. OR < 1 indicates that the exposure factor is negatively correlated with the disease, and the exposure factor has a protective effect on preventing the occurrence of the disease. Parity (OR = 3.795), exposure to second-hand or third-hand smoke (OR = 2.886), depression (OR = 1.193), and Type D personality (OR = 1.148) were risk factors of ICVD. OR > 1 means that the exposure factor is positively correlated with the disease, and the exposure factor increases the risk of disease occurrence.ConclusionsFor postmenopausal women, in the future, in addition to prevention and management of the conventional risks, the conditions of their mentality and social support should be paid attention to, at the same time, and if they can, try to choose a good community environment to live in, which could better reduce the incidence and mortality of ICVD in postmenopausal women.

The association between shift work exposure and the variations in age at natural menopause among adult Canadian workers: results from the Canadian Longitudinal Study on Aging (CLSA).

A wide range of negative health outcomes have been associated with shift work (SW) particularly night and rotating SW. However, little is known about effects of SW exposure on reproductive health outcomes. The objective of our study is to prospectively investigate the association between SW exposure and the variations in age at natural menopause among adult Canadian workers. Secondary data analyses were performed using the Canadian Longitudinal Study on Aging database. Premenopausal women (N = 3,688) at baseline were followed prospectively for 3 years. Three derived variables were used to measure SW primary exposure: 1) ever exposed to SW, 2) SW exposure in current job, and 3) SW exposure in the longest job. Cox proportional hazard regression models were used to evaluate risk of variations in age at natural menopause after adjusting for potential confounders. One out of five women (20%) reported to be ever exposed to SW during their jobs. Overall, women who were ever exposed to SW were significantly associated with a delayed onset of menopause compared with daytime workers (hazard ratios [HR] = 0.77, 95% CI, 0.61-0.98). Particularly, when compared with daytime workers, rotating shift worker in the current and longest job were significantly related to delayed onset of menopause (HR = 0.64, 95% CI, 0.46-0.89 and HR = 0.65, 95% CI, 0.49-0.86), respectively. Our results suggest a relationship between rotating shift and delayed onset of menopause. We speculate that disruptive circadian stimuli may play a role in menopausal onset and this warrants further investigation.Video Summary:http://links.lww.com/MENO/A940 .