Natural Menopause Research Articles

The dose-response relationship of pre-menopausal alcohol consumption with age at menopause: a population study of 280 497 women in Norway.

Previous research suggests that alcohol consumption is associated with high age at menopause. Yet, knowledge about the dose-response relationship is inconsistent. Thus, we studied the pattern of the association of pre-menopausal alcohol consumption with age at natural menopause. We performed a retrospective population-based study using self-reported data from 280 497 women aged 50-69 years attending the Norwegian breast cancer screening programme (BreastScreen Norway) during 2006-15. Associations of weekly alcohol consumption between the age of 20 and 49 years with age at menopause were estimated as hazard ratios (HRs) using Cox proportional hazard models with restricted cubic splines to allow for non-linear associations. We adjusted for year and place of birth, number of childbirths, educational level, body mass index and smoking habits. Mean age at natural menopause was 51.20 years (interquartile range: 49-54 years). The adjusted HR of reaching menopause was highest for women with no alcohol consumption (reference) and the HR decreased by alcohol consumption up to 50 grams per week (adjusted HR 0.87; 95% CI: 0.86-0.88). Above 50 grams, there was no further decrease in the HR of reaching menopause (P for non-linearity of <0.001). Women who did not consume alcohol were youngest at menopause. The lack of a dose-response association among alcohol consumers implies virtually no relation of alcohol consumption with age at menopause. Our findings may suggest that characteristics of the women who did not consume alcohol, not accounted for in the data analyses, explain their younger age at menopause.

The effect of genetic variation in estrogen transportation and metabolism on the severity of menopause symptoms: A study from the RIGHT 10K cohort.

The severity of menopause-related symptoms varies considerably among women. The determinants of this variation are incompletely understood. The aim of this study was to assess the association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. This was a cross-sectional study of 60 peri- and postmenopausal women in the Mayo Clinic RIGHT study (which involved sequencing of genes involved in drug metabolism and transport), who had also been evaluated in the Women's Health Clinic at Mayo Clinic in Rochester, MN. All participants completed the Menopause Rating Scale (MRS) for assessment of menopause symptoms, including hot flashes. The association between severity of menopause symptoms and the variation in genes encoding 8 enzymes and transporters involved in estrogen metabolism was evaluated. Lower CYP3A4 activity and higher COMT activity were associated with lower severity of somatic menopause symptoms (p=0.04 and 0.06, respectively). These associations did not persist after adjustment for hormone therapy use. No differences in MRS scores or hot flash severity were noted among other genetic variant groups. Age at natural menopause was not affected by variations in the genes studied. The current study did not show an association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. Further studies with larger sample sizes may be required to understand this potentially complex association.

Age at Natural Menopause and Influencing Factors in Women Attending the Gynecological Outpatient Clinic at a Tertiary Care Hospital.

Menopause is the irreversible cessation of menstruation that results from the lack of ovarian follicular function and is diagnosed after 12 consecutive months of amenorrhea without reasonable cause. This study aims to determine the average age at natural menopause and identify its associated factors among Somali women. This is a cross-sectional study conducted at the Mogadishu Somalia Türkiye Recep Tayyip Erdogan research and training hospital's Obstetrics and Gynecology outpatient clinic between June 1 and July 1, 2023. Data was collected from subjects during the data collection period using face-to-face interviews with structured questionnaires consisting of sociodemographic, lifestyle, dietary, and reproductive characteristics. A multivariate logistic regression analysis was conducted to find the association between menopause age and target variables. Out of the 188 participants recruited for the study, the median age of menopause was 45.00 (95% CI = 44.50-45.62), and 48.9% had either premature or early menopause. The majority (53.7%) of the participants had a minimum of eight children. In Spearman's rank correlation analysis, we found a significantly positive correlation between menopausal age and age at first (p<0.01), last childbirth (p<0.01), number of parities (p<0.05), and age at marriage (p<0.05). In multivariate logistic regression, we found that the odds of developing premature or early menopause among unemployed women were 59% lower than those of employed women (AOR = 0.41, 95% CI = 0.18-0.93). In this study, we established that the age of natural menopause was lower than the findings reported by previous authors. We also found that employment status, education, history of contraceptive use, BMI, age at first and last childbirth, and parity were associated with age at natural menopause, suggesting that social, lifestyle, and reproductive factors may have an impact on menopausal age.

Early menopause and premature ovarian insufficiency are associated with increased risk of dementia: A systematic review and meta-analysis of observational studies.

Among other risk factors, the decline in estrogen concentrations during menopause may compromise cognitive function. Whether early menopause (EM) is associated with an increased risk of dementia remains unclear. The purpose of this study was to systematically review and meta-analyze current evidence regarding the association between EM or premature ovarian insufficiency (POI) and the risk of dementia of any type. A comprehensive literature search was conducted through the PubMed, Scopus and CENTRAL databases up to August 2022. Study quality was assessed using the Newcastle-Ottawa scale. Associations were calculated as odds ratio (OR) with 95% confidence interval (CI). The I2 index was employed for heterogeneity. Eleven studies (nine assessed as of good and two as of fair quality) were included in the meta-analysis (n=4,716,862). Women with EM demonstrated a greater risk of dementia of any type than women of normal age at menopause (OR 1.37, 95% CI 1.22-1.54; I2 93%). However, after excluding a large retrospective cohort study, the results were altered (OR 1.07, 95% CI 0.78-1.48; I2 94%). Increased risk of dementia was also found in women with POI (OR 1.18, 95% CI 1.15-1.21; I2 0%). Subgroup analysis showed that this risk was mostly evident in cohort studies, and those which included women with natural menopause. Women with EM or POI may be at increased risk of dementia compared with women of normal age at menopause, but further research investigating that hypothesis is warranted.

Alternative therapy of menopausal vegetative disorders in women taking the metabolic status into account

Research objectives: to study the clinical effectiveness of alternative complex therapy of vegetative syndrome in menopausal patients using L-arginine and xylitol drugs. Materials and methods. The clinical prospective study included 50 patients in the early postmenopausal period with natural menopause, neurovegetative and psychoemotional manifestations of the climacteric syndrome. According to the Life extension strategy, patients received intravenous L-arginine (Tivortin drug) and xylitol solution with electrolytes (Xylat drug) for endothelial protection and correction of insulin resistance in order to treat climacteric syndrome. Modified Kupperman menopausal index, serum triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, and very-low-density lipoprotein levels were determined in all women. Examinations were performed before the start of therapy and 3 months after the end of treatment.Results. The Life extension therapeutic strategy as an alternative comprehensive therapy of the vegetative syndrome in menopausal patients contributed to a reliable reduction of the manifestations of the climacteric syndrome. The advantage of combined therapy involving L-arginine and xylitol was manifested in a significant decrease in diastolic blood pressure (p = 0.043); reduction of the Kupperman index (p = 0.002) and the average score of vasomotor symptoms (p = 0.02). There was also a significant decrease in the serum level of insulin (p = 0.00007), HOMA index (p = 0.01), low-density lipoproteins (p = 0.04), and triglycerides (p = 0.03). The selected therapy was well tolerated during the observation period.Conclusions. The combined therapy involving L-arginine and xylitol in the early postmenopausal period with neurovegetative and psychoemotional manifestations of the climacteric syndrome had a pronounced clinical effect, which consisted in a significant reduction of vegetative disorders and stabilization of carbohydrate and lipid metabolism. The given therapeutic strategy can be considered as an alternative therapy in patients with climacteric disorders when phytotherapy is ineffective and when there are contraindications or limitations to menopausal hormone therapy. The results of this study showed the safety of the Life extension strategy.

Identification and Management of Radiation-Induced Premature Ovarian Failure

Premature ovarian failure (POF) is the dysfunction of ovarian follicles resulting in amenorrhea before the natural age of menopause. For women with locally advanced cervical cancer (LACC), POF is caused by chemoradiation due to the cytotoxic effects of radiation on the ovary. The diagnosis is confirmed with an FSH level in the postmenopausal range. The recommendation is for all patients with POF to take hormone replacement therapy (HRT) through the average age of natural menopause (age 50-51). The goal of this study is to determine how POF was managed in a large cohort of premenopausal women with LACC receiving pelvic RT. We retrospectively reviewed medical charts of premenopausal patients who underwent RT for LACC at an academic hospital from 2010 to 2020. Data regarding the type and duration of RT, demographics, and survival was obtained. The following data points were obtained from clinic notes documented after radiation treatment started: FSH levels, estradiol levels, menstrual history, menopausal symptoms. Additionally, data regarding HRT initiation was extracted, including the type of HRT and the department of the prescribing provider. Descriptive analysis was performed to determine the frequency of each variable of interest including patient characteristics, receipt hormone therapy, type of hormone therapy and menopausal symptoms. A total of 45 premenopausal patients treated for locally advanced cervical cancer with a median age of 39 (range 22- 50 years) were included. 51% (n = 23) of the patients were started on hormone therapy either during or post radiation treatment. 20 patients had documented menopausal symptoms. Most frequently reported symptoms included hot flashes (80%), fatigue (25%) and anxiety (15%). Most (78%) women received combination oral contraceptive pills (OCP) and some also received an estrogen patch/cream. 38% (n = 7) of patients started the HRT post RT while 61% (11) patients started during RT treatment. Of the available data, HRT was prescribed by a radiation oncologist 39% of the time and a gynecologic oncologist 35% of the time. The onset of POF was identified clinically by the onset of hypo-estrogen vasomotor symptoms. FSH levels were not routinely checked prior to prescribing HRT. The most commonly prescribed HRT was the combination oral contraceptive pill, which was prescribed and managed by both radiation oncologists and gynecologic oncologists. Our study illustrates the need for a standardized method to routinely assess the onset of POF while undergoing radiation treatment. With frequent follow-ups, radiation oncologists have the opportunity to identify early signs POF and provide adequate treatment. Additional studies are needed to evaluate if patients initiated and maintained HRT for the recommended length of time.

Ethnic Differences in the Association Between Age at Natural Menopause and Risk of Type 2 Diabetes Among Postmenopausal Women: A Pooled Analysis of Individual Data From 13 Cohort Studies.

To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI) (natural menopause before age 40 years), and incident type 2 diabetes (T2D) and identify any variations by ethnicity. We pooled individual-level data of 338,059 women from 13 cohort studies without T2D before menopause from six ethnic groups: White (n = 177,674), Chinese (n = 146,008), Japanese (n = 9,061), South/Southeast Asian (n = 2,228), Black (n = 1,838), and mixed/other (n = 1,250). Hazard ratios (HRs) of T2D associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI. Over 9 years of follow-up, 20,064 (5.9%) women developed T2D. Overall, POI (vs. menopause at age 50-51 years) was associated with an increased risk of T2D (HR 1.31; 95% CI 1.20-1.44), and there was an interaction between age at menopause and ethnicity (P < 0.0001). T2D risk associated with POI was higher in White (1.53; 1.36-1.73), Japanese (4.04; 1.97-8.27), and Chinese women born in 1950 or later (2.79; 2.11-3.70); although less precise, the risk estimates were consistent in women of South/Southeast Asian (1.46; 0.89-2.40), Black (1.72; 0.95-3.12), and mixed/other (2.16; 0.83-5.57) ethnic groups. A similar pattern, but with a smaller increased risk of T2D, was observed with early menopause overall (1.16; 1.10-1.23) and for White, Japanese, and Chinese women born in 1950 or later. POI and early menopause are risk factors for T2D in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2D among women.

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.

Premenstrual Disorders, Timing of Menopause, and Severity of Vasomotor Symptoms

Although premenstrual disorders (PMDs) end at menopause, it is unclear whether they are associated with the timing and symptom severity of menopause. To prospectively examine whether women with PMDs have increased risks of early menopause and menopause-related vasomotor symptoms (VMS). This population-based cohort study was nested in the Nurses' Health Study II (data collected from questionnaire sent between June 1991 and June 2017). Analysis of menopause timing included participants who did not have natural or surgical menopause before study entry, while the analysis of VMS was restricted to women who provided information on VMS. Data were analyzed from August 2022 to March 2023. PMDs were identified by self-reported diagnosis and confirmed with symptom questionnaires from 1991 to 2005. Participants were age-matched to women without PMD diagnoses and confirmed absence of or minimal premenstrual symptoms. During follow-up through 2017, timing of natural menopause was assessed biennially, and VMS were assessed in 2009, 2013, and 2017. The association of PMDs with early menopause was assessed by Cox proportional hazards models and with VMS by logistic regression models. Of 1220 included women with PMDs, the median (IQR) age was 40.7 (37.3-43.8) years; of 2415 included women without PMDs, the median (IQR) age was 41.7 (38.3-44.8) years. The median (IQR) follow-up in this study was 20.3 (17.8-22-2) years. Early natural menopause (menopause before age 45 years) was reported by 17 women with PMDs (7.1 per 1000 person-years) and 12 women without PMDs (2.7 per 1000 person-years; adjusted hazard ratio, 2.67; 95% CI, 1.27-5.59). In addition, 795 women with PMDs (68.3%) and 1313 women without PMDs (55.3%) reported moderate or severe VMS (adjusted odds ratio, 1.68; 95% CI, 1.32-2.14). There was no observed association between PMDs and mild VMS (adjusted odds ratio, 0.99; 95% CI, 0.76-1.28). In this cohort study of US women, PMDs were associated with increased risks of early menopause and moderate or severe VMS. PMDs may be indicative of underlying physiology linked to early menopause and VMS, suggesting a phenotype observable during the reproductive years that may allow clinicians to target women at risk of earlier menopause and subsequent health risks later in the life course.

Menopause age, reproductive span and hormone therapy duration predict the volume of medial temporal lobe brain structures in postmenopausal women

Medial temporal lobe (MTL) atrophy is correlated with risk and severity of Alzheimer disease (AD) pathology and cognitive decline. Increasing evidence suggest that oestrogens affect the aging of MTL structures. Here we investigate the relationship between reproductive hormone exposure, polygenic scores for AD risk and oestradiol concentration, MTL anatomy and cognitive performance in postmenopausal women. To this end, we used data from 10,924 female participants in the UK Biobank from whom brain MRI and genetic data were available. We fitted linear regression models to test whether the volume of structures comprising the MTL were predicted by a) timing related to menopause, b) the use and timing of hormone replacement therapy (HRT) and c) polygenic scores for AD risk and oestradiol concentration. Results showed that longer use of HRT was associated with larger parahippocampal volumes (2.53 mm3/year, p = 0.042). A later age of natural menopause, and a longer reproductive span, was associated with larger hippocampal (6.08 and 5.72 mm3/year, p = 0.0006 and 0.0005), parahippocampal (4.17 mm3 and 4.19 mm3/year, p = 0.00006 and 0.00001), amygdala (2.10 and 2.22 mm3/year, p = 0.028 and 0.01) and perirhinal cortical (2.56 and 2.95 mm3/year, p = 0.028 and 0.008) volumes. Superior prospective memory performance was associated with later age at natural menopause, and a longer reproductive span (ß = 0.05 and 0.05 respectively, p = 0.019 and 0.019). Polygenic scores for AD risk and for oestradiol concentration were not associated with MTL volume and did not interact with menopause-related factors to affect MTL structure. Our results suggest that HRT use did not have any detrimental effects on cognition or brain structure, whilst greater exposure to reproductive hormones across time is associated both with slightly larger volumes of specific MTL structures and marginally superior memory performance, independent of genetic risk for AD and genetic predisposition for higher oestradiol levels. However, the clinical utility of maintenance of oestrogens post-menopause for brain health and protection against cognitive decline is curtailed by the small effect sizes observed.

Review of mendelian randomization studies on age at natural menopause.

Menopause marks the end of the reproductive phase of life. Based on epidemiological studies, abnormal age at natural menopause (ANM) is thought to contribute to a number of adverse outcomes, such as osteoporosis, cardiovascular disease, and cancer. However, the causality of these associations remains unclear. A powerful epidemiological method known as Mendelian randomization (MR) can be used to clarify the causality between ANM and other diseases or traits. The present review describes MR studies that included ANM as an exposure, outcome and mediator. The findings of MR analyses on ANM have revealed that higher body mass index, poor educational level, early age at menarche, early age at first live birth, early age at first sexual intercourse, and autoimmune thyroid disease appear to be involved in early ANM etiology. The etiology of late ANM appears to be influenced by higher free thyroxine 4 and methylene tetrahydrofolate reductase gene mutations. Furthermore, early ANM has been found to be causally associated with an increased risk of osteoporosis, fracture, type 2 diabetes mellitus, glycosylated hemoglobin, and the homeostasis model of insulin resistance level. In addition, late ANM has been found to be causally associated with an increased systolic blood pressure, higher risk of breast cancer, endometrial cancer, endometrioid ovarian carcinoma, lung cancer, longevity, airflow obstruction, and lower risk of Parkinson's disease. ANM is also a mediator for breast cancer caused by birth weight and childhood body size. However, due to the different instrumental variables used, some results of studies are inconsistent. Future studies with more valid genetic variants are needed for traits with discrepancies between MRs or between MR and other types of epidemiological studies.

Association between female-specific reproductive factors and leukocyte telomere length.

What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)? Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL. Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear. This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010. Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL. After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05). Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds. Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors. This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose. N/A.

Prevalence, impact and management of postmenopausal symptoms among postmenopausal women in Rwanda

Objective This study aimed at evaluating the prevalence and management of postmenopausal symptoms among Rwandan women. Methods A descriptive cross-sectional study was conducted at the four largest Rwandan referral hospitals from August 2017 to March 2018 among postmenopausal women. Data on postmenopausal symptoms were collected using the Modified Blatt–Kupperman Menopausal Index and score ranges of 0–6, 7–15, 16–30 and >30 were used to rate the degree of severity as none, mild, moderate, and severe, respectively. Results Six hundred participants were recruited. The mean age at natural menopause was 51.7 ± 5.6 years. Common symptoms were hot flushes (82%), sexual complaints (66%) and headache (61%). The mean Blatt–Kupperman index score was 21.2 (1–58). Participants’ symptoms were classified as severe (35.8%), moderate (49.0%), mild (11.3%) and none (3.8%). Among 41.2% who had sought medical care, 1.7% were given hormonal replacement and 36% were given only pain medications. Age >50 years and lack of a male partner were significantly associated with higher scores. Conclusions Postmenopausal symptoms remain a burden among Rwandan women and little consideration is given for optimal management. There is a need for health managers to consider this inevitable phase of life on the health policy agenda for equitable healthy aging.

Prevalence of premature ovarian insufficiency (POI) and its relationship with female reproductive factors in Iranian women: a cross-sectional study from the Persian (Shahedieh) cohort data

BackgroundIn premature ovarian insufficiency, the cessation of menstruation, and cessation of ovarian function occurs before the age of 40, and this phenomenon is associated with many complications and problems for women. Since several factors can affect this situation, this study was conducted to determine the relationship between fertility history, and premature ovarian failure.MethodsThis cross-sectional study was conducted on the data of the first phase of cohort study, which was a sample of 10,000 people from an Iranian adult population (age: 35–70 years). 1276 women were included who naturally experienced menopause from this population. They were separated into three groups based on the age of menopause: premature ovarian failure for those who reached menopause before the age of 40, early menopause for those who reached menopause between the ages of 40 and 45, and natural menopause for those who reached menopause at or after the age of 45. The demographic and fertility characteristics of two groups of women, one with premature ovarian failure and the other with early menopause, were compared with a group of women experiencing normal menopause. The comparison was based on frequency and percentage. Moreover, the odds ratio (OR) of these two groups compared to normal group was crudely calculated, and adjusted based on age at the time of the interview using a logistic regression model. SPSS 23 software was used to fit models and calculations.ResultsThe prevalence of premature ovarian failure was 3%. The likelihood of premature ovarian failure decreases as the number of live births rises. The risk is considerably higher for births ranging from zero to three children compared to those with more than four. Increased duration of breastfeeding is associated to a reduced risk of premature ovarian failure compared to the spontaneous occurrence (OR = 0.98, 95% CI (0.97, 0.99)). This relationship is maintained even after adjusting for age (OR = 0.98, 95% CI (0.97, 0.99).ConclusionBased on the results of present study, it can be concluded that the factor of the number of births, and the duration of breastfeeding affect reducing the occurrence of POI, therefore, in health and treatment programs and policies, encouragement to have children, which is now part of the policies population of Iran, and the importance, and benefits of breastfeeding for mother and baby should be emphasized more.

Associations between childhood adversity and age at natural menopause.

Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause. This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders. A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, -3.2 to 0.6; P = 0.18). Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause.

Factors predicting age at menopause among Iranian women in the Bandare-Kong cohort study (a cross-sectional survey of PERSIAN cohort study)

BackgroundMenopause is a natural period in women’s life and can be affected by several factors. The aim of this study was to identify the associated factors for age of natural menopause and among women with early and premature menopause based on a cohort study in Iran.MethodsThis population-based study was conducted on 894 post menopause women between 35 and 70 years old who participated in the Bandare-Kong Non-Communicable Diseases (BKNCD) Cohort Study, a part of Prospective Epidemiological Research Studies in Iran (PERSIAN) from March 2016 to February 2019. All women completed a standard self-reported questionnaire. Data were analyzed using chi-square test, independent t test, and ANOVA as well as a multivariable linear regression model.ResultsThe mean age at natural menopause was 48.31 ± 6.34 years. After adjusting other variables, gravida, history of cardiac disease, socioeconomic status and residence status were predictive of age at menopause (P < 0.001). Among the premature menopause group, the mean age at menopause was significantly higher among women with diabetes compared to women without diabetes group (35.68 ± 2.92 vs. 33.82 ± 3.06; P = 0.043), while the mean age at menopause was significantly lower in women with infertility compared to women without infertility (29.13 ± 5.22 vs. 34.84 ± 2.826; P = 0.048).ConclusionsThis study suggests that the predictors of menopausal age differed in women with premature menopause compared to overall menopause age. Prospective studies are needed to evaluation the effects of these factors on menopausal age.

Reproductive factors in the risk of bladder cancer and upper urinary tract cancer: The Japan Public Health Center-based Prospective Study.

Reproductive factors are hypothesized to play a role in the incidence of bladder cancer (BC) and upper urinary tract cancer (together, urothelial cancer (UC)). However, evidence regarding these associations is limited, particularly in Asian populations. We analyzed data from 55,882 females aged 40-69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model). During an average of 20.2 years of follow-up, 194 UC cases (145 BC cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared to 49-51 years) increased BC risk in the reproductive model (HR=2.09 (95% CI=1.04-4.20)). An association between UC/BC and age at menopause, including both natural and surgical/induced, was significant in the reproductive model [HR=1.74 (95% CI=1.09-2.77), and HR=1.94 (95% CI=1.15-3.28), respectively]. Early age at natural menopause was suggested to increase UC risk in the reproductive model (HR=1.78 (95% CI=0.93-3.42)). Our findings suggest a significant association between age at menopause and incidence of UC/BC among Asian populations. This study aids understanding the role of reproductive factors in UC/BC incidence. In Japanese populations, age at menopause is suggested to be associated with UC/BC incidence, especially regarding early natural menopause.

Quality of life in heterosexual menopausal women: The indirect effect of sexual and marital satisfaction, menopause representations, and psychological morbidity

Menopause may negatively impact Quality of Life (QoL). Our study used a cross-sectional design and research participants were 99 women in natural menopause. In our study, we analyzed the relationship between age at menopause onset, hormone therapy use, duration of couple relationship, menopause duration, psychological morbidity, marital satisfaction, menopause representations, and QoL following the Wilson and Cleary Health-Related QoL conceptual model. The authors found that negative representations, lower marital satisfaction, psychological morbidity, and shorter duration of menopause contributed to lower QoL. Moreover, the authors found that psychological morbidity and menopause representations (identity and control/cure dimensions) had an indirect effect between marital satisfaction and vasomotor, psychosocial, and sexual QoL. Also, we found that age at the onset of menopause showed a moderating effect in the final model. Future studies should replicate these results in a longitudinal design and analyze how the variables that showed a moderating role and indirect effects will function as moderators and mediators, respectively, over time.

Genetic insights into the age-specific biological mechanisms governing human ovarian aging

There is currently little evidence that the genetic basis of human phenotype varies significantly across the lifespan. However, time-to-event phenotypes are understudied and can be thought of as reflecting an underlying hazard, which is unlikely to be constant through life when values take a broad range. Here, we find that 74% of 245 genome-wide significant genetic associations with age at natural menopause (ANM) in the UK Biobank show a form of age-specific effect. Nineteen of these replicated discoveries are identified only by our modeling framework, which determines the time dependency of DNA-variant age-at-onset associations without a significant multiple-testing burden. Across the range of early to late menopause, we find evidence for significantly different underlying biological pathways, changes in the signs of genetic correlations of ANM to health indicators and outcomes, and differences in inferred causal relationships. We find that DNA damage response processes only act to shape ovarian reserve and depletion for women of early ANM. Genetically mediated delays in ANM were associated with increased relative risk of breast cancer and leiomyoma at all ages and with high cholesterol and heart failure for late-ANM women. These findings suggest that a better understanding of the age dependency of genetic risk factor relationships among health indicators and outcomes is achievable through appropriate statistical modeling of large-scale biobank data.

Reproductive period duration and cognitive function in postmenopausal Latina women in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

A shorter reproductive period, a marker of estrogen exposure, has been related to cognitive impairment among older (>65years) non-Hispanic White women. We explored whether reproductive period duration, age at menarche, and age at menopause are related to cognitive function among postmenopausal Hispanic/Latina women. This cross-sectional analysis used baseline (Visit 1: 2008-2011) data from 3630 postmenopausal women in the Hispanic Community Health Study/Study of Latinos. Reproductive period duration, age at menarche, and age at menopause were assessed by self-report. Cognitive function variables included global cognition, verbal learning, memory, verbal fluency, and processing speed. Associations between each reproductive event and cognitive function were examined using multivariable linear and logistic regression analyses accounting for the complex survey design of the study and adjusting for socio-demographics, parity, and cardiovascular risk factors. We assessed whether associations differed by type of menopause (natural versus surgical) and hormone therapy use. The study population was on average aged 59years, with a mean reproductive period duration of 35years. Older age at menopause and a longer reproductive period were related to higher verbal learning (β=0.04, SE=0.02; p<0.05) and processing speed (ß=0.16, SE=0.04; p<0.001); associations were more pronounced for women with natural menopause. Older age at menarche was associated with lower scores on the digit symbol substitution test (ß=-0.62, SE=0.15; p<0.0001). There were no associations with global cognition. Among postmenopausal Hispanic/Latinas, a longer reproductive period was related to more favorable cognitive measures of verbal learning and processing speed. Our findings support the hypothesis that greater lifetime exposure to estrogens may be associated with higher cognitive performance.