The aim of this study was to investigate the potentially modifiable factors affecting age at natural menopause (ANM) in Chinese women.We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million (0.3 million women) Chinese adults aged 30 to 79 from 2004 to 2008. Multinomial logistic regression models were used to examine the relationships between ANM and various factors recorded at baseline.Among 87,349 postmenopausal women, the mean ANM (SD) was 48.7 (4.3) years. Older age, being a housewife, earlier menarche, and passive smoking were associated with both premature menopause (PM, ie, ANM <40 years) and early menopause (EM, ie, ANM between 40 and 44 years). A higher odds for EM was observed in women who were widowed (odds ratio: 1.10, 95% confidence interval: 1.04-1.16), had spontaneous abortions (1.33 [1.05-1.69]), current regular smoking (1.19 [1.07-1.37]), and frequent spicy food intake (1.11 [1.05-1.08]). Higher socioeconomic status; later first birth; more live births and induced abortions; longer breastfeeding; tea drinking, as well as intakes of meat, fruits, dairy, and soybean products; and increased body mass index gain were inversely associated with PM and/or EM. In contrast, women who had more pregnancies, occasional alcohol drinking, higher levels of physical activity or body mass index, vitamin intake, and hypertension were more likely to have a later age at menopause (LM, ie, ANM ≥53 years).This large epidemiological study found a wide range of sociodemographic, lifestyle, dietary, and reproductive factors related to PM, EM, and LM in Chinese women.Copyright © 2021 by The North American Menopause Society.

How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature?The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI.Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI.The guideline was developed according to the structured methodology for development of ESHRE guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and health care professionals. Literature searches and assessment were then performed. Papers published up to January 30, 2024, and written in English were included in the guideline. An integrity review was conducted for the randomised controlled trials (RCTs) on POI included in the guideline.Based on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly on those on provision of care. A stakeholder review was organised after finalisation of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee.New data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help health care professionals to apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including hormone therapy. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated FSH >25 IU is required for diagnosis of POI and guidance that AMH testing, repeat FSH measurement and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care.The guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI.The guideline provides health care professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI.The guideline was developed and funded by ESHRE, American Society for Reproductive Medicine (ASRM), Centre for Research Excellence in Women's Health in Repoduction Life (CRE-WHiRL) and International Menopause Society (IMS), covering expenses associated with the guideline meetings, literature searches and dissemination of the guideline. The guideline group members did not receive payments. N.P. declared grants from Bayer Pharma (research and consultancy), and NIHR - research POISE; consulting fees from Abbott, Astellas, Bayer, Besins, Lawley, Mithra, Theramex, Viatris; honoraria from Astellas, Bayer, Besins, Gedeon Richter, Theramex, Viatris; support for attending meetings and/or travel from Astellas, Bayer, Theramex, Viatris; President, International Menopause Society, Medical Advisory Committee member, British Menopause Society, Patron Daisy Network. A.J.V. declared grants from Amgen Australia, Australian NHMRC, and Australian MRFF; consulting fees from IQ Fertility; honoraria from the Australasian Menopause Society; participation on a Data Safety Monitoring Board or Advisory Board of Astellas; Board Member of the International Menopause Society (2020 to current) and Past president of the Australasian Menopause Society (2017-2019); R.A.A. declared grants from Roche (Research support, to institution), and participation on a Data Safety Monitoring Board of Bayer. M.C. declared grants from NHI; payments or honoraria from Up-to-Date (as editor/reviewer); Board Member of American Society of Reproductive Medicine, and of American Gynecological and Obstetrical Society. M.D. declared (NIHR - HTA Reference Number: NIHR133461; NIHR - HTA Reference Number: NIHR128757; Action Medical Research and Borne: GN2818); consulting fees from a small personal medical practice, support for attending meetings and/or travel from ESHRE, Bayer and UCLH special Trustees; Participation on the Advisory Board from the British Menopause Society, UKSTORE project, the Progress Educational Trust, and the Turner Syndrome Support Society UK; Leadership or fiduciary roles in the British Fertility Society (Trustee), Elizabeth Garrett Anderson Hospital Charity (chair of Trustees), and the Essex Wynter charitable trust (Trustee). C.E. declared being Chair of a SIG from the Royal Australian College of General Practitioners Integrative Medicine Specific Interest Group and Program Lead for Next Practice Western Sydney Integrative Health. C.H.G. declared grants from Novo Nordisk Foundation (Nos. NNF15OC0016474 and NNF20OC0060610), sygesikringen danmark (No 2022-0189), and the Independent Research Fund Denmark (Nos. 0134-00406 and 0134-00130B); consulting fees from Novo Nordisk, Merck, and Astra Zeneca. S.K. declared grants from Roche diagnostics. A.K. declared grants from NIH R01 5R01HD101475; consulting fees as Medical Reviewer for Flo and for Healthline; honoraria as Medical Consultant for Summus; support for attending meetings from the Reproductive Scientist Development Program; Society for Reproductive Investigation Council Member and Society for Assisted Reproduction Registry / Validation Chair; R.N. declared consulting fees from Astellas, Bayer Pharma, Besins Healthcare, Fidia, Theramex; honoraria from Abbott, Astellas, Exeltis, Fidia, Gedeon Richter, Merck & Co, Novo Nordisk, Shionogi Limited, Theramex, Viatris; payment for expert testimony from Vichy Laboratories; Participation in Data Safety Monitoring Board of Advisory board from Astellas and Bayer Healthcare; President elect of the International Menopause Society (IMS). H.T. declared a grant from NHMRC Centre for Research Excellence for women's health in reproductive life. A.B. declared being chair of the Daisy Network Charity. The other authors have no conflicts of interest to declare.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

The typical age at menopause is 50-51 years in high-income countries. However, early menopause is common, with around 8% of women in high-income countries and 12% of women globally experiencing menopause between the ages of 40 years and 44 years. Menopause before age 40 years (premature ovarian insufficiency) affects an additional 2-4% of women. Both early menopause and premature ovarian insufficiency can herald an increased risk of chronic disease, including osteoporosis and cardiovascular disease. People who enter menopause at younger ages might also experience distress and feel less supported than those who reach menopause at the average age. Clinical practice guidelines are available for the diagnosis and management of premature ovarian insufficiency, but there is a gap in clinical guidance for early menopause. We argue that instead of distinct age thresholds being applied, early menopause should be seen on a spectrum between premature ovarian insufficiency and menopause at the average age. This Series paper presents evidence for the short-term and long-term consequences of early menopause. We offer a practical framework for clinicians to guide diagnosis and management of early menopause, which considers the nature and severity of symptoms, age and medical history, and the individual's wishes and priorities to optimise their quality of life and short-term and long-term health. We conclude with recommendations for future research to address key gaps in the current evidence.Copyright © 2024 Elsevier Ltd. All rights reserved.

Premature ovarian insufficiency (POI) is highly heterogeneous, both in phenotype and etiology. They are not yet clearly stated and correlated.To characterize clinical presentations of a large, well-phenotyped cohort of women with POI, and correlate phenotypes with etiologies to draw a comprehensive clinical picture of POI.In this retrospective study, a total of 955 Chinese women with overt POI between 2006 and 2015 were systemically evaluated and analyzed. The phenotypic features, including menstrual characteristics, hormone profiles, ovarian ultrasonography/biopsy, pregnancy/family history, and genetic/autoimmune/iatrogenic etiologies were assessed and further compared within different subgroups.Among 955 women with POI, 85.97% presented with secondary amenorrhea (SA) and 14.03% with primary amenorrhea (PA). PA represented the most severe ovarian dysfunction and more chromosomal aberrations than SA. The decline of ovarian function in patients with SA progressed quickly. They had shortened reproductive periods (approximately 10 years) and developed amenorrhea within 1 to 2 years after menstrual irregularity. The ovaries were invisible or small, and the presence of follicles (28.43%) was correlated with other good reproductive indicators. Familial patients (12.25%) manifested better ovarian status and fewer chromosomal aberrations than sporadic patients. The etiologies consisted of genetic (13.15%), autoimmune (12.04%), and iatrogenic (7.29%), approximately 68% remaining idiopathic. There were significant differences among different etiologies, with the genetic group representing the most severe phenotype.Our results regarding distinct phenotypic characteristics and association with different etiologies further confirmed the high heterogeneity of POI. Additional longitudinal clinical studies and pathogenesis research are warranted.Copyright © 2017 Endocrine Society

To determine the relative importance of family history as a predictor of early menopause.Case-control study. From a population-based survey of 10,606 women between 45 and 54 years of age, we selected 344 cases with early menopause (average age 42.2 years) and 344 age-matched controls who were still menstruating or who had a menopause after age 46 years. Subjects were interviewed about their medical and family history and blood was drawn for identification of women who were carriers for the classic or Duarte variant of galactosemia, a potential hereditary factor for early menopause. Logistic regression analysis was used to estimate the risk of an early menopause in women with and without a family history of early menopause.Overall 129 (37.5%) of the early menopause cases reported a family history of menopause before age 46 years in a mother, sister, aunt, or grandmother compared to 31 (9.0%) of controls yielding an odds ratio (OR) of 6.1 (95% confidence interval [CI] of 3.9 to 9.4) after adjustment for smoking history, education, parity, and body mass index. Risk for early menopause associated with family history of same was greatest: for family history in a sister, OR = 9.1 (95% CI 3.1 to 26.5); multiple relatives, OR = 12.4 (95% CI 4.4 to 34.2); and cases menopausal before age 40 years, OR = 8.4 (95% CI 2.5 to 31.2). Cases with a family history of early menopause were not more likely to have errors of galactose metabolism compared with cases without a family history or to all controls, nor did they possess Turner's stigmata such as short stature, but they were less likely to have brothers in their sibships.Although preferential recall of family history by women with early menopause could contribute to the association between family history and early menopause observed in this study, a genetic factor is also plausible including partial deletions of the X chromosome compatible with the deficiency of male siblings in cases with family history of early menopause.

Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing1. Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2 and SAMHD1). The SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility1, with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518A are associated with shorter reproductive lifespan—that is, earlier age at menopause (by 5.61 years) and later age at menarche (by 0.56 years). Finally, using 8,089 sequenced trios from the 100,000 Genomes Project (100kGP), we observe that common genetic variants associated with earlier ovarian ageing associate with an increased rate of maternally derived de novo mutations. Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk.

Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage.This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed.Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents.Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed.Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically.© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

We determined the best model available for natural follicle decline in healthy women and used this to calculate the radiosensitivity of the human oocyte.Ovarian failure was diagnosed in six patients with a median age of 13.2 years (range 12.5-16.0) who were treated with total body irradiation (14.4 Gy) at 11.5 years of age (4.9-15.1). We previously estimated the dose of radiation required to destroy 50% of the oocytes (LD(50)) to be <4 Gy. This estimate is an oversimplification, because decay represents an instantaneous rate of temporal change based upon the remaining population pool, expressed as a differential equation: dy/dx = -y[0.0595 + 3716/(11780 + y)], with initial value y(0) = 701 200.Solving the differential equation, we have estimated the number of follicles left after irradiation given as sol(51 - s + r), where r equals age at treatment, s equals age at diagnosis of ovarian failure, and 51 years is the average age of menopause. The surviving fraction of oocytes as a percentage is 100 times this value divided by sol(r). The mean surviving fraction for the six cases is 0.66%. We obtain a function, g(z), which decreases in value from 100% at zero dosage to mean value at dosage z = 14.4 Gy. We have g(z) = 10(mx+c), where c = log(10)100 = 2, and m = [log(10)(0.66) - c]/14.4. Solving g(z) = 50 gives an LD(50) of 1.99.Based on new data and a revised mathematical model of natural oocyte decline, we have determined the surviving fraction of oocytes following irradiation and estimate the LD(50) of the human oocyte to be <2 Gy.

To determine the age of menopause after premenopausal unilateral oophorectomy (UO) and to establish whether UO at a young age leads to menopause at a younger age than if UO occurs at an older age.A cohort of 28 731 women, of whom 17 781 (62%) were menopausal, was investigated. Information on menopause was obtained from self-reported questionnaires. Surgical data were obtained from the National Patient Register to avoid recollection bias. Age of menopause after UO/not UO was determined using Kaplan-Meier curves. Cox regression was used to identify factors of importance for early menopause.UO was performed in 1148 women. Women with UO after the age of 45 years, premenopausal hysterectomy, bilateral oophorectomy and cancer were excluded, leaving 236 in the analysis. Menopause occurred 1.8 years earlier after UO compared to women with two intact ovaries (mean 49.5 vs. 51.3 years), and younger age at UO was significantly linearly correlated to younger age at menopause. UO (hazard ratio 1.23) and smoking (hazard ratio 1.12) significantly decreased the age of menopause.Premenopausal unilateral oophorectomy significantly reduces the age of menopause by 1.8 years. Younger age at UO leads to significantly younger age at menopause.

To prospectively estimate the risk for earlier ovarian failure among women undergoing hysterectomy with ovarian preservation, as compared with women of similar age without hysterectomy.A prospective cohort study was conducted among women aged 30 to 47 years undergoing hysterectomy without bilateral oophorectomy (n=406) and women with intact uteri (n=465). Blood samples and questionnaire data were obtained at baseline and annually for up to 5 years. Hazard ratios (HR) for ovarian failure, defined as follicle-stimulating hormone levels 40 international units/L or higher, were calculated using Cox proportional hazards models.Ovarian failure occurred among 60 of the women with hysterectomy and 46 of the women in the control group. Women undergoing hysterectomy were at nearly a twofold increased risk for ovarian failure as compared with women with intact uteri (HR 1.92, 95% confidence interval [CI] 1.29-2.86). The proportional hazards model further estimated that 14.8% of women with hysterectomies experienced ovarian failure after 4 years of follow-up compared with 8.0% of the women in the control group. Risk for ovarian failure was greater for women who had a unilateral oophorectomy along with their hysterectomy (HR 2.93, 95% CI 1.57-5.49), but also it was significantly increased for women who retained both ovaries (HR 1.74, 95% CI 1.14-2.65).Increased risk of earlier ovarian failure is a possible consequence of premenopausal hysterectomy. Although it is unresolved whether it is the surgery itself or the underlying condition leading to hysterectomy that is the cause of earlier ovarian failure, physicians and patients should take into account this possible sequela when considering options for treatment of benign conditions of the uterus.II.

Menopause that occurs before the age of 45 and is not medically induced (referred to here as 'early natural menopause') affects around one in 10 women and has serious health consequences. These consequences include increased risk of all-cause mortality, cardiovascular disease, osteoporosis, and type 2 diabetes.We investigate risk factors for the onset of natural menopause before the age of 45 in two population-based prospective cohort studies in Britain: the 1958 cohort following 8959 women and the 1970 cohort following 8655 women. These studies follow women from birth to adulthood, and we use harmonized data on birth and early life characteristics, reproductive health, health behaviour, and socioeconomic characteristics for 6805 women who were pre-menopausal, peri-menopausal or had undergone natural menopause. Of these 6805 women, 3614 participated in the 1958 cohort (of which 368 had early menopause) and 3191 participated in the 1970 cohort (of which 206 had early menopause). Taking a life course approach, we focus on three distinct life stages - birth/early life, childhood, and early adulthood - to understand when risk factors are most harmful. Respecting the temporal sequence of exposures, we use a series of multivariable logistic regression models to estimate associations between early menopause and each potential risk factor adjusted for confounders.We find that early menopause is influenced by circumstances at birth. Women born in lower social class families, whose mother smoked during the pregnancy or who were breastfed 1 month or less were more likely to undergo early menopause. Early menopause is also associated with poorer cognitive ability and smoking in childhood. Adult health behaviour also matters. Smoking is positively correlated with early menopause, while regular exercise and moderate frequency of alcohol drinking in women's early thirties are associated with reduced risk of early menopause. The occurrence of gynaecological problems by women's early thirties is also linked to early menopause.We demonstrate that characteristics at different periods of life are associated with early menopause. Some of these associations relate to modifiable behaviours and thus the risks of early menopause and the adverse health outcomes associated with it may be preventable.© 2022. The Author(s).

Early onset of menopause poses a risk for various health issues in women. This study aimed to primarily examine the link between early menopause and indoor air pollution (IAP) and demonstrate this association within the Indian population, considering their place of residence.This longitudinal study included 24,862 eligible participants out of 73,000 surveyed. Logistic regression analyses, both crude and adjusted odds ratios (aOR), were used to examine the association between early menopause and various sociodemographic factors, IAP, and place of residence (rural/urban).The study identified a significant correlation between early menopause and body mass index (BMI), educational status, marital status, occupation, physical activity, self-rated health, and smoking status. Women using unclean fuels did not show increased odds of early menopause (aOR: 1.00, 95% confidence interval [CI]: 0.93-1.08). Poor ventilation was linked to a slightly higher incidence (28.1% vs. 26.9%, aOR: 1.07, 95% CI: 0.99-1.15). Exposure to pollution-generating sources was significantly associated with early menopause (28.8%, aOR: 1.10, 95% CI: 1.02-1.18), especially in urban areas (aOR: 1.17, 95% CI: 1.01-1.36) but not rural (aOR: 1.08, 95% CI: 0.99-1.17). Indoor smoking was linked to higher odds (aOR: 1.09, 95% CI: 1.02-1.17), particularly in rural areas (aOR: 1.09, 95% CI: 1.01-1.18). Overall, IAP was significantly associated with early menopause (aOR: 1.07, 95% CI: 1.01-1.15).The findings reveal that IAP, from sources such as smoke and pollutants, significantly increases the risk of early menopause among Indian women. Urban women are more affected by pollution, whereas indoor smoking impacts both urban and rural women. Enhancing indoor air quality could reduce early menopause and improve women's health in India.Copyright: © 2025 Journal of Family Medicine and Primary Care.

To comprehensively investigate and evaluate the prevalence, severity, and associated factors of menopausal symptoms in women with premature ovarian insufficiency (POI). In this study, the specific symptomatology experienced by women with POI and women with natural menopause was also compared.In this cross-sectional study, 293 Chinese women with POI from an outpatient clinic were recruited between June 2014 and January 2019. The prevalence and severity of menopausal symptoms were assessed with modified Kupperman Menopausal Index. Participants completed a structured questionnaire, including medical history, menstrual characteristics, and sociodemographic data. Serum levels of reproductive hormones were measured.Among 293 women with POI (33.76 ± 5.47 y), the most prevalent symptoms were mood swings (73.4%), insomnia (58.7%), sexual problems (58.7%), and fatigue (57.3%). Moderate-to-severe mood swings were most frequently reported (23.9%), followed by formication (17.4%) and hot flashes/sweating (17.1%). Compared with women with natural menopause, women with POI exhibited significantly higher risks for fatigue (odds ratio  = 1.42; 95% confidence interval, 1.04-1.94), melancholia (3.12; 1.94-5.01), mood swings (3.57; 2.33-5.45), insomnia (1.41; 1.02-1.96), and significantly lower risks for moderate-to-severe sexual problems (0.40; 0.23-0.69), any and moderate-to-severe muscle/joint pain (0.41; 0.27-0.62 and 0.45; 0.25-0.78, respectively). Living in urban areas and higher gravidity were independently associated with menopausal symptoms in women with POI.Women with POI experienced a high prevalence of menopausal symptoms, particularly related to psychological and sexual domains. Furthermore, women with POI tended to have more distressing menopausal symptoms compared with women with natural menopause.Copyright © 2021 by The North American Menopause Society.

To explore symptoms, understanding of menopausal therapies, medication use and health-related behavior in women with and without premature menopause.Cross-sectional, questionnaire-based study involving a community-based sample of 77 women in Australia: 23 premenopausal, 25 with premature ovarian failure (POF) and 29 with medically induced premature menopause (MIPM).The median (interquartile range) age of each group was: premenopausal = 29 (13) years, POF = 36 (8.0) years and MIPM = 38 (4.0) years (p < 0.001). The reported frequency of menopausal symptoms differed across the groups for difficulty sleeping (premenopausal = 26%, POF = 44%, MIPM = 69%, p = 0.01), some depression symptoms (premenopausal = 4.4-22%, POF = 20-25%, MIPM = 38-59%, p < 0.05), hot flushes (premenopausal = 4.4%, POF = 28%, MIPM = 59%, p < 0.001), sweating at night (premenopausal = 4.4%, POF = 20%, MIPM = 52%, p < 0.001) and loss of interest in sex (premenopausal = 17%, POF = 52%, MIPM = 54%, p = 0.02). More women with premature menopause than premenopausal women reported taking prescription medication (premenopausal = 52%, POF = 92%, MIPM = 86%, p = 0.002), perceived that hormone therapy (HT) was associated with increased breast cancer risk (premenopausal = 43%, POF = 56%, MIPM = 79%, p = 0.03) and that HT prevented fractures (premenopausal = 13%, POF = 56%, MIPM = 39%, p = 0.01). Most women reported not knowing risks/benefits of bioidentical hormone therapy (premenopausal = 86%, POF = 56%, MIPM = 75%, p = 0.06). Regarding health-related behavior around prevention and screening, varying rates of bone densitometry (premenopausal = 4.4%, POF = 64%, MIPM = 59%, p < 0.001), blood glucose testing (premenopausal = 39%, POF = 67%, MIPM = 57%, p = 0.16) and cholesterol testing (premenopausal = 22%, POF = 71%, MIPM = 54%, p = 0.003) were reported.Differences in understanding of menopausal therapies and health-related behavior exist among women with premature menopause of differing etiology and premenopausal women. While perceived understanding of HT was greater than other therapies, targeted education is needed regarding specific risks/benefits of menopausal therapies and regarding preventive health screening after premature menopause.

What is the frequency of, and predictors for, osteoporosis, fractures, and osteoporosis management (investigation, treatment) in women with premature ovarian insufficiency (POI; menopause &lt;40 years) and early menopause (EM; menopause 40–44years)?

Supplemental Digital Content is available in the text.

Premature onset of menopause is associated with increased short-term risk of coronary heart disease (CHD), but the associated long-term CHD risk and whether this differs by self-identified race are not known.

How does the risk of cardiovascular disease (CVD) vary with type and age of menopause?

The aim of the study is to evaluate the cross-sectional and longitudinal association of early natural menopause with changes in cardiovascular risk factors (CVRFs).Postmenopausal women from the Swiss CoLaus study, reporting age at natural menopause (ANM) and having CVRFs measurements (blood lipids, blood pressure, glucose, homeostatic model assessment for insulin resistance [HOMA-IR], and inflammatory markers) at baseline (2003-2006) and first follow-up (2009-2012) were eligible for analysis. Age at natural menopause was analyzed as a continuous variable and in categories (ANM <45 and ≥45 y old). Linear regression analysis and linear mixed models were used to assess whether ANM is associated cross-sectionally and longitudinally with changes in CVRFs. Models were adjusted for demographic characteristics, lifestyle-related factors, time since menopause, medication, and clinical conditions.We analyzed 981 postmenopausal women. The cross-sectional analysis showed that women with ANM younger than 45 years had lower diastolic blood pressure (β = -3.76 mm Hg; 95% confidence interval [CI] = -5.86 to -1.65) compared with women whose ANM was 45 years or older. In the longitudinal analysis, ANM younger than 45 years was associated with changes in log insulin (β = 0.26; 95% CI = 0.08 to 0.45) and log homeostatic model assessment for insulin resistance levels (β = 0.28; 95% CI = 0.08 to 0.48). No associations were found between ANM and other CVRFs.Early menopause may be associated with changes in glucose metabolism, while it may have little to no impact on other CVRFs. Larger longitudinal studies are needed to replicate our findings.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.

Premature ovarian insufficiency (POI), marked by ovarian function loss before age 40, is linked to a higher risk of dementia, including Alzheimer's disease (AD). However, the associated brain structural changes remain poorly understood.

In a cohort of 19,731 Norwegian postmenopausal women, the authors analyzed relations between the age at natural menopause and all-cause mortality. A total of 18,533 women died during the 37 years of follow-up from 1961 to 1997. An inverse relation was found between the age at menopause and the all-cause mortality rate (p = 0.003). The strength of the association was moderate, however, with 1.6% (95% confidence interval: 0.6, 2.7) reduced mortality per 3 years' increase in age at menopause. The impact appeared to be stronger in women with an attained age of less than 70 years (3.7% reduction in risk) than in women aged 80 years or more (1.0%). The inverse relation could not be explained by extreme mortality rates in women with very early (<40 years) or late (>55 years) menopause or by possible confounding variables like birth cohort, place of residence, occupational category (own or husband's occupation), body mass index, age at menarche, and first and last delivery or parity. The smoking prevalence was low in the underlying population, and the use of hormone replacement therapy was very rare. The authors conclude that age at natural menopause is inversely related to all-cause mortality.

Women with premature ovarian insufficiency (POI) are exposed to a long period of estrogenic deficiency, which potentially brings higher health risks, especially regarding bone health. We performed a systematic review of the literature to evaluate the effect of hormone therapy (HT) on bone mineral density (BMD) in women with POI.A systematic search was performed of the MEDLINE and EMBASE databases up to September 2021. We included studies that analyzed women with idiopathic (spontaneous) POI treated with HT, and those who had BMD evaluated. Analysis of risk of bias of studies selected was performed.We found 335 articles and selected 16 studies according to the inclusion criteria. Most of the studies revealed lower bone density in both the femoral neck and lumbar spine of women with POI compared with healthy women. Bone mass had the tendency to remain stable in women treated with estrogen + progestin therapy. However, in women already with bone mass loss, the therapy - in the doses most frequently used - was not able to revert the loss. Higher doses of estrogen seem to have a positive impact on BMD, as did combined oral contraceptives used continuously. Also, the interruption of HT for longer than one year was linked to significant bone loss.Although HT brings clear benefits, further studies are needed to establish its long-term effects, as well as doses and formulations with better protective effects on the bone mass of these women.Copyright © 2022 Elsevier B.V. All rights reserved.

Premature ovarian insufficiency (POI, defined as age at menopause < 40 years) affects 1%–3% of postmenopausal women. It is positively associated with an increased risk of diabetes mellitus, arterial hypertension, cardiovascular disease, osteoporosis, fractures, cognitive impairment, and depression. Early menopause (EM, defined as age at menopause < 45 years) is also associated with these adverse health consequences, in most cases to the same degree as in POI. Therefore, a unifying term for EM and POI, such as ‘premature menopause’, may be proposed, using the age threshold of < 45 years. This could provide broader coverage of these women, substantiating the need for prompt administration of menopausal hormone therapy (in this case, ‘hormone replacement therapy’). However, the benefits of this approach, which precludes a higher oestrogen dose up to the normal age of menopause, need to be proven in well‐designed randomized controlled trials.

Menopausal symptoms are common in midlife women and have broad impacts on their daily functioning and quality of life. Black cohosh extracts have been widely used to relieve menopausal symptoms. However, the comparative benefits of different combined black cohosh regimens remain inconclusive. The aim of the current updated meta-analysis is to address the comparative efficacies of different black cohosh regimens in improving menopausal symptoms.Random-effect model pairwise meta-analysis of randomized controlled trials was conducted to investigate the treatment effect on menopausal symptoms by the black cohosh extract both alone or combined with other related active ingredients. The outcomes studied were changes in menopausal symptoms after treatment with black cohosh extracts in menopausal women.Twenty-two articles including information on 2,310 menopausal women were included in the analyses. Black cohosh extracts were associated with significant improvements in overall menopausal symptoms (Hedges' g = 0.575, 95% CI = 0.283 to 0.867, P < 0.001), as well as in hot flashes (Hedges' g = 0.315, 95% CIs = 0.107 to 0.524, P = 0.003), and somatic symptoms (Hedges' g = 0.418, 95% CI = 0.165 to 0.670, P = 0.001), compared with placebo. However, black cohosh did not significantly improve anxiety (Hedges' g = 0.194, 95% CI = -0.296 to 0.684, P = 0.438) or depressive symptoms (Hedges' g = 0.406, 95% CI = -0.121 to 0.932, P = 0.131). The dropout rate for black cohosh products was similar to that for placebo (odds ratio = 0.911, 95% CI = 0.660 to 1.256, P = 0.568).This study provides updated evidence regarding the potentially beneficial effects of black cohosh extracts for relieving menopausal symptoms in menopausal women.Copyright © 2023 by The North American Menopause Society.