Menopausal Transition Research Articles

Developing an educational resource for people experiencing eating disorders during the menopause transition: A qualitative co-design study.

The pronounced changes in reproductive hormones, such as oestradiol and progesterone, that occur during the menopause transition can contribute to increased risk of eating disorder onset or exacerbate a pre-existing eating disorder. Despite this heightened risk, there is a lack of available education and support that takes into consideration the unique challenges of experiencing an eating disorder during the menopause transition. This research aimed to qualitatively explore the perspectives of people with a lived experience of an eating disorder during the menopause transition, and to co-design a support option that addressed their unmet needs. A Double Diamond co-design process was followed involving four phases: discover, define, develop, and deliver. Seventeen women in Australia with a lived experience of an eating disorder during the menopause transition participated in online workshops across the four phases to identify their unmet health educational needs in experiencing an eating disorder during this transition, develop potential solutions and ultimately deliver a prototype solution in the final phase. All online workshops were recorded, transcribed verbatim and analysed using qualitative thematic analysis. The findings from the previous phase informed the next leading to the prototype creation. Qualitative thematic analysis identified six major themes across the four phases; lack of awareness of the intersection of menopause and eating disorders, lack of education, limited and stigmatising services, learning from lived experience, resource impact and resource development. Findings from this study provided preliminary acceptability of a novel online resource to address the unmet educational needs of people experiencing an eating disorder during the menopause transition. Overall positive feedback on the potential for the resource to improve knowledge and empower treatment-seeking was provided by women with lived experience.

Abstract 4135993: Body Composition and Mortality Throughout the Reproductive Cycle: Findings from the Multi-Ethnic Study of Atherosclerosis

Introduction: Changes in body composition throughout the reproductive cycle accelerate during the 2 years following the final menstrual period (FMP), known as the menopausal transition (MT). During MT, an increase in fat mass (FM) and a decrease in fat free mass (FFM) are usually seen, but the relationship between these changes and cardiovascular events is not well understood. We aim to explore how FM and FFM are associated with cardiovascular events and total mortality across the reproductive cycle in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: This study included 3439 women from exam 1 of MESA. Outcomes of interest were either MACE (heart failure, myocardial infarction, coronary revascularization, cardiac arrest, or stroke) or all-cause mortality. Equations to determine FM and FFM at exam 1 were validated with the NHANES 2003 population and derived from regression models based on bioelectrical impedance analysis results at exam 5 and anthropometric and demographic measures. Women were divided into 3 groups based on time since FMP: reproductive phase (before FMP), MT phase (<2 years after FMP), and late menopause phase (>2 years after FMP). Adjusted Cox multivariate models assessed the association between FM, FFM and MACE or all-cause mortality. Results: Median follow-up time was 14.1 years. FM was associated with MACE in the late menopause group, whereas FFM was not associated with MACE (Table). With respect to all-cause mortality, FM had a positive association (HR=1.19, P=0.03) while FFM had a negative association (HR=0.68, P=0.04) in the MT phase. The late menopause group showed similar relationships between FM, FFM, and all-cause mortality. The reproductive group showed no significant associations (Table). Conclusion: In this cohort, FM is associated with a higher risk of mortality whereas FFM is associated with a lower risk. We observed these associations to be more pronounced during the MT, a time of accelerated body composition change. Our results suggest and will need further investigation to confirm that the MT may be a critical time in the female lifespan to initiate interventions which positively impact muscle mass with a view to improving survival.

Factors influencing seogeulpeum among middle-aged Korean women

Objective This study aimed to examine factors associated with seogeulpeum (a feeling of loneliness and solitude) – including aging anxiety, menopausal symptoms, social support and self-efficacy – in middle-aged women to provide fundamental data for future research endeavors. Methods One hundred and fifty-nine women aged 40–60 years were recruited from two cities in Gyeongnam Province and Busan City. Gu and Eun’s Seogeulpeum Scale was employed to evaluate seogeulpeum, alongside questionnaires to assess menopause status and symptoms, self-efficacy, social support and aging anxiety. To determine factors influencing seogeulpeum, a multiple stepwise regression analysis was conducted. Results The average seogeulpeum score was 2.4 ± 0.44, indicating a moderate level of seogeulpeum experienced by the participants. Seogeulpeum was positively correlated with aging anxiety and menopausal symptoms, and negatively with self-efficacy and social support, among which aging anxiety most significantly influenced seogeulpeum. Aging anxiety, menopausal symptoms and social support combined accounted for 60.9% of the variation observed in seogeulpeum. Conclusions The findings indicate the importance of health interventions aimed at reducing aging anxiety and menopausal symptoms and enhancing social support for promoting well-being and facilitating a healthy menopausal transition among middle-aged women. Additionally, seogeulpeum can serve as a valuable process indicator during this stage of multiple transitions for women.

Quality of Life Among Natural Menopausal Women and Early Surgical Menopausal Women: A Study from Greece

Background/Objectives: The general health and well-being of middle-aged women have become a major public health issue worldwide. More than 80% of women experience physical or psychological symptoms during the transition to menopause. This study aims to compare the effect of menopause on quality of life (QOL) in two groups of women undergoing natural and surgical menopause. Methods: The sample consisted of 100 female patients from a Greek hospital in Athens, with an average age of 44.5 years, half of whom had natural menopause, while the remaining women had iatrogenic menopause after surgery for any reason other than malignancy. A questionnaire related to the QOL in menopause was used to collect the data. The scale used to evaluate the QOL of women is the Utian QOL Scale (UQOL), translated into Greek. Results: From the analysis of the data, it was found that there is no statistically significant difference between the QOL of women with natural and surgical menopause. Menopausal symptoms, psychosocial and sexual health, as well as the general health of the two groups, showed similar rates (OR: 63.7–66.6, p = 0.248). The only statistically significant difference found was in weight gain, with natural menopausal women having greater weight gain compared to surgically menopausal women (p = 0.041). Conclusions: Menopausal symptoms are associated with a decrease in women’s QOL. However, QOL is affected regardless of the type of menopause transition. This study was not registered.

Switch to Integrase Strand Transfer Inhibitors during the Menopausal Transition is Associated with Accelerated Body Composition Change in Women with HIV.

Integrase strand transfer inhibitors (INSTIs) and the menopausal transition have separately been associated with body composition changes in women with HIV (WWH), but their interaction is unknown. From 2006-2019, 1131 non-pregnant WWH with viral suppression [(419 who switched to INSTI (INSTI+); 712 who did not switch (INSTI-)] and 887 women without HIV (WWOH) from the Women's Interagency HIV Study were included. Mixed effect models were used to evaluate change in waist circumference (WC) and BMI by menopausal phase defined using anti-Müllerian hormone, a biomarker of ovarian reserve. During premenopause, WWH had increases in WC (INSTI+: 0.01cm per 6 month (mo); 95%CI:-0.29,0.32 and INSTI-: 0.22cm per 6mo;95%CI:-0.01,0.44) that were not statistically significantly different from WWOH; there was also little difference by INSTI status. In late perimenopause, INSTI+ had faster increases in WC (0.37cm per 6mo;95%CI:0.15,0.60) while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.06,0.34) compared to WWOH. In menopause, INSTI+ had faster increases peaking at 43mo then declining while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.02,0.30). Compared to INSTI-, in late perimenopause, INSTI+ had 0.26 cm per 6mo (95%CI:0.02,0.50) faster linear increases in WC and in menopause, INSTI+ was associated with faster increases peaking at 41mo. BMI trajectories were similar to WC in late peri- and menopausal women. Switching to an INSTI-based regimen during late peri- and menopause is associated with faster increases in WC and BMI when compared to women who did not switch. Menopausal status should be considered when switching to an INSTI.

Common mental health diagnoses arising from or coinciding with menopausal transition and prescribing of SSRIs/SNRIs medications and other psychotropic medications.

Women with menopausal transition (MT) have an elevated risk of experiencing common mental health diagnoses (CMHD: depression or anxiety). There is no recent data comparing the rate, and treatment, of CMHD between men and women. In this population-based study, incidence rates (IR) per 100 person-years-at-risk (PYAR) for men and women ≥45years registered with an UK primary care practice between 2010 and 2021 were estimated. Incidence rate ratios (IRR) with 95% confidence intervals (CIs) of CMHD were estimated using men as a reference. We measured first prescriptions for psychotropic medications received within 12months after CMHD. For selective serotonin reuptake inhibitors (SSRIs) /selective norepinephrine reuptake inhibitors (SNRIs), we measured the IR of prescribing per 100 PYAR, by 10-year bands. Proportion of SSRIs/SNRIs prescribing was estimated per 100 persons. Rates of anxiety and depressive disorders were 1.68 and 1.69 per 100 PYAR in women aged 45-54years-old compared to 0.91 and 1.20 per 100 PYAR in men, with IRR of 1.84 (95% CI 1.72-1.97) and 1.44 (1.35-1.53) respectively. SSRIs/SNRIs were the most prescribed medication; in 2021, IRs for SSRIs/SNRIs were 13.4 per 100 PYAR in both sexes. In 2021, the proportion of SSRIs/SNRIs prescribing was 50.67 per 100 women and 41.91 per 100 men. MT is assumed based on women's age as menopause onset is rarely recorded in primary care databases. Women ≥45years experienced more CMHD compared to men, especially 45-54years-olds, which coincides with MT. The proportion of SSRIs/SNRIs prescribing was higher in women.

Musculoskeletal pain during menopausal transition.

Musculoskeletal pain during menopausal transition.

The need for biopsychosocial menopause care: a narrative review.

Menopause is a reproductive transition affecting half the world's population. Stigma and limited availability of evidence-based treatments that support biopsychosocial well-being mean that this life stage is often associated with challenging symptoms and reduced quality of life (QoL). The aim of this review was to examine the extent literature on psychological and mind-body interventions to manage perimenopausal and postmenopausal symptoms, and apply an interdisciplinary clinical, research, and cultural knowledge framework to guide recommendations for improving QoL and healthy aging in this population. We also aimed to understand the ideal delivery mode for such interventions. Using Scopus, Medline, and PubMed, a review of systematic reviews, guidelines, and randomized controlled trials was undertaken to examine the use of psychological and mind-body interventions to improve menopause-related QoL and symptoms, including hot flushes, depression, anxiety, fatigue, pain, and sleep; conclusions were based on an analysis of this available evidence and linked to clinical and cultural considerations. Empirical support exists for a number of psychological and mind-body approaches to support QoL and symptoms during the menopause transition. The literature also identifies the need for menopause care that is culturally responsive.An online multimodal model of menopause care is thus recommended, incorporating evidence-based treatments (eg, cognitive behavioral therapy, yoga, hypnosis) and treatment techniques (eg, mindfulness, and education including nutrition support), as well as First Nations wisdom. We also recommend financial well-being approaches to support people undergoing menopause. Integrated, multimodal approaches should be available online to remove time, location, and healthcare access barriers, and be designed with diverse consumers to ensure equity for those underserved due to region, LGBTIQ+ assigned female at birth status, and for multicultural and First Nations people.

Sexual health in menopausal women with symptoms of pelvic floor disorders.

Sexual dysfunction in women is usually associated with the menopausal transition and menopause; however, there are factors that can also influence the sexual function of women in menopause. The aim of this study is to determine the association between pelvic floor disorders and sexual dysfunction in women in menopause. A cross-sectional study was carried out in Spain with menopausal women recruited by convenience sampling. Data were collected on background and health status. To evaluate the presence of pelvic floor problems, the Pelvic Floor Distress Inventory (PFDI-20) was used. Regarding the evaluation of female sexual function, the validated Sexual Function of Women (FSM-2) tool was used. Crude (OR) and adjusted odds ratios (AOR) were obtained using the SPSS 28.0 statistical program. A total of 197 women participated. The mean age was 57.7 years (SD=8.4), 51.3% (101 women) reported experiencing some form of sexual dysfunction. Despite this, the majority (79.5%; 155 women) indicated that they were satisfied with their sexual health. However, 25.5% (50 women) mentioned they faced difficulties when trying to initiate sexual intercourse. Additionally, 22.9% (45 women) reported having moderate to severe issues achieving orgasm. Furthermore, 29% (57 women) stated that they had never or only occasionally felt arousal in the past month. Women who experienced urinary incontinence and pelvic pain had a higher frequency of sexual dysfunction. The main associated factor observed was the risk of pelvic floor dysfunction through the PFDI-20 scale. For each point of this instrument, there was a small but increased risk of sexual dysfunction (OR=1.01; p<0.001). Type of birth or maternal disorders, such mental illness or gastrointestinal disorder, did not show any statistical association with sexual dysfunction. Pelvic floor dysfunctions symptoms in menopausal women are associated with their sexual health. Pelvic floor dysfunctions that influence sexual function are colorectal, urinary, and prolapse. Pelvic floor disorders such as urinary incontinence and pelvic pain are those that most influence sexual function.

Lipid changes across menopause status point to increased cardiovascular risk

Abstract Background While women develop cardiovascular disease (CVD) approximately ten years later than men, risk of CVD in women rises precipitously following menopause. The mechanisms underlying this acceleration in CVD risk are not well elucidated, but adverse changes in lipid measures are known to occur during the perimenopause period. Previous investigations have been largely restricted to traditional lipid measures and have not examined changes in lipoprotein particles including lipid subfractions and particle number. Purpose We sought to examine longitudinal changes in lipoprotein particles that occur during the menopause transition. Methods A total of 1305 participants in the Dallas Heart Study with known menopause status underwent measurement of LDL-P, HDL-P, sd-LDL, and ld-HDL by NMR LipoProfile LP4 algorithm (LabCorp, Raleigh Durham, NC, U.S.A.) at 2 examinations (between 7-8 years between DHS studies). We compared longitudinal changes in lipoprotein measures between pre-, peri-, post-menopausal women and men using multivariable adjusted linear regression models. For our analysis peri- is the group that was pre-menopause at DHS I and post-menopause at DHS 2, not to mean the period before menopause. Results There 1346 men (referent group) included in the study with a mean age of 43 ± 9.4 years. There was a total of 1246 women with a mean age of 42 ± 5.6 for peri-group, 54 ± 6.2 for post-group, and 34 ± 3.08 for the pre-group. Of the women 440 (35.3%) were pre-menopausal, 298 (23.9%) were peri-menopausal, and 508 (40.8%) were post-menopausal. Over a median follow-up time of 7 years. All three groups had an increase in LDL-P but the greatest percent change is between peri and post, 18.30 (SE 3.05, P&amp;lt;0.001). When compared to men the post-group has the greatest percent change of HDL-P with a negative change of 4.77 (SE 0.948 P&amp;lt;0.0001). Small-dense LDL had the highest percent change in the peri- group when compared to men with a change of 578.62 (SE 288.45, P&amp;lt;0.045). Large-dense HDL had greatest percent change in the post- group when compared to men with negative change of 37.84 (SE 12.83, P&amp;lt;0.0032). Conclusions We found that menopause is associated with adverse changes in lipoprotein profiles, with the most pronounced changes in LDL-particles and subfractions observed for peri-menopausal women. By contrast, post-menopausal women demonstrated the greatest reductions in HDL-particles and subfractions. Taken together, these changes suggest that menopause is associated with a transition to a more atherogenic lipoprotein profile. Further research is needed to investigate whether these adverse changes in lipoproteins translate to greater CV risk.

Atrial cardiomyopathy in postmenopausal female healthcare professionals- a single-center study

Abstract Background Atrial cardiomyopathy (ACM) is a new clinical entity with significant importance, because of its potential to be a determinant of heart failure, atrial fibrillation and thromboembolic complications¹. Defining different atrial phenotypes is challenging, because of the lack of consensus for the diagnosis of ACM²'³. Menopausal transition is associated with adverse changes in women’s health such as obesity and hypertension, both known risk factors for ACM⁴. Aim To investigate left atrial (LA) structural and functional echocardiographic parameters in postmenopausal female healthcare professionals and to define atrial phenotype in this population. Methods Consecutive asymptomatic, postmenopausal, middle-age women (n=105), healthcare professionals from our hospital, were separated in 3 groups according to co-morbidities : with obesity (n=50), obesity and hypertension (n=24), healthy control (n=31). All patients underwent 2D echocardiographic examination with volumetric and speckle tracking analysis of LA. Results There were significant differences in LA structural and functional indices between 3 groups- table 1. Higher body mass index was associated with increased LA volume index (p&amp;lt;0.001, r= 0.56), reduced LA total emptying fraction- LATEF (p&amp;lt;0.001, r= -0.62), Peak atrial longitudinal strain-PALS (p&amp;lt;0.001, r= -0.59 ) and Peak atrial contractile strain- PACS (p&amp;lt;0.001, r= 0.56 ). ROC analysis was performed for identifying atrial phenotype of obese women with hypertension: LAVi 16.5ml/m2,(sensitivity 0.833, specificity 0.839, AUC 0.875), PALS 46.55% (sensitivity 0.903, specificity 0.875, AUC 0.951), PACS -20.75% (sensitivity 0.806, specificity 0.708, AUC 0.855), LATEF 69% (sensitivity 0.903, specificity 0.792, AUC 0.920)- figure 1. Conclusion Postmenopausal women with obesity and hypertension are at risk for asymptomatic ACM. Further investigations are needed to confirm this concept.

Menopause is having a moment: power to pause?

This paper features four different women who represent different aspects of the menopausal journey. Women lose lean muscle mass and bone minerals as they age, a process that accelerates during the menopause transition, and then continues at a lower rate afterwards. The loss of muscle mass and strength can result in falls, functional decline and a subjective feeling of weakness, all of which are commonly associated with ageing and the menopause. From a metabolic, strength and functional perceptive, it is essential to health to maintain lean muscle mass across the lifespan. Research has shown that many menopausal symptoms can be improved by increasing levels of exercise and activity. As experts in movement and pelvic health, pelvic health physiotherapists are uniquely positioned to play a crucial role.

What is new on peri- and postmenopause?

Menopause is an increasingly discussed topic in recent years. More women are demanding consultancy and help from their doctors via different channels, be it online or in menopause centers.The term genitourinary syndrome of menopause (GSM) comprises vaginal and urological symptoms such as mucosal dryness, itching and burning, dysuria or bleeding and pain during sexual intercourse. GSM can strongly affect quality of life, is common if estrogen deficiency has lasted for 3 months and can be treated locally with very low doses of the weak estrogen estriol."Not feeling like myself anymore" - symptomatic perimenopause may present with sleep disturbances, mastalgia, mood swings, palpitations, panic attacks, but also entail joint pain, vertigo, headache, and brain fog - even years before menopause and in the presence of still adequate estrogen levels. In an online study, 20% of women in the menopausal transition reported symptoms which they could not explain, and which may cause fears of serious illness. This can lead to extensive medical work-ups if the possibility of perimenopause as the cause is disregarded.(Peri-)menopausal complaints last much longer than previously thought: The Study of women's health across the nation (SWAN) reported longer duration of vasomotor symptoms (median: 11,8 years) in women who were already affected in early perimenopause, while those in whom VMS started only after menopause experienced a shorter duration of symptoms (median: 3,4 years).Female hormones protect women from fatty streaks and hypertension, but menopausal hormone therapy (MHT) has positive effects only if started in the first decade after menopause. The interaction with stress, aging and lifestyle factors is complex.For the treatment of VMS, German and international guidelines list both drug and non-drug or non-prescription options, although there is no clear data on their effectiveness.Fezolinetant, a Neurokinin-3 receptor antagonist, is now available in Germany for the treatment of vasomotor symptoms in postmenopausal women with contraindications or aversion against steroid hormones. It modulates the thermoregulation center in the hypothalamus by blocking the KNDy-neurons. Studies on Elinzanetant, another representative of this class of drugs, are still ongoing.

A Novel Low-Impact Resistance Exercise Program Increases Strength and Balance in Females Irrespective of Menopause Status.

The reduction in sex hormone production across the menopause transition is thought to accelerate age-related decline in muscle mass, strength, and stability, increasing the risk of falls and fractures. We aimed to investigate whether a novel low-impact resistance exercise program could improve strength, balance, and body composition and whether any improvement was affected by menopause status. Seventy healthy, moderately active pre- (PRE; 46.7 ± (SD) 3.2 years), peri- (PERI; 52.3 ± 2.2 years) or post- (POST; 57.0 ± 2.5 years) menopausal females, not taking hormone replacement therapy (HRT), were randomised to continue habitual physical activity (CON; n = 25) or complete a supervised resistance exercise program 4 days/week for 12 weeks (EXC; n = 45). Strength at the hip and shoulder (isokinetic dynamometer), dynamic balance (Y-balance), flexibility (sit-and-reach & back-scratch), muscle thickness (rectus femoris, vastus intermedius (VI) and medial deltoid), and lean and %body fat (dual-energy X-ray absorptiometry) were measured before and after training. Results: Hip abduction and flexion peak torque (19 ± 48 and 20 ± 17%, respectively, P < 0.05), posterolateral and posteromedial balance (12 ± 15 and 13 ± 15%, respectively, P < 0.001), flexibility (21 ± 36%, P < 0.001), VI thickness (12 ± 19%, P = 0.032), lean mass (2 ± 2%, P = 0.007), all increased over 12 weeks in EXC, but not CON, with no difference in response between PRE, PERI or POST. The changes in shoulder strength and body mass over 12 weeks were not different between CON and EXC. This is the first study to demonstrate that the decline in sex hormones, and increase in age, across the menopause transition does not affect the ability of lower limb (hip) strength and balance to adapt to a low-impact resistance exercise training program in females not taking HRT.

Follicle-stimulating hormone induces depression-like phenotype by affecting synaptic function.

Depression is one of the most common affective disorders in people's life. Women are susceptibility to depression during puberty, peripartum and menopause transition, when they are suffering from sex hormone fluctuation. A lot of studies have demonstrated the neuroprotective effect of estrogen on depression in women, however, the effect of FSH on depression is unclear. In this study, we investigated the role of FSH on depression in mice. Our study demonstrated that FSH induced depression-like behaviors in mice in a dose-dependent manner. This induction was associated with elevated levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α in both serum and hippocampal tissues. Additionally, FSH treatment resulted in impaired synaptic plasticity and a reduction in the expression of key synaptic proteins. It is noteworthy that the depression-like behaviors, inflammatory cytokines expression and synaptic plasticity impairment induced by FSH could be alleviated by knocking down the expression of FSH receptor (FSHR) in the hippocampus of the mice. Therefore, our findings reveal that FSH may play an important role in the pathogenesis of depression and targeting FSH may be a potential therapeutic strategy for depression during hormone fluctuation in women.

Impact of Obesity, Menopause, and Depression in Women's Health: An Attempt to Decipher the Complex Relationship.

Menopause symptoms may be distressing, especially when they appear at a time when women are expected to play significant responsibilities in society. Numerous biological systems are influenced by the hormonal changes that start during the menopausal transition. This review attempts to decipher the complex relationship between obesity, menopause, and depression, citing some recent longitudinal and cross-sectional studies. Additionally, this study provides a summary of the different phytoestrogens, their sources, and probable mechanisms of action in addition to available therapeutic alternatives. For this review purpose, the authors have gone through a vast number of articles from various scientific databases like PubMed, Google Scholar, and Web of Science. It is becoming clear that the physiological basis for these menopausal symptoms is complicated and connected to estrogen deficiency, but not alone. Other hormones like FSH, LH, progesterone, and inhibin B are the major ones that are both directly and indirectly responsible for most of the menopausal symptoms. Numerous longitudinal and cross-sectional studies have found a direct relationship between the incidence of menopause and depression as well as obesity. Phytoestrogens like stilbene, lignans, isoflavone, and coumestan have been reported to be the alternatives to synthetic estrogen with lesser side effects, as reported in various studies. The complex relationship between depression, menopause, and obesity presents a complex obstacle to women's health and overall well-being. There might be a lot of promising prospects for revolutionary advancements in women's health during the menopausal stage in the future. Promising drug development that targets not just one but also the three conditions -obesity, menopause, and depression - as well as more thorough research are needed to improve the healthcare system for women who suffer from these conditions.

Morning tiredness and insomnia symptoms are associated with increased blood pressure in midlife women

ObjectivesThe objective of this study was to investigate how blood pressure, sleep architecture, sleep-disordered breathing, body habitus, and levels of serum follicle-stimulating hormone are associated with symptoms of insomnia and sleep quality during menopausal transition. Methods64 healthy premenopausal women (aged 45–47 years) were recruited to the study. Data were collected at baseline and at 10-year follow-up during sleep laboratory and laboratory visits. A sleep questionnaire was used to evaluate sleep quality and insomnia symptoms. Data were analysed using multiple linear and logistic regression with a backward method. ResultsDuring the menopausal transition, a change in insomnia symptoms was associated with a change in morning systolic blood pressure (β = 0.114 (CI95% 0.023–0.205), p = 0.016). At follow-up, at the age of 56, a higher percentage of REM sleep was associated with a lower odds of restless sleep (OR = 0.842 (95 % CI 0.742–0.954), p = 0.007), while both higher systolic and diastolic evening blood pressure was associated with an increased odds of morning tiredness.OR = 1.047 (95 % CI 1.003–1.092), p = 0.034 and OR = 1.126 (95 % CI 1.018–1.245), p = 0.007, respectively. ConclusionsIn healthy midlife women, a change blood pressure is related to the development of insomnia symptoms during menopausal transition. In postmenopausal women, a high evening blood pressure may be associated with morning tiredness and a reduced amount of REM sleep may be perceived as restless sleep.

7985 Insights into the Menopausal Transition: A Comparative Analysis of Hypothalamic Reproductive Aging in Women and a Mouse Model of Menopause

Abstract Disclosure: J.C. Bloom: None. S.A. Pereira: None. E. Torres Jimenez: None. D.C. Page: None. V.M. Navarro: None. Menopause onset is the major determinant of reproductive lifespan in women and is characterized by the decline in estrogen production from the ovary. While much of our current understanding of the menopause transition in humans comes from a series of observational longitudinal studies initiated in the 1980s and 1990s, the mechanisms by which reproductive aging impacts healthy brain aging remains a profoundly under-studied aspect of women’s health. The hypothalamus, a hub of homeostatic and temperature regulation, is highly sensitive to changes in sex steroid levels. Recently, activation of the neurokinin 3 receptor (NK3R) by neurokinin B (NKB) has been linked to the onset of vasomotor symptoms (VMS) during menopausal transition. NKB is secreted by hypothalamic Kisspeptin, NKB, Dynorphin (KNDy) neurons in response to decreasing estradiol levels. Here, we present a comparative study of the expression trajectories of the KNDy genes (KISS1, TAC3, PDYN, respectively) and NK3R (TACR3) in hypothalamic samples of humans across menopause and a mouse model of peri- and post-menopause (short- and long-term ovariectomy (OVX), respectively). RNA-sequencing data of human and mouse hypothalamic samples revealed a high correlation in the expression profile of the KNDy/NK3R genes between both species. Further investigation has revealed a highly conserved pool of genes in human and mouse hypothalami that correlate with TACR3 upon decline of circulating sex steroids. Thus, by examining conserved gene expression patterns across this critical reproductive period, we have been able to identify novel candidate targets involved in menopausal transition which may serve to better elucidate the biology of menopause-associated conditions affecting the brain, such as VMS and cognitive decline. Presentation: 6/2/2024

7985 Insights into the Menopausal Transition: A Comparative Analysis of Hypothalamic Reproductive Aging in Women and a Mouse Model of Menopause

Abstract Disclosure: J.C. Bloom: None. S.A. Pereira: None. E. Torres Jimenez: None. D.C. Page: None. V.M. Navarro: None. Menopause onset is the major determinant of reproductive lifespan in women and is characterized by the decline in estrogen production from the ovary. While much of our current understanding of the menopause transition in humans comes from a series of observational longitudinal studies initiated in the 1980s and 1990s, the mechanisms by which reproductive aging impacts healthy brain aging remains a profoundly under-studied aspect of women’s health. The hypothalamus, a hub of homeostatic and temperature regulation, is highly sensitive to changes in sex steroid levels. Recently, activation of the neurokinin 3 receptor (NK3R) by neurokinin B (NKB) has been linked to the onset of vasomotor symptoms (VMS) during menopausal transition. NKB is secreted by hypothalamic Kisspeptin, NKB, Dynorphin (KNDy) neurons in response to decreasing estradiol levels. Here, we present a comparative study of the expression trajectories of the KNDy genes (KISS1, TAC3, PDYN, respectively) and NK3R (TACR3) in hypothalamic samples of humans across menopause and a mouse model of peri- and post-menopause (short- and long-term ovariectomy (OVX), respectively). RNA-sequencing data of human and mouse hypothalamic samples revealed a high correlation in the expression profile of the KNDy/NK3R genes between both species. Further investigation has revealed a highly conserved pool of genes in human and mouse hypothalami that correlate with TACR3 upon decline of circulating sex steroids. Thus, by examining conserved gene expression patterns across this critical reproductive period, we have been able to identify novel candidate targets involved in menopausal transition which may serve to better elucidate the biology of menopause-associated conditions affecting the brain, such as VMS and cognitive decline. Presentation: 6/2/2024

7863 Polycystic Ovary Syndrome in Relation to Clinical, Biochemical, and Functional Musculoskeletal Health Outcomes During Midlife: A Longitudinal Cohort Study

Abstract Disclosure: M. Kazemi: None. S. Rifas-Shiman: None. E. Yu: None. S. Wang: None. M. Hivert: None. W. Perng: None. V. Fitz: None. J. Shifren: None. E. Oken: None. J. Chavarro: None. Background: Research about musculoskeletal composition and function in women with polycystic ovary syndrome (PCOS) is conflicting and primarily derived from cross-sectional analyses in clinical populations, raising concerns about the generalizability of findings and the temporal relation of observed associations. We tested the hypothesis that PCOS status is associated with adverse musculoskeletal outcomes during the menopausal transition. Methods: We enrolled 405 women in early pregnancy in 1999-2002 and followed them for ∼17y. Women with a PCOS clinical diagnosis were classified as “diagnosed PCOS” (N=26) 3y post-enrollment. In women without a PCOS diagnosis, we defined “probable PCOS” (N=40) as the presence of ≥2 PCOS traits, including ovulatory dysfunction (cycle length&amp;lt;21, ≥35d, or too irregular to determine length), elevated testosterone (&amp;gt;75th%) or elevated anti-Müllerian hormone (&amp;gt;75th%). We classified the remaining women as “no PCOS" (N=339). Musculoskeletal health outcomes (lean body mass [LBM], bone mineral density [BMD], and fat mass by dual-energy X-ray absorptiometry; plasma procollagen type I N-propeptide [PINP] and C-terminal telopeptide of type I collagen [CTX-I]; handgrip strength; and fractures) were assessed at 17y visit. We evaluated associations using linear regression models with log-transformed outcomes adjusted for age (mean [SD] 37 [5]y) and BMI (25.7 [5.4] kg/m2) at 3y visit. Further, we stratified analyses by menopausal status at 17y visit (self-reported amenorrhea for 12mos) to account for known effects of menopause on musculoskeletal health. Results: At the 17y follow-up, women were 51 (5)y; BMI, 27.9 (6.3) kg/m2. Diagnosed and probable PCOS were unrelated to spine (log β [95%CI]: 0.03 [-0.01, 0.07]) and hip (0.02 [-0.01, 0.06]) BMD (g/cm2) vs. no PCOS. However, diagnosed and probable PCOS were associated with increases in lower limbs (0.04 [0.01, 0.06]) and total (0.03 [0.004, 0.05]) BMD (g/cm2), without differences between PCOS groups. Compared to no PCOS, probable (-0.26 [-0.41, -0.11]) but not diagnosed PCOS (0.00 [-0.18, 0.18]) was inversely related to plasma CTX-I (ng/dL); a similar pattern was observed for PINP. In analyses stratified by menopausal status, PCOS was unrelated to BMD in postmenopausal women but remained positively associated with lower limb (0.04 [0.01, 0.06]) BMD (g/cm2) in premenopausal women. Conversely, associations between probable PCOS and plasma CTX-I were stronger in postmenopausal (-0.41 [-0.71, -0.11]) than in premenopausal women (-0.16 [-0.33, 0.01] ng/dL). Similarly, probable PCOS was inversely associated with PINP (-0.40 [-0.78, -0.01] mg/L) in postmenopausal, unlike premenopausal women. Diagnosed and probable PCOS were unrelated to LBM, fat mass, handgrip strength, or fracture risk. Conclusions: Any BMI-independent protective effects of PCOS on BMD may be offset during menopausal transition. Presentation: 6/2/2024