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BACKGROUND: Fibroids are non-cancerous uterine tumors potentially associated with cardiovascular risk factors. We examined prospectively associations of glucose, insulin, sex hormone binding globulin (SHBG), and diabetes with incidence of fibroid diagnoses in midlife. METHODS: Participants in the Study of Women's Health Across the Nation (SWAN) cohort (n=2570) reported fibroid diagnoses at enrollment (1996-1997) and 13 follow-up visits (1996-2013). At all visits, we measured glucose, insulin, and SHBG in fasting blood samples and calculated homeostatic model assessment for insulin resistance (HOMA-IR). Diabetes was defined using glucose levels, self-reported diabetes, or diabetes medication use. We used discrete-time survival models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of time-varying biomarkers and diabetes with incident fibroid diagnoses, adjusted for demographics and healthcare utilization. We also evaluated effect modification by menopausal status. RESULTS: At baseline, 2.7% of participants (n=70) were using diabetes medication. Time-varying glucose, insulin, HOMA-IR, and SHBG were not associated with fibroid diagnosis. However, diabetes was associated with a 28% lower incidence of fibroid diagnosis (adjusted HR: 0.72, 95% CI: 0.44, 1.17), driven by participants using metformin (adjusted HR: 0.49, 95% CI: 0.21, 1.12), though precision was limited. After stratification by menopausal status, higher HOMA-IR and insulin were associated with greater incidence of fibroid diagnosis during premenopause but not perimenopause, while the inverse association between diabetes and fibroids was strongest during perimenopause. CONCLUSION: The effect of diabetes and biomarkers on fibroids may vary by menopausal status. Fibroid risk may increase with insulin resistance and decrease with diabetes treatment.

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AIMS: The impact of life-course different adiposity indices on diabetes mellitus (DM) is poorly understood. We aimed to do trajectory analysis with repeated measurements of adiposity indices in the development of DM among women across the lifespan. METHODS: This study prospectively investigated the 1,681 population of Tehran Lipid and Glucose Study. At baseline, all individuals were free of diabetes. Trajectory analysis was used to identify homogeneous distinct clusters of adiposity indices trajectories and assign individuals to unique clusters. RESULTS: Of the 1681 healthy women, 320 progressed to the DM. Three distinct body mass index (BMI) trajectories and 2 distinct trajectories of other adiposity indices (waist circumstance (WC), conicity index (C-index), and body roundness index (BRI)) were chosen as the best fitting of the latent class growth mixture model. In the adjusted model, total participants [HR (CI 95%): 2.83 (2.05, 3.91); p < 0.001], and menopause [1.35 (1.10, 2.11); p = 0.001] and reproductive-age women [2.93 (1.80, 4.78); p = 0.003] of the high BMI trajectory compared to the ones in the low trajectory of BMI were more likely to develop DM. The high BRI in menopause had a significantly higher risk of DM compared to the low trajectory. In menopause (1.80 (1.26, 2.58)) and reproductive-age women (4.32 (2.49, 7.47)) with high trajectory of C-index, the DM risk decreased after adjustment. CONCLUSIONS: The risk of DM was greater for high BMI, WC, C-index, and BRI trajectories than for lower trajectories. Hence, the development of general, abdominal, and visceral obesity trajectories in the prevention of DM should be considered by clinicians.

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Purpose: Risk factors for presbyopia have not been fully determined although previous studies suggested presbyopia was associate with age, dry eye, and retinal ganglion cell complex thickness (GCC). We accessed these signs and common ocular symptoms in the middle-aged population focusing on sex differences when women have drastic hormonal change. Methods: This cohort study consecutively enrolled 2743 patients aged 36-45 years (n=1000), 46-55 years (n=1000), and 56-65 years (n=743). All underwent ocular surface tests and had near add power and GCC measured. Common ocular symptoms were asked using questionnaire. Results: Among female participants, visual symptoms (eye strain and photophobia) were more prevalent in the age group 46-55, whereas non-visual symptoms (dryness, irritation, and pain) were not. We identified symptomatic presbyopia (near add power ≥ 1.5D) in 14.4%, 73.8%, and 97.8%, positive corneal staining in 29.1%, 23.8%, and 23.9%, and a mean GCC of 98.2 µm, 105.3 µm, and 89.6 µm in the age groups 36-45, 46-55, and 56-65, respectively. Mean tear break-up time were 3.3, 3.5, and 3.3 seconds, respectively. Results indicated a large progression of presbyopia (P<0.01) from the period of 36-45 years onward and significantly increased GCC (P<0.01) in women of age group 46-55. No notable tendency was observed in symptoms and GCC for male participants. Conclusion: Visual symptoms in women were worse between 46 and 55 years than before or after these ages. The increase of symptomatic presbyopia and GCC may be contributing to visual symptoms in addition to menopausal transition symptoms in this age group.

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Background: Evidence suggests a connection between DNA methylation (DNAm) aging and reproductive aging. However, the causal relationship between DNAm and age at menopause remains uncertain. Methods: Employing established DNAm epigenetic clocks, such as DNAm Hannum age acceleration (Hannum), Intrinsic epigenetic age acceleration (IEAA), DNAm-estimated granulocyte proportions (Gran), DNAm GrimAge acceleration (GrimAgeAccel), DNAm PhenoAge acceleration (PhenoAgeAccel), and DNAm-estimated plasminogen activator inhibitor-1 levels (DNAmPAIadjAge), a bidirectional Mendelian randomization (MR) study was carried out to explore the potential causality between DNAm and menopausal age. The primary analytical method used was the inverse variance weighted (IVW) estimation model, supplemented by various other estimation techniques. Results: DNAm aging acceleration or deceleration, as indicated by Hannum, IEAA, Gran, GrimAgeAccel, PhenoAgeAccel, and DNAmPAIadjAge, did not exhibit a statistically significant causal effect on menopausal age according to forward MR analysis. However, there was a suggestive positive causal association between age at menopause and Gran (Beta = 0.0010; 95% confidence interval (CI): 0.0004, 0.0020) in reverse MR analysis. Conclusion: The observed increase in granulocyte DNAm levels in relation to menopausal age could potentially serve as a valuable indicator for evaluating the physiological status at the onset of menopause.

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To inform endpoints for future work, we explored the utility of pre-workout (i.e., an acute dose before training) beetroot juice (BRJ) combined with exercise (BRJ+EX) to augment indices of physical function in postmenopausal women compared to exercise only (EX). A two-arm pilot was employed to compare 24 postmenopausal women following an 8-wk, circuit-based exercise intervention. Participants were randomized to BRJ+EX (n = 12) or EX (n = 12). BRJ+EX participants consumed 140-mL of BRJ 120-180 min (only) before training for 7-wk, then discontinued during the final week to mitigate carryover effects. Physical function indices were: 6-min walk test (6MWT), estimated V̇O2peak, heart rate recovery (HRR), and maximal knee extensor power (Pmax). A treadmill task was used to measure V̇O2 on-kinetics wherein mean response time (MRT) coincided with the duration to reach 63% of steady-state V̇O2. Results showed greater changes (Δ) among BRJ+EX participants for 6MWT distance (40 ± 23 m vs. 8 ± 25 m; p = 0.003, d = 1.35), ΔV̇O2peak (1.5 ± 0.9 mLꞏkg-1ꞏmin-1 vs. 0.3 ± 1.0 mLꞏkg-1ꞏmin-1; p = 0.008, d = 1.20), and ΔHRR (-10 ± 6 bpm vs. -1 ± 9 bpm; p = 0.017, d = 1.05). Large and medium effect sizes favoring BRJ+EX were detected for ΔPmax (p = 0.07, d = 0.83) and ΔMRT (p = 0.257, d = 0.50), respectively. In postmenopausal women, BRJ+EX appears to magnify some adaptive benefits to physical function including aerobic capacity and recovery beyond that of training without BRJ. Investigation into contributing mechanisms is needed.

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OBJECTIVE: This article reports on UK sexual minority cisgender women's experiences of menopause health and healthcare, based on a data subset from a study exploring lesbian, gay, bisexual, and queer (LGBTQ+) menopause. METHODS: An online survey was conducted with UK LGBTQ + individuals who went through/are going through the menopause. Quantitative data were analysed using simple descriptive statistics. Qualitative data were analysed using thematic analysis. RESULTS: Cisgender respondents comprised 51 lesbian, gay, bisexual, pansexual, queer, and 'other' women, aged between 17 and 89 years. They reported similar types and levels of menopause symptoms as heterosexual cisgender women in other studies, apart from higher levels of anxiety and depression, especially bisexual women. Dissatisfaction regarding menopause healthcare services related to access, information, and heteronormative/heterosexist provision. CONCLUSIONS: Healthcare providers must ensure they provide inclusive menopause services to sexual minority cisgender women.

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OBJECTIVE: This study aimed to investigate the effects of red clover isoflavones on menopausal symptoms and the lipid profile in menopausal females. METHODS: This study included postmenopausal women with dyslipidemia. The red clover group (n = 39) received 40 mg isoflavone red clover capsule twice daily for 6 months, while placebo (n = 36) was 40 mg starch capsule twice daily. Data were collected at baseline, 3 months and 6 months. The Menopause Rating Scale (MRS) was applied to calculate subdimension and total scores. RESULTS: The two groups were similar in terms of age, MRS and lipid profile at baseline. In the red clover group, MRS scores decreased significantly at both 3 and 6 months. Similarly, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglyceride levels decreased at both 3 months and 6 months. High-density lipoprotein cholesterol increased significantly from baseline to 3 months and 6 months. Except for LDL-C and MRS urogenital score at 3 months, the improvements were significantly in favor of red clover isoflavone treatment. CONCLUSIONS: Red clover treatment for 3-6 months demonstrated significant improvements in lipid profiles and menopausal symptoms. While promising, further research is crucial to ascertain long-term safety and recommend the use of red clover isoflavones during menopause.

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OBJECTIVES: The use of digital healthcare technologies to enhance healthcare delivery has seen significant growth. However, a notable a notable research gap exists in the application of clinical scales for menopause management by general practitioners (GPs). This study aims to investigate willingness of GPs to use specific menopausal scale tools in the care of females for menopause management. METHOD: An anonymous online survey was developed, which received responses from 348 French GPs in 2023. Multiple backward logistic regression was performed to identify the factors influencing the willingness to use a practical menopause management scale. RESULTS: In total, 87.93% of GPs are not familiar with the Greene Climacteric Scale and 90.52% are not familiar with the Menopause Quick 6 scale. In contrast, 90.52% would be interested in having access to such scales. The willingness to use a menopause management scale is associated with caring for menopausal females (odds ratio [OR] = 6.13, 95% confidence interval [CI] [2.08-18.08], p = 0.001), less experience (OR = 7.10, 95% CI [2.05-25.22], p = 0.002), the importance of health prevention in daily practice (comparing 'very important' to 'not', OR = 12.98, 95% CI [1.68-97.60], p = 0.004) and the use of a digital scale in daily practice for menopausal management (OR = 2.13, 95% CI [1.04-5.83], p = 0.014). CONCLUSION: Future research is essential in representative population to confirm these findings in menopause management.

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OBJECTIVES: Sleep difficulties are common in the menopause transition and increase risk for a variety of physical and psychological problems. The current study investigated potential interactions between psychosocial variables and within-person changes in ovarian hormones in predicting perimenopausal sleep problems as well as the potential interactions between poor sleep and psychosocial factors in predicting worsened mood, affect, and attention. STUDY DESIGN: The sample included 101 perimenopausal individuals. Participants completed 12 weekly assessments of self-reported sleep outcomes, depressive mood and affect, and attention function, and of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) levels (urinary metabolites of estradiol and progesterone, respectively); they also had 24-h tracking of vasomotor symptoms. Other psychosocial variables such as trauma history and stressful life events were assessed at baseline. RESULTS: A history of depression, baseline depressive symptoms, trait anxiety, and more severe and bothersome vasomotor symptoms predicted worsened sleep outcomes. Recent stressful life events, trauma history, and person-centred E1G and PdG changes did not predict sleep outcomes. However, there was an interaction whereby person-centred E1G decreases predicted lower sleep efficiency in those with higher baseline depressive symptoms. Higher baseline depression and trauma history also amplified the effect of vasomotor symptoms on sleep outcomes. In evaluating the effect of poor sleep on psychological and cognitive outcomes, stressful life events emerged as a moderating factor. Finally, trauma history and poor sleep interacted to predict worsened attention function. CONCLUSIONS: The current study suggests that certain individuals may be at greater risk of perimenopausal sleep problems and the resulting negative effects on mood and cognition.

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DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: While the gold standard for vasomotor symptoms remains hormone therapy, prescription menopause therapies are significantly underutilized. Nonhormone therapies represent an alternative treatment modality that may improve access to care for patients who cannot or choose not to take hormones. This review aims to update pharmacists on the evidence behind new-to-market fezolinetant and all other nonhormone prescription treatment options for menopausal vasomotor symptoms. SUMMARY: Prescription nonhormone therapy options for vasomotor symptoms include selective serotonin reuptake inhibitors, including Food and Drug Administration-approved low-dose paroxetine, serotonin-norepinephrine reuptake inhibitors, gabapentin, pregabalin, oxybutynin, and fezolinetant. Evidence supporting the use of these options is summarized in this review. All have an important place in treatment for those unable to take the gold standard of hormone therapy; however, most offer only mild to moderate improvement in symptoms. Fezolinetant has been shown to result in a significant reduction in vasomotor symptom frequency when compared to other nonhormone therapies and was not different when compared to hormone therapies. However, additional studies and efforts to address the affordability of fezolinetant and head-to-head comparisons with other agents are needed. CONCLUSION: Vasomotor symptoms of menopause can severely impact the health and well-being of individuals. However, treatment of these symptoms is underutilized due to real and perceived drawbacks of therapy. Pharmacists are ideally suited to bridge this gap, but first it is important for pharmacists to be knowledgeable about and comfortable with the evidence supporting all treatment options.

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CONTEXT: SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia). OBJECTIVE: This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (PMO; NCT04664959). DESIGN: The study included 457 PMO patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at Month 0 and Month 6. At Month 12, patients were re-randomized to continue with the assigned treatment or switch from DEN to SB16 up to Month 18. This report includes results up to Month 12. METHODS: The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for Month 12), total hip and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen [CTX] and procollagen type I N-terminal propeptide [P1NP]), safety, and immunogenicity profiles were measured up to Month 12. RESULTS: The least-squares mean differences in percent change from baseline in lumbar spine BMD at Month 12 were 0.33% (90% confidence interval [CI]: -0.25, 0.91) in the full analysis set and 0.39% (95% CI: -0.36, 1.13) in the per-protocol set; both within the pre-defined equivalence margin. The secondary endpoints were comparable between the two treatment groups. CONCLUSION: The reported efficacy, PK, PD, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.

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Background: Hysteroscopy is known as the gold standard for endometrial polyps diagnosis and its findings on vascularity, size, and number of polyps can indicate malignancy, but it is a relatively expensive method with some complications. Ultrasound is a common part of the gynecological examination, and with technological advances, its ability to predict pathological outcomes has increased. This study aimed to determine the accuracy of ultrasound in diagnosing the characteristics of endometrial polyps. Materials and Methods: This diagnostic value study was performed on 300 premenopausal and postmenopausal women over 40 years of age with endometrial polyps referred to Alzahra and Beheshti hospitals in Isfahan. The characteristics of endometrial polyps were evaluated by transvaginal ultrasonography and hysteroscopy and biopsy specimens were sent for pathological evaluations. Results: In this study, 103 premenopausal women and 197 postmenopausal women were evaluated. Malignancy was confirmed by pathology in 4 premenopausal women (2%) and 2 postmenopausal women (2%). In both hysteroscopy and ultrasound methods, the frequency of vascularity was significantly different in postmenopausal and premenopausal women, but the other features of the polyp were not significantly different in them. Ultrasonic sensitivity in detecting the presence of vascularity, polyps larger than 1.5 mm, more than 1 polyp, and the presence of pedicle were 39.04, 57.38%, 91.93 and 94.95%, respectively, its specificity were 98.94, 36.47, 99.57 and 98.89% respectively. Conclusion: A comparison of the characteristics of polyps in both ultrasound and hysteroscopy methods shows that hysteroscopy has been more effective in diagnosing malignancy and ultrasound has not have acceptable sensitivity in diagnosing size and vascularity.

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The increase in the incidence of dementia over the last century correlates strongly with the increases in post-reproductive lifespan during this time. As post-reproductive lifespan continues to increase it is likely that the incidence of dementia will also increase unless therapies are developed to prevent, slow or cure dementia. A growing body of evidence implicates age-related endocrine dyscrasia and the length of time that the brain is subjected to this endocrine dyscrasia, as a key causal event leading to the cognitive decline associated with aging and Alzheimer's disease (AD), the major form of dementia in our society. In particular, the elevations in circulating gonadotropins, resulting from the loss of gonadal sex hormone production with menopause and andropause, appear central to the development of AD neuropathology and cognitive decline. This is supported by numerous cell biology, preclinical animal, and epidemiological studies, as well as human clinical studies where suppression of circulating luteinizing hormone and/or follicle-stimulating hormone with either gonadotropin-releasing hormone analogues, or via physiological hormone replacement therapy, has been demonstrated to halt or significantly slow cognitive decline in those with AD. This review provides an overview of past and present studies demonstrating the importance of hypothalamic-pituitary-gonadal hormone balance for normal cognitive functioning, and how targeting age-related endocrine dyscrasia with hormone rebalancing strategies provides an alternative treatment route for those with AD.

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BACKGROUND: Women may be vulnerable to elevated depressive symptoms during the menopause transition (MT). Studies generally have not considered premenopausal depressive symptom history or examined symptoms in relation to the final menstrual period (FMP). OBJECTIVE: To identify specific time points in relation to the FMP when depressive symptoms increase or decrease. METHODS: Participants were 1582 multiracial/ethnic women from the longitudinal Study of Women's Health Across the Nation (SWAN). Biological, psychosocial, and depressive symptom data were collected approximately annually. Depressive symptoms were measured by the Center for Epidemiological Studies-Depression (CESD) scale. RESULTS: Women with high baseline depressive symptoms (CES-D ≥ 16) declined in symptoms (M = -1.04/yr., 95 % CI = -1.58, -0.50) until 4 years before the FMP, followed by a smaller decrease (M = -0.50/yr., 95 % CI = -0.72, -0.28) until 18 months after the FMP. Depressive symptoms increased (M = 0.21/yr., 95 % CI = 0.11, 0.30) in those with low baseline symptoms until 1 year before the FMP, and decreased (M = -0.06/yr., 95 % CI = -0.11, -0.008) going forward. Greater social support, higher levels of follicle stimulating hormone and estradiol, and less sleep disturbance contributed to greater decline in depressive symptoms among those with high baseline depressive symptoms. Anxiety, experiencing stressful life events, lower body mass index, and poor role-physical function contributed to an increase in depressive symptoms among those with low baseline symptoms. LIMITATIONS: Excluded women had higher baseline CES-D scores. Lacked pre-MT depression for pre/early perimenopausal women at baseline. CONCLUSION: Accounting for baseline depressive symptom level and focusing on the FMP more precisely characterize depressive symptom change over the MT.

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Sirtuins 1 (SIRT1) and Forkhead box protein O1 (FOXO1) expression have been associated with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Exercise and/or docosahexaenoic acid (DHA) supplementation have shown beneficial effects on MASLD. The current study aims to assess the relationships between Sirt1, Foxo1 mRNA levels and several MASLD biomarkers, as well as the effects of DHA-rich n-3 PUFA supplementation and/or exercise in the steatotic liver of aged obese female mice, and in peripheral blood mononuclear cells (PBMCs) of postmenopausal women with overweight/obesity. In the liver of 18-month-old mice, Sirt1 levels positively correlated with the expression of genes related to fatty acid oxidation, and negatively correlated with lipogenic and proinflammatory genes. Exercise (long-term treadmill training), especially when combined with DHA, upregulated hepatic Sirt1 mRNA levels. Liver Foxo1 mRNA levels positively associated with hepatic triglycerides (TG) content and the expression of lipogenic and pro-inflammatory genes, while negatively correlated with the lipolytic gene Hsl. In PBMCs of postmenopausal women with overweight/obesity, FOXO1 mRNA expression negatively correlated with the hepatic steatosis index (HSI) and the Zhejiang University index (ZJU). After 16-weeks of DHA-rich PUFA supplementation and/or progressive resistance training (RT), most groups exhibited reduced MASLD biomarkers and risk indexes accompanying with body fat mass reduction, but no significant changes were found between the intervention groups. However, in PBMCs n-3 supplementation upregulated FOXO1 expression, and the RT groups exhibited higher SIRT1 expression. In summary, SIRT1 and FOXO1 could be involved in the beneficial mechanisms of exercise and n-3 PUFA supplementation related to MASLD manifestation.

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BACKGROUND: The onset of menopause leads to diminished estrogen exposure, resulting in a high morbidity burden related to menopausal symptoms. Menopausal hormonal therapy is an effective therapy that offers more advantages than disadvantages for women aged less than 60 years or who have had menopause for less than 10 years. OBJECTIVE: This study aimed to assess the prevalence of menopausal symptoms, identify factors associated with menopausal symptoms, and assess the use of menopausal hormone therapy among women aged 40-60 who visited the gynecological clinics of three hospitals in Addis Ababa, Ethiopia. METHODS: A facility-based cross-sectional study was conducted from January 2022 to June 2022 at Gandhi Memorial Hospital, Tikur Anbessa Hospital, and Zewditu Memorial Hospital on 296 middle-aged women. Data were collected using an interviewer-administered structured questionnaire and analyzed for sociodemographic factors, utilization of menopausal hormone therapy, and prevalence of menopausal symptoms using the menopause rating scale. Data were analyzed using SPSS version 25. Bivariate and multivariate logistic regression analyses were performed to identify independent predictors of each subscale of menopausal symptoms. The strength of the association was measured using odds ratios with 95% confidence intervals, and statistical significance was set at a value of P < 0.05. RESULT: The prevalence of menopausal symptoms was 89.9%. According to the menopausal rating scale, the frequency of reported symptoms was hot flushes (54.7%), muscle and joint pain (32.1%) on the somatic subscale; physical and mental exhaustion (55.1%), irritability (48.6%) on psychological subscale; and sexual problems (41.3%), bladder problems (39.2%) on urogenital subscale. This study also showed that the age of women [aOR: 0.317, 95%CI (0.102, 0.990)], and monthly family income [aOR = 0.182, 95% CI (0.041, 0.912)] were significantly associated with somatic menopausal symptoms. There was no utilization of menopausal hormonal therapy to treat menopausal symptoms and to prevent complications. CONCLUSION: The prevalence of menopausal symptoms is high; however, the utilization of individualized administration of menopausal hormone therapy according to symptoms is negligible. It appears essential for these institutions to work on service availability and delivery of menopausal hormone therapy for those in need of wider benefits for their clients.

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BACKGROUND: Most women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown. We aimed to investigate whether there were intervention-dependent effects two years after a 15-week RTI on MS-VMS frequency, HRQoL, and cardiovascular risk markers in postmenopausal women. METHODS: This observational prospective cohort study is a follow-up to a randomized controlled trial (RCT) on a 15-week RTI in postmenopausal women (n = 57). The control group had unchanged low physical activity during these first 15 weeks. At the follow-up contact two years post-intervention, 35 women agreed to participate in an additional physical visit at the clinic with clinical testing, blood sampling, and magnetic resonance imaging, identical to the protocol at the baseline visit at the start of the RCT. RESULTS: Although all women showed reduced MS-VMS and increased moderate-to-vigorous physical activity (MVPA) over the 2-year follow-up compared to baseline, the groups from the original RCT (intervention group; IG, control group; CG) changed differently over time (p < 0.001 and p = 0.006, respectively) regarding MS-VMS. The IG maintained a significantly lower MS-VMS frequency than the CG at the 6-month follow-up. At the 2-year follow-up, there was no significant difference between the original RCT groups. No significant changes over time or differences between groups were found in HRQoL or cardiovascular risk markers. However, significant interactions between original RCT groups and time were found for visceral adipose tissue (p = 0.041), ferritin (p = 0.045), and testosterone (p = 0.010). CONCLUSIONS: A 15-week resistance training intervention reduced MS-VMS frequency up to six months post-intervention compared to a CG, but the effect was not maintained after two years. The RTI did neither contribute to preserved improvements of cardiovascular risk markers nor improved HRQoL after two years compared to a CG. TRIAL REGISTRATION: Clinical trials.gov registered ID: NCT01987778, trial registration date 2013-11-19.

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Telomere length (TL) is an important cellular marker of biological aging impacting the brain and heart. However, how it is related to the brain (e.g., cognitive function and neuroanatomic architecture), and how these relationships may vary by sex and reproductive status, is not well established. Here we assessed the association between leukocyte TL and memory circuitry regional brain volumes and memory performance in early midlife, in relation to sex and reproductive status. Participants (N = 198; 95 females, 103 males; ages 45-55) underwent structural MRI and neuropsychological assessments of verbal, associative, and working memory. Overall, shorter TL was associated with smaller white matter volume in the parahippocampal gyrus and dorsolateral prefrontal cortex. In males, shorter TL was associated with worse working memory performance and corresponding smaller white matter volumes in the parahippocampal gyrus, anterior cingulate cortex, and dorsolateral prefrontal cortex. In females, the impact of cellular aging was revealed over the menopausal transition. In postmenopausal females, shorter TL was associated with poor associative memory performance and smaller grey matter volume in the right hippocampus. In contrast, TL was not related to memory performance or grey and white matter volumes in any memory circuitry region in pre/perimenopausal females. Results demonstrated that shorter TL is associated with worse memory function and smaller volume in memory circuitry regions in early midlife, an association that differs by sex and reproductive status. Taken together, TL may serve as an early indicator of sex-dependent brain abnormalities in early midlife.

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OBJECTIVES: Menopausal symptoms severely impact women's quality of life (QoL). Digital health interventions provide an accessible, personalized alternative for managing menopausal symptoms. In this study, we validated the Menopause Assistant Manager (MAMA®; Hudit, Seoul, S. Korea) app developed to provide personalized information, exercise coaching, and management of appointments and medications to menopausal women, and evaluated its efficacy on their QoL. STUDY DESIGN: This nonrandomized interventional trial enrolled 48 peri- and postmenopausal women into experimental (MAMA) and control (Waitlist) groups (n = 24 each). Participants in the MAMA group used the app for 8 weeks, whereas the Waitlist group received no intervention. Both groups continued their usual treatments. MAIN OUTCOME MEASURES: Clinical assessments at baseline and study completion included the World Health Organization Quality of Life Brief Version (WHOQOL-BREF), Menopause Rating Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-15 (PHQ-15), Menopause Emotional Symptom Questionnaire, and Subjective Memory Complaints Questionnaire. RESULTS: Compared with the Waitlist group, the MAMA group showed postintervention improvements in WHOQOL-BREF physical health (F = 4.84, P = .03) and environmental (F = 5.01, P = .03) domains and GAD-7 (F = 5.53, P = .02) and PHQ-15 (F = 4.14, P = .048) scores. Changes in WHOQOL-BREF physical health scores negatively correlated with PHQ-15 scores (ρ = -0.53, P = .004). CONCLUSION: By increasing treatment accessibility, the app improved physical and environmental QoL and reduced anxiety and somatic symptoms. App-based exercise coaching alleviated somatic symptoms, and the in-app psychological content reduced anxiety by normalizing menopausal symptoms, providing accurate information, decreasing uncertainty, and improving symptom perception. TRIAL REGISTRATION: Clinical Research Information Service KCT 0008603; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=25078&status=5&seq_group=25078&search_page=M.

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PROBLEM: Little is known about the impact of menopausal symptoms on healthcare students' ability to study at higher education level. BACKGROUND: Attention on menopause is rapidly increasing in both the literature and media and is gaining political attention with particular focus on supporting those experiencing menopausal symptoms in the workplace. Policies are being developed to support individuals to remain in work for longer, reducing the number of people leaving the workplace due to challenging menopausal symptoms. However there is no evidence to suggest that support for higher education students experiencing menopausal symptoms is widespread. Whilst some higher education institutions and organisations are developing policies to support staff and, sometimes students, current literature does not reflect how students and their studies may be affected by menopausal symptoms. This is relevant to institutions where healthcare professions courses are delivered as this is thought to have contributed to the overall increase in the number of female students attending universities both in the UK and globally. A continued lack of understanding of menopausal symptoms' impact on students could not only be detrimental to the student experience, but it could also affect institutional reputations for being good places to study, resulting in increased attrition rates due to students withdrawing from courses because of the impact their symptoms have on their ability to continue studying. AIM: In this Contemporary Issues article our aim is to raise awareness of how menopausal symptoms may affect a student's ability to study, and to reinforce the need for university policy makers and educators to recognise and support women at this turbulent time of their lives to continue to study.