Association between type of menopause and mild cognitive impairment: The REDLINC XII study.

OBJECTIVE: To evaluate the association between type of menopause (spontaneous or surgical) and mild cognitive impairment (MCI). STUDY DESIGN: This study was a cross-sectional, observational, and sub-analytical investigation conducted within gynecological consultations across nine Latin American countries. METHOD: We assessed sociodemographic, clinical, and anthropometric data, family history of dementia, and the presence of MCI using the Montreal Cognitive Assessment (MoCA) tool. RESULTS: The study involved 1185 postmenopausal women with a mean age of 55.3 years and a body mass index of 26.4 kg/m2. They had an average of 13.3 years of education, and 37 % were homemakers. Three hundred ninety-nine experienced menopause before 40, including 136 with surgical menopause (bilateral oophorectomy). Out of the 786 women who experienced menopause at 40 or more years, 110 did so due to bilateral oophorectomy. There were no differences in MoCA scores among women who experienced menopause before or after the age of 40. However, lower MoCA scores were observed in women with surgical menopause than in those with spontaneous menopause (23.8 ± 4.9 vs. 25.0 ± 4.3 points, respectively, p < 0.001). Our logistic regression model with clustering of patients within countries found a significant association between MCI and surgical menopause (OR 1.47, 95 % CI: 1.01-2.16), use (ever) of menopausal hormone therapy (OR 0.33, 95 % CI: 0.21-0.50), and having >12 years of education (OR 0.21, 95 % CI: 0.14-0.30). CONCLUSION: When comparing women who experience spontaneous menopause over the age of 40 with those who undergo it before this age, there was no observed increased risk of developing MCI, while those with surgical menopause, independent of age, are more prone to cognitive decline. Women who have ever used menopausal hormone therapy have a lower MCI risk. Further research is warranted to delve deeper into this topic.

Systematic review and meta-analysis of the effects of progestins on depression in post-menopausal women: An evaluation of randomized clinical studies that used validated questionnaires.

OBJECTIVE: Hormone therapy (HT) can relieve symptoms of menopause and treat chronic diseases. Its effectiveness in treating psychological symptoms is still debated. Several progestins can be used in HT, but their effects on mood, in particular depressive symptoms, is still unclear. This systematic review evaluates the evidence from randomized clinical trials with postmenopausal women on the effect of adjunctive progestins on symptoms of depression assessed by validated questionnaires. The primary aim was to evaluate scores on the Center for Epidemiologic Studies Depression Scale (CESD). The secondary aim was to assess scores on the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAMD), and the Zung Self-Rating Depression Scale (SDS). METHODS: A systematic review and meta-analysis were conducted to identify the most reliable evidence of the effects of progestin on depression to inform decision-making. A PICO- and PRISMA-based framework was established to formulate explicit and reasoned recommendations. The pre-/post-treatment effect was evaluated using standardized mean change (SMC). RESULTS: We selected and analyzed 16 randomized clinical trials qualitatively and 12 studies quantitatively out of 9320 items identified. Most of the studies used medroxyprogesterone acetate as progestin. The results indicate that depressive symptoms do not increase with the addition of a progestin to estrogen HT. Depressive symptoms improved over time in the progestins-estrogen HT group, independent of progestin type (SMC CES-D -0.08 CI.95-0.10/-0.06, BDI -0.19 CI.95-0.32/-0.06, HAM-D -1.13 CI.95-1.47/-0.78, and SDS -0.11 CI.95-0.82/0.60). Yet similar effects were observed with estrogens alone and did not significantly differ from control groups on placebo. In one study, the addition of fluoxetine greatly increased the reduction of depressive symptoms observed with estrogen-progestin HT. CONCLUSIONS: In summary, in randomized clinical trials using validated questionnaires adjunctive progestin with estrogens did not increase depressive symptoms of postmenopausal women. Overall, depressive symptoms decreased with estrogen-progestin HT but also with estrogen alone. The decrease was not so pronounced to differ from controls on placebo. HT does not hamper the clinical efficacy of fluoxetine. The scarcity of randomized studies makes it difficult to determine the exact effect on depressive symptoms of different types of progestins. Project protocol registered in PROSPERO, registration number CRD42023454099.

Sexual health and wellbeing and the menopause: An EMAS clinical guide.

INTRODUCTION: Sexual health and wellbeing are significant aspects of quality of life. However, taking a sexual history is often avoided in medical practice, leaving a void in management and awareness. As the menopause can have a major impact on sexual health, it is imperative that healthcare providers are appropriately trained in sexual health and wellbeing and the aligned disciplines in order to achieve optimal care. AIM: To provide an evidence-based clinical guide for the assessment and management of sexual problems at the menopause and beyond. MATERIALS AND METHODS: Review of the literature and consensus of expert opinion. RESULTS AND CONCLUSION: The assessment of sexual problems includes history taking, examination and laboratory investigation (if indicated), and occasionally the use of specific validated questionnaires. Management of sexual problems requires a multidimensional approach using biopsychosocial measures. Medical management and psychosexual counselling include pharmacological and non-pharmacological interventions, and sex therapy and psychoeducation. Furthermore, perimenopausal women should be advised about the need for contraception if they wish to avoid pregnancy. Also, sexually transmitted diseases can be acquired at any age. To conclude, taking a sexual history should be incorporated into medical practice and healthcare providers should be appropriately trained to assess and manage sexual problems at the menopause and beyond.

Disordered eating behaviours during the menopausal transition: a systematic review.

Disordered eating refers to a range of eating behaviours and attitudes towards weight and food that can negatively influence physical and psychosocial well-being. The menopausal transition could be a vulnerable period for disordered eating due to major hormonal fluctuations, menopausal symptoms, common body composition shifts, and an increased risk of psychological challenges. This systematic review aimed to summarize evidence on the associations between the menopausal transition and disordered eating. Records published before October 2023 were identified through MEDLINE, PsycINFO, Scopus, Embase, and CINAHL. Studies investigating associations between menopausal status, menopausal symptoms, or reproductive hormone levels, and disordered eating during the menopausal transition were sought. A total of 1301 non-duplicate records were screened, with 10 studies deemed eligible for inclusion. Most included studies used a cross-sectional design (n = 9). Findings include potentially higher levels of binge eating during the perimenopausal stage, whereas restrictive eating behaviours appeared more common during postmenopause compared to premenopause. Both studies investigating menopausal symptoms found strong positive associations with disordered eating. Nonetheless, findings are equivocal with contrasting results and limited methodological quality across studies. Further research is needed to verify these findings and better assist health professionals in supporting healthy eating behaviours in menopausal women during this complex transition. (PROSPERO ID: CRD42021290736).

Brown Adipose Tissue Activity and Childhood Exposure to Cold Are Associated With Hot Flashes at Menopause.

OBJECTIVE: Hot flashes (HFs) are experienced as sudden sensations of heat. We hypothesized that brown adipose tissue (BAT) activation could increase the likelihood of HFs in winter. The aim of this study was to test whether women with more BAT activity were more likely to experience self-reported or biometrically measured HFs. METHODS: Women aged 45-55 years (n = 270) participated in face-to-face interviews and anthropometric and ambulatory measures. Level of BAT activity was estimated from the difference in supraclavicular skin temperature measured by infrared thermography before and after cooling. Logistic regressions were applied to examine whether bothersome HFs (yes/no) during the past 2 weeks were associated with BAT activity, adjusting for menopausal status, childhood exposure to cold, waist/hip ratio, and self-reported health. Linear regressions were used to examine the frequency of self-reported and biometrically measured HFs during the study period and BAT activity, adjusting for potential confounders. RESULTS: Menopausal status, childhood exposure to cold, waist-to-hip ratio (WHR), and self-reported health were associated with both BAT activity and HFs. After adjusting for potential confounders, an increase in BAT activity almost tripled the likelihood of bothersome HFs (OR 2.84, 95% CI 1.26-6.43). In linear regressions, BAT activity was not associated with frequency of subjective or objective HFs during the study period, but childhood exposure to cold was associated with subjective HF report (ß = 0.163, p = 0.010). CONCLUSION: To our knowledge, this is the first study of BAT activation and HFs. Our results support a role for BAT activity in HF experience. Therefore, we encourage further examination of the role of BAT, as well as childhood exposure to cold, in HFs.

Impact of adiposity indices changes across the lifespan on risk of diabetes in women: trajectory modeling approach.

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.

Prior pre-eclampsia does not diminish the vascular protective effect of menopausal hormone therapy.

OBJECTIVE: Women with prior pre-eclampsia are at increased risk of cardiovascular disease (CVD). Menopausal hormone therapy (MHT) may affect this risk. We evaluated the impact of MHT use on cardiovascular risk between women with and without prior pre-eclampsia. STUDY DESIGN AND MAIN OUTCOME MEASURES: We assessed the occurrence of any CVD, myocardial infarction (MI) and stroke in MHT users (n = 9700) and non-users (n = 19,914) with prior pre-eclampsia, and likewise in MHT users (n = 27,764) and non-users (n = 58,248) without prior pre-eclampsia over the period 1994-2019. Follow-up started at MHT initiation (mean age 50.4 in pre-eclamptic women and 50.3 in non-pre-eclamptic women) and lasted for a mean of 13.3 years. RESULTS: The use of MHT in prior pre-eclamptic women was associated with significant risk reductions for any CVD (HR 0.85, 95 % CI 0.78-0.91), MI (HR 0.66, 95 % CI 0.55-0.78) and stroke events (HR 0.71, 95 % CI 0.63-0.81) in comparison with non-users with prior pre-eclampsia. The risk reductions for cardiovascular deaths were even more pronounced (HR 0.43, 95 % CI 0.31-0.59 for any CVD death; HR 0.49, 95 % CI 0.30-0.80 for MI death; HR 0.25, 95 % CI 0.10-0.64 for stroke death). However, none of these risk reductions differed from those seen in MHT users without prior pre-eclampsia. The risk of any CVD decreased already within five years of MHT use in women with prior pre-eclampsia but not in those without prior pre-eclampsia. CONCLUSIONS: The use of MHT is associated with reduced CVD risk in women with prior pre-eclampsia. This is important to clinicians considering the initiation of MHT for recently menopausal women with prior pre-eclampsia.

Presbyopia, Dry Eye, and Retinal Thickness in the Middle-Aged Population: Focusing on Sex Differences.

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.

Depressive symptoms over the final menstrual period: Study of Women's Health Across the Nation (SWAN).

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.

Exploring the causal association between epigenetic clocks and menopause age: insights from a bidirectional Mendelian randomization study.

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.

Endocrine Dyscrasia in the Etiology and Therapy of Alzheimer's Disease.

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.

Postmenopausal status increases the risk of uric acid stones.

OBJECTIVE: This study investigated the impact of menopause on stone composition in women with urolithiasis. STUDY DESIGN: A cross-sectional study was conducted from March 2013 to March 2018. Women with urolithiasis patients were divided into two groups according to their menopause status. MAIN OUTCOME MEASURES: The clinical demographic characteristics, stone removal, stone composition, and urine chemistry were investigated. Univariate and multivariate survival analyses were performed to identify risk factors for the risk of uric acid stones. RESULTS: Our study enrolled 1221 female patients with stone diseases, 783 (64.1 %) of whom were postmenopausal (66 patients surgically menopause and 717 patients naturally menopause). Postmenopausal women had higher rates of diabetes and hyperuricemia, a higher serum uric acid level, a higher urinary specific gravity, and a lower estimated glomerular filtration rate. Stone analysis revealed calcium oxalate stones in 66.2 % of the patients, apatite stones in 19.4 %, calcium oxalate and calcium phosphate stones in 7.7 %, uric acid stones in 4.4 %, struvite stones in 2.0 %, and brushite stones in 0.2 %. Postmenopausal women had a higher rate of uric acid stones. Multivariate analysis confirmed that postmenopausal status and hyperuricemia were independent risk factors of uric acid stones. Postmenopausal women required more invasive procedures to remove the stones, and they had lower self-voiding rates. CONCLUSIONS: Postmenopausal women had higher rates of stone episodes, specifically related to uric acid stones. Given the prevalence and impact of chronic kidney diseases, factors that impede optimal renal function management in women must be identified to provide tailored treatment recommendations.

Cognitive Training During Midlife: A Systematic Review and Meta-Analysis.

Midlife has been suggested to be a crucial time to introduce interventions for improving cognitive functions. The effects of cognitive training (CT) in healthy middle-aged populations and more specifically during the menopausal transition have not been systematically investigated. To investigate the effects of CT on cognition in healthy middle-aged adults and specifically in females during the menopause transition, literature was searched inception to July 2023 and studies were included that examined the effects of CT on a defined cognitive outcome. The improvement on cognitive performance following CT was the main outcome measured as mean difference (from baseline to immediate post) estimates with corresponding 95% confidence intervals (CI) in meta-analysis and was discussed with the support of subgroup analysis based on outcome type (i.e., far or near-transfer) and cluster tabulations. Nineteen articles were included in the qualitative synthesis with a total of 7765 individuals, and eight articles were included in the meta-analyses. CT was categorized into six type clusters: Game-based CT, General CT, Speed of Processing Training, Working Memory Training, Strategy-based CT, and Cognitive Remediation. Cognitive outcome was divided into six clusters: working memory, verbal memory, language, executive function, attention/processing speed, and visual memory. Meta-analysis reported significant improvement in the domain of executive function (0.48, 95% CI 0.08-0.87), verbal memory (0.22, 95% CI 0.11-0.33), and working memory (0.16, 95% CI 0.05-0.26). CT confers benefits on various cognitive domains, suggesting a potential role of CT to promote optimal cognitive functioning in the midlife and specifically in women during the menopause transition.

Biopsychosocial factors intersecting with weekly sleep difficulties in the menopause transition.

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.

Gap in Sexual Dysfunction Management Between Male and Female Patients Seen in Primary Care: An Observational Study.

BACKGROUND: Female sexual dysfunction (FSD), defined as clinically distressing problems with desire, arousal, orgasm, or pain, affects 12% of US women. Despite availability of medications for FSD, primary care physicians (PCPs) report feeling underprepared to manage it. In contrast, erectile dysfunction (ED) is frequently treated in primary care. OBJECTIVE: To describe differences in patterns of FSD and ED diagnosis and management in primary care patients. DESIGN: Retrospective observational study. SUBJECTS: Primary care patients with an incident diagnosis of FSD or ED seen at a large, integrated health system between 2016 and 2022. MAIN MEASURES: Sexual dysfunction management (referral or prescription of a guideline-concordant medication within 3 days of diagnosis), patient characteristics (age, race, insurance type, marital status), and specialty of physician who diagnosed sexual dysfunction. We estimated the odds of FSD and ED management using mixed effects logistic regression in separate models. KEY RESULTS: The sample included 6540 female patients newly diagnosed with FSD and 16,591 male patients newly diagnosed with ED. Twenty-two percent of FSD diagnoses were made by PCPs, and 38% by OB/GYNs. Forty percent of ED diagnoses were made by PCPs and 20% by urologists. Patients with FSD were managed less frequently (33%) than ED patients (41%). The majority of FSD and ED patients who were managed received a medication (96% and 97%, respectively). In the multivariable models, compared to diagnosis by a specialist, diagnosis by a PCP was associated with lower odds of management for FSD patients (aOR, 0.59; 95% CI, 0.51-0.69) and higher odds of management (aOR, 1.52; 95% CI, 1.36-1.64) for ED patients. CONCLUSIONS: Primary care patients with FSD are less likely to receive management if they are diagnosed by a PCP than by an OB/GYN. The opposite was true of ED patients, exposing a gap in the quality of care female patients receive.

Leukocyte telomere length and memory circuitry and cognition in early aging: Impact of sex and menopausal status.

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.

Analysis of combinatory effects of free weight resistance training and a high-protein diet on body composition and strength capacity in postmenopausal women - A 12-week randomized controlled trial.

BACKGROUND: Menopause has a significant impact on the endocrine system of middle-aged women, resulting in a loss of skeletal muscle mass (SMM), changes in fat mass (FM) and a reduction in strength capacity. Resistance training (RT) and a high-protein diet (HPD) are effective methods for maintaining or increasing SMM. This study aims to determine the effects of HPD and RT on body composition, muscle thickness and strength capacity in postmenopausal women. METHODS: In total 55 healthy postmenopausal women (age: 58.2 ± 5.6 years, weight 69.1 ± 9.6 kg, height 166.5 ± 6.5 cm) successfully participated in the study. The women were randomly assigned to either group: training + protein (2.5 g/kg fat-free mass (FFM)) (n = 15; TP); only training (n = 12; T); only protein (2.5 g/kg FFM) (n = 14; CP) or control (n = 14; C). TP and T performed RT for 12 weeks with three training sessions and five exercises each. CP and C were prohibited from training during the period. The main parameters analysed for body composition were FFM, SMM, FM, muscle thickness of the M. rectus femoris, M. biceps femoris, M. triceps brachii and M. biceps brachii muscles. Strength was tested using a dynamometer for grip strength and 1-RM in the squat (BBS) and deadlift (DL). RESULTS: The SMM significantly increased by RT (TP: (Δ+1.4 ± 0.9 kg; p < 0.05; d = 0.4; T: Δ+1.2 ± 1.3kg; p < 0.05; d = 0.3) and FM could be reduced only in T: (Δ-2.4 ± 2.9 kg; p < 0.05; d = 0.3). In muscle thickness a significant increase in the M. biceps brachii in both training groups (TP: (Δ+0.4 ± 0.3 cm; p < 0.05; d = 1.6; T: (Δ+0.3 ± 0.3 cm; p < 0.05; d = 0.9) and in M. biceps femoris only in TP (Δ+0.3 ± 0.4 cm; p < 0.05; d = 0.9) were observed. HPD without training does not affect body composition, A significant increase in grip strength (TP: Δ+4.7 ± 2.4 kg; (p < 0.05; d = 1.5; T: (Δ+3.6 ± 3.0 kg; p < 0.05; d = 0.8), in BBS (TP: (Δ+30.0 ± 14.2 kg; p < 0.05; d = 1.5; T: (Δ+34.0 ± 12.0 kg; p < 0.05; d = 2.4) and in DL (TP: (Δ+20.8 ± 10.3 kg; p < 0.05; d = 1.6; T: (Δ+22.1 ± 7.6 kg; p < 0.05; d = 2.0) was observed in both training groups. The CP also recorded a significant increase in the BBS (Δ+7.5 ± 5.4 kg; p < 0.05; d = 0.4) and in DL (Δ+5.5 ± 7.7 kg; p < 0.05; d = 0.5). No significant differences were detected for TP and T for any of the parameters. CONCLUSION: The results indicate that RT enhances body composition and strength capacity in postmenopausal women and is a preventive strategy against muscle atrophy. Besides HPD without training has a trivial significant effect on BBS and DL. HPD with RT has no clear additive effect on body composition and strength capacity. Further studies are needed to confirm these observations.

Cooling the flames: Navigating menopausal vasomotor symptoms with nonhormone medications.

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.

Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in Postmenopausal Osteoporosis: Phase 3 Results Up to Month 12.

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.

Comparison of Endometrial Polyp Characteristics in Transvaginal Sonography and Hysteroscopy in Predicting Endometrial Malignancies in Premenopausal and Postmenopausal Women.

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.