Menopause: The Journal of The North American Menopause Society最新文献

Objective: To analyze the association between decreased bone mineral density (BMD) and dynapenia in postmenopausal women.

Methods: An age-matched case-control study was conducted in postmenopausal women with and without dynapenia. Assessments were carried out by measuring dominant handgrip strength with a Jamar dynamometer; BMI-adjusted cut-off points were applied. BMD was evaluated according to the World Health Organization criteria (T-score ≤-1 SD), using dual-energy x-ray absorptiometry (Hologic Horizon). The study included sociodemographic, anthropometric, body composition, biochemical, and lifestyle variables. Descriptive and inferential statistical analyses were performed, and unconditional logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CIs); statistical significance was set at P≤0.05. The study adhered to national and international ethical standards.

Results: A total of 201 women were included in the study: 67 with dynapenia (cases) and 134 without (controls). Median ages were 68 years for cases and 66 years for controls. Dynapenia was significantly associated with decreased BMD (OR=3.89, 95% CI=1.31-11.56), high-very high visceral fat levels (OR=3.12, 95% CI=1.26-7.72), and polypharmacy (OR=2.16, 95% CI=1.05-4.63).

Conclusions: Decreased BMD is associated with dynapenia in postmenopausal women, as well as with high-very high visceral fat levels and polypharmacy. These findings highlight the importance of a comprehensive assessment of musculoskeletal and metabolic risk factors in this population.

Transdermal estradiol is licensed to treat estradiol deficiency symptoms and prevent osteoporosis in postmenopausal women. There is no one-size-fits-all estradiol dose or serum concentration that will achieve symptom relief and bone protection in all women. Dose is usually titrated to symptom response, but measurement of serum estradiol concentration can be used to support or inform dose decisions in certain clinical scenarios. The optimal level for an individual varies according to tissue sensitivity (pharmacodynamic effects), the method used for estradiol quantitation (immunoassay vs. mass spectrometry), the clinical endpoint (symptoms vs. bone protection), and treatment goals, including patient preferences. An understanding of transdermal estradiol pharmacokinetics and pharmacodynamics, and the limitations of the methods used to measure serum estradiol, is essential to ensure that all women who choose to use menopausal hormone therapy (MHT) can reap the benefits and avoid the harms of over-treatment and under-treatment. Achieving and maintaining optimal estradiol levels for all MHT users is consistent with menopause guidelines that promote high-quality, patient-centred, personalized menopause care.

Objective: To explore associations between vasomotor symptoms (VMS), sleep disturbances, and frequent mood changes, and predictors of each, in women transitioning menopause.

Methods: Data were analyzed from the baseline and first 10 annual follow-up visits (1996-2008) from 2,066 participants in the Study of Women's Health Across the Nation who had reached natural menopause. The visit closest to the final menstrual period (FMP) was considered as FMP 0; visits 5 years before/after were relabeled accordingly. Associations between symptoms over time were determined using generalized additive mixed models (GAMMS, for individual symptoms). Predictors of symptom groups were determined using Bayesian multinomial regression.

Results: Prevalence of VMS and sleep disturbances increased up to FMP+1, remaining >50% thereafter; frequent mood changes gradually decreased (47%-33%). In the GAMMs, VMS and sleep disturbances were each associated with double the odds of the other, and VMS and frequent mood changes were associated with ~50%-60% increased odds of the other. In the Bayesian models, the probability of experiencing VMS and sleep disturbances together increased with increasing age at FMP (~1.3 percentage points/year); the strongest predictors of experiencing all symptoms concurrently were high level of depression (an increase of 10 percentage points per 10-point increase in depression score) and high anxiety (46% vs. 15% probability for low anxiety).

Conclusions: Our findings underscore the importance of identifying, monitoring and addressing VMS, sleep disturbances, and frequent mood changes specifically and collectively, and support a personalized approach to menopausal symptom management, with anxiety and depression being important considerations.

Objectives: A urethral caruncle is a common benign vulvar lesion in postmenopausal women. We describe a case of malignant melanoma that originally presented as a caruncle.

Methods: A 73-year-old female presented to the urogynecology office for prolapse. Initially, she was diagnosed with a urethral caruncle that was noted to be enlarging on a subsequent exam. A biopsy was taken, which returned with poorly differentiated malignant melanoma.

Results: The patient was referred to gynecologic oncology and underwent wide local excision of the urethral mass and urethral reconstruction with bilateral sentinel inguinal lymph node biopsy and mapping. The final pathology was consistent with stage pT4b N0 (sn) pMx malignant melanoma. She is currently undergoing adjuvant immunotherapy.

Conclusions: Malignant melanoma of the urogenital tract is more common in postmenopausal women and can present as a urethral caruncle. When urethral caruncles are not responsive to initial medical therapy, providers should maintain a broad differential, including vulvar malignancies and biopsy when indicated.

Objective: Fezolinetant (Veozah) was approved as a nonhormone treatment for moderate-to-severe vasomotor symptoms of menopause in May 2023, providing a novel treatment option for women with contraindications to menopausal hormone therapy. The objective of the study was to characterize the uptake and utilization of fezolinetant in a real-world setting.

Methods: We conducted a retrospective cohort study using TriNetX data, which includes 108 health care organizations and over 156 million patients. Females with an initial prescription for fezolinetant between May 1, 2023, and December 31, 2024, were included. We described baseline clinical and demographic characteristics and assessed the uptake of fezolinetant over time.

Results: Our cohort included 9,853 women, including 1,315 (13.3%) who were over the age of 65 and 2,022 (20.5%) with a breast cancer diagnosis. Among the 7,222 individuals with at least 3 months of continuous enrollment, 1,477 (20.5%) had persistent use, defined as having a second fezolinetant prescription between 28 and 90 days of the initial fezolinetant prescription. Among persistent users, 42% received liver function testing in the 3 months after initiating fezolinetant, though regular monitoring is required after starting treatment. The total number of fezolinetant prescriptions increased over time, from 233 prescriptions between May 1 through July 31, 2023, to 1,871 prescriptions between May 1 and July 31, 2024.

Conclusions: Our findings highlight a need for future postmarketing safety and effectiveness studies, especially among survivors of breast cancer and women 65 years and older, who were excluded from the randomized controlled trials.

Objective: To analyze the effects of two 16-week physical exercise programs (jazz dance [JD] and concurrent training [CT]) compared with a control group (CG), as well as the impact of detraining (6 mo and 12 mo follow-ups), on menopausal symptoms in postmenopausal women.

Methods: This is a randomized clinical trial with follow-up at 6 and 12 months. A total of 70 postmenopausal women (mean age: 53.19 ± 3.39 y) were included. Participants were randomly allocated into 3 groups: jazz dance, concurrent training, and control. The severity of menopausal symptoms was assessed using the Menopause Rating Scale (MRS). A linear mixed-effect model with random effects was used for statistical analysis under 2 approaches: intention-to-treat (ITT) and protocol adherence. A paired t test analysis of score changes was also conducted as a complementary descriptive analysis, between baseline and subsequent time points.

Results: Significant time-related changes in somatic, psychological, urogenital, and total symptoms were observed in both the ITT and per-protocol analyses (P < 0.005), although no significant group×time interactions were identified. All 3 groups (JD, CT, and even the CG) showed improvements in menopausal symptoms over time, with benefits persisting during follow-up. Regarding changes over time, the CT group experienced the greatest reduction in symptoms over time, reducing the total questionnaire score by more than 7 points postintervention, more than 9 points at the 6-month follow-up, and maintaining the benefits even after one year. JD also reduced symptoms, but to a lesser extent compared with CT, by almost 4 points postintervention, and 6 points at the 6-month follow-up, with benefits also persisting after 1 year. Although the CG also showed some improvement, it was less pronounced compared with the intervention groups.

Conclusions: Although improvements in menopausal symptoms were observed over time within all groups, including the control group, no significant group×time interactions were found. Therefore, this study did not demonstrate a superior effect of JD or CT compared with the CG, only the results that compare the interventions and CG over time are interpretable.

Objective: While evidence suggests that gonadotropins may play an important role in aging-related changes in body composition and health outcomes, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) patterns have not been well characterized in older women. We characterized patterns of FSH and LH change over time after menopause.

Methods: In a sample of 291 postmenopausal women from the Women's Health Initiative OsteoPerio study who were not using hormone therapy, we estimated FSH and LH trajectories over a 20-year period using group-based trajectory modeling. Descriptive statistics identified differences according to hormone trajectory group.

Results: We estimated 3 FSH trajectories. The low FSH trajectory (36.1% of sample) showed had stable FSH, the moderate FSH trajectory (52.9%) showed FSH increased 30 years after menopause, and the high FSH trajectory (11.0%) showed FSH initially declined then increased 20 years after menopause. The moderate and high FSH trajectory groups were more likely to be never smokers, had lower measures of adiposity, and more severe hot flashes. We estimated 3 LH trajectories. The low LH trajectory (29.6%) showed LH declined over time, the moderate LH trajectory (56.0%) initially declined then increased 30 years after menopause, and the high LH trajectory (14.4%) initially decline then steeply increase 30 years after menopause. The moderate and high LH trajectory groups had lower measures of adiposity at baseline.

Conclusion: There is variability in gonadotropin levels during the postmenopausal period in women not using hormone therapy. Research is needed to study whether postmenopausal gonadotropin patterns are associated with aging-related outcomes.

Objective: To assess the direct and indirect associations between obesity and the severity of menopausal symptoms in postmenopausal women, considering related conditions such as chronic diseases and physical activity.

Methods: This observational subanalysis utilized data from the REDLINC XII multinational study, which included 722 postmenopausal women aged 70 or younger from 9 Latin American countries. Menopausal symptoms were measured using the Menopause Rating Scale (MRS). Clinical, behavioral, and sociodemographic data were obtained through physician-administered surveys. Generalized Structural Equation Modeling was employed to examine the direct and indirect relationships between obesity, chronic cardiovascular and respiratory diseases, chronic hypertension, diabetes mellitus, and physical activity, and MRS scores. Odds ratios (ORs) were calculated to enhance interpretability.

Results: A total of 722 participants were included. Obesity was directly associated with higher MRS scores (OR = 1.75). In addition, obesity exhibited indirect associations with MRS scores, with an odds ratio of 19.07, through chronic arterial hypertension, diabetes mellitus, physical inactivity, and chronic cardiovascular or respiratory diseases. The total association between obesity and MRS scores was reflected in an OR of 33.45. Furthermore, physical inactivity and the use of antidepressants were associated with greater symptom severity, whereas higher educational attainment, regular physical activity, and menopausal hormone therapy were associated with lower MRS scores.

Conclusions: Obesity is strongly associated with more severe menopausal symptoms, both directly and through related chronic conditions and behavioral factors. Longitudinal studies are needed to establish temporal and causal inferences.

Objective: To investigate the pharmacokinetic profile of estradiol delivery after the subcutaneous insertion of a 25 mg estradiol bioabsorbable implant in hysterectomized women presenting with menopause-associated symptoms.

Methods: This was a prospective, open-label, single-arm study conducted at a single center between December 2023 and October 2024. Twenty hysterectomized participants received a 25 mg subcutaneous estradiol implant and were followed at weeks 4, 12, and 24 for clinical assessments, symptom evaluation, and safety monitoring. Hormone levels were measured using liquid chromatography-tandem mass spectrometry and electrochemiluminescence immunoassay. Adverse events were recorded, and menopause symptoms were assessed using the Menopause Rating Scale (MRS).

Results: Serum estradiol levels increased after treatment, rising from 31.6±7.0 pg/mL preinsertion to 105.2±10.7 pg/mL (mean±SD) at week 1, remaining stable (~80 pg/mL) through Week 20 and above pre-insertion levels until week 24. Estrone had a similar profile. Follicle-stimulating hormone and luteinizing hormone levels decreased throughout the treatment. Sex hormone-binding globulin, total and free testosterone, and prolactin showed minimal variation throughout the study. Subcutaneous estradiol delivery resulted in a sustained pharmacokinetic profile characterized by a Tmax of 75.6 hours and a 6439 hours notably extended half-life (T1/2). Vasomotor and psychological symptoms decreased significantly after 4 weeks of treatment, and the reduction in Menopause Rating Scale score was observed until Week 24. No serious adverse event was reported.

Conclusion: The 25 mg estradiol implant provided sustained serum concentration of estradiol over a 24-week period of treatment, effective symptom relief, and an acceptable safety profile in hysterectomized women, thereby offering a novel therapeutic option for hormone therapy.

Importance: Black cohosh (BC) is a herbal medicine being prescribed for the management of climacteric complaints. This is the first review to assess the quality of evidence for BC as measured by adherence to Consolidated Standards of Reporting Trials (CONSORT) extensions for herbal interventions and harms.

Objective: Herbal medicines such as Actaea racemosa (A. racemosa; synonym Cimicifuga racemosa, BC) are commonly being used by women seeking relief from menopausal (climacteric) complaints. Our objective is to evaluate the quality of reporting of clinical trials investigating A. racemosa for climacteric complaints, by grading their adherence to both the CONSORT extensions for herbal interventions, and for reporting adverse events (harms).

Evidence review: A systematic search of the databases: AMED, CINAHL, EBSCO, Academic Search Ultimate, Google Scholar, PubMed and Science Direct, was conducted in April 2023 and another search done March 2024. The search phrase employed included relevant herbal or herbal product keywords ["black cohosh," "actaea racemosa," "cimicifuga racemosa," "BNO 1055," "remifemin," "Ze 450"] combined using the Boolean operator term AND with keywords regarding climacteric complaints ["menopausal symptoms," "menopause," "climacteric complaints"]. Additional citation searching was conducted to identify any other published studies. Articles were included if they were clinical trials of oral use of A. racemosa in humans. Quality assessment of included articles was undertaken to review adherence to the CONSORT Statement Extensions for reporting on herbal interventions, and harms (adverse events).

Findings: Fourteen records were included in the final analysis. Adherence to the herbal extension for the CONSORT ranged between 39% and 87%, with four of them receiving an adherence rating of 50% or less. Adherence to the Harms Extension for the CONSORT ranged between 6% and 90%, with three of the articles receiving an adherence rating of 50% or less.

Conclusions and relevance: This is the first time a systematic review of the quality of clinical trial reports of BC, using the CONSORT herbal extension and harms checklists, has been conducted. The wide range of ratings found in our quality assessment suggests the need for further high-quality investigation of this widely used herbal preparation.