Climacteric最新文献

Objective: The association of hormone therapy (HT) combined with statin use for primary prevention of cardiovascular disease remains uncertain. This study aimed to assess the effect of HT, initiated before the age of 60 years, on all-cause mortality and cardiovascular events in females using statins for primary prevention.

Method: This population-based, retrospective cohort study included all females aged 40-60 years in British Columbia, Canada, who used statins for primary prevention. The exposure was defined as systemic HT, including estrogen alone or combined with a progestogen, excluding local preparations of estrogen. The study used Cox proportional hazards models from the study start date to the outcome.

Results: After exact matching on age using up to a 1-to-4 match, 685 (20%) of the 3,425 statin users initiated HT within the first year of follow-up. HT use was not significantly associated with all-cause mortality after adjusting for confounders (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 0.87-1.58). Similarly, for the secondary outcome of composite cardiovascular events, HT use did not significantly increase risk (aHR, 0.95; 95% CI, 0.75-1.20).

Conclusion: This study found that HT, when initiated before age 60 years, was not associated with an increased risk of all-cause mortality or cardiovascular events in females using statins for primary prevention.

Objective: This study examined the effect of hormone therapy (HT) on tryptophan-kynurenine pathway metabolites and associations with atherosclerosis among postmenopausal women.

Methods: Eighty early postmenopausal participants from the Early versus Late Intervention Trial with Estradiol (40 each from HT vs. placebo) were selected for analysis. Tryptophan, N-acetyltryptophan, kynurenine, kynurenic acid and N-acetylkynurenine baseline and 36-month levels were measured by mass spectrometry. Mixed models tested HT effects on each metabolite, association of estradiol (E2) level with change in metabolite levels and association between change of metabolite with carotid artery intima-media thickness (CIMT) progression.

Results: Compared with placebo, HT significantly reduced kynurenic acid (mean change HT minus placebo -0.27; 95% confidence interval [CI] - 0.42, -0.12; p = 0.0007) and N-acetylkynurenine (-0.38; 95% CI -0.68, -0.08; p = 0.04) levels. Reduction in kynurenic acid was inversely associated with higher E2 levels. Decreased CIMT progression was associated with lower kynurenic acid (0.0131 µm/year per unit; 95% CI 0.0049, 0.0212; p = 0.002) and N-acetylkynurenine (0.0061 µm/year per unit; 95% CI 0.0020, 0.0103; p = 0.004) levels.

Conclusions: Plasma tryptophan-kynurenine pathway metabolites were reduced by HT and these reduced metabolite levels were associated with decreased atherosclerosis progression. Reduction of kynurenic acid by HT was supported by its association with E2 levels, which may explain, in part, the reduction in atherosclerosis progression with HT in early postmenopausal women.

Objective: This study aimed to explore the effects of blinding on patient-reported outcomes.

Method: Findings from this prospective open-label extension study were compared to a previous double-blind sham-controlled randomized trial. Women with any postmenopausal vaginal symptom previously receiving either active or sham vaginal fractional CO₂ laser were recruited from the index randomized controlled trial (RCT), and underwent an active laser protocol. Symptom severity was assessed by co-primary outcomes of a visual analog scale (VAS) for overall and most bothersome symptom and the Vulvovaginal Symptom Questionnaire (VSQ) to 12 months.

Results: Of the 25 participants, there was a significant improvement in the co-primary outcomes at 6 months from baseline (mean difference: overall vaginal symptoms VAS, 22.0 [95% confidence interval (CI) -32.2, -11.8]; most bothersome symptom VAS, -22.1 [95% CI -36.7, -7.5]; VSQ, -2.2 [95% CI -3.8, -0.6]). At 12 months, there was significant improvement in most bothersome symptom VAS (-17.8 [95% CI -35.3, -0.3]) and VSQ (-2.3 [95% CI -3.9, -0.8]) scores. There was no significant difference in the post-treatment improvement of the co-primary outcomes at 6 and 12 months following open-label laser treatment, when compared to index RCT outcomes following active laser and sham laser treatment, respectively.

Conclusion: Blinding in randomized trials is essential for correctly interpreting clinical outcomes using lasers for genitourinary symptoms of menopause.

Objective: Using real-world data, the current study compared the risk of major adverse cardiovascular events (MACE) between two regulated combined oral hormonal products that are currently available to women in the USA: body-identical oral 17β-estradiol/micronized progesterone (E2/P4) and conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA).

Methods: Women aged ≥40 years treated with E2/P4 or CEE/MPA were selected from a US claims database (April 2019-June 2021). The E2/P4 or CEE/MPA cohorts were defined based on the first dispensation of E2/P4 or CEE/MPA (index) as prescribed in the real world. Women with pre-index MACE hospitalization were excluded. Confounding was controlled via inverse probability of treatment (IPT) weighting. MACE risk was compared between the IPT-weighted cohorts using Cox and Poisson/negative binomial regression models.

Results: The E2/P4 and CEE/MPA cohorts included 6520 and 29,426 women respectively (mean follow-up 1.2 and 1.4 years). In the IPT-weighted analyses, MACE rates were 23.5 versus 85.4 per 10,000 women-years among women treated with E2/P4 and CEE/MPA (IPT-weighted incidence rate ratio [IRR] 0.28, 95% confidence interval [CI] 0.17 - 0.45; IPT-weighted hazard ratio [HR] 0.37, 95% CI 0.27 - 0.50).

Conclusions: Real-world evidence suggests that the MACE risk is significantly lower among women treated with E2/P4 compared to CEE/MPA.

Objective: Tamoxifen (TMX) is known to increase the risk of endometrial cancer (EC) in postmenopausal women, but data on the effects in premenopausal and perimenopausal women remain inconsistent and not well illuminated. This study aimed to evaluate whether TMX increases the risks of gynecological symptoms and EC in premenopausal and perimenopausal women receiving adjuvant therapy for estrogen receptor-positive breast cancer.

Methods: Systematic searches in PubMed, Cochrane and Web Of Science yielded 319 relevant articles, of which 38 were analyzed after excluding duplicates and non-qualifying studies. The Oxford Criteria were used to ensure consistent evaluation before final inclusion. No meta-analysis was conducted due to study heterogeneity.

Results: Ten studies (two meta-analyses, one systematic review, four retrospective cohort studies, one retrospective comparative study, one prospective cohort study and one case-control study) were included. TMX was associated with an increased risk of EC in premenopausal and perimenopausal women (mean relative risk 2.25; standard deviation 0.9) compared to no treatment or treatment with raloxifene or aromatase inhibitors. Risk appeared in some studies to increase with treatment duration and persisted for ≥5 years post treatment. TMX also significantly increased the risk of gynecological symptoms, benign and premalignant endometrial pathology, intrauterine procedures and hysterectomy (p < 0.001).

Conclusions: TMX seems to increase EC risk and significantly increase the risk of gynecological symptoms in premenopausal and perimenopausal women, with risk persisting years following treatment cessation. Healthcare professionals should counsel these women on potential risks and emphasize prompt evaluation of gynecological symptoms.

Objective: Menopausal hormone therapy (MHT) is the most effective treatment for menopausal symptoms. While guidelines recommend an individualized risk-benefit assessment of MHT, real-world studies on use of MHT are limited.

Method: Nationwide claims data in South Korea (2015-2020) were used to assess the prevalence of hospital visits for menopausal symptoms and use of MHT among women aged 40-59 years. MHT was classified into three classes including estrogen therapy (ET), estrogen plus progestogen therapy (EPT) and tibolone, with routes of administration categorized as systemic (oral, transdermal) and local (transvaginal). A longitudinal study was conducted to evaluate treatment patterns of MHT.

Results: Approximately 9% of women visited hospitals for menopausal symptoms, with fewer than half prescribed MHT. Of 1,774,674 women with menopausal symptoms, 1,036,294 were prescribed MHT: 89,237 patients were started on systemic ET, 300,999 on systemic EPT, 306,538 on tibolone and 378,764 on local ET. Use of tibolone and local ET increased over time, while systemic ET and EPT decreased. Systemic MHT was discontinued after an average of 13.2 months, while local MHT was discontinued after 2.4 months.

Conclusion: Despite guidelines recommending MHT for treating menopausal symptoms, many women remain untreated and continued MHT for an average of only 1 year.

Sarcopenic obesity, defined as the coexistence of excess adiposity and sarcopenia, represents a high-risk clinical condition that amplifies the adverse effects of each disorder. When accompanied by bone loss, the entity progresses to osteo-sarcopenic obesity (OSO), which further compromises physical function, metabolic health and overall prognosis. Affected individuals face an increased risk of falls, fractures, functional disability, hospitalization, cardiometabolic complications and premature mortality. In women transitioning through menopause, declining estrogen levels accelerate fat accumulation and muscle loss, while also heightening susceptibility to osteoporosis, insulin resistance, hypertension, dyslipidemia, type 2 diabetes and certain cancers. These interrelated changes underscore the need for heightened awareness, early identification and multidisciplinary management of the OSO syndrome. Establishing clear and universally accepted diagnostic criteria, integrating patient education and implementing preventive strategies - including lifestyle, nutritional and medical interventions - are essential to address this complex and emerging clinical entity, ultimately improving health outcomes and quality of life for midlife and older women.

For women with mild-to-moderate menopausal symptoms, lifestyle changes and over-the-counter products and services can be beneficial for symptom management, especially for those who are contraindicated or averse to using menopausal hormone therapy (MHT). Lifestyle changes, such as increased exercise and improvements in diet, enhance overall health and are suggested by some low-level evidence - largely from observational studies - to alleviate menopausal symptoms. Over-the-counter dietary and herbal supplements are a popular alternative to MHT. While evidence is mainly low-level, some of these products have shown efficacy and tolerability in menopausal symptom management through meta-analyses, systematic reviews and randomized controlled trials (RCTs). However, mixed evidence and inconsistencies in product dosage, components and quality remain an issue. In addition, caution is advised for women on other medications or with conditions such as breast cancer that could interact with or be impacted by these products. There is high-level evidence from RCTs supporting the efficacy of behavioral therapies, in particular cognitive behavioral therapy, in menopausal symptom management, and clinicians should consider their implementation. Education on menopause and its management is essential. The authors recommend a three-step approach for treating women with self-reported mild-to-moderate menopausal symptoms who prefer to avoid prescription medications even after being informed about their benefit-risk profiles: 1) lifestyle changes; 2) non-prescription options and over-the-counter products; and 3) prescription therapies, if still necessary and with patient agreement. This approach broadens access to menopausal symptom management, providing relief to a wide range of women.