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IMS Menopause Live

Commentaries from the IMS on recently published scientific papers that may be of interest. The latest articles are available to Members only when logged in. Selected articles are open to public.

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Hysterectomy with and without oophorectomy, tubal ligation, and risk of cardiovascular disease in the Nurses' Health Study II

12 June 2023

Summary

Hysterectomy, oophorectomy, and tubal ligation are common surgical procedures; however, reports linking cardiovascular disease (CVD) risk after these surgeries have basically focused on oophorectomy with limited research on hysterectomy or tubal ligation. Recently, Farland et al. [1] reported on data of participants of the Nurses' Health Study II (n = 116,429) who were followed from 1989 to 2017. Self-reported gynecologic surgery was categorized as follows: no surgery, hysterectomy alone, hysterectomy with unilateral oophorectomy, and hysterectomy with bilateral oophorectomy; the authors separately investigated tubal ligation alone. The primary outcome was CVD based on medical-record confirmed fatal and non-fatal myocardial infarction, fatal coronary heart disease, or fatal and nonfatal stroke. Secondary outcome expanded CVD to include coronary revascularization (coronary artery bypass graft surgery, angioplasty, stent placement). The authors used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CIs), a priori adjusted for confounding factors. Differences by age at surgery (≤50, >50) and menopausal hormone therapy usage was analyzed. Average age of participants at baseline was 34 years. During 2,899,787 person-years, the investigators observed 1,864 CVD cases. Hysterectomy in combination with any oophorectomy (unilateral or bilateral) was associated with a greater risk of CVD in multivariable-adjusted models. Hysterectomy alone, hysterectomy with oophorectomy (unilateral and bilateral), and tubal ligation were also associated with an increased risk of combined CVD and coronary revascularization (HR 1.19; HR 1.29; HR 1.22, and HR 1.16, respectively). The association between hysterectomy/oophorectomy and the risk of CVD and coronary revascularization varied by age when surgery was performed, with the strongest association observed if surgery was before age 50. The authors finally conclude that hysterectomy, alone or in combination with oophorectomy (any type), as well as tubal ligation, seems to be associated with a higher risk of CVD and coronary revascularization; indicating that these findings extend previous research finding that oophorectomy is associated with CVD.

Read more …Hysterectomy with and without oophorectomy, tubal ligation, and risk of cardiovascular disease in...

Efficacy and safety of fezolinetant for the treatment of moderate-to-severe menopausal related vasomotor symptoms

22 May 2023

Summary

Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause. Recently, Johnson et al. [1] published the results of SKYLIGHT 2, a phase 3 double-blind placebo controlled RCT aimed at assessing the efficacy and safety of fezolinetant for the treatment of moderate-to-severe menopause related VMS. Women, age 40-65 years with a minimum mean of 7 moderate-to-severe VMS per day, were randomized to receive 12 weeks once-daily fezolinetant 30 mg, fezolinetant 45 mg or placebo. Those who completed 12 weeks were re-randomized to fezolinetant 30mg or 45 mg for 40 additional weeks. Primary endpoints were mean daily change of frequency and severity of VMS from baseline to W4 and W12. The study reported that both fezolinetant doses significantly reduced moderate-to-severe VMS frequency and severity at W4 and W12 in comparison to placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo was: fezolinetant 30 mg, -1.82 (0.46; p < 0.001); 45 mg, -2.55 (0.46; p < 0.001); W12: 30 mg, -1.86 (0.55; p < 0.001); 45 mg, -2.53 (0.55; p < 0.001). For VMS severity (scale 0-3) results were:  W4: 30 mg, -0.15 (0.06; p< 0.05); 45 mg, -0.29 (0.06; p < 0.001); W12: 30 mg, -0.16 (0.08; p <0.05); 45 mg, -0.29 (0.08; p < 0.001). Significant improvement in VMS frequency (30 and 45 mg) and severity (45 mg) was observed by W1 and was maintained through W12. Serious treatment-emergent adverse events were infrequent: 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively; liver function abnormalities were rare and transient. The authors concluded that daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for the treatment of moderate-to-severe menopause related VMS.

Read more …Efficacy and safety of fezolinetant for the treatment of moderate-to-severe menopausal related...

Rhythm-centered music making in community living elderly: a randomized pilot study

19 May 2023

Summary

Rhythm-centered music making (RMM) has shown to improve physical, psychological and social health. Yap et al. [1] carried out a pilot randomized controlled trial with cross over aimed to explore the effects of RMM on quality of life, depressive mood, sleep quality and social isolation in elder individuals. A total of 54 participants were enrolled (27 in each arm). During phase 1, group A underwent the intervention with group B as the control; in phase 2 cross-over was performed. The intervention involved 10 weekly RMM sessions. Before intervention, at the 11th and at the 22nd week participants were evaluated with the European Quality of Life-5 Dimensions (EQ5D), the Geriatric Depression Scale (GDS), the Pittsburg Sleep Quality Index (PSQI) and the Lubben Social Network Scale (LSNS). At the end of the study 31 participants were analyzed. Mean age was 74.65 ± 6.40 years. Participation in RMM resulted in a non-significant reduction in the EQ5D by 0.004 (95% CI: -0.097-0.105), the GDS score by 0.479 (95% CI: -0.329-1.287), the PSQI score by 0.929 (95% CI: - 0.523-2.381) and an improvement in the LSNS by 1.125 (95% CI: -2.381-0.523). Upon binary analysis, participation in RMM resulted in a 37% (OR = 1.370, 95% CI: 0.355-5.290), 55.3% (OR = 1.553, 95% CI: 0.438-5.501), 124.1% (OR = 2.241, 95% CI = 0.677-7.419) and 14.5% (OR = 1.145, 95% CI = 0.331-3.963) non-significant increase in odds of improvement in the EQ5D, GDS, PSQI and LSNS scores respectively. The authors conclude that participation in RMM did not show any statistically significant difference in the quality of life of the participants; however, as they mention it is an interesting alternative tool to use in the field of integrative medicine. They recommend moving forward to a larger study that will better aid at investigating the effects of RMM on elder individuals with the inclusion of a qualitative component.

Read more …Rhythm-centered music making in community living elderly: a randomized pilot study

Obesity indicators as mediators of the association between age at menopause and blood pressure values

11 April 2023

Summary

A later age at menopause onset has been associated with presenting a higher blood pressure (BP) value, although the mediation pathways remain unclear. Recently Wu et al. [1] examined in quantitative manner the mediation effects of various obesity indicators using baseline data from the Guangzhou Biobank Cohort Study (Phase 4). Authors used product of coefficients approach and bootstrapping procedures to assess the mediation effects of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) on the association between age at menopause and BP values. They adjusted for various co-variates such as age, education, occupation, family income, smoking, drinking, diet, physical activity, age at menarche, number of births, fasting glucose, triglycerides, and HDL-C. Of a total of 5,429 women with natural menopause, the mean age and mean age at menopause were 60.0 ± 5.8 and 50.3 ± 3.1 years, respectively. The prevalence of hypertension was 29.6%. In women with an age at menopause onset of ≥ 50 years, BMI, WC, WHR and WHtR showed significant mediation effects on the positive association between menopausal age and BP. The adjusted proportion (95% confidence interval) of the mediation effects for those variables were 26.04% (10.40-116.82%), 25.92% (10.19-108.57%), 14.11% (3.59-62.78%), and 23.17% (8.70-95.81%), respectively, for systolic BP values and 22.59% (10.72-53.60%), 20.67% (9.83-49.31%), 9.21% (2.73-23.92%), and 17.19% (7.56-41.31%) for diastolic BP values. In women with a menopausal age of <50 years, no significant association between age at menopause and systolic/diastolic BP values was found. The authors conclude that obesity indicators showed significant mediating effects on the association between having a later age at menopause (50 years or more) and having a higher BP value. They recommend that further longitudinal studies with detailed and accurate measurements of metabolic changes after menopause and sufficient follow-up are needed to confirm these results.

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Lower back pain is worsened by inadequate vitamin D and obesity in postmenopausal women

13 March 2023

Summary

Postmenopausal women are significantly more likely to suffer from vitamin D deficiency and obesity. It is common for postmenopausal women to have lower back pain (LBP), impaired muscle strength, and poor muscle function due to 25(OH)D deficiency. Obesity may also have a relationship with reduced muscle strength. On the basis of serum 25(OH)D concentration and body mass index (BMI), In an observational study, Chen et al. [1] studied 365 postmenopausal women with chronic LBP who were divided into four groups. Serum 25(OH)D concentrations in combination with BMI were assessed for their influence on paraspinal muscle (PSM) atrophy, fat infiltration, and severity of LBP. Results show that people with increased BMI and vitamin D inadequacy have less sun exposure time, decreased hand grip strength (HGS), decreased level of physical activity (lower Short Physical Performance Battery [SPPB] score), and PSM cross-sectional area than controls. However, this group's fat infiltration degree of the PSMs and visual analog scale (VAS) score was significantly increased. The authors conclude that high BMI and vitamin D insufficiency/deficiency have a significant positive additive interaction in terms of fat infiltration and impaired muscle strength of PSM.

Read more …Lower back pain is worsened by inadequate vitamin D and obesity in postmenopausal women

Menopausal vasomotor symptoms and white matter hyperintensities in midlife women

13 February 2023

Summary

Recently, Thurston et al. [1] investigated whether vasomotor symptoms (VMS), when rigorously assessed using physiologic measures, were associated among midlife women with greater white matter hyperintensity volume (WMHV). The authors considered a range of potential explanatory factors in these associations and explored whether VMS were associated with the spatial distribution of WMHV. For this, women aged 45-67 (n=226) who were free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were analyzed in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, occipital) and additional covariates including sleep. The investigators found that physiologically-assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest significant associations observed for sleep VMS [24-hour VMS, wake VMS, sleep VMS]. Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep, periventricular and frontal lobe WMHV. The authors conclude that VMS, particularly those occurring during sleep, were associated with greater WMHV. In addition, they recommend the crucial need of finding female-specific midlife markers of poor brain health later in life in order to identify women who warrant early intervention and prevention. VMS have the potential to serve as this female-specific midlife marker of brain health in women.

Read more …Menopausal vasomotor symptoms and white matter hyperintensities in midlife women

Impact of hormone therapy on the bone density of women with premature ovarian insufficiency

31 January 2023

Summary

Women with premature ovarian insufficiency (POI) are exposed to a long period of estrogenic deficiency, which potentially brings higher health risks, especially regarding bone health. Recently Costa et al. [1] performed a systematic review of the literature to evaluate the effect of hormone therapy (HT) on bone mineral density (BMD) in women with POI. They performed a search in MEDLINE and EMBASE databases up to September 2021 and included studies that analyzed women with spontaneous idiopathic POI treated with HT, to whom BMD was evaluated. Analysis of risk of bias of the selected studies was also performed. The authors found 335 articles and selected 16 studies according to the inclusion criteria. Most of the studies revealed lower bone density in both the femoral neck and lumbar spine in women with POI compared with healthy women. Bone mass had the tendency to remain stable in women treated with estrogen + progestin therapy; however, in those already with bone mass loss, the therapy - in the doses most frequently used - was not able to revert the loss. Higher estrogenic doses seemed to have a positive impact on BMD, as did combined oral contraceptives used continuously. In addition, the interruption of HT for longer than one year was associated with significant bone loss. The authors conclude that although HT brings clear benefits, further studies are needed to establish its long-term effects, as well as doses and formulations with better protective effects on the bone mass of women with POI.

Read more …Impact of hormone therapy on the bone density of women with premature ovarian insufficiency

Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer

23 January 2023

Summary

Recently, Rye et al. [1] investigated the association of the use of tamoxifen with the risk of endometrial cancer and other uterine diseases in premenopausal women with breast cancer (BC). For this the authors carried out a nationwide, population-based, retrospective longitudinal cohort study with an 18-year study period using data obtained from the Korean National Health Insurance Service. Premenopausal women aged 20 to 50 years with BC diagnoses between January 2003 and December 2018 were included, with data analysis being performed from April to December 2021. Tamoxifen treatment was the main exposure variable and outcomes included: the incidence of uterine diseases, including endometrial cancer (EC), endometrial hyperplasia (EH), endometrial polyps (EP), and other uterine cancers. The incidence of uterine diseases was compared between tamoxifen users and non-users. A total 78,320 female participants were included (mean age 42.1), 34,637 (44.2%) were tamoxifen users and 43,683 (55.8%) were non-users. During the mean follow-up 6.13 years, among tamoxifen users the incidence of newly diagnosed EP, EH, EC and uterine cancers was 20.13, 13.49, 2.01 and 0.45 cases per 1,000 person-years, respectively. The risk of EC was higher in the tamoxifen group than in the control group after adjusting for age, body mass index, history of diabetes, and other co-variates. The authors conclude that premenopausal Korean women with BC who received tamoxifen as adjuvant hormone therapy, as compared to those who did not, had a significantly increased risk of studied uterine diseases, suggesting that clinicians should consider this risk in premenopausal women.

Read more …Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment...

Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular disease in the Canadian Longitudinal Study on Aging

17 January 2023

Summary

The risk of cardiovascular disease (CVD) is higher in the postmenopausal period. The effect that the type of menopause, natural versus surgical, or the age at natural onset of menopause has on CVD needs further investigation. This prompted Price et al. [1] to study of the association between the type and timing of menopause and the 10-year office based Framingham Risk Score (FRS) in women (45 to 85 years) from the Canadian Longitudinal Study on Aging. Women included were menopausal at time of recruitment and had no prior CVD. As main covariates, the authors examined age, education, province of residency, and the use of hormone therapy. A total of 10,090 women (8,200 natural menopausal and 1,890 surgical menopausal) were eligible for the study. Surgical menopause was associated with a higher mean FRS compared with natural menopause (CVD risk 12.4% vs 10.8%, p<0.001). Compared to women with an age at natural menopause from 50 to 54 years (CVD risk 10.2%), natural menopause before age 40, 40 to 44, or 45 to 49 years had a higher CVD risk (12.2%, 11.4%, and 10.6%, respectively, p<0.001). The author conclude that their study supports an association between the type of menopause and its timing over CVD risk prediction and highlights the need to be judicious about surgical menopause.

Read more …Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular...

Loss of muscle mass in women with premature ovarian insufficiency as compared with healthy controls

19 December 2022

Summary

Estrogen, mediated by both genomic and non-genomic pathways, contributes to the preservation of muscle mass and strength via effects on mitochondrial function, satellite cell regeneration, apoptosis, protein turnover, inflammation and myosin binding [1]. Earlier age at natural menopause is associated with reduced physical function parameters [2]. Although bone loss and osteoporosis are well recognised and feared consequences of premature ovarian insufficiency (POI) [3], data regarding muscle is lacking [1]; with previous investigations in women with POI showing conflicting results. The recent cross-sectional study by Li and co-workers [4] helps to address this knowledge gap by demonstrating in Chinese women with spontaneous POI (n=59) a greater prevalence of decreased muscle mass as well as lower appendicular skeletal muscle mass (ASM) and total skeletal muscle mass (TSMM), which was independent of age, body mass index (BMI) and lifestyle factors as compared with premenopausal controls (n=57).

Read more …Loss of muscle mass in women with premature ovarian insufficiency as compared with healthy controls

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