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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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Hormonal and menopausal symptom correlates of cognition during the perimenopause

20 June 2022

Summary

Weber et al. [1] reported on a longitudinal study that was conducted over three waves from 2005 through 2016. For the duration of the study, all 85 subjects were in their perimenopause stage (STRAW+10 stage -2 to stage +1a) and evaluated over 400 bi-annual visits. A comprehensive neuropsychological battery was administered, menopausal symptoms evaluated and 17β-estradiol and follicle stimulating hormone (FSH) measured. Multilevel latent profile analysis was used to identify cognitive profiles. All of the recorded visits were sorted into 4 subgroups according to cognitive profiles. After adjusting for STRAW+10 stages and demographic factors, the regression analyses were conducted to determine differences in hormones and symptoms. Most women showed no global impairment, while a significant minority developed weaknesses in verbal learning and memory that were related to both hormonal flux and menopausal symptoms. Compared to women who were cognitively normal, those who had weaknesses in verbal learning and memory were differentiated by less hormonal variability and more sleep disturbance, while women with strength in verbal learning and memory had fewer depressive and vasomotor symptoms (VMS). The investigation showed a significant heterogeneity in cognition during the perimenopause. The authors suggested that cognitive profile analysis should be taken into account to identify at risk populations in order to provide appropriate interventions.

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Can menopausal hormone therapy improve quality of sleep?

30 May 2022

Summary

Recently a systematic review and meta-analysis was conducted at West China School of Medical, Sichuan University, China, aimed at investigating whether menopausal hormone therapy can improve sleep quality [1]. The authors included randomized controlled trials (RCTs) from multiple databases, abstracts, and other full-text sources. Fifteen studies were included (n=27,715). The meta-analysis showed that hormone therapy improved self-reported sleep quality, but did not improve polysomnograms (PSG), compared with the control group. Estrogen/progestogen combined therapy improved sleep, but estrogen-only therapy did not. Among estrogen regimens, 17β estradiol and conjugated equine estrogens improved sleep quality, especially the former, but estradiol valerate did not. Transdermal estrogen improved sleep better than oral administration. Comparing different progestogen types, micronized progesterone and medroxyprogesterone acetate showed improvement effects on sleep. The authors concluded that hormone therapy has a beneficial effect on sleep disturbance to some extent, and the formulations and routes of administration of hormonal agents influence the effect size.

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Estetrol a promising native estrogen for oral contraception and the relief of menopausal symptoms

23 May 2022

Summary

The use of hormonal therapy has been associated with an increased risk of venous thromboembolism (VTE) and breast cancer. Recently, Gérard et al. [1] reported in a narrative review the profile of estetrol (E4), an estrogen produced by the human fetal liver, with properties that may provide a better safety profile. Unlike other estrogens, E4 activates the nuclear estrogen receptor (ER) α signaling pathway but does not activate membrane ERα signaling pathway in specific tissues. It is considered the first Native Estrogen with Selective action in Tissues (NEST) due to its differential activation of the nuclear and membrane ERα pathways. E4 does not stimulate the membrane ERα and antagonizes the estradiol-induced membrane effects. E4 has recently been approved in Europe and several countries (USA, Canada, Australia) as a new estrogenic component of a combined oral contraceptive, associated with drospirenone. The association of 15 mg of E4 plus drospirenone 3 mg has good contraceptive efficacy, safety, and user tolerability. E4 has a low impact on the liver and the breast, and a higher effect on the endometrium, vaginal epithelium, and the cardiovascular system. In comparison to other contraceptives, the association of E4/drospirenone showed less impact on several parameters, including laboratory markers of hypercoagulability. Finally, in addition to its use in contraception, E4 has the potential to be used in the treatment for menopausal symptoms.

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Association between parity and bone mineral density in postmenopausal women

16 May 2022

Summary

Pregnancy has been considered a risk factor for developing osteoporosis. Although there has been much research in the field of bone health, the relationship between parity and bone mineral density (BMD) is still controversial. Recently, Yang et al. [1] reported the results of a cross-sectional study that used data from the National Health and Nutrition Examination Survey (NHANES) in order to investigate the relationship between parity and BMD of the femoral neck and lumbar spine in 924 postmenopausal women aged 45 to 65. The authors applied three linear regression models, Model 1 (unadjusted), Model 2 (adjusted for age and body mass index, and Model 3 (adjusted for all covariates). Also, the p value trend of BMD in the different parity groups was mutually verified with the results of multiple regression. Multiple logistic regression models were used to assess the relationship between parity and osteoporosis. After adjustment for potential confounders, women with a parity of ≥ 6 had significantly lower BMD at the lumbar spine than women with a parity of 1-2 (β = - 0.072, 95% CI: - 0.125, - 0.018, p = 0.009). Despite this, there was no correlation found between parity and femoral neck BMD in any of the three regression models. Furthermore, parity of ≥ 6 was associated with a significantly higher prevalence of lumbar spine osteoporosis compared to parity 1-2 (OR = 3.876, 95% CI: 1.637, 9.175, p = 0.002). The authors conclude that after adjusting for BMD-related risk factors, in postmenopausal women, a parity of 6 or more was associated with decreased lumbar spine BMD but not femoral neck BMD. Authors suggest that postmenopausal women with high parity are at increased risk of lumbar osteoporotic fractures and should pay more attention to their bone health.

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Aerobic exercise with Mediterranean-DASH Intervention for Neurodegenerative Delay Diet improves cognitive function in postmenopausal women

27 April 2022

Summary

Cognitive functions are essential for the performance of daily life activities, particularly for older adults who present a higher prevalence of cognitive disorders. Problems related to these specific brains skills can range from mild cognitive impairment (MCI) to dementia. Dementia reduces quality of life (QoL) and is related to serious economic consequences. Recently, Elsayed et al. [1] reported the results of a parallel randomized clinical trial involving sixty-eight postmenopausal women (60 to 75 years/body mass index [BMI]: 30 to 39.9 kg/m2), in order to investigate the combined impact of aerobic exercise and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on brain cell longevity. Participants were assigned to one of two groups (the experimental and the control). The experimental group followed moderate-intensity treadmill exercise three times/week for twelve weeks plus MIND diet and the control group followed the MIND diet alone. Serum sex hormones were measured (estradiol, total testosterone [TT], free testosterone [FT], sex hormone binding globulin [SHBG]) at baseline and at 12 weeks; in addition to the assessment of cognitive function and functional activity level determined with validated scales (i.e the Rowland Universal Dementia Assessment Scale [RUDAS] and the Functional Independence Measures Scale [FIM], respectively). After intervention, the experimental group displayed significant changes in sex hormones, cognitive functions, and functional levels compared with the control group. In addition, no correlation was found between the measured variables in both groups after intervention. Authors conclude that aerobic exercise in combination with the proposed MIND diet improves cognitive and functional levels and sex hormones in postmenopausal women.

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Multimorbidity among midlife women in India: well-being beyond reproductive age

18 April 2022

Summary

Ageing is an inevitable natural process usually related to declining health conditions. There are no universal criteria for healthy ageing but can be broadly regarded as the maintenance of robust physical, mental, and social health, leading to overall well-being [1]. The demographic and epidemiological transition in low-and-middle-income countries (LMICs) has led to a rise in the co-existence of two or more long-term conditions known as multimorbidity [2]. Estimates suggest that adults aged 45 or more will constitute over 40 percent of the Indian population by 2050 [3]. Recently, Puri et al. [4] reported the results of a descriptive study aimed at determining the magnitude and correlates of early onset of multimorbidity and explore its linkages with selected indicators of health-related quality of life (HRQoL) among mid-aged women from India. The authors used for the analysis data of a total of 23,951 women aged 45-65 from the first round of the Longitudinal Ageing Study in India (LASI, 2017-2019). Ordered logistic regression was conducted and proportional odds reported to identify the correlates of multimorbidity. Multimorbidity was reported in 29.8% of the mid-aged cohort. Punjab state and Chandigarh, its capital, reported the highest prevalence of multimorbidity (52.8 per 100 women and 54.8 per 100 women, respectively). Women with multimorbidity reported compromised HRQoL indicators such as self-rated health, work-limiting health conditions, mobility, and daily living activities. The authors conclude that multimorbidity is increasingly prevalent in mid-aged women and associated with impaired quality of life. Recommendation is that reproductive health programs should be carried out for women, focusing on mid-life multimorbidity and overall well-being.

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The safety and efficacy of compound bioidentical hormone therapy in peri- and postmenopausal women

12 April 2022

Summary

Due to the results of the 2002 WHI, many women decided to follow the advice of their doctors and switch from using synthetic hormones to using compounded bioidentical hormone therapy (cBHT). This led to an increase in the prescription of these compounds in the last decade to up to around 33 million annual prescriptions and with a progressive increasing trend. This prompted the FDA to ask NASEM (National Academy of Science, Engineering, and Medicine) to evaluate the available evidence on cBHT, concluding that there was a lack of high-quality research establishing the safety and efficacy of cBHT, and that studies with a higher level of evidence were needed, as well as a systematic review and a meta-analysis. Bearing this in mind, Liu and collaborators [1], carried out a systematic review and meta-analysis based on protocols registered in PROSPERO and carried out in accordance with the Cochrane Manual for Systematic Reviews of Interventions and the checklist of 27 items Preferred Reporting Items for Systematic Review and Meta-Analysis Statement (PRISMA) [2,3], in order to evaluate the existing evidence related to the safety and efficacy of cBHT that are prescribed to peri- and postmenopausal women. The authors searched across systems, choosing for analysis randomized controlled trials (RCTs) that compared outcomes in peri- and postmenopausal women using cBHT against placebo or FDA-approved hormonal products. They analyzed bias, according to the Cochrane risk of bias tool and took primary outcomes of safety (changes in lipid profile and glucose metabolism) and efficacy (changes in symptoms of vaginal atrophy). Secondary outcomes included changes in the endometrium, risk of adverse events, vasomotor symptoms, change in hormone levels, and change in bone mineral density.

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Ageing, weight change and breast cancer

28 March 2022

Summary

The role of obesity and weight change in breast-cancer development is complex and incompletely understood. Recently, Ellingjord-Dale et al. [1] recently reported the results of a study that investigated the effects of long-term weight change and the risk of breast-cancer risk taking into account body mass index (BMI) at 20 years of age, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. The authors used data related to weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study in order to analyze the association between weight change since age 20 up to mid-adulthood and risk of breast cancer. A total of 150,257 women (median age 51 years at cohort entry) were followed for a mean 14 years (standard deviation = 3.9) during which 6,532 breast-cancer cases occurred. In comparison to those with stable weight (± 2.5 kg), long-term weight gain of more than 10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% CI 1.22–1.65], were ever HRT users (HR = 1.23; 95% CI 1.04–1.44), never HRT users (HR = 1.40; 95% CI 1.16–1.68) and in estrogen and progesterone receptor positive (ER+PR+) breast cancer cases (HR = 1.46; 95% CI 1.15–1.85). The authors conclude that long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer.

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Long-term risks of hysterectomy for benign indication: what is known?

21 March 2022

Summary

Hysterectomy is the most common treatment option for women with uterine fibroids, providing definitive relief of the associated burdensome symptoms. Nevertheless, as with all surgical interventions, it is associated with the risk of complications, short-term morbidities, and mortality. Although all these aspects have previously been described, information regarding the potential long-term risks of hysterectomy is only recently becoming available. Bearing this in mind, recently, Madueke-Laveaux et al. [1] conducted a systematic review of the literature to identify long-term risks related to hysterectomies performed for uterine fibroids with or without oophorectomies since the short-term risks of both morbidity and mortality have already been widely studied. They included in their review studies published between 2005 and December 2020 that assessed the long-term impact of hysterectomy for benign pathology in women, identifying 29 relevant studies. The review of the identified articles showed that hysterectomy even with ovarian preservation can increase the risk of cardiovascular events (very strongly associated with hypoestrogenism), certain cancers (i.e urinary tract), the need for further surgery, and premature ovarian failure and menopause that lead to long-term sequelae such as fragility fractures, cognitive impairment and impairment of quality of life in different domains. In addition, when hysterectomy was performed in younger women (< 44 years) a significant higher rate of depression was found after 10 years of follow-up when compared to menopausal women over 50 years with established menopause. The authors remark that it is important to recognize that the available studies examine possible associations and hypotheses rather than causality, hence the results should be taken with caution.

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Breast cancer prevention: Time for Change

14 March 2022

Summary

The preventive management of breast cancer often involves endocrine targeted treatments including tamoxifen and aromatase inhibitors. These have shown to lead to fewer diagnosis of estrogen receptor-positive breast cancers but have not consistently demonstrated reduced mortality related to breast cancer. The following paper to be commented is a review of the evidence of different treatments to reduce risk of future breast cancer [1]. A meta-analysis of four randomised prevention trials has shown that tamoxifen reduced the 10 year cumulative incidence of invasive breast cancers by 33% [2]. However, there was no beneficial effect on mortality demonstrated. Interventions such as magnetic resonance imaging screening and risk reduction bilateral mastectomy have shown to be effective interventions. Despite this, in the Women’s Health Initiative (WHI) randomized, controlled trial, ER-positive, PR-negative cancers were statistically significantly reduced in the group given conjugated equine estrogen and also deaths from breast cancer were reduced by 40% [3]. This finding has not been demonstrated for any other pharmacological intervention. This information needs to be widely disseminated to clinicians.

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