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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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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.

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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.

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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.

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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.

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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.

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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).

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Vaginal laser therapy versus hyaluronic acid suppositories for women with symptoms of urogenital atrophy after treatment for breast cancer: A randomized controlled trial

28 November 2022

Summary

Urogenital atrophy affects more than half of women after breast cancer (BC) and in this population there is reluctance to use local estrogen. Therapies free of hormones such as intravaginal laser and hyaluronic acid suppositories have shown to produce symptom relief in women with BC and urogenital atrophy. However, they have not been tested against each other. In sense, recently, Gold et al. [1] have published data of randomized controlled trial aimed at comparing these non-hormonal modalities in women with urogenital atrophy after BC. They randomly assigned 43 women (aged 49-58 years, mean 54) with urogenital atrophy and a history of BC to receive intravaginal laser therapy (n=22, 2 courses within 1 month) or hyaluronic acid suppositories (n=21, 3 times/week continuously for three months). Their primary endpoint was the score of the Vaginal Health Index (VHI) after 3 months. Secondary endpoints were subjective bother on a numeric rating scale for all urogenital atrophy domains, quality of life, sexual health and pelvic organ prolapse symptoms using validated questionnaires. After 3 months VHI scores improved significantly in both groups, without significant differences observed between treatment groups. Significant improvement was also seen in both groups for subjective bother of urogenital atrophy, quality of life and sexual health, without significant differences seen between both groups. The authors conclude that both, intravaginal laser therapy and hyaluronic acid suppositories, were effective treatment options for women after BC suffering from urogenital atrophy.

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Menopause impacts the human brain structure, connectivity, energy metabolism, and amyloid‑beta deposition

21 November 2022

Summary

The menopause transition (MT) is a neuro-endocrine process that impacts the aging trajectories of multiple organ and systems including the brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. However, the way this process impacts the human brain remains unclear. Recently Mosconi et al. [1] reported a multi-modality neuroimaging study that indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-, peri- and post-menopause). These effects involved brain regions sub-serving higher-order cognitive processes and were specific to menopausal endocrine aging rather than chronological aging, as determined by comparison to age-matched males. Brain biomarkers largely stabilized during postmenopause, and gray matter volume (GMV) recovered in key brain regions for cognitive aging. Notably, GMV recovery and in vivo brain mitochondria ATP production correlated with preservation of cognitive performance in the postmenopausal stage, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-β deposition was more pronounced in peri- and postmenopausal women carrying the apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer’s disease (AD), relative to genotype-matched males.

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Disruption of Sleep continuity during the Perimenopause - is there an association with female reproductive hormone?

31 October 2022

Summary

Sleep problems are frequently encountered during the menopausal transition, which have been related to various factors and can impair female quality of life [1]; however, direct relation with hormonal changes of the menopausal transition is still unclear. Recently Coborn et al. [2] reported a study that aimed at determining the association between female reproductive hormones and sleep discontinuity independent of night vasomotor symptoms (VMS) and depressive symptoms (DepS) in perimenopausal women. For this, daily sleep and VMS diaries, as well as weekly serum measurements of female reproductive hormones were obtained for 8 consecutive weeks among 45 perimenopausal women with night VMS and mild DepS. Women with primary sleep problems were excluded. Estimating equations were used to examine associations of estradiol, progesterone, and FSH with the mean number of nightly awakenings, wakefulness after sleep onset (WASO) and sleep-onset latency (SOL), adjusting for night VMS and DepS. The authors found that sleep disruption was common (awakenings/night, WASO and SOL). In adjusted models, a higher rate of awakenings was associated with postmenopausal estradiol levels and higher FSH levels, but not with progesterone. Female reproductive hormones were not associated with WASO or SOL. The authors conclude that the relationship of more awakenings with lower estradiol and higher FSH levels gives support for sleep discontinuity in the perimenopause linked with female reproductive hormone changes, independent of night VMS and DepSx.

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Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: recommendation statement of the US Preventive Services Task Force

24 October 2022

Summary

The US Preventive Services Task Force (USPSTF) published a recommendation on statin use for primary prevention in 2016 [1]. Now the task force has commissioned a new review of the evidence on the benefits and harms of statins as the basis for an update of the 2016 guidelines [2]. There were 26 studies included in the review, 23 randomised trials and three observational studies. Since the 2016 review, there was only one new trial but separate primary prevention data had become available from some other studies. The main finding was that there is moderate certainty that statin use offers moderate net benefit (in terms of reduced risk of cardiovascular disease (CVD) events and all-cause mortality) for adults aged 40-75 years with no history of cardiovascular disease but have at least one CVD risk factor and an estimated 10-year risk of a CVD event of at least 10% [3]. This recommendation does not apply to people with a LDL cholesterol level above 4.92 mmol/L, those with familial hypercholesterolaemia or adults aged over 75 years. The USPSTF also recommends that statins could be considered for adults aged 40-75 years with no history of CVD and at least one CVD risk factor and an estimated 10-year risk of a CVD event of between 7.5 and 10%.

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