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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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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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Cow's milk intake and risk of coronary heart disease in Korean postmenopausal women

17 October 2022

Summary

Numerous publications have reported conflicting results on the association between cow's milk intake and coronary heart disease (CHD). However, studies involving postmenopausal women are very limited. Recently, Ha et al. [1] reported the results of a study that aimed to identify the relationship between cow's milk intake and the risk of CHD in postmenopausal women. For this purpose, the authors used data from the 6th Korean National Health and Nutrition Assessment Survey, including in the analysis 1,825 postmenopausal women aged 50 to 64 years. The frequency of cow's milk consumption for each participant was determined using the semi-quantitative food frequency questionnaire, classifying women into four groups: Q1, those who did not drink milk (n= 666); Q2, frequency of milk intake per week ≤ 1 (n=453); Q3, milk consumption per week ≤ 3 (n=319); and Q4, milk intake >3 times per week (n=387). General characteristics such as education, region (large city, medium or small city, rural), family income, and level of obesity were compared among the 4 groups. Percentages of daily nutrient intake were estimated in comparison with the Korean Dietary Reference Intake recommendations, determining as indicators of CHD risk: the Framingham risk score (FRS), the atherogenic index (AI) and atherogenic index of plasma (AIP). Except for family income, there were no differences among the four groups in terms of age, education, area of ​​residence, or obesity. Comparing the Dietary Reference Intake, the proportion of intake of calcium, phosphorus and riboflavin was higher in the Q4 group than in the Q1-Q3 groups. HDL cholesterol (HDL-C) was higher in Q4 than in Q1. CHD risk factors, represented by FRS, AI, and AIP, were lower in the Q4 group compared to the other groups (FRS [%]: Q1 9.4, Q4 8.5; AI: Q1 3.06, Q4 2.83, and AIP: Q1 0.37, Q2 0.31, Q4 0.32). It was observed that the FRS had a significant positive correlation with the AI ​​or the AIP, and a negative correlation with the frequency of consumption of cow's milk and calcium intake. The authors conclude that compared to women who have not consumed cow's milk, those who have -and frequently- had a better nutritional status of calcium, phosphorus and vitamin B12, higher levels of HDL-C and lower values of CHD risk indicators, such as FRS, AI, and AIP, which would contribute to a decrease in CHD risk over a 10-year period. Therefore, to prevent the risk of CHD in postmenopausal women, it is recommended that there should be a greater emphasis on the consumption of cow's milk, four or more times per week.

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Bisphosphonate treatment and drug holiday

10 October 2022

Summary

Hayes et al. [1] recently reported a study that aimed at examining the comparative risks of drug holidays after long-term (≥3 years, 80% adherence) oral bisphosphonate treatment. This was a population-based cohort study that used province-wide health care administrative databases that provided comprehensive coverage to 120,000 Ontario residents aged 65 years or older.  Data were collected between November 2000 and March 2020 in those who had long-term risedronate therapy and a drug holiday matched 1:1 with those who had long-term alendronate therapy and a drug holiday. Primary outcome was hip fracture within 3 years after at least 120-day ascertainment period, with exclusion of those who died, had a hip or vertebral fracture, entered long-term care, or started another osteoporosis therapy during this 120-day time window. Secondary analyses included shorter follow-up and sex-specific estimates. A total of 25,077 propensity score-matched pairs were eligible (average age 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1,000 patient-years). The association was attenuated with shorter drug holidays (1 year: HR, 1.03 [95% CI, 0.85-1.24]; 2 years: HR, 1.14 [95% CI, 0.96-1.32]). Finally, the researchers concluded that drug holidays after long-term treatment with risedronate were associated with a small increase in risk for hip fracture compared to alendronate drug holidays. The authors noted that they used health care administrative data that did not contain certain important fracture risk factors, which were therefore not included in the study analyses.

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Pelvic floor muscle strength and female sexual function

27 September 2022

Summary 

Sexual dysfunction is a common problem around the menopause and postmenopause which is multifactorial. In this retrospective cross-sectional study from Brazil the authors looked at female sexual function (as measured by the Female Sexual Function Index: FSFI) in relation to pelvic floor muscle strength, as well as age and other demographic data [1]. The sample of almost 1,000 women were volunteers selected from previous studies on the databases from laboratories. All had given their prior consent and only those with a complete data set were included in the final analysis. Women with neurological, collagen or muscle related diseases were excluded as were those with prolapse (> grade 3), those with apical prolapse and those with previous pelvic floor muscle training (PFMT) by a health professional. Pelvic floor muscle strength (PFMS) was tested by vaginal examination using the modified oxford scale (MOS) which is a recognized scale that runs from 0-5: 0 = no contraction; 1 = minor muscle ‘flicker’; 2 = weak muscle contraction; 3 = moderate muscle contraction; 4 = good muscle contraction and 5 = strong muscle contraction. Sexual function was assessed using the FSFI with scores that range from 2-36. The higher the score the better the sexual function. A total score of 26.55 was taken as a cut off value so any woman with a score <26.55 was considered to have sexual dysfunction. Finally, 982 women were included in the study with an average age of 45.76 (range: 30.51 -61.01). 69% had a total FSFI score < 26.55 i.e. sexual dysfunction, 31% had FSFI > 26.55 i.e. normal sexual function. Characteristics of those with highest scores when compared with the lower scores: had age < 45, were white, single, had higher education, higher income, a body mass index ( BMI) < 25, lower parity, undertook regular physical activity and had a higher PFMS (MOS 4-5). Women with MOS 4-5 had higher desire, arousal, lubrication and orgasm and those with MOS 3-5 had higher satisfaction and less pain. The authors conclude that women good PFMS had less complaints about sexual dysfunction.

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