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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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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 disruption 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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Behavioral interventions to improve sleep outcomes in menopausal women: a systematic review and meta-analysis

20 September 2022

Summary

Lam et al. [1] recently reported a systematic review and meta-analysis aimed at assessing the efficacy of behavioral interventions on sleep outcomes among peri- and postmenopausal women, as measured by standardized scales and objective methods (polysomnography, actigraphy). Secondarily they evaluated the safety of these methods through the occurrence of adverse events. The authors performed searches within MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science using an appropriate search strategy in order to retrieve relevant papers of randomized controlled trials (RCTs) evaluating the effects of behavioral interventions on sleep quality. Risk of bias was also assessed with classical tools used for this purpose. All data were pooled in a meta-analysis using a random-effects model. A total of nineteen articles reporting results from 16 RCTs were included, representing a total of 2,108 peri- and postmenopausal women. Overall, behavioral interventions showed a statistically significant effect on sleep outcomes. Subgroup analyses revealed that cognitive behavioral therapy (CBT), physical exercise and mindfulness/relaxation improved sleep, as measured using both subjective (i.e the Pittsburg Sleep Quality Index) and objective measures. Low- and moderate-intensity exercise also improved sleep outcomes. No serious adverse events were reported. Overall risk of bias ranged from some concern to serious, and the certainty of the body of evidence was assessed to be of very low quality. The investigators conclude that their meta-analysis provides evidence that behavioral interventions, specifically, CBT, physical exercise, and mindfulness/relaxation, are effective treatments to improving sleep outcomes among peri- and postmenopausal women.

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Endometriosis in women undergoing ovarian tissue transplantation due to spontaneous or induced premature menopause

12 September 2022

Summary

Recently, Lotz et al. [1] reported the results of a retrospective study carried out on 17 women with premature menopause (spontaneous or induced) who had undergone ovarian tissue transplantation to restore their fertility, and were diagnosed with endometriosis during laparoscopic transplantation. The authors were interested in determining how endometriotic lesions after cytotoxic treatment and premature menopause might be explained, and whether endometriosis affects pregnancy rates. During surgery, it was found that twelve women had stage I endometriosis and five stage II endometriosis according to the rASRM classification; endometriosis foci were completely removed and ovarian tissue was transplanted into the pelvic peritoneum. Of the 17 women with endometriosis, 4 women were reported to have dysmenorrhea complaints, but none of the women reported general pelvic pain or dyspareunia. Prior to transplantation, four women who had taken hormone replacement therapy, four oral contraceptives and two tamoxifen. Following ovarian transplantation, pregnancy rate was 41.2% and the live birth rate was 35.3%. Pregnancy occurred in three cases after spontaneous conception, in four women after a natural cycle IVF/ICSI. The investigators concluded that there is an under-researched association between endometriosis in women entering premature or early menopause either after gonadotoxic treatment or due to primary ovarian insufficiency, recommending that specialists need to be aware of this condition as more and more women will use cryopreserved ovarian tissue transplant as an option to fulfill their desire to have children.

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The effects of exercise on vasomotor symptoms in menopausal women:

a systematic review and meta-analysis

22 August 2022

Summary

Liu et al. [1] recently reported a systematic review and meta-analysis that evaluated the potential of structured exercise to alleviate the subjective frequency and severity of vasomotor symptoms (VMS). For this, the authors searched four databases in order to identify randomized controlled trials (RCTs) that evaluated the effect of structured exercise (i.e. aerobic training) on the severity and/or frequency of VMS in menopausal women. Two reviewers independently screened records for eligibility, extracted data and assessed risks of bias and evidence certainty using the Cochrane and the GRADE tools (Grading of Recommendations Assessment, Development and Evaluation). Data were pooled, when appropriate, using random-effect meta-analyses. The researchers appraised a total of twenty-one RCTs involving 2,884 participants. Compared to no-treatment (controls), exercise significantly improved severity of VMS (10 studies, standardized mean difference [SMD] = 0.25; 95% CI: 0.04 to 0.47, p = 0.02, very low certainty of evidence). The effect size was attenuated when studies with a high risk of bias were excluded (SMD = 0.11, 95% CI: -0.03 to 0.26, p = 0.13). No significant changes in vasomotor frequency were found between exercise and controls (SMD = 0.14, 95% CI: -0.03 to 0.31, p = 0.12, high certainty of evidence). The authors conclude that exercise might improve VMS severity, indicating that future rigorous randomized clinical trials (RCTs) addressing the limitations of their review are warranted to explore the optimal exercise prescription to target the severity of VMS. 

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Low sexual function is associated with menopausal status in mid-aged women with HIV infection

15 August 2022

Summary

Recently, Mezones-Holguin et al. [1] reported the results of a study aimed at evaluating the association between menopausal status and female sexual function among mid-aged women with human immunodeficiency virus (HIV) infection. This was a cross-sectional study performed on 221 sexually active HIV-infected women aged 40 to 59, based on a secondary analysis of a three-hospital survey performed in Lima, Perú. Menopausal status was classified according to Stages of Reproductive Aging Workshop criteria (STRAW+10), the exposure variable was categorized as binary (non-postmenopausal and postmenopausal) and as multinomial (pre-, peri-, and postmenopausal). The 6-item Female Sexual Function Index (FSFI, total score 19 or less) was used to define low sexual function (LSF). In addition, socio-demographic and clinical variables were assessed that included age, used highly active antiretroviral therapy scheme, disease duration (time since diagnosis), depressive symptoms, and co-morbidities. Poisson generalized linear models were used. Studied women women had a median age of 47.0 years (interquartile range: 7.5), 25.3% were premenopausal, 25.8% were perimenopausal, and 48.9% were postmenopausal. The authors found that 64.3% had LSF. The frequency of LSF was 53.6% among non-postmenopausal women and 75.0% in postmenopausal ones. Postmenopausal status was associated with LSF in both the crude (cPR= 1.39; 95% CI: 1.13-1.71) and the adjusted regression models (aPR= 1.38; 95% CI: 1.12-1.71). The authors conclude that HIV-infected postmenopausal women have a higher prevalence of LSF than those non-postmenopausal ones, even when adjusting for multiple potential confounders.

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