IMS Menopause Live

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.

a prospective cohort sub study of the Aspree trial.

8 August 2022

Summary

Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the 7^th decade after which concentrations increase and are restored to those of reproductive age women in the 8^th decade. The present commented study [1], which was a prospective cohort sub-study of the longitudinal randomized ASPREE trial aimed to establish the association between the concentration of testosterone in the blood and the risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Women using hormonal or steroid therapy were ineligible for inclusion. Concentrations of sex steroids were measured with liquid chromatography-tandem mass spectrometry whilst SHBG was measured with immunoassay. Results were divided into four quartiles and lower and higher concentrations were compared. Primary endpoints were risk of MACE and all cause mortality. Associations with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidemia, impaired renal function, and treatment allocations in the Aspree trial (aspirin vs placebo). A total of 5,535 women were included in the final analysis. Median age at entry was 74.0 years (interquartile range [IQR] 71.7-77.7). During a median follow up of 4.4 years (24,553 person years) 144 (2.6%) women had a first MACE (incidence 5.9 per 1,000 person years). During a median 4.6 years (IQR 3.8-5.6) of follow up (25,295 person years) 200 (3.6%) of the 5,535 women died, an incidence rate of 7.9 per 1,000 person years. In the fully adjusted models, higher concentrations of testosterone were associated with lower incidences of MACE (quartile 4 vs quartile 1 HR 0.57 [95% CI: 0.36-0.91] as were higher concentrations of DHEA (Q4 vs Q1 0.61 [95% CI 0.38-0.97]. For Oestrone, a lower risk of MACE was observed for Q2 only when compared to Q1. No association was seen between SHBG and MACE or between any hormone or SHBG and all-cause mortality. Blood concentrations of testosterone and DHEA above the lowest quartile in older women were associated with first ever MACE. Given that physiological effects of DHEA are mediated through its steroid metabolites, if these findings were to be replicated, trials investigating testosterone therapy for the primary prevention of ischemic cardiovascular disease events in older women would be warranted.

25 July 2022

Summary

Recent studies have shown that women aged 70 years and older have blood testosterone (T) concentrations similar to those of premenopausal women [1,2,], and that circulating T concentrations tend to increase with age from the 8th decade, while concentrations of T’s adrenal precursor dehydroepiandrosterone (DHEA) decline [3,4]. This lead Islam and collaborators to investigate the associations between these sex steroids and cardiovascular disease (CVD) in a large cohort of women aged at least 70 years [5]. They reported on first major adverse (ischaemic) cardiovascular events (MACE) in 5,535 women, mean age 74 years, followed-up for a median of 4.4 years. After adjusting for established risk factors for MACE and study treatment allocation, Islam et al. [5] reported that women with blood T and /or DHEA concentrations in the lowest quartile had almost a 2-fold greater risk of a first MACE compared with women with higher T/DHEA levels (i.e hazard ratios for the highest quartile versus the lowest quartile were 0.57 [95% CI, 0.36 to 0.91, p=0.02] for T and 0.61 [95% CI, 0.38 to 0.97, p=0.04] for DHEA. No meaningful findings for oestrone or sex hormone binding globulin (SHBG) were seen. Divergence of the cumulative hazard curves for MACE for the lowest quartiles of T and DHEA were statistically significantly different from the other higher quartiles by the third year of follow-up. The authors concluded that higher androgen blood levels are not deleterious to cardiovascular health in older women and that further studies of T and MACE in older women are needed.

18 July 2022

Summary

Gambacciani et al. [1] performed a prospective pilot study to evaluate the effects of associating a neodymium:yt-trium–aluminum–garnet (Nd:YAG) laser with a vaginal erbium laser (VEL), as a non-ablative photothermal therapy for superficial dyspareunia in postmenopausal women (PMW) suffering of the genitourinary syndrome of menopause (GSM). Two groups of sexually active PMW reporting superficial dyspareunia were selected: one (n= 15, VEL) was treated using an erbium:yttrium–aluminum–garnet laser crystal with a wavelength of 2,940 nm; and the other group (n =15, VEL + Nd:YAG) was treated with VEL and after by Nd:YAG laser treatment. Treatment consisted of three laser applications at 30-day intervals. Symptoms were assessed before, after each laser application and after 1 and 3 months from the end of the treatment, using the subjective visual analog scale (VAS) for superficial dyspareunia. All the participants (n = 30) of the both groups showed a rapid and significant improvement of superficial dyspareunia over time independently of age and years since menopause. The VEL + Nd:YAG group showed a greater improvement of superficial dyspareunia; this difference was evident since the first treatment and remained stable over time. Authors conclude that this pilot study demonstrates that the addition of Nd:YAG to VEL may induce greater improvement in superficial dyspareunia in PMW with GSM.

11 July 2022

Summary

A recent cross-sectional study was conducted by an Indian university on whether women's cognitive abilities are sensitive to the severity of menopausal symptoms [1]. The study involved 404 rural women aged 40 to 65 years who completed the Green Climacteric Scale to assess the severity of menopausal symptoms and the Hindi Mini-Mental State Examination scale to assess certain cognitive performances. Possible associations of the menopausal symptoms were assessed to the overall cognitive performance and five cognitive domains (orientation, registration, attention, recall, and language/visuo-spatial skills). The results found that women experiencing severe menopausal symptoms (higher Total Greene climacteric score) presented significantly lower average values for orientation, registration, attention, recall, and language/visuo-spatial skills as compared to women with mild menopausal symptoms. Multivariate linear regression analysis found that severe depression and sexual dysfunction were significantly and negatively associated with overall cognitive scores. The authors conclude that the cognitive performance of women was sensitive to severe depression and sexual dysfunction.

27 June 2022

Summary

Vulvar lichen sclerous (VLS) is an important concern after the menopause and is caused by chronic vulvar inflammation associated to low levels of estrogen. Pruritus and burning sensation in the affected areas of depigmentation are usually the most frequently reported symptoms, causing dyspareunia and sexual dysfunction. Topic corticoid treatment, although effective, is often discontinued after a long time due to the low adherence [1,2]. In this sense, alternative treatments have been proposed such as microablative fractional radiofrequency (MFR). In a recent pilot study, Kamilos et al. [3] assessed the effects of MFR (including clinical response and histomorphometrics) in 26 postmenopausal women with symptomatic and histologically confirmed VLS divided into three groups according to previous management with corticosteroids: G1, no previous corticosteroid treatment; G2, treated with corticosteroid for up to 5 years; and G3, treated for more than 5 years. After each session they were examined for their symptoms on a visual analog scale and completed a satisfaction questionnaire. Morphometric findings of vulvar biopsies were performed at enrollment and after the last treatment session in 11 cases. After two to three MFR sessions, most participants in all groups became either ‘‘asymptomatic’’ or ‘‘much better’’ than prior to treatment and were ‘‘very satisfied’’ or ‘‘satisfied’’ with the intervention. Upon enrollment, pruritus and burning sensation were the most frequently reported symptoms. Nearly 40% of women in all groups reported complete remission of symptoms. The improvement was rated as moderate or higher by 80%, 76%, and 66% of participants in groups 1, 2, and 3, respectively. The symptomatic improvement persisted for a mean of 11 months (range, 7–16) after the treatment. Type III collagen concentration significantly increased and was associated with important symptom improvement. The authors conclude in their pilot study that may be an effective and safe treatment for symptomatic VLS.

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.

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.

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.

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.