April 2023

1. Zuercher MD, Harvey DJ, Au LE, Shadyab AH, Nassir R, Robbins JA, Seldin MF, Garcia L. Genetic admixture and cardiovascular disease risk in postmenopausal Hispanic women. Int J Cardiol. 2022;367:99-104.

Background
Hispanics are a heterogeneous population with differences in the prevalence of cardiovascular disease (CVD) and its related risk factors among ethnic sub-groups.

Objective
To evaluate the association of genetic admixture and CVD in self-identified Hispanic women from the Women’s Health Initiative (WHI).

Design

https://pubmed.ncbi.nlm.nih.gov/35961613/

2. Kojima G, Taniguchi Y, Ogawa K, Aoyama R, Urano T. Age at menopause is negatively associated with frailty: A systematic review and meta-analysis. Maturitas. 2022;165:94-99.

Background
Menopause and related changes may be associated with frailty and contribute to higher frailty risk.

Objective
To analyze the association between menopause and frailty.

Design

• This systematic review of the literature and meta-analysis combines the findings from studies of community-dwelling women.
• PubMed was systematically searched in March 2021 with a timeframe from 2000 to March 2021 without language restriction.
• Potentially eligible studies were those that provided cross-sectional or prospective observational data on associations between menopause and frailty in community-dwelling women.
• Reference lists of relevant articles and the included studies were reviewed for additional studies.
• The same effect sizes were combined using a meta-analysis involving the generic inverse variance method.

Main findings

• From 131 studies identified, cross-sectional data on age at menopause from three studies and longitudinal data on surgical menopause from two studies were used for meta-analysis.
• Each one-year increase in age at menopause was significantly associated with a 2% decreased risk of prevalent frailty (pooled odds ratio = 0.98, 95% CI (confidence interval) = 0.96-0.99, p < 0.001).
• Surgical menopause did not predict incident frailty (pooled OR = 1.02, 95% CI = 0.82-1.28, p = 0.23).

Take-home messages

• This systematic review and meta-analysis showed that later age at menopause was significantly associated with a lower risk of prevalent frailty.
• In a clinical setting, age at menopause can be useful information to help clinicians to evaluate and stratify frailty risk in postmenopausal women.
• Hormonal changes after menopause may be related to the link between age at menopause and frailty and thus warrant further investigation.

https://pubmed.ncbi.nlm.nih.gov/35940027/

3. Duggan C, Tapsoba JD, Scheel J, Wang CY, McTiernan A. Weight loss reduces circulating micro-RNA related to obesity and breast cancer in postmenopausal women. Epigenetics. 2022;17(13):2082-2095.

Background

• Postmenopausal women with overweight or obesity have an increased risk of developing breast cancer but many of the mechanisms underlying this association remain to be elucidated.
• MicroRNAs (miRNAs), short non-coding single-stranded RNAs, regulate many physiological processes by controlling post-transcriptional regulation of mRNA.

Objective          
To analyze the relationship between weight loss and circulating micro-RNA related to obesity and breast cancer in postmenopausal women.

Design

• The authors measured circulating miRNA from 192 overweight/obese postmenopausal women (50-75 years) who were part of a randomized controlled trial, comparing independent and combined effects of a 12-month reduced-calorie weight-loss diet and exercise programme, versus control.
• RNA was extracted from stored plasma samples, and 23 a priori selected miRNA targets related to aetiology of breast cancer or obesity were measured using NanoString nCounter miRNA Expression assays.
• Changes from baseline to 12-months between controls and women in the diet/exercise weight loss arms were analysed using generalized estimating equations modification of linear regression, adjusted for confounders.
• Authors next examined changes in levels of circulating miRNA by amount of weight loss (0-10% versus ≥10%).

Main findings

• Participants randomized to weight-loss interventions had statistically significantly greater reductions in miR-122 (-7.25%), compared to controls (+ 33.5%, P = 0.009), and miR-122 levels were statistically significantly correlated with weight loss (rho = 0.24; P = 0.001).
• Increasing weight loss was associated with greater reductions in miR-122 versus controls (-11.7% (≥10% weight loss); +2.0% (0-10% weight loss) +33.5% (controls); P trend = 0.006), though this was not significant after correction for multiple testing (P = 0.05/23).

Take-home message
The present study supports the effect of weight loss on regulation of miRNA.

https://pubmed.ncbi.nlm.nih.gov/35938852/

4. Clayton GL, Soares AG, Kilpi F, Fraser A, Welsh P, Sattar N, Nelson SM, Tilling K, Lawlor DA. Cardiovascular health in the menopause transition: a longitudinal study of up to 3892 women with up to four repeated measures of risk factors. BMC Med. 2022;20(1):299.

Background
Women experience adverse changes in cardiovascular health in mid-life; whether the menopausal transition influences these remains strongly debated.

Objective
To examine associations of reproductive age (time since final menstrual period (FMP)) with change in carotid intima media thickness (CIMT) and cardiovascular risk factors and determine the role of chronological and reproductive age.

Design

• Authors used data from 1,702 women from a pregnancy-based UK cohort who had up to four repeat cardiovascular health measures between mean age 51 (SD = 4.0) and 56 (SD = 3.6) years and experienced a natural menopause.
• Multilevel models were used to assess the relationship between cardiovascular measures and time since FMP (reproductive age), whilst adjusting for the underlying effects of chronological age and confounders (socioeconomic factors, body mass index, smoking, alcohol, parity, age at menarche).
• In addition, researchers looked at the relationship between cardiovascular measures by chronological age according to menopausal stages (pre-, peri- and postmenopause) using information from women who had and had not experienced menopause (n = 3,892).

Main findings

• There was no strong evidence that reproductive age was associated with CIMT (difference in mean 0.8 μm/year, 95% CI – 0.4, 2.1), whereas there was a strong positive association of chronological age (7.6 μm/year, 95% CI 6.3, 8.9).
• Consistent with this, authors found weaker linear associations of reproductive compared with chronological age for atherosclerotic risk factors, such as with systolic blood pressure (- 0.1 mmHg/year, 95% CI – 0.3, 0.1, and 0.4 mmHg/year, 95% CI 0.2, 0.5, respectively) and non-HDL-cholesterol (0.02 mmol/l/year, 95% CI 0.005, 0.03, and 0.06, 95% CI 0.04, 0.07, respectively).
• In contrast, associations with fat mass (0.06 kg/m2/year, 95% CI 0.03, 0.10, and 0 kg/m2/year, 95% CI – 0.04, 0.04, respectively) and C-reactive protein (0.01, 95% CI 0.001, 0.02, and 0.01, 95% CI – 0.001, 0.02 natural logged mg/l/year, respectively) were stronger for reproductive compared with chronological age.
• Both reproductive and chronological age were (weakly) positively associated with glucose (0.002, 95% CI 0.0001, 0.003, and 0.002, 95% CI 0.0001, 0.003 natural logged mmol/l/year, respectively).

Take-home messages

• This study suggests that going through the menopausal transition does not further increase women’s risk of atherosclerosis (measured by CIMT) beyond effects of ageing.
• Menopausal transition may, in additional to ageing, modestly increase adiposity and glucose levels and therefore a possible associated diabetes risk.

https://pubmed.ncbi.nlm.nih.gov/35974322/

5. Blümel JE, Aedo S, Murray N, Vallejo MS, Chedraui P. Health screening of middle-aged women: what factors impact longevity? Menopause. 2022;29(9):1008-1013.

Objective
To measure the impact of different risk factors in middle-aged women on longevity evaluated after three decades of an initial health screening.

Design

• Women who received an annual check-up between 1990 and 1993 were recruited.
• Anamnesis and physical examination were recorded.
• Blood samples for the measurement of glycemia and lipids were taken.
• Data are reported as of December 2021.

Main findings

• A total of 1,158 women aged 40 to 60 were studied.
• At 30.9 years of follow-up, the Kaplan-Meier overall survival was 75.6% (95% confidence interval, 72.6-78.3).
• The main causes of the 260 deaths observed were the following: cancer ( n = 88; 33.8%), cardiovascular disease ( n = 55; 21.2%), and infectious disease ( n = 41; 15.8%).
• The following hazard ratios were found with the flexible parametric survival model: personal history of fracture (hazard ratio, 2.55; 95% confidence interval, 1.29-5.02; P = 0.007), type 2 diabetes mellitus (2.14; 1.18-3.88; P = 0.012), personal history of heart disease (1.85; 1.09-3.13; P = 0.022), chronic arterial hypertension (1.65; 1.25-2.17; P < 0.001), postmenopausal status (1.60; 1.13-2.26; P = 0.008), unskilled jobs (1.56; 1.17-2.07; P = 0.002), cigarette smoking (1.51; 1.17-1.94; P = 0.002), age (1.06; 1.03-1.09; P < 0.001), body mass index (1.04; 1.01-1.07; P = 0.004), multiparous (0.72; 0.56-0.93; P = 0.012), and active sexual intercourse (0.68; 0.52-0.87; P = 0.003).
• Lipid disorders did not reach statistical significance as a risk factor.

Take-home messages

• In this cohort, it was observed that most of the classic risk factors for mortality were present; however, a history of fracture appears in middle-aged women as a strong predictor of mortality, surpassing diabetes and arterial hypertension.
• Multiparity, on the other hand, was a protective factor.

https://pubmed.ncbi.nlm.nih.gov/35969889/

6. Santoro AM, Simpson CA, Cong E, Haas A, Sullivan RR, Parziale S, Deng Y, Insogna KL. Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study. Menopause. 2022;29(10):1200-1203.

Objective
To examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women.

Design

• Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study.
• All participants received micronized progesterone for 12 days per month.

Main findings

• There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms.
• In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group.
• Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms.
• Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months.
• Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment.

Take-home messages

• Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, were different within the first 12 months of estrogen replacement depending on the preparation; however, this difference was transient, in that there were no differences at 36 or 48 months.
• These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or insufficient.

https://pubmed.ncbi.nlm.nih.gov/35969885/

7. Dam TV, Dalgaard LB, Johansen FT, Bengtsen MB, Mose M, Lauritsen KM, Gravholt CH, Hansen M. Effects of transdermal estrogen therapy on satellite cell number and molecular markers for muscle hypertrophy in response to resistance training in early postmenopausal women. Eur J Appl Physiol. 2023;123(3):667-681.

Objective
To investigate the effects of resistance training with or without transdermal estrogen therapy (TET) on satellite cell (SC) number and molecular markers for muscle hypertrophy in early postmenopausal women.

Design

• Using a double-blinded randomized controlled design, the authors allocated healthy, untrained postmenopausal women to perform 12 weeks of resistance training with placebo (PLC, n = 16) or TET (n = 15).
• Muscle biopsies obtained before and after the intervention, and two hours after the last training session were analyzed for fiber type, SC number and molecular markers for muscle hypertrophy and degradation (real-time PCR, western blotting).

Main findings

• The analysis of SCs per Type I fiber showed a time x treatment interaction caused by a 47% decrease in PLC, and a 26% increase after TET after the training period.
• Also, SCs per Type II fiber area was lower after the intervention driven by a 57% decrease in PLC.
• Most molecular markers changed similarly in the two groups.

Take-home message
A decline in SC per muscle fiber was observed after the 12-week training period in postmenopausal women, which was counteracted when combined with use of transdermal TET.

https://pubmed.ncbi.nlm.nih.gov/36585491/

8. Yoshikata R, Yamaguchi M, Mase Y, Tatsuyuki A, Myint KZY, Ohta H. Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial. PLoS One. 2022;17(12):e0270242.

Background

• As estrogen level decreases with aging, the vaginal mucosa gets thinner, and collagen amount decreases.
• In addition, the population of Lactobacillus in the vagina declines, increasing the risk of atrophic vaginitis, bacterial vaginosis, and genitourinary symptoms in the postmenopausal women.

Objective
To evaluate the effects of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women.

Design

• This was a pilot randomized controlled trial in 35 premenopausal and 35 postmenopausal healthy women.
• For four weeks, treatment 1 group (14 premenopausal and 16 postmenopausal women) used the Lactobacillus-containing feminine soap and cream, and treatment 2 group (15 premenopausal and 14 postmenopausal women) used Lactobacillus-containing feminine gel in addition to soap and cream.
• The remaining six premenopausal and five postmenopausal women served as controls without using any products.
• Authors then compared the changes in the vaginal microbiota, genitourinary symptoms, and other related biomarkers after completion of treatment.

Main findings

• Vaginal pH and pathogenic flora were reduced in both treatment groups compared to control group, which was more significant in the treatment 2 group of postmenopausal women.
• Genitourinary symptoms significantly improved in 60% of premenopausal women in treatment 1 group and 81.3% of postmenopausal women in treatment 2 group, compared to control group (0%, p = 0.043 and p<0.01 respectively).
• Overactive bladder symptom scores were significantly improved after using the products in eleven out of twelve postmenopausal women suspected of having overactive bladder.

Take-home message
The use of Lactobacillus-containing feminine products was associated with improved vaginal ecosystem and urogenital health compared to control group, especially in those women using feminine gel.

https://pubmed.ncbi.nlm.nih.gov/36584204/

9. Lopez Gavilanez E, Navarro Chávez M, Gavilanes AWD, Cedeño German R, Chedraui P. Decreasing incidence rates of osteoporotic hip fractures in Ecuador during the COVID-19 pandemic. Arch Osteoporos. 2022;18(1):15.

Background
The impact that the COVID-19 pandemic has had on fragility fractures is being recently evaluated in the literature. Despite this, data from Latin America in this regard is scarce.

Objective
To compare the incidence rate of hip fractures before and during the COVID-19 pandemic in older adults who received care in the public and private health system of Ecuador.

Design

• This was a descriptive and retrospective study that analyzed data of individuals aged 60 years and older who had hip fractures before and during the COVID-19 pandemic.
• The information was obtained from the National Hospital Discharge Yearbook.
• Authors calculated the incidence, average length of hospital-stay, mortality, and case-fatality rate associated with hip fractures.

Main findings

• There was a significant reduction in the incidence of hip fractures in adults 60 or older during the period of social isolation due to COVID-19.
• Between March and December 2019, there was an incidence of 152 hip fractures per 100,000 inhabitants, whereas during the same period but in 2020 in the incidence was 110 per 100,000 inhabitants (p < 0.0001).
• The main decrease was observed in women aged 80 or more.
• The average length of hospital stay did not show significant changes.
• Mortality displayed a non-significant decrease (p = 0.14), although this decrease was significant among women (p = 0.02).
• Case-fatality rate showed a non-significant increase for the whole group (p = 0.68) and for men (p = 0.09).

Take-home messages

• Hip fracture rates decreased significantly in adults aged 60 and older in 2020 compared to 2019.
• This decrease of hip fracture incidence rates was mainly due to the reductions observed in older people and women.
• The average length of hospital-stay, mortality, and case-fatality rate associated with hip fractures did not show significant changes during the pandemic.

https://pubmed.ncbi.nlm.nih.gov/36574063/

10. Lello S, Paris I, Cagnacci A, Sartori D, Caruso S, Iop A. Vasomotor symptoms and management of women undergoing treatment for breast cancer: literature review with focus on the therapeutic potential of cytoplasmic pollen extract. Gynecol Endocrinol. 2023 Jan 2:1-6. doi: 10.1080/09513590.2022.2162035.

Background
Effective management of vasomotor symptoms (VMS) in patients undergoing treatment for breast cancer (BC) represents a critical but frequent unmet need.

Objective
To summarize the epidemiology, pathophysiology, and clinical features of VMS in patients with BC and provide a synopsis of the complementary and alternative medicine (CAM) approaches in relieving VMS with a focus on purified cytoplasm of pollen (PCP).

Design
The authors reviewed the literature on VMS epidemiology, pathophysiology, clinical burden, and CAM treatment in healthy women and patients with BC.

Main findings

• VMS are common in patients with BC undergoing hormonal treatment and negatively impact quality of life, leading to treatment discontinuation in up to 25% of patients with detrimental impact on risk of BC recurrence and overall survival.
• CAM approaches to treat VMS in patients with BC include vitamin E, phytoestrogens, and black cohosh, even if there is a lack of solid evidence to guide clinicians in the choice of treatment.
• PCP, obtained according to standards of good manufacturing practice, has a definite pharmacological mechanism of action, is devoid of estrogen activity, and has shown clinical efficacy on menopause-associated symptoms with a favorable safety profile and high compliance.
• As such, it appears to represent a valid management option to improve quality of life in patients with pre- and postmenopausal BC.

Take-home messages

• Physicians should actively investigate the presence and impact of VMS in patients receiving therapy for BC.
• Additional and appropriately sized randomized clinical trials are needed to provide clear evidence on how to best meet the needs of patients with BC suffering from menopause-associated symptoms.

https://pubmed.ncbi.nlm.nih.gov/36591791/