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President’s Report

Dear Friends and Colleagues,

Happy New Year to you all. The year brings with it hope for a light at the end of the tunnel, but we continue to live and work in unprecedented times. The IMS remains resilient and adaptable, which was evident in our first Board meeting on 13th December 2020, when we discussed our plans to deliver a diverse range of educational activities, CAMS and the launch of our new and improved website later this month.

As you know, we invited IMS members to join Board Committees, which will begin meeting from this month. The Committees will focus on delivering the IMS strategic plan. The Executive and Committee members are listed below for your information. I would like to take the opportunity to thank everyone for their valuable contributions.

Executive – Chair: Steven Goldstein (President), Nick Panay (President Elect), Susan Davis (Past President), Rossella Nappi (General Secretary), Ang Seng Bin (Treasurer)

Finance Committee – Chair: Ang Seng Bin, Sunila Khandelwal, James Pickar

Ethical Standards Committee – Chair: Sonia Cerdas, Pauline Maki, Florence Tremollieres, Jenifer Sassarini

Governance Committee – Chair: Rossella Nappi, Robert Langer, Amos Pines, Santiago Palacios

Education Committee – Chair: Amos Pines, Co-Chair: Wendy Wolfman, Amanda Vincent, Marla Shapiro, Peter Schnatz

Awards Committee – Chair: Tim Hillard, Xiangyan Ruan, Tobie de Villiers, Risa Kagan

Scientific Programme Committee – Chair: Pauline Maki, Rossella Nappi, Tim Hillard

Media Outreach Committee – Chair: Marla Shapiro, Rossella Nappi

Membership Committee – Chair: Robert Langer, Xiangyan Ruan, Peter Chedraui, Denise Black, Louise Newson

Business Development Committee – Chair: Nick Panay, Susan Davis, Amos Pines, Santiago Palacios, Ang Seng Bin, Antonina Smetnik

I would also like to congratulate Anne Gompel, Etka Kapoor and Fatima Stanford for the excellent December webinar, ‘Dealing with a big issue: Weight gain at midlife’. The popularity of these webinars continues to grow, and we are looking forward to announcing the future topics soon.

Between July and December 2020, we had over 2,000 registrants across the English and Spanish versions of IMPART. We will be launching more languages this year, including but not limited to Portuguese, Chinese and Russian. Please encourage fellow health-care professionals to register for this free online course.

We are planning an exciting World Congress with a superior scientific programme in Lisbon on 26–29th October, 2022. Put these important dates in your calendar. We will keep you updated with developments.

Stay safe and well.

Best regards,

Steven Goldstein

General update

The IMS is delivering a symposium, on Tuesday 19th January at 15:00 (CET). The symposium, sponsored by Pfizer, is titled ‘2021 Vision: Practical Steps to Optimize Your Benefit–Risk Discussions for a New Decade’. This event will be chaired by Professor Rodney Baber, Australia with three keynote presentations on the following topics followed by a Q&A session:

Presentation 1: 2021 Vision: Clarity for a New Decade of Menopause Care, Professor Rodney Baber, Australia 

Presentation 2: A Fresh Perspective on a Familiar Challenge: Relatable Risk Communications, Merryn McKinnon PhD, Australia

Presentation 3: Shared Decision-making in Benefit–Risk Conversations, Rossella E. Nappi, MD, PhD, Italy

More details on how to book will be sent out this month.

The December webinar ‘Dealing with a big issue: Weight gain at midlife’ chaired by Anne Gompel with speakers Etka Kapoor and Fatima Stanford is now available on the IMS YouTube Channel: https://youtu.be/jN_Ib6i_Go

El Khoudary SR, Aggarwal B, Beckie TM, et al. Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American Heart Association. Circulation 2020 Nov 30

Background

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk. Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk.

Design

Scientific statement from the American Heart Association.

Objective

To provide an up-to-date synthesis of the existing data on the MT and how it relates to CVD.

Take-home messages

1. The median age of natural menopause is 50 years. Natural menopause is considered premature if it occurs before 40 years of age and early if it occurs between 40 and 45 years of age.

2. Because of the trends for increases in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives postmenopausal.

3. Earlier age at natural menopause is generally reported as a marker of greater CVD risk and linked to being Black or Hispanic, having a short menstrual cycle length, having a low parity, being a smoker, and having a worse cardiovascular health profile during reproductive life. Of note, the studies on age of natural menopause and incident morbidity and mortality are not entirely consistent, which may be the result of different formulations of the composite outcomes.

4. Iatrogenically induced menopause (i.e. bilateral salpingo-oophorectomy) during the premenopausal period is associated with higher CVD risk. Hysterectomy, regardless of ovarian status, does not influence CVD risk factors before or after menopause. Guidelines from the North American Menopause Society endorse menopausal hormone therapy (MHT) use among women with premature or early natural or surgical menopause, with treatment until at least the median age of menopause (in the absence of contraindications).

5. Vasomotor symptoms are associated with worse CVD risk factor levels and measures of subclinical atherosclerosis. These associations may depend on the timing of these symptoms during the MT.

6. Sleep disturbance, a common complaint during the MT, is linked to a greater risk of subclinical CVD and worse cardiovascular health indexes in midlife women.

7. Depression occurs more frequently during the perimenopausal and postmenopausal years and is related to both vasomotor symptoms and incident CVD.

8. The perimenopause stage begins with the onset of intermenstrual cycle irregularities or other menopause-related symptoms. This stage extends 12 months after menopause and has been identified as a stage of vulnerability accompanied by significant alterations in several cardiometabolic and vascular health parameters strongly linked to higher CVD risk.

9. Central/visceral fat increases and lean muscle mass decreases are more pronounced during the MT. The increased central adiposity is associated with an increased risk of mortality, even among those with normal body mass index.

10. Paracardial fat volumes are higher after menopause, independently of age, and could be influenced by estradiol levels or MHT use.

11. Increases in lipids (low density lipoprotein cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the MT more than aging, whereas increases in blood pressure, insulin, and glucose are likely more influenced by chronological aging.

12. Novel data show a reversal in the associations of high density lipoprotein cholesterol (HDL-C) with CVD risk over the MT, suggesting that higher HDL-C levels may not consistently reflect good cardiovascular health in midlife women.

13. Limited data exist on the current status of ideal cardiovascular health components in women during the MT. According to this limited literature, only 7.2% of women traversing menopause report a physical activity level that matches the current recommendation.

14. Although the data are limited, randomized trial results suggest that a multidimensional lifestyle intervention can prevent weight gain while reducing triglycerides, systolic and diastolic blood pressure, as well as blood glucose, insulin, and subclinical carotid atherosclerosis, among women undergoing the MT.

15. Regardless of the strong line of observational evidence showing the MT as a period of accelerated cardiovascular risk, randomized controlled trials of lifestyle and behavioral interventions have not adequately represented this high-risk population.

16. The literature supporting a critical role for the time of initiation of MHT use relative to menopause, with initiation at <60 years of age or within 10 years of menopause appearing to be associated with reduced CVD risk, strongly calls for further research assessing MHT use, including potential contrasts by form, route, and duration of administration, on cardiometabolic effects in women traversing menopause, a large proportion of whom experience menopausal symptoms before even reaching menopause.

17. Data for primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions remain elusive for women, with further study required for evidence-based recommendations to be developed specifically for women.

https://pubmed.ncbi.nlm.nih.gov/33251828/

Nolan BJ, Liang B, Cheung AS. Efficacy of micronised progesterone for sleep: a systematic review and meta-analysis of randomised controlled trial data. J Clin Endocrinol Metab 2020 Nov 27:dgaa873

Background

Pre-clinical data have shown progesterone metabolites improve sleep parameters through positive allosteric modulation of the GABA-A receptor.

Objective

To assess the effect of micronized progesterone treatment on sleep outcomes.

Design

  • Systematic review and meta-analysis of randomized controlled trials
  • Nine randomized controlled trials comprising 388 participants

Main findings

  • Compared with placebo, micronized progesterone improved various sleep parameters as measured by polysomnography, including total sleep time and sleep onset latency, though studies were inconsistent.
  • Meta-analysis of four trials favored micronized progesterone for sleep onset latency but not total sleep time or sleep efficiency
  • Self-reported sleep outcomes improved in most trials
  • Concomitant estradiol administration and improvement in vasomotor symptoms limit conclusions in some studies

Take-home messages

  • Micronized progesterone improves various sleep outcomes in randomized controlled trials, predominantly in studies enrolling postmenopausal women
  • Further research could evaluate the efficacy of micronized progesterone monotherapy using polysomnography or validated questionnaires in larger cohorts

https://pubmed.ncbi.nlm.nih.gov/33245776/

LaMonte MJ, Larson JC, Manson JE, et al. Association of sedentary time and incident heart failure hospitalization in postmenopausal women. Heart Fail 2020 Nov 24: CIRCHEARTFAILURE120007508

Background

The 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB’s role in heart failure (HF) is unclear.

Design and subjects

  • Women’s Health Initiative Observational Study
  • 80,982 women aged 50–79 years, who were without known HF and reported ability to walk ≥1 block unassisted at baseline
  • Mean follow-up was 9 years
  • SB was assessed repeatedly by questionnaire

Main findings

  • Higher HF risk was observed across incremental tertiles of time-varying total SB and sitting time
  • Inverse trends remained significant after further controlling for comorbidities including time-varying myocardial infarction and coronary revascularization and for baseline physical activity

Take-home messages

  • Sedentary behavior is associated with increased risk of incident HF hospitalization in postmenopausal women
  • Targeted efforts to reduce SB could enhance HF prevention in later life

https://pubmed.ncbi.nlm.nih.gov/33228398/

Li H, Hart JE, Mahalingaiah S, et al. Long-term exposure to particulate matter and roadway proximity with age at natural menopause in the Nurses’ Health Study II Cohort. Environ Pollut 2020 Dec 3;269:116216

Background

Evidence has shown associations between air pollution and traffic-related exposure with accelerated aging, but no study to date has linked the exposure with age at natural menopause, an important indicator of reproductive aging.

Objective

To examine the associations of residential exposure to ambient particulate matter (PM) and distance to major roadways with age at natural menopause.

Design and subjects

  • Nurses’ Health Study II (NHS II), prospective cohort study
  • 105,996 premenopausal participants were included at age 40 and followed through 2015

Main findings

  • A 10 μg/m3 increase in the cumulative average exposure to PM10, PM2.5-10, and PM2.5 and living within 50 m to a major road at age 40 were associated with slightly earlier menopause
  • No statistically significant effect modification was found, although the associations of PM were slightly stronger for women who lived in the West and for never smokers

 

Take-home messages

  • Exposure to ambient PM and traffic in midlife was associated with slightly earlier onset of natural menopause
  • Exposure to air pollution and traffic may accelerate reproductive aging

https://pubmed.ncbi.nlm.nih.gov/33316492/

Santoro N, Waldbaum A, Lederman S, et al. Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA). Menopause 2020 Dec;27(12):1350-6

Background

In the primary analysis of the phase 2b VESTA study, oral fezolinetant reduced frequency and severity of menopausal vasomotor symptoms (VMS) compared with placebo.

Objective

To evaluates the effects of fezolinetant on responder rates and patient-reported outcomes (PROs).

Design and subjects

  • Secondary analysis of the phase 2b VESTA double-blind randomized study of fezolinetant 15, 30, 60, or 90 mg BID or 30, 60, or 120 mg QD versus placebo
  • 12 weeks
  • 352 postmenopausal women with moderate/severe VMS were treated and analyzed
  • Changes from baseline in PROs (Menopause-Specific Quality of Life questionnaire, Hot Flash-Related Daily Interference Scale, Greene Climacteric Scale) were evaluated

Main findings

  • A greater proportion of women receiving fezolinetant versus placebo met definitions of response at week 12
  • For all doses, mean changes from baseline in Menopause-Specific Quality of Life questionnaire VMS scores exceeded the minimally important differences (MID) at weeks 4 and 12
  • Mean changes in Hot Flash-Related Daily Interference Scale at weeks 4 and 12 exceeded the MID
  • Greene Climacteric Scale-VMS domain scores improved for most fezolinetant doses versus placebo

Take-home message

Oral fezolinetant is associated with higher responder rates than placebo and larger improvements in quality of life and other patient-reported outcomes measures, including a reduction in VMS-related interference with daily life.

https://pubmed.ncbi.nlm.nih.gov/32769757/

Mishra SR, Waller M, Chung HF, Mishra GD. Association of the length of oestrogen exposure with risk of incident stroke in postmenopausal women: Insights from a 20-year prospective study. Int J Cardiol 2020 Dec 12:S0167-5273(20)34270-4

Background

Endogenous estrogen exposure may lower risk of stroke in postmenopausal women.

Objective

To examine the relationship between the length of estrogen exposure and risk of incident stroke.

Design and subjects

  • Prospective Australian longitudinal study on Women’s Health
  • 5632 postmenopausal women without a prior history of stroke
  • 18-year follow-up
  • Five indices of estrogen exposure were evaluated, including reproductive lifespan (RLS) (age at menopause – age at menarche), endogenous estrogen and total estrogen exposure (which included menopausal hormone therapy (MHT use)

Main findings

  • Mean (SD) for RLS was 37.9 (4.3) years
  • A shorter RLS (≤34 years) was associated with a higher risk of incident stroke, compared with 38–40 years
  • 7% decrease in risk of stroke per 1-year increase in RLS
  • Endogenous estrogen and of total estrogen exposure (including MHT use) did not improve the model of just using RLS as a predictor of incident stroke

Take-home message

A shorter RLS (≤34 years) is associated with higher risk of incident stroke compared to medium RLS.

https://pubmed.ncbi.nlm.nih.gov/33321126/

Kalleinen N, Aittokallio J, Lampio L, et al. Sleep during menopausal transition: a 10-year follow-up. Sleep 2020 Dec 16:zsaa283

Background

Sleep complaints are more common for women than men at any phase of their life and the incidence of complaints increases markedly in women during menopausal transition. Sleep architecture also changes across the life span, but the effect of menopausal transition is controversial.

Objective

To evaluate the changes in sleep architecture during the menopausal transition.

Design and subjects

  • Observational follow-up study
  • Fifty-seven premenopausal women (mean age 46 years, SD 0.9) were studied at baseline and after a 10-year follow-up
  • Polysomnography (PSG) and the serum follicle-stimulating hormone (S-FSH) concentration were evaluated at baseline and after a 10-year follow-up

Main findings

  • Higher S-FSH level was associated with longer sleep latency
  • Aging of 10 years was associated with shorter sleep latency, shorter latency to stage 2 sleep, decreased stage 2 sleep and increased slow wave sleep

Take-home messages

  • Sleep as measured by PSG in middle-aged women does not worsen over a 10-year time span due to menopausal transition
  • Observed changes seem to be rather age- than menopause-dependent

https://pubmed.ncbi.nlm.nih.gov/33326582/

George SM, Reedy J, Cespedes Feliciano EM, et al. Alignment of dietary patterns with the Dietary Guidelines for Americans 2015-2020 and risk of all-cause and cause-specific mortality in the Women’s Health Initiative Observational Study. Am J Epidemiol 2020 Dec 16:kwaa268

Background

Poor diet quality is a leading risk factor for death in the United States (U.S.).

Objective

To examine the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all-causes, cardiovascular disease (CVD), cancer, Alzheimer’s disease and dementia not otherwise specified (NOS) among postmenopausal women.

Design and subjects

  • Women’s Health Initiative Observational Study
  • 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD and diabetes at enrollment
  • Healthy Eating Index (HEI)-2015 quintiles were evaluated, with higher scores reflecting more optimal diet quality
  • Median follow up of 18.2 years

Main findings

  • 9,679 total deaths, 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer’s disease and dementia NOS occurred
  • Compared to those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause mortality and 21% lower risk of cancer mortality
  • HEI-2015 scores were not associated with mortality from CVD, Alzheimer’s disease and dementia NOS

Take-home message

Consuming a diet aligned with 2015-2020 U.S. Dietary Guidelines may have beneficial impacts for preventing death from cancer and overall.

https://pubmed.ncbi.nlm.nih.gov/33325511/

Lawn RB, Nishimi KM, Kim Y, et al. Posttraumatic stress disorder and likelihood of hormone therapy use among women in the Nurses’ Health Study II: a 26-year prospective analysis. Cancer Epidemiol Biomarkers Prev 2020 Dec 21: cebp.1227.2020

Background

Posttraumatic stress disorder (PTSD) is associated with higher risk of certain chronic diseases, including ovarian cancer, but underlying mechanisms remain unclear. While prior work has linked menopausal hormone therapy (MHT) use with elevated ovarian cancer risk, little research considers PTSD to likelihood of MHT use.

Objective

To examine whether PTSD was prospectively associated with greater likelihood of initiating MHT use over 26 years.

Design and subjects

  • Nurses’ Health Study II cohort study
  •  Subjects with trauma and PTSD (symptoms and onset date) assessed by screener in 2008 and MHT assessed by biennial survey

 Main findings

  • 22,352 of 43,025 women reported initiating MHT use
  •  Compared to women with no trauma, the hazard ratio (HR) for initiating MHT was 1.18 for those with trauma/1–3 PTSD symptoms
  •  Compared to women with no trauma, the hazard ratio (HR) for initiating MHT was 1.31 for those with trauma/4–7 PTSD symptoms

Take-home message

Trauma and number of PTSD symptoms are associated with greater likelihood of initiating MHT use in a dose–response manner.

https://pubmed.ncbi.nlm.nih.gov/33355196/

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