EXECUTIVE SUMMARY

Data from research that examined the use of different oral and transdermal hormone therapy agents and their associations between heart fat accumulation and atherosclerosis progression indicated that in comparison to transdermal estradiol patch, oral conjugated equine estrogen appears to slow the adverse effects of increasing paracardial adipose tissue on the progression of atherosclerosis.

• Women in menopause are more likely to accumulate abdominal visceral fat, as well as fat deposition around the heart. Heart fat deposition has been linked to atherosclerosis progression, which also increases between perimenopause and postmenopause.


This year, more than 50 million U.S. women will be older than age 51 years, the mean age when menopause occurs. With an estimated 75% of women reporting symptoms, such as hot flashes or night sweats during the perimenopausal transition and beyond, what options are available to treat these symptoms?1

As women move through menopause, they are more likely to accumulate abdominal visceral fat, as well as fat around the heart.2 Heart fat deposition has been linked to atherosclerosis progression, which also increases between perimenopause and postmenopause.3

A study examined the use of different oral and transdermal hormone therapy agents and the associations between heart fat accumulation and atherosclerosis progression. Data indicated that in comparison to transdermal estradiol patch, oral conjugated equine estrogen appeared to slow down the adverse effects of increasing paracardial adipose tissue on the progression of atherosclerosis.4

Researchers studied 467 healthy women ages 42-58 years who were enrolled in the Kronos Early Estrogen Prevention Study, a multicenter, randomized, placebo-controlled clinical trial. Participants enrolled between 2005 and 2008 and were followed for four years. Measuring carotid intima-media thickness allowed scientists to determine if there were associations between heart fat accumulation and progression of atherosclerosis. Epicardial and paracardial adipose tissue volumes were quantified by computed tomography.

Findings suggested that when compared with the estradiol patch, the oral conjugated equine estrogen appeared to slow the adverse effect of increasing paracardial adipose tissue on progression of atherosclerosis.4

Samar El Khoudary, PhD, MPH, associate professor of epidemiology at the University of Pittsburgh Graduate School of Public Health and lead author of the study, says more research is needed to help clinicians individualize hormone therapy prescription. “In our study, we could not determine if the beneficial effect of oral conjugated equine estrogens on how paracardial fat associates with carotid intima-media thickness was due to conjugated equine estrogens or the oral route of administration,” she explains. “Future research should address this question by comparing same estrogen type using different route of administration. Additional research is needed to assess the role of hormone therapy formulation, route of administration, and duration on cardiometabolic health.”

The current study shows a “distinct effect” of hormone therapy on the link between heart fat deposits and atherosclerosis progression based on the type of estrogen or the route of administration used, says Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society.

“Additional research is needed to allow clinicians to individualize hormone therapy prescribing to optimize benefit and minimize risk,” says Faubion.

Educate Women on Heart Health

In both the prospective randomized Women’s Health Initiative (WHI) and the Early Versus Late Intervention Trial, findings indicated that starting hormone treatment within five to 10 years of menopause can offer cardioprotection in postmenopausal women without adverse effects.5 Further analysis of the WHI data suggested that beginning hormone treatment within the first decade after menopause is safe and effective.6

Educate women on the key risk factors for heart disease: high blood pressure, high low-density lipoprotein (LDL) cholesterol, and smoking. Explain that other conditions, such as diabetes, being overweight or obese, eating an unhealthy diet, physical inactivity, and drinking too much alcohol, can add to risk for heart problems.

Suggest such lifestyle changes as smoking cessation; eating more fruits, vegetables, grains, beans, low-fat dairy products, fish, and lean meats and poultry; weight reduction; exercising at least 30 minutes most days; and controlling blood pressure, using medication if necessary.

Review heart attack symptoms with patients, and explain that heart attacks in women often show different symptoms than in men. Tell women that they should seek medical care as soon as possible if one or more of the following symptoms are present:

• chest pain, pressure, or squeezing;

• pain in the jaw, arms, back, or neck;

• extreme fatigue;

• shortness of breath;

• nausea;

• unusual sweating;

• upper stomach pain.

REFERENCES

  1. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100:3975-4011.
  2. Karvonen-Gutierrez C, Kim C. Association of mid-life changes in body size, body composition and obesity status with the menopausal transition. Healthcare (Basel) 2016; doi:10.3390/healthcare4030042.
  3. Huang G, Wang D, Zeb I, et al. Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS). Atherosclerosis 2012;221:198-205.
  4. El Khoudary SR, Venugopal V, Manson JE, et al. Heart fat and carotid artery atherosclerosis progression in recently menopausal women: Impact of menopausal hormone therapy: The KEEPS trial. Menopause 2020; doi:10.1097/GME.0000000000001472.
  5. Naftolin F, Friedenthal J, Nachtigall R, et al. Cardiovascular health and the menopausal woman: The role of estrogen and when to begin and end hormone treatment. F1000Res 2019; doi:10.12688/f1000research.15548.1
  6. Chester RC, Kling JM, Manson JE. What the Women’s Health Initiative has taught us about menopausal hormone therapy. Clin Cardiol 2018;41:247-252.