Sex Hormone Imbalance Increases Heart Disease Incidence in Post-Menopausal Women

by Bianca Garilli, ND
For women, the pre- and post-menopausal years represent a time of major change in many aspects of life including spiritual, emotional, and physical. From a physical perspective, shifting levels of sex hormones such as dehydroepiandrosterone (DHEA), testosterone, and estrogen play critical roles in the transition in and through menopause. It’s during this chapter of a woman’s life that the number of ovarian follicles begin to decline. Their eventual depletion cause the ovaries to no longer respond to FSH and LH from the pituitary, resulting in cessation of estrogen and progesterone production from the ovaries.1 Declining estrogen levels typically begin several years before the final menstrual period (FMP)- which is defined as the cessation of the menstrual period for at least 1 year- and stabilize around two years after the FMP.2

In a similar fashion, testosterone levels change in women during the menopausal timeframe, although this sex hormone does not seem to experience as dramatic of a decline as estrogen. Frequently this results in a higher ratio of testosterone to estrogen in the post-menopausal timeframe.3 This higher testosterone level as compared to estrogen level has been associated with higher risk factors for cardiovascular disease (CVD) in women, although the impact on incident events of CVD, coronary heart disease (CHD), and heart failure (HF) in response to this sex hormone ratio is less clear.4

A study published in the Journal of the American College of Cardiology studied 2,834 post-menopausal women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with a mean age of 64.9 years and without CVD at baseline.4 Levels of testosterone, estradiol, DHEA, and sex hormone-binding globulin (SHBG) were assessed at the beginning of the study; participants were followed for an average of 12.1 years.4 Levels of sex hormones were evaluated for association with incident CVD, CHD, and HF. Adjustments were made for relevant variables including demographics, CVD risk factors, and hormone therapy use.4

The study found no associations between DHEA nor SHBG levels with incident CVD, CHD, and HF outcomes.4 However, an elevated risk for incident CVD, CHD, and HF events was found to be associated with a higher testosterone/estradiol ratio, with higher testosterone levels associated with higher CVD and CHD.4 Conversely, higher estradiol levels were associated with a lower CHD risk, leading the authors of this study to conclude that “sex hormone levels after menopause are associated with women’s increased CVD risk later in life”.4

Why is this Clinically Relevant?

• Hormone levels and their ratios are important biomarkers to review pre- and post-menopause
• It’s important to support balanced testosterone/estradiol ratios in post-menopausal women
• Women experiencing risk factors for CVD disease should discuss testing for sex hormone levels to mitigate additional risk through an imbalance of testosterone/estradiol levels

View the abstract
Citations

1. Dalal PK, Agarwal M. Postmenopausal syndrome. Indian J Psychiatry. 2015;57(Suppl 2):S222–S232.
2. Santoro N, Randolph JF Jr. Reproductive hormones and the menopause transition. Obstet Gynecol Clin North Am. 2011;38(3):455–466.
3. Kim C, Harlow SD, Zheng H, McConnell DS, Randolph JF Jr. Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition. Womens Midlife Health. 2017;3:9.
4. Zhao D, Guallar E, Ouyang P, et al. Endogenous sex hormones and incident cardiovascular disease in post-menopausal women. J Am Coll Cardiol 2018;71(22)2555-2566.