High Androgens in Postmenopausal Women and the Risk for Atherosclerosis and Cardiovascular Disease: The Rotterdam Study

J Clin Endocrinol Metab. 2018 Apr 1;103(4):1622-1630. doi: 10.1210/jc.2017-02421.

Abstract

Context: Polycystic ovary syndrome (PCOS) is closely linked to hyperandrogenism (HA). In PCOS, HA has been associated with metabolic disturbances that increase the risk for cardiovascular disease (CVD).

Objective: To assess the association of high serum androgen levels, as a postmenopausal remnant of PCOS, with the prevalence of atherosclerosis and incidence of CVD in postmenopausal women.

Design: The Rotterdam Study, a prospective population-based cohort study. Median follow-up was 11.36 years.

Setting: General community.

Participants: A total of 2578 women aged >55 years. Exclusion criteria were missing informed consent or follow-up data, perimenopausal status, and menopause by surgical intervention or at an unnatural age (age <40 or >62).

Intervention: None.

Main outcomes and measures: Linear, logistic, and Cox regression models assessed the association of top quartiles (P75) of serum testosterone, free androgen index (FAI), dehydroepiandrosterone, and androstenedione and sex hormone-binding globulin with coronary artery calcium, carotid intima-media thickness (IMT), pulse wave velocity, peripheral artery disease, and incidence of coronary heart disease (CHD), stroke, and CVD.

Results: Mean age (standard deviation) was 70.19 (8.71) years, and average time since menopause was 19.85 (9.94) years. Highest quartile FAI was associated with higher pulse wave velocity (β [95% confidence interval (CI)], 0.009 [0.000 to 0.018]). Highest quartile dehydroepiandrosterone [β (95% CI), -0.008 (-0.015 to -0.001)] and androstenedione [β (95% CI), -0.010 (-0.017 to -0.003)] levels were associated with a lower IMT. We found no association between high androgen levels and incident stroke, CHD, or CVD.

Conclusion: Postmenopausal high androgen levels were not associated with an elevated risk for CVD. Cardiovascular health in women with PCOS might be better than was anticipated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgens / blood*
  • Androstenedione / blood
  • Atherosclerosis / blood
  • Atherosclerosis / epidemiology*
  • Calcium / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Carotid Intima-Media Thickness
  • Dehydroepiandrosterone / blood
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Postmenopause / blood*
  • Prevalence
  • Risk Factors
  • Sex Hormone-Binding Globulin / metabolism
  • Testosterone / blood*

Substances

  • Androgens
  • Sex Hormone-Binding Globulin
  • Testosterone
  • Androstenedione
  • Dehydroepiandrosterone
  • Calcium