Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic
Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen
levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition.
what is known already: Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes
of low as well as high androgen levels have been associated with increased CVD risk in both men and women.
study design, size, duration: This cross-sectional study included 680 women with polycystic ovary syndrome (PCOS), premature
ovarian insufficiency (POI), natural post-menopausal women (NM), or regular menstrual cycles (RC) (170 women per group).
participants/materials, setting, methods: Measurements of serum testosterone, androstenedione and dehydroepiandrosterone
sulfate were performed using liquid chromatography-tandem mass spectrometry. Assessments were taken of body mass index
(BMI), blood pressure, lipid profiles, glucose, insulin and SHBG, and the bioactive fraction of circulating testosterone was calculated using the
free androgen index (FAI).
main results and the role of chance: PCOS women were hyperandrogenic [median FAI ¼ 4.9 (IQR 3.6–7.4)], and POI
women were hypoandrogenic [FAI ¼ 1.2 (0.8–1.7)], compared with RC women [FAI ¼ 1.7 (1.1–2.8)], after adjustment for age, ethnicity,
smoking and BMI (P , 0.001). After adjustment for age, there were no significant differences in androgens between POI and NM (P ¼ 0.15)
women and betweenNMand RC (P ¼ 0.27) women, the latter indicating that chronological aging rather than ovarian aging influences the differences
between pre- and post-menopausal women. A high FAI was associated with elevated triglycerides (b log FAI for PCOS: 0.45, P , 0.001,
POI: 0.25, P , 0.001, NM: 0.20, P ¼ 0.002), insulin (b log FAI for PCOS: 0.77, POI: 0.44, NM: 0.40, all P , 0.001), HOMA-IR (b log FAI for
PCOS: 0.82, POI: 0.46, NM: 0.47, all P , 0.001) and mean arterial pressure (b log FAI for PCOS: 0.05, P ¼ 0.002, POI: 0.07, P , 0.001,
NM: 0.04, P ¼ 0.04) in all women; with increased glucose (b log FAI for PCOS: 0.05, P ¼ 0.003, NM: 0.07, P , 0.001) and decreased
high-density lipoprotein (b log FAI for PCOS: 20.23, P , 0.001, NM: 20.09, P ¼ 0.03) in PCOS and NM women; and with increased
low-density lipoprotein (b log FAI for POI: 0.083, P ¼ 0.041) in POI women. Adjustment for BMI attenuated the observed associations. Associations
between FAI and cardiometabolic features were the strongest in PCOS women, even after adjustment for BMI.
limitations, reasons for caution:
Associations between androgen levels and cardiometabolic features were assessed inPCOS,
POI and NM women only, due to a lack of available data in RC women. Due to the cross-sectional design of the current study, the potential
associations between androgen levels and actual future cardiovascular events could not be assessed.
Human Reproduction, Vol.0, No.0 pp. 1–11, 2015