Endogenous androgens, diabetes, and cardiovascular disease in women: the Rancho Bernardo study
For >50 years female cardioprotection was attributed to premenopausal endogenous estrogen levels. We describe here how cardioprotection is greatly reduced in the presence of diabetes and endogenous testosterone levels.
Forty years ago we measured total and bioavailable testosterone (bioT), total and bioavailable estradiol, and SHBG in community-dwelling older men and women from the Rancho Bernardo Study, using organic solvent extraction and celite column chromatography prior to radioimmunoassay (SSC Yen). Participants were followed to the present. SHBG was used to directly measure bioavailable sex hormones in this cohort; it was not associated with the 19-year risk of heart disease or CVD mortality in men or women.
During menopause, total testosterone levels decrease 35%, later increasing to levels near the lower range in intact women. After bilateral oophorectomy and loss of ovarian stromal cells, women had 38% lower testosterone levels; after hysterectomy without oophorectomy women still had somewhat lower testosterone levels.
In women without diabetes, FPG was positively associated with bioT levels, but not with estrone or total estradiol. Women in the highest quartile of bioT had a 2.9-fold increased risk of developing diabetes (by OGTT criteria). Older women with IGT or diabetes had higher bioT levels than normoglycemic women.
Total testosterone was positively associated with HDL and inversely with triglycerides in both sexes. In contrast, bioT was positively associated with body mass index, waist girth, and cholesterol in women but not in men. Women with higher bioT levels had more metabolic syndrome (MetS) components, while men with lower total T had more MetS components. Women with lower total T had a poorer 20-year cumulative CHD-event-free survival. In contrast, both extremes of bio-T levels predicted the poorest survival in women. Endogenous testosterone appears to be a critical component of diabetes-related sex differences in cardiovascular disease.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.