Low Testosterone Independent Risk Factor for CHD Death

Consider Measuring Hormone Levels in Postmenopausal Women, Particularly after Hysterectomy

CHICAGO—The clinical significance of low testosterone levels in women is still subject to debate among physicians. Now surprising evidence from a new study shows that low levels of this hormone are associated with an increased risk of mortality from coronary heart disease (CHD) in postmenopausal women, independent of any cardiovascular (CV) risk factors, reported Gail A. Laughlin, PhD, at the American Heart Association annual meeting.

Women’s favorable CV risk compared with men’s is usually explained by endogenous estrogen levels. However, the role of naturally circulating testosterone on CV risk has not been widely studied. Hyperandrogenemia in young women with polycystic ovary syndrome is associated with increased CV risk factors, carotid atherosclerosis, and impaired vascular function, said Dr Laughlin, assistant professor of family and preventive medicine, University of California, San Diego.

“This analysis was designed to answer the question of whether the association of low testosterone with mortality was specific to CHD or was related to other causes as well,” said Dr Laughlin. “We found that low testosterone specifically predicted the risk of CHD death.” It was not related to death from cancer or other causes.

Using enrollees from the Rancho Bernardo Study, an ongoing population-based study of healthy aging among residents of a Southern California community, Dr Laughlin assessed the incidence of CHD events in 678 postmenopausal women aged 50 to 90 years over a 20-year follow-up period. Participants were evaluated for CHD risk factors at baseline, and blood samples were drawn to measure sex hormones. None of the women was a current user of estrogen therapy.

Women were stratified into quintiles based on testosterone levels; those in the lowest quintile had testosterone levels of ≤80 pg/mL, an abnormally low level. “The normal testosterone level for women in this age-group is about 170 pg/mL,” she noted.

Compared with women with higher levels of testosterone, those in the lowest quintile had double the risk of prevalent CHD, incident CHD (defined as a first-ever myocardial infarction or revascularization procedure), and CHD mortality.

Further analysis showed that the association between low testosterone level and increased cardiac risk was independent of the presence of any CHD risk factors, diabetes, or the metabolic syndrome.

Examination of lipid levels, inflammatory markers, and coexistent disease did not explain this association.

“The primary reason for low testosterone in this cohort was bilateral oophorectomy, which results in about 40% lower testosterone levels in women past menopause,” she said. “Even hysterectomy with retention of the ovaries seems to have some impact on testosterone levels.” Women with low testosterone levels also tended to be leaner than women with high levels.

Whether the results also apply to women who are current users of estrogen awaits further study. For now, physicians may wish to assess testosterone levels in older women and advise preventive measures, especially in those who have had oophorectomy.

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• The normal testosterone level for postmenopausal women is about 170 pg/mL.

• Levels as low as 80 pg/mL in this study population were caused mostly by bilateral oophorectomy.

• These reduced levels were significantly linked to risk of cardiac death, even in women with no CV risk factors.