Higher Testosterone in Men Linked With Cardiovascular Risk Factors

By Nancy A. Melville

SAN DIEGO -- Higher levels of testosterone and lower levels of oestrogen in men show an association with cardiovascular risk factors that could help explain higher rates of heart disease in men, according to research presented on March 7 at the 97th Annual Meeting of the Endocrine Society (ENDO).

Cardiovascular disease is known to be more prevalent among men than among premenopausal women; however, research on the roles of testosterone and oestrogen in that risk has shown widely varying results.

Elaine W. Yu, MD, MMSc, Harvard Medical School, Cambridge, and Massacshuetts General Hospital, Boston, Massachusetts and colleagues recruited 400 healthy men aged 20 years to 50 years; all received goserelin acetate 3.6 mg every 4 weeks to suppress their endogenous testosterone and oestradiol.

The men were then divided into 2 cohorts: In Cohort 1 (n = 198), men received either 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel or a placebo gel daily for 16 weeks, establishing a cohort ranging from very low to high-normal testosterone levels.

In Cohort 2 (n = 202), the men received the same testosterone dosing regimen, but also received anastrozole 1 mg/d to block the conversion of testosterone to oestrogen.

As planned, the mean serum testosterone levels at 4 months ranged from prepubertal to high normal in both cohorts, while mean oestrogen levels increased along with testosterone dose in Cohort 1, but remained low (<3 pg/mL) in Cohort 2.

Measurements at 16 weeks showed that serum high-density lipoprotein (HDL), or “good” cholesterol and leptin levels were inversely associated, with higher testosterone levels associated with lower HDL in both cohorts (P < .001 for all testosterone dose levels).

Lower oestrogen levels were not shown to have an effect on the levels of HDL or leptin.

“This relationship was not altered by suppressing oestrogen production, indicating that testosterone alone regulates these measures,” the authors noted.

All men in Cohort 2 did, however, have significant increases in fasting glucose, worsened insulin resistance, and more intramuscular fat, regardless of their testosterone dose, to levels that were higher than in Cohort 1 (P < .05 for all dose groups), underscoring the role of oestrogen in regulating those measures that are key risk factors for diabetes, and, therefore, heart disease.

Other factors, including levels of blood pressure, low-density lipoprotein (LDL) cholesterol and body weight, were not significantly associated with either testosterone or oestrogen levels.

“These observations may help explain why men have a higher risk of cardiovascular disease,” Dr. Yu said in a press statement.

Funding for this study was provided by grants from the National Institutes of Health and AbbVie, North Chicago, Illinois. The drugmakers provided the medications used in this study at no cost.

[Presentation title: Effects of Androgens and Estrogens on Cardiometabolic Parameters in Young Adult Men. Abstract OR34-1]