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Metabolic syndrome risk rises with increased testosterone levels during menopause, new data suggest

Wednesday, August 13 2008 | Comments
Evidence Grade 1 What's This?
As levels of bioavailable testosterone increase during the menopausal transition, the prevalence of metabolic syndrome increases, independent of aging and other important covariates, suggest finding from a large longitudinal study.

For this 9-year study, researchers looked at data from an analytic sample of 949 women enrolled in the Study of Women's Health Across the Nation (SWAN), a multiethnic, community-based, longitudinal cohort study of the natural history of the menopausal transition of 3,302 women.

Participants in the analytic sample, who were enrolled at 7 sites in the United States, had not received hormone therapy and did not have diabetes or metabolic syndrome at baseline.

The primary outcome was the presence of metabolic syndrome using the National Cholesterol Education Program Adult Treatment Panel III definition. The researchers also evaluated the components of metabolic syndrome--including waist circumference, glucose level, triglyceride level, HDL cholesterol level, and systolic blood pressure--as secondary outcomes.

Because the participants experienced menopause at varying times in the 8 years of follow-up, the researchers aligned each measurement from each woman according to the date of her final menstrual period (FMP), summarizing the accumulated data in a 13-year time scale (from 6 years before to 6 years after the FMP). Longitudinal analyses, centered at the FMP, were adjusted for age at menopause, ethnicity, study site, marital status, education, body mass index, smoking, and aging.

By the FMP, 13.7% of the women had new-onset metabolic syndrome (n=130).

The odds of developing the metabolic syndrome increased 45% per year during the perimenopausal years (adjusted OR, 1.45; 95% CI, 1.35-1.56; P<.001) and 24% per year during the postmenopausal years (adjusted OR, 1.24; 95% CI, 1.18-1.30; P<.001).

Although changes in total estradiol and total testosterone levels were unrelated to the development of metabolic syndrome, an increase in the bioavailable testosterone level was significantly related to metabolic syndrome. For every 1-SD increase in bioavailable testosterone level, the odds of developing metabolic syndrome increased by 10% (adjusted OR, 1.10; 95% CI, 1.01-1.20; P=.02).

In addition, for every 1-SD decrease in the level of sex hormone-binding globulin (SHBG)--an indirect marker of bioavailable androgen--the odds of developing metabolic syndrome increased by 13% (adjusted OR, 0.87; 95% CI, 0.81-0.93; P<.001).

Furthermore, changes in bioavailable testosterone and SHBG were associated with changes in 3 of the 5 components of metabolic syndrome (waist circumference, HDL cholesterol, and glucose levels).

"Menopause-related testosterone predominance appears to be implicated as a key hormonal change that is associated with the incidence of the metabolic syndrome, independent of aging and other standard cardiovascular disease risk factors," the authors concluded. (Janssen I, et al. Arch Intern Med 2008;168:1568-1575.)

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