TORONTO – Higher free testosterone levels appear to be associated with metabolic dysfunction in women from the general population, according to a cross-sectional study of more than 1,600 women in the Framingham Heart Study Offspring Cohort.
Free testosterone was positively associated with body mass index (BMI), waist circumference, diabetes, metabolic syndrome, and systolic and diastolic blood pressure in a community-based sample of women. The findings raise questions about whether higher testosterone levels predispose women to increased cardiovascular risks, lead investigator Dr. Andrea Coviello of Boston University said at the annual meeting of the Endocrine Society.
Studies have shown that women with polycystic ovary syndrome (PCOS) are at a fourfold increased risk for developing diabetes and a twofold increased risk for developing metabolic syndrome. But there are many unanswered questions about the clinical consequences of androgen excess in women who have mild to moderate hyperandrogenism without accompanying PCOS, Dr. Coviello said.
Dr. Coviello and her colleagues measured circulating testosterone levels in 1,678 women from the Framingham Heart Study Offspring Cohort in an effort to find out if healthy women with higher testosterone levels face risks for metabolic problems. They assessed circulating testosterone levels using liquid chromatography tandem mass spectrometry, which has a sensitivity of about 2 ng/dL, and measured sex hormone-binding globulin (SHBG) through immuno-lourometric assay. They also evaluated the relationship between testosterone and metabolic dysfunction, particularly metabolic syndrome and diabetes.
The women in the sample ranged in age from 33 to 87 years, with a mean age of 61. Most of the group was postmenopausal, Dr. Coviello said. They had a mean SHBG of 92 nmol/L, a mean total testosterone of 30 ng/dL, and a mean free testosterone of 3 pg/mL.
The investigators found that free testosterone was positively correlated with BMI, waist circumference, both systolic and diastolic blood pressure, triglycerides, total cholesterol, LDL cholesterol, and fasting glucose. Free testosterone was inversely associated with HDL cholesterol.
In addition, diabetic women had higher free testosterone and lower SHBG levels than women without diabetes. SHBG was inversely correlated with most of the components of metabolic syndrome. For example, higher BMI and waist circumference was associated with lower SHBG. Higher blood pressure, higher total cholesterol, higher triglycerides, and higher LDL cholesterol were all associated with lower SHBG. Higher fasting glucose was associated with a lower SHBG.
For total testosterone, only HDL cholesterol and triglycerides were significantly correlated. HDL cholesterol was positively correlated with total testosterone, and triglycerides were negatively correlated.
There were a number of limitations. The sample included only Caucasian individuals, and there was no information on the timing of the blood draws in relation to menstrual cycle among the premenopausal women. In addition, the reproductive histories were not adequate to determine whether women in the sample had PCOS, Dr. Coviello said.
The study was funded by grants from the National Institutes of Health.