Changes in Physiologically Free Circulating Estradiol and Testosterone during Exposure to Levonorgestrel

The biological activity of circulating sex steroids is dependent upon the relative binding to sex hormone-binding globulin (SHBG). Only that fraction which is not specifically bound to the high affinity binding protein is available to the receptors or for metabolism. Levonorgestrel (d-Ng), a synthetic gestagen used for contraception, decreases hepatic production of SHBG. Volunteers wearing contraceptive vaginal rings containing estradiol (E2) and d-Ng were studied to determine the changes in sex steroid binding which occur when d-Ng is administered in a sustained release fashion. The percentage of steroid not specifically bound to SHBG was measured by fractionatingthe serum proteins with ammonium sulfate precipitation. A binding capacity assay was used to quantitate SHBG. During normal menstrual cycles in control subjects, the unbound fractions of both E2 and testosterone (T) remained constant throughout the cycle at about 25% of total E2 and 10% of total T. During treatment with d-Ng, however, the percen...