Biologic effects of 17α-dihydroequilin sulfate

To determine the independent biologic effects of 17α-dihydroequilin sulfate. Prospective randomized study. University of Southern California Medical Center. Twenty-one postmenopausal women, mean age 50±2 (±SEM) years, and mean body mass index 27±2. Women were randomized to receive daily oral doses of either 1.25mg of estrone sulfate (E1S), 0.2mg of 17α-dihydroequilin sulfate, or a combination. Three blood and urine samples were obtained before and after 30 and 90days of treatment. After 30 and 90days of treatment, E1S alone increased sex hormone-binding globulin (SHBG) levels significantly, 19.7%±6.0% and 61.3%±13.0%, whereas 17α-dihydroe-quilin sulfate reduced SHBG levels, 20.8%±68% and 12.4%±7.5%, respectively. Nevertheless, the combination of E1S and 17α-dihydroequilin sulfate significantly increased SHBG levels, 103%±27.9% and 98.2%±19.1%, compared with baseline at 30 and 90days. Fewer changes were evident with corticosteroid-binding globulin (CBG). After 90days of treatment, CBG levels significantly increased 30.9%±5.5% with E1S, decreased by 7.2%±5.0% with 17α-dihydroequilin sulfate, and, with the combination, significantly increased by 10.5%±2.4% compared with baseline. Changes in lipids and lipoproteins were more variable. However, high-density-lipoprotein cholesterol increased significantly with E1S at 30 and 90days compared with baseline, 96.5%±39% and 91.5%±22.6%, and with the combination increased 66.4%±13.3% and 79.2%±24.4%, respectively. Fewer changes were evident with 17α-dihydroequilin sulfate alone, decreasing 4.4%±22% and 2.6%±21.3%. Urinary ratios of bone collagen equivalents-creatinine and calcium-creatinine decreased in all three groups. However, the combination group resulted in a significantly greater percentage decrease in bone collagen equivalents-creatinine than with E1S alone. 17α-Dihydroequilin sulfate could modify some of the first-pass effects of conjugated equine estrogens and act synergistically with other conjugated equine estrogens to reduce bone resorption.