METABOLIC-CLEARANCE RATE OF EQUILIN SULFATE AND ITS CONVERSION TO PLASMA EQUILIN, CONJUGATED AND UNCONJUGATED EQUILENIN, 17-BETA-DIHYDROEQUILIN, AND 17-BETA-DIHYDROEQUILENIN IN NORMAL POSTMENOPAUSAL WOMEN AND MEN UNDER STEADY-STATE CONDITIONS

The constant infusion of [H-3]equilin sulfate ([H-3]EqS) was used to e stimate the MCR of equilin sulfate (EqS) and to measure the conversion of this estrogen to equilin (Eq), equilenin (Eqn), equilenin sulfate (EqnS), 17 beta-dihydroequilin (17 beta-Eq), 17 beta-dihydroequilin su lfate (17 beta EqS), 17 beta-dihydroequilenin (17 beta-Eqn), and 17 be ta-dihydroequilenin sulfate (17 beta-EqnS) in normal postmenopausal wo men and men. Infusion of [H-3]EqS was started in five postmenopausal w omen and two men 30 min after a priming dose and continued at a consta nt rate of 12-15 mu Ci/h for 3 h. Blood samples were taken 15 min befo re the end of infusion, at the end of the infusion, and 15 min after t he end of infusion. Unconjugated and sulfate-conjugated Eq, Eqn, 17 be ta-Eq, and 17 beta-Eqn were isolated from plasma. The mean MCR of EqS was calculated to be 280 +/- 24 L/day or 170 +/- 18 L/day.m(2). The me an conversion ratios for precursor EqS to product 17 beta-EqS, EqnS, 1 7 beta-EqnS, 17 beta-Eq, Eq, Eqn, and 17 beta-Eqn were 0.300, 0.190, 0 .100, 0.020, 0.016, 0.008, and 0.004 respectively. In both the sulfate -conjugated and unconjugated forms, 17 beta-Eq was the most abundant m etabolite formed. 17 beta-Eq estrogen is a potent uterotropic agent an d has a much higher affinity for estrogen receptors than Eq. Its forma tion may be of importance in the overall biological activity of EqS pr esent in conjugated equine estrogen preparations.