Metabolic profiles of endogenous and ethynyl steroids in plasma and urine from women during administration of oral contraceptives

Abstract

Conjugated ethynyl and endogenous steroids in plasma and urine from two women taking an oral contraceptive (Conlumin ®) containing 1 mg norethindrone and 50 μg mestranol have been analyzed by methods based on aruon and ligand exchange chromatography and gas chromatography-mass spectrometry. Conjugated norethindrone and its reduced metabolites with 3α,5α, 3α,5β, 3β,5β and 3β,5α configurations were identified in the fluids. The quantitatively major metabolites in plasma were a disulphate of the 3α,5α isomer and a monosulphate of the 3α,5β isomer. The renal clearance of the former compound was low. The major urinary metabolite of norethindrone was the 3α,5β isomer conjugated with glucuronic or sulphuric acid. Disulphates constituted only a small portion of urinary ethynyl steroids. Metabolic profiles of endogenous neutral steroids in plasma and urine during the contraceptive cycle were compared with profiles during a physiological menstrual cycle. The concentrations of steroids in plasma during contraception were similar to those during the follicular and mid phases of the menstrual cycle, whereas levels of progesterone metabolites were higher in the luteal phase. The urinary excretion of steroids was 15–30% lower during the contraceptive cycle, due to a decrease in excretion of C 21O 5 steroids, 11-oxygenated androgens and etiocholanolone. The increase of urinary progesterone metabolites seen during the luteal phase was not observed during contraception, but the excretion of 5β-pregnane-3α,20α-diol glucuronide was higher than during the follicular and mid phases of the menstrual cycle.