Disposition of serum steroids in response to combined oral contraceptives and menstrual cycle phases: A double-blind, randomized, placebo-controlled study.

Abstract

To analyze doping control samples from female athletes demands understanding of non-doping factors that affect the steroid profile. These could be physiological factors such as exercise, alcohol consumption, hormonal changes during the menstrual cycle, or the effect of commonly used approved drugs like combined oral contraceptives. Urine samples have been the main way of doping testing, but serum samples are proposed as a complement. Testosterone, dihydrotestosterone, or the ratio of testosterone and androstenedione has been proposed as a biomarker for testosterone doping because it increases after transdermal testosterone administration. In this double-blind, randomized, placebo-controlled study of 340 healthy females, we analyzed the serum steroid levels, including glucuronide metabolites, before and after 3 months of combined oral contraceptives or placebo. At follow up, sample collection in the placebo group was randomly distributed between different menstrual cycle phases. This enabled to analyze changes in concentrations between the follicular, ovulation, and luteal phases. Combined oral contraceptives decreased all serum steroids including the glucuronide metabolites. As expected, serum testosterone levels increased during the ovulation phase, and also androstenedione and androstenediol, whereas the glucuronide metabolites remained unaffected. Neither combined oral contraceptives nor menstrual cycle phases did affect the ratio of testosterone and androstenedione in serum, and consequentlythis ratio seems promising as a marker of doping with endogenous anabolic androgenic steroids in women.