Disposition of Urinary and Serum Steroid Metabolites in Response to Testosterone Administration in Healthy Women

Abstract

Context Little is known about how exogenous testosterone (T) affects the steroid profile in women. More knowledge would give the antidoping community keys as to how to interpret tests and detect doping. Objective This work aimed to investigate the steroid profile in serum and urine in young healthy women after T administration. Methods In a randomized, double-blind, placebo-controlled study, 48 healthy young women were assigned to daily treatment with T cream (10 mg) or placebo (1:1) for 10 weeks. Urine and blood were collected before and at the end of treatment. Serum steroids were analyzed with liquid chromatography–tandem mass spectrometry, and urine levels of T, epitestosterone (E), and metabolites included in the Athlete Biological Passport (ABP) were analyzed with gas chromatography–tandem mass spectrometry. Results In serum, T and dihydrotestosterone levels increased, whereas sex hormone–binding globulin and 17-hydroxyprogesterone decreased after T treatment as compared to placebo. In urine, T and 5α-androstanediol increased in the T group. The median T increase in serum was 5.0-fold (range, 1.2-18.2) and correlated to a 2.2-fold (range, 0.4-14.4) median increase in T/E in urine (rs = 0.76). Only 2 of the 24 women receiving T reached the T/E cutoff ratio of 4, whereas when the results were added to the ABP, 6 of 15 participants showed atypically high T/E (40%). In comparison, 22/24 women in the T group increased serum T more than 99.9% of the upper confidence interval of nontreated values. Conclusion It seems that the T/E ratio is not sufficient to detect exogenous T in women. Serum total T concentrations could serve as a complementary marker of doping.

Urinary Steroid Profile in Elite Female Athletes in Relation to Serum Androgens and in Comparison With Untrained Controls

“…We, and others, have previously shown that implementation of the ABP increases the chance to detect testosterone intake in men as compared to traditional population based cut-off values after administration of low dose of testosterone (Strahm et al, 2015;Nair et al, 2020). Furthermore, in women the longitudinal ABP approach is superior to the population-based thresholds to detect administered T, however, not all women are identified as having atypical findings (Handelsman and Bermon, 2019;Knutsson et al, 2020;Salamin et al, 2020). It has been shown that after 10 weeks of transdermal T application in healthy women, only 40% were identified as having atypical passport findings (Knutsson et al, 2020) even though their serum T levels were elevated to concentrations associated with performance enhancing effects (Hirschberg et al, 2020).…”

“…Furthermore, in women the longitudinal ABP approach is superior to the population-based thresholds to detect administered T, however, not all women are identified as having atypical findings (Handelsman and Bermon, 2019;Knutsson et al, 2020;Salamin et al, 2020). It has been shown that after 10 weeks of transdermal T application in healthy women, only 40% were identified as having atypical passport findings (Knutsson et al, 2020) even though their serum T levels were elevated to concentrations associated with performance enhancing effects (Hirschberg et al, 2020). As a supplementary method, the serum concentration of T, androstenedione and dihydrotestosterone may be co-monitored (Salamin et al, 2020) and subsequently there is an interest to understand the relation between the serum steroid concentrations and urinary excretion rate of the ABP metabolites.…”

The Specificities of Elite Female Athletes: A Multidisciplinary Approach

“…Recently, Mullen et al [ 413 ] demonstrated that the variability of the ABP biomarkers in Swedish and Norwegian athletes was higher in females compared to males. Last, Knutsson et al [ 414 ] observed lower levels of E in PeO and higher levels of 5αAdiol in L in women with moderate to high self-reported levels of recreational physical activity.…”

“…The ADAMS platform indicated that 10 of the 11 passports were clearly suspicious, with most of the ratios exceeding the individual threshold. Knutsson et al [ 414 ] studied in 24 women the impact of 10 weeks of treatment with 10 mg testosterone cream and reported atypical results, mainly for the T/E ratio in 6 subjects, with only 2 subjects having an atypical 5αAdiol/E ratio [ 418 , 419 ]. Sometimes, athletes can only be tested once, and in such cases, the interpretation of a stand-alone data item can be complicated, especially for female athletes.…”

Testosterone and depressive symptoms during the late menopause transition

“…For the current sub-study, the urine samples of the last 50 participants were assayed for urinary testosterone at weeks 3, 6, 9, and 12. Urinary testosterone is recognized as a valid measure of testosterone production [ 17 ] that has been shown to correlate highly with serum testosterone levels following administration of exogenous testosterone in both young women ( r = 0.69) [ 18 ] and male athletes ( r = 0.56) [ 19 ]. The Research Ethics Board of the University of Regina approved the study protocol.…”