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

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.

Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women.

Background: Recently, it was shown that exogenously administered testosterone enhances endurance capacity in women. In this study, our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded. Methods: In a double-blinded, randomized, placebo-controlled trial, 48 healthy active women were randomized to 10 weeks of daily application of 10 mg of testosterone cream or placebo. Before and after the intervention, VO2 max, body composition, total hemoglobin (Hb) mass and blood volumes were assessed. Biopsies from the vastus lateralis muscle were obtained before and after the intervention to assess mitochondrial protein abundance, capillary density, capillary-to-fiber (C/F) ratio, and skeletal muscle oxidative capacity. Results: Maximal oxygen consumption per muscle mass, Hb mass, blood, plasma and red blood cell volumes, capillary density, and the abundance of mitochondrial protein levels (i.e., citrate synthase, complexes I, II, III, IV-subunit 2, IV-subunit 4, and V) were unchanged by the intervention. However, the C/F ratio, specific mitochondrial respiratory flux activating complex I and linked complex I and II, uncoupled respiration and electron transport system capacity, but not leak respiration or fat respiration, were significantly increased following testosterone administration compared to placebo. Conclusion: This study provides novel insights into physiological actions of increased testosterone exposure on key determinants of oxygen diffusion and utilization in skeletal muscle of women. Our findings show that higher skeletal muscle oxidative capacity coupled to higher C/F ratio could be major contributing factors that improve endurance performance following moderately increased testosterone exposure.

Effects of moderately increased testosterone concentration on physical performance in young women: a double blind, randomised, placebo controlled study.

OBJECTIVE: To investigate the effects of a moderate increase in serum testosterone on physical performance in young, physically active, healthy women. METHODS: A double blind, randomised, placebo controlled trial was conducted between May 2017 and June 2018 (ClinicalTrials.gov ID: NCT03210558). 48 healthy, physically active women aged 18-35 years were randomised to 10 weeks of treatment with 10 mg of testosterone cream daily or placebo (1:1). All participants completed the study. The primary outcome measure was aerobic performance measured by running time to exhaustion (TTE). Secondary outcomes were anaerobic performance (Wingate test) and muscle strength (squat jump (SJ), counter movement jump (CMJ) and knee extension peak torque). Hormone levels were analysed and body composition assessed by dual energy X-ray absorptiometry. RESULTS: Serum levels of testosterone increased from 0.9 (0.4) nmol/L to 4.3 (2.8) nmol/L in the testosterone supplemented group. TTE increased significantly by 21.17 s (8.5%) in the testosterone group compared with the placebo group (mean difference 15.5 s; P=0.045). Wingate average power, which increased by 15.2 W in the testosterone group compared with 3.2 W in the placebo group, was not significantly different between the groups (P=0.084). There were no significant changes in CMJ, SJ and knee extension. Mean change from baseline in total lean mass was 923 g for the testosterone group and 135 g for the placebo group (P=0.040). Mean change in lean mass in the lower limbs was 398 g and 91 g, respectively (P=0.041). CONCLUSION: The study supports a causal effect of testosterone in the increase in aerobic running time as well as lean mass in young, physically active women.