The present data suggest that endogenous androgens are associated with a more anabolic body composition and enhanced performance in women athletes. These results are of importance for the current discussion regarding hyperandrogenism in women athletes.

We thank our colleagues for their constructive comments that relate to our two articles in the July 2017 issue of BJSM. Bermon and Garnier StudyThe main criticisms expressed about the data used and our statistical analysis were (1) our 'concentration' on free testosterone (fT) rather than total testosterone (T) 3 (presumably because the T results were only presented in the Internet version of the paper), (2) the fact that 17.3% of the athletes were sampled at both World Championships (Daegu and Moscow), 3 (3) the fact that no correlation analysis was performed other than comparison of fT or T tertiles, 3 (4) the absence of statistical comparison between a group with high T levels and a group with normal T levels 4 and (5) the lack of adjustment for multiple comparisons (suggesting that the significant differences observed in our study could have happened by chance). 5Taking this last criticism first, we note that we presented an exploratory study, without no attempt to claim confirmatory results. In fact, the exploratory evidence presented in the study is strong, and correction for multiplicity may be too conservative. But we agree that the results should be put into context. At the type 1 error level of 0.05, we could expect 1 of 20 hypotheses tested to be significant merely by chance, that is, p <0.05. In this study, we have observed significant correlations at the 0.05 level in five events, out of 21 events in total. Therefore, it is very unlikely that all these findings are caused by chance. Moreover, the five flagged events were showing similar findings in both fT and T, which indicates that the evidence and findings are robust.Franklin et al report that, using Fisher's combination test, they were unable to reject the hypothesis that the p values calculated from the published data were not inconsistent with there being no advantage to high fT women in any of the five events, 5 but they do not explain their analysis in any detail or support their conclusion with any evidence. Their suggestion to conduct one single test of correlation across all 21 events combined is inappropriate because the hypothesis is that elevated testosterone levels enhance performance in certain events but not others. Combining results from the events of long sprint to middle-distance running shows with additional statistical calculation a p value of 0.003 for the correlation between testosterone levels and competition results, which is very strong statistical evidence for a true correlation not caused by chance. additional SenSitivity analySeSTo address the other criticisms, we have now performed a sensitivity analysis using a modified data set in which (1) observations from athletes who participated in both World Championships were only counted once, that is, the first observed value, and (2) only T concentrations were used (not fT). As for aggregating results, we used running events from 400 m up to 1 mile, on the basis that that is where T produces its greatest performance-enhancing effects (by increasing lean body mass and the...

Background: The second to fourth digit ratio (2D:4D ratio) is suggested to be a negative correlate of prenatal testosterone. Little is known about the role of the 2D:4D ratio in relation to serum and urinary androgens for physical performance in female athletes. We aimed to compare the 2D:4D ratio in female Olympic athletes with sedentary controls, and to investigate the 2D:4D ratio in relation to serum and urinary androgens and physical performance in the athletes. Methods: This cross-sectional study included 104 Swedish female Olympic athletes participating in power, endurance and technical sports and 117 sedentary controls. The 2D:4D ratio was calculated using direct digit measurements. Serum androgens and urinary androgen metabolites were analyzed by liquid chromatography-tandem mass spectrometry. The athletes performed standardized physical performance tests and body composition was established by dual-energy X-ray absorptiometry. Results: The 2D:4D ratio was significantly lower in the athletes compared with controls although serum testosterone levels were comparable between groups and within normal reference values. The 2D:4D ratio correlated negatively with urinary levels of testosterone glucuronide and 5α-and 5βAdiol-17G, whereas there were no correlations to serum androgen levels. Furthermore, the 2D:4D ratio correlated negatively with strength tests and positively with 3,000-meter running in the athletes. Conclusion: Female Olympic athletes had a lower 2D:4D ratio, possibly reflecting a higher prenatal androgen exposure, than sedentary controls. Furthermore, the 2D:4D ratio was related to urinary levels of androgen metabolites and physical performance in the athletes but not to serum androgen levels. It is suggested that the 2D:4D ratio could reflect androgen metabolism and may be of importance for sporting success in female athletes.

IntroductionIn female athletes, the interpretation of doping tests is complex due to hormonal variations during the menstrual cycle and hormonal contraceptive use, both influencing the urinary steroid profile. Exercise is suggested to affect circulating steroid hormone levels, and in women, the urinary steroid profile differs between in competition testing and out of competition testing. No previous study has investigated the relationship between amount of exercise and the urinary steroid profile in female elite athletes.PurposeTo compare the urinary steroid profile between female Olympic athletes and age- and BMI-matched untrained controls, and to study the urinary steroid profile in relation to serum hormones and amount of exercise.MethodsIn this cross-sectional study conducted at the Women’s Health Research Unit, Karolinska University Hospital, Stockholm, 94 female elite athletes and 86 untrained controls were included. Serum estrogens and testosterone and the urinary steroid profile were analyzed by liquid chromatography–tandem mass spectrometry and gas chromatography-tandem mass spectrometry, respectively. Exercise hours/week were evaluated by questionnaire.ResultsAlthough serum steroid hormones were comparable between groups, the athletes demonstrated approximately 30% lower urinary steroid metabolites of testosterone, epitestosterone, androsterone, etiocholanolone, 5α-androstan-3α, 17β-diol, and 5β-androstan-3α, 17β-diol compared to the controls. The urinary steroid metabolites correlated positively with serum steroid hormones. In the athletes, urinary steroid metabolites: androsterone (rs = −0.28, p = 0.007), epitestosterone (rs = −0.22, p = 0.034), 5αAdiol (rs = −0.31, p = 0.002) and testosterone (rs = −0.24, p = 0.026), were negatively correlated with amount of training (hours per week).ConclusionThe urinary concentrations of steroid metabolites were lower in elite athletes than in sedentary controls, although serum steroids were comparable between groups. Moreover, exercise time was negatively associated with the urinary concentrations. Our findings suggest alternative excretion routes of androgens in the athletes related to training.

Concentrations of urinary steroids are measured in anti-doping test programs to detect doping with endogenous steroids. These concentrations are combined into ratios and followed over time in the steroidal module of the Athlete Biological Passport (ABP). The most important ratio in the ABP is the testosterone/epitestosterone (T/E) ratio but this ratio is subject to intra-individual variations, especially large in women, which complicates interpretation. In addition, there are other factors affecting T/E. Pregnancy, for example, is known to affect the urinary excretion rate of epitestosterone and hence the T/E ratio. However, the extent of this variation and how pregnancy affect other ratios has not been fully evaluated. Here we have studied the urinary steroid profile, including 19-norandrosterone (19-NA), in 67 pregnant women and compared to postpartum. Epitestosterone was higher and, consequently, the T/E and 5αAdiol/E ratios were lower in the pregnant women. Androsterone/etiocholanolone (A/Etio) and 5αAdiol/5βAdiol, on the other hand, were higher in the first trimester as compared to postpartum (p<0.0001 and p=0.0396, respectively). There was no difference in A/T during pregnancy or after. 19-NA was present in 90.5% of the urine samples collected from pregnant women. In this study, we have shown that the steroid profile of the ABP is affected by pregnancy, and hence can cause atypical passport findings. These atypical findings would lead to unnecessary confirmation procedures, if the patterns of pregnancy are not recognized by the ABP management units.