Endocrine profile in female Olympic athletes : of importance for physical performance and impact on anti-doping testing

Endogenous androgens and insulin-like growth factor-I (IGF-I) are anabolic hormones that may contribute to increased muscle mass and possibly enhanced athletic performance. Furthermore, the second to fourth digit ratio (2D:4D ratio), suggested as an indirect measurement of prenatal androgen exposure, has been related to athletic ability. However, there is limited knowledge on the role of endogenous anabolic hormones for body composition and physical performance in female Olympic athletes. Moreover, the 2D:4D ratio has not been studied in relation to serum and urinary androgens and athletic performance in female elite athletes. In men, there are known genetic variations in genes coding for androgen metabolizing enzymes that affect the urinary androgen profile evaluated in doping tests. For women, less is known concerning the impact of genetic variations on the urinary androgens. In addition, the effects of hormonal contraceptive use on urinary steroid levels need to be investigated further.

The aim of this thesis was to evaluate the anabolic hormonal profile and the 2D:4D ratio in female Olympic athletes compared to untrained controls and in relation to body composition and physical performance. In addition, we aimed to investigate the relationship between the 2D:4D ratio and serum and urinary androgens. Furthermore, we studied the impact of hormonal contraceptives and genetic variations on the urinary steroid profile in female elite athletes and compared the urinary steroid between female athletes and controls.

In this cross-sectional study, including female Olympic athletes (n=106) and age- and BMI matched untrained controls (n=117), we found significantly higher precursor androgens dehydroepiandrosterone (DHEA), androstenediol (5-DIOL) as well as IGF-I, age-adjusted IGF-I and insulin-like growth factor binding protein-1 (IGFBP-1) in the athletes compared to controls. The 2D:4D ratio was significantly lower in the athletes indicating higher exposure to androgens during fetal life. The precursor androgens, IGF-I and IGFBP-1 were related to increased muscle mass and lower fat percentage. In the athletes, precursor androgens, dihydrotestosterone (DHT), IGF-I, IGFBP-1 and the 2D:4D ratio were associated with better performance in physical fitness tests. In addition, the 2D:4D ratio was associated with urinary androgens but not serum androgens. The controls excreted significantly higher concentrations of urinary androgen metabolites compared to the athletes, however serum androgens were comparable or higher among the athletes. For the athletes, training hours per week were negatively associated with some urinary androgens. Moreover, we found that genetic variations in UGT2B17 and CYP17A1 and hormonal contraceptive use had a significant impact on the urinary steroid profile in women.

In conclusion, endogenous anabolic hormones are associated with an anabolic body composition and enhanced physical performance in female Olympic athletes. Prenatal androgen exposure may also be of importance for athletic capacity in female Olympic athletes and possibly reflect androgen metabolism, since the 2D:4D ratio was associated with urinary androgen metabolite concentrations. Both genetic variations in UGT2B17, CYP17A1 and hormonal contraceptive use affects the urinary androgen levels in women. Our finding of higher urinary androgen concentrations in controls compared to the athletes and the negative association between training hours and urinary androgens is hypothetically due to increased androgen excretion via alternative excretion routes in female athletes.

List of scientific papers

I. Eklund E, Berglund B, Labrie F, Carlström K, Ekström L, Hirschberg AL. Serum androgen profile and physical performance in women Olympic athletes. British journal of sports medicine. 2017;51(17):1301-8.
https://doi.org/10.1136/bjsports-2017-097582

II. Eklund E, Ekström L, Thörngren J-O, Ericsson M, Berglund B, Hirschberg AL. Digit Ratio (2D:4D) and Physical Performance in Female Olympic Athletes. Frontiers in Endocrinology. 2020;11(292):1-8.
https://doi.org/10.3389/fendo.2020.00292

III. Eklund E, Hellberg A, Berglund B, Brismar K, Hirschberg AL. IGF-I and IGFBP-1 in relation to body composition and physical performance in female Olympic athletes. [Submitted]

IV. Schulze JJ*, Mullen JE*, Berglund Lindgren E, Ericsson M, Ekström L, Hirschberg AL. The impact of genetics and hormonal contraceptives on the steroid profile in female athletes. Frontiers in Endocrinoly. 2014;5(50):1-6. *Shared first author.
https://doi.org/10.3389/fendo.2014.00050

V. Eklund E, Andersson A, Ekström L, Hirschberg AL. Urinary steroid profile in elite female athletes in relation to serum androgens and in comparison with untrained controls. [Submitted]