Daniel Salamon

Reproductive dysfunction is frequent in women with hyperandrogenism and obesity, like polycystic ovary syndrome (PCOS). On the other hand, hyperandrogenism can be beneficial for physical performance and is common among female athletes. Differences of sex development (DSD) and androgen receptor (AR) dysfunction are rare disorders of reproductive failure. There is a need for improved diagnostics and treatment.The aim is to:elucidate the role of androgens in female athletic performance and reproduction, and the impact on the steroid profile for anti-doping testingdevelop a technique for the assessment of AR sensitivity in vivoexplore perturbed circadian genome organization as a novel mechanism and therapeutic target in PCOScompare semaglutide and metformin in improving reproductive and metabolic health in PCOS.The effect of testosterone on physical performance and reproduction, and the influence on the steroid profile is evaluated in a randomized clinical trial (RCT). A method for quantification of AR activity in vivo is developed to characterize different genetic variants leading to hyperandrogenism and DSD. Transcriptional circadian rhythms in blood and in target tissues in PCOS are investigated by qRT-PCRs and qPCR. Semaglutide and metformin are compared in a RCT to identify the most effective insulin-sensitizing therapy in PCOS. The overall anticipated outcome is improved fertility and metabolic health in women with common and rare reproductive disorders.