Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study

St John's wort extract (SJW; Hypericum perforatum L.) is taken extensively as a putative herbal antidepressant. It has been shown to induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the clearance of numerous drugs and steroids such as cortisol and ethinyl estradiol. This study was conducted to determine if SJW exposure also alters the concentrations of circulating androgenic steroid hormones. The study was conducted using healthy volunteers (6M, 6F) studied before and after a 14-day treatment period with a SJW preparation previously demonstrated to induce the activity of CYP3A4. Plasma concentrations of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and the combined concentrations of androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were measured by immunoassay methods. The results of analysis demonstrated that SJW did not significantly alter the majority of the androgens studied (p > 0.05) although the combined concentrations of the 5alpha-reduced steroids, AoS and epiAoS, significantly declined following treatment in all subjects (p = 0.02), and in males (p = 0.04). Furthermore, the testosterone to DHT ratio was increased in both men and women. Although the latter increase did not reach statistical significance, it is also consistent with the possible inhibition of 5alpha-reductase by SJW. It is concluded that despite significant induction of CYP3A4, short term administration of SJW does not significantly alter the concentrations of most circulating androgens in men and women but may produce a dimunition in some of the circulating 5alpha-reduced androgens.