Effects of Oral Administration of Androstenedione on Plasma Androgens in Young Women Using Hormonal Contraception

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Androstenedione is an increasingly popular dietary supplement or prohormone that increases circulating testosterone (T) and purportedly increases lean body mass, strength, energy, sports performance, and libido. Because most published work on the effects of androstenedione have focused on men, the investigators planned a double-blind crossover study in 10 women 20 to 32 years of age who used hormonal contraception. To avoid contamination, an in-house oral formulation of androstenedione was prepared and its effects compared with those of a lactose placebo. Blood was drawn at frequent intervals up to 8 hours after an oral dose of 100 mg and again at 24 hours. A washout period of at least 2 weeks separated the treatments. Peak plasma androgen levels were substantially above the upper limit of reference ranges cited for women. Circulating concentrations were 121 to 346 nmol/L for androstenedione, 14 to 54 nmol/L for T, 11 to 32 nmol/L for 5α-dihydrotestosterone (DHT), and 23 to 90 nmol/L for 3α-androstanediol glucuronide. Comparable changes were observed in the free androgen index. Compared with the control condition, the approximate mean change in area under the plasma concentration–time curve (AUC) from baseline to 24 hours was 7-fold for androstenedione, 16-fold for T, 9-fold for DHT, and 5-fold for 3α-androstanediol glucuronide. The mean conversion ratio of androstenedione to T was 12.5% with a range of 7.8% to 21.6%. Increases in the AUC for T correlated with the level of sex hormone-binding globulin (SHBG). There was no significant difference between SHBG levels in the treatment and control conditions. It is expected that women taking large doses of androstenedione over a lengthy period will lead to persisting supraphysiological concentrations of T and DHT. Plasma levels of SHBG presumably would decline, increasing the level of free T and in this way enhancing the androgenic effects. Long-term studies will be needed to determine how oral androstenedione compares with conventional hormone replacement therapy in postmenopausal women. The investigators believe that sales of androstenedione should be restricted.