Tetrahydrogestrinone (THG) is a recently discovered steroid that has never been marketed and is used unlawfully to enhance sports performance. Structurally, THG resembles trenbolone, a veterinary androgen. Using a yeast-based in vitro bioassay, the investigators examined the biologic interactions of THG with the human androgen receptor (AR), progesterone receptor (PR), and estrogen receptor (ER). THG agonist activity in the AR bioassay was compared with that of gestrinone, its parent compound, the structurally similar steroid trenbolone, and nandrolone, used as a positive androgen control. THG strongly activated AR transactivation when compared with the other steroids. THG exhibited progestin activity that was 7-fold greater than that of progesterone. In contrast, gestrinone and trenbolone had much less progestin activity than progesterone. THG did not inhibit activation of the androgen receptor by testosterone or activation of the progesterone receptor by progesterone. No ER agonist or antagonist activity was observed. None of the steroids caused cellular toxicity. These findings indicate that THG is a potent androgen and progestin. It does not alter ER action and has no antagonistic effects against any of the sex steroid receptors. The discovery of this designer androgen prompts concern that a range of novel androgens might be produced from marketed progestins and other synthetic sex steroids.