DMAU, the 17-undecanoic acid ester of dimethandrolone (DMA: 7,11-dimethyl-19-nortestosterone) is a potent androgen currently in development for therapeutic uses in men. Cleavage of the 17-ester bond liberates the biologically active DMA. In this study, we investigated the activity of DMAU and DMA both in vivo and in vitro. DMAU was active orally in castrate rat bioassays, and when administered sc, a single dose produced prolonged androgenic activity and suppression of LH with sustained circulating levels of DMA. DMA, other 19-norandrogens, and C-19 androgens bound to recombinant rat androgen receptor (AR) with high affinity and were equipotent in stimulating luciferase activity (EC₅₀'s: 10^-10 to 10^-9 M) in CV-1 cells cotransfected with a human AR expression vector and 3XHRE-LUC. As various 19-norandrogens are also known to bind to progestin receptors (PR) and to possess progestational activity in vivo, we evaluated the binding affinity of DMA for rabbit PR and recombinant human PR-A and PR-B and its ability to induce PR-mediated transcription and endogenous alkaline phosphatase activity in T47DCO human breast cancer cells. DMA and related 19-norandrogens bound with high affinity to both rabbit and human PR, whereas the less active 11-methyl stereoisomer of DMA and C-19 androgens showed low or negligible binding to PR. In T47DCO cells, 10^-8 M DMA and other 19-norandrogens stimulated transcription of PRE₂-tk-LUC to the same extent as R5020, the potent progestin promegestone (EC₅₀'s: 10^-9 M), but C-19 androgens had no effect. Antiprogestins were potent inhibitors of transactivation and alkaline phosphatase activity induced by DMA and other 19-norandrogens in T47DCO cells, whereas antiandrogens were weak inhibitors. DMA and DMAU also exhibited dose-dependent progestational activity in the estrogen-primed immature female rabbit as assessed by induction of endometrial gland arborization. The dual androgenic and progestational activities of DMA make it a potential candidate for a single-agent male contraceptive, as well as for androgen therapy in men, pending a successful outcome of pharmacokinetic and toxicity studies currently in progress.