Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on suppression of gonadotropins and thus of testicular function and spermatogenesis, and has been investigated for several decades. This approach can achieve sufficient suppression of spermatogenesis for effective contraception in most men, but not all; the basis for these men responding insufficiently is unclear. Alternatively, the nonhormonal approach is based on identifying specific processes in sperm development, maturation and function. A range of targets has been identified in animal models, and targeted effectively. This approach, however, remains in the pre-clinical domain at present. There are, therefore, grounds for considering that safe, effective and reversible methods of contraception for men can be developed.

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Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder-in-capsule taken with food are well-tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in SEDDS, with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, ten men received single, escalating, oral doses of DMAU (100 mg, 200 mg, and 400 mg) and two subjects received placebo. All doses were evaluated both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p< 0.007) and average concentrations (p<0.002) at the 400mg dose, compared with the 200mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p=0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400mg DMAU when administered with food but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well-tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be advantageous for the application of DMAU as a male contraceptive.

Short-term sex steroid withdrawal in healthy men causes adverse changes in body composition. These findings support the role of estradiol as a determinant of adiposity in men.