Abstract
High global rates of unintended pregnancy (>40% of all pregnancies) are relatively stagnant despite a broad array of female contraceptive options. Data suggest many men are enthusiastic to utilize novel, reversible, male contraceptives, particularly those that may be administered orally. Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit endocrine negative feedback, interrupting the hypothalamic-pituitary-testicular axis to suppress spermatogenesis. Modifications of testosterone allow for tailoring of steroid activity and show promise as single agent hormonal male contraceptives. The addition of progestin activity by molecular modification of testosterone could enhance the degree and speed of sperm suppression compared to testosterone alone using a single, exogenous steroid. Moreover, modifications that block reduction of testosterone to dihydrotestosterone could diminish androgenic stimulation of prostate tissue. This review summarizes data in the development of modified androgens for male hormonal contraception and suggest a path forward for these molecules in helping to fill the gap in contraceptive technologies for men.