New endocrine method of oral male contraception.

Essential for hormonal male contraception (HMC) is the inhibition of follicle-stimulating hormone (FSH), the hormone responsible for spermatogenesis. No drugs exist that can selectively suppress FSH without also inhibiting luteinizing hormone (LH), the hormone responsible for the biosynthesis of testosterone (T) and estradiol (E2) in men. The consequences are a loss of T and E2, with the accompanying symptoms and signs of T deficiency and E2 deficiency, respectively. The loss of T causes sexual function problems, including reduced libido and problems with erection and ejaculation. Moreover, T is not orally bioavailable, and there is a lack of suitable, orally bioavailable androgens to replace the loss of T. This has led to the use of nonoral T replacements, such as patches, gels, or parenteral administration of T or other androgens in current methods for HMC under development. In case these new HMC methods do not contain a testosterone preparation that is metabolized into E2, the suppression of LH will cause loss of E2 and symptoms of estrogen deficiency. We propose to investigate a new oral endocrine approach for HMC using a triple hormone drug called MANTE (Male oral contraception by a GnRH ANtagonist, Testosterone and an Estrogen). This method combines three novelties: (1) the use of an oral gonadotrophin-releasing hormone antagonist to suppress FSH and spermatogenesis, (2) a high dose of the natural adrenal androgen dehydroepiandrosterone to replace T, and (3) a low dose of an orally bioavailable estrogen, preferably estetrol (E4), to prevent signs and symptoms of estrogen deficiency.