Male hormonal contraception: concept proven, product in sight?
Current male hormonal contraceptive (MHC) regimens act at various levels within the hypothalamic pituitary testicular axis, principally to induce the withdrawal of the pituitary gonadotrophins and in turn intratesticular androgen production and spermatogenesis. Azoospermia or severe oligozoospermia result from the inhibition of spermatogonial maturation and sperm release (spermiation). All regimens include an androgen to maintain virilization, while in many the suppression of gonadotrophins/spermatogenesis is augmented by the addition of another anti-gonadotrophic agent (progestin, GnRH antagonist). The suppression of sperm concentration to 1 x 10(6)/ml appears to provide comparable contraceptive efficacy to female hormonal methods, but the confidence intervals around these estimates remain relatively large, reflecting the limited number of exposure years reported. Also, inconsistencies in the rapidity and depth of spermatogenic suppression, potential for secondary escape of sperm into the ejaculate and onset of fertility return not readily explainable by analysis of subject serum hormone levels, germ cell number or intratesticular steroidogenesis, are apparent. As such, a better understanding of the endocrine and genetic regulation of spermatogenesis is necessary and may allow for new treatment paradigms. The development of an effective, consumer-friendly male contraceptive remains challenging, as it requires strong translational cooperation not only between basic scientists and clinicians but also between public and private sectors. At present, a prototype MHC product using a long-acting injectable testosterone and depot progestin is well advanced.
Matthiesson
Kati L
KL
Department of Obstetrics and Gynaecology, Prince Henry's Institute of Medical Research, Monash University, Monash Medical Centre, Clayton, Victoria 3168, Australia. kati.matthiesson@princehenrys.org
McLachlan
Robert I
RI
D000728:Androgens / Q000008:administration & dosage; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000009:adverse effects / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology*; D013092:Spermatogenesis-Blocking Agents / Q000494:pharmacology; D013739:Testosterone
D000728:Androgens; D003272:Contraceptive Agents, Male; D006062:Gonadotropins; D006728:Hormones; D013092:Spermatogenesis-Blocking Agents; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone