madman
Super Moderator
Purpose of review
Rates of unintended pregnancy have remained relatively stagnant for many years, despite a broad array of female contraceptive options. Recent restrictions on access to abortion in some countries have increased the urgency for expanding contraceptive options. Increasing data suggest men are keen to utilize novel reversible male contraceptives.
Recent findings
Despite decades of clinical research in male contraception, no reversible hormonal product currently exists. Nestorone/testosterone, among other novel androgens, shows promise to finally move to pivotal Phase 3 studies and introduction to the marketplace.
Summary
Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit negative feedback that regulates the hypothalamic-pituitary-testicular axis. By suppressing release of gonadotropins, these agents markedly decrease endogenous testosterone production, lower intratesticular testosterone and suppress spermatogenesis. The addition of a progestin enhances the degree and speed of sperm suppression. The androgen component preserves a state of symptomatic eugonadism in the male. There is growing demand and acceptance of male contraceptive options in various forms. As these formulations progress through stages of drug development, regulatory oversight and communication with developers around safety and efficacy standards and garnering industry support for advancing the production of male contraceptives will be imperative.
* PHYSIOLOGY OF MALE REPRODUCTION
* HORMONAL MALE CONTRACEPTIVE EFFICACY TRIALS
* ADDITIONAL HORMONAL CONTRACEPTIVE METHODS USING TESTOSTERONE OR NOVEL ANDROGENS
- Gonadotropin-releasing hormone antagonists
- 7-Alpha-methyl-19-nortestosterone
- Dimethandrolone undecanoate and 11-betamethyl-19-nortestosterone
CONCLUSION: FUTURE DEVELOPMENT OF HORMONAL MALE CONTRACEPTIVES
Clinical trials over the last 50 years have demonstrated the effectiveness and safety of androgen based HMC. Importantly, recent data from older men has provided additional reassurance regarding the safety of exogenous testosterone when given at physiologic dosing [54–56], the backbone of combined androgen-progestin HMC. So why is there no HMC on the market? To perform pivotal Phase 3 studies, both funding and regulatory guidance is required to allow developers to appropriately evaluate longer term safety and efficacy. Surveys of men and women suggest a rapidly expanding desire for male contraceptive options and interest in sharing the burden of contraception [57]. Co-ordinated efforts between investigators, regulators, investors and the public are required to get male contraceptives to the market, a need that is increasingly urgent in the face of the economic and health impacts of unplanned pregnancies. Such efforts will hopefully result in novel, reversible male contraceptives in the next decade.
Rates of unintended pregnancy have remained relatively stagnant for many years, despite a broad array of female contraceptive options. Recent restrictions on access to abortion in some countries have increased the urgency for expanding contraceptive options. Increasing data suggest men are keen to utilize novel reversible male contraceptives.
Recent findings
Despite decades of clinical research in male contraception, no reversible hormonal product currently exists. Nestorone/testosterone, among other novel androgens, shows promise to finally move to pivotal Phase 3 studies and introduction to the marketplace.
Summary
Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit negative feedback that regulates the hypothalamic-pituitary-testicular axis. By suppressing release of gonadotropins, these agents markedly decrease endogenous testosterone production, lower intratesticular testosterone and suppress spermatogenesis. The addition of a progestin enhances the degree and speed of sperm suppression. The androgen component preserves a state of symptomatic eugonadism in the male. There is growing demand and acceptance of male contraceptive options in various forms. As these formulations progress through stages of drug development, regulatory oversight and communication with developers around safety and efficacy standards and garnering industry support for advancing the production of male contraceptives will be imperative.
* PHYSIOLOGY OF MALE REPRODUCTION
* HORMONAL MALE CONTRACEPTIVE EFFICACY TRIALS
* ADDITIONAL HORMONAL CONTRACEPTIVE METHODS USING TESTOSTERONE OR NOVEL ANDROGENS
- Gonadotropin-releasing hormone antagonists
- 7-Alpha-methyl-19-nortestosterone
- Dimethandrolone undecanoate and 11-betamethyl-19-nortestosterone
CONCLUSION: FUTURE DEVELOPMENT OF HORMONAL MALE CONTRACEPTIVES
Clinical trials over the last 50 years have demonstrated the effectiveness and safety of androgen based HMC. Importantly, recent data from older men has provided additional reassurance regarding the safety of exogenous testosterone when given at physiologic dosing [54–56], the backbone of combined androgen-progestin HMC. So why is there no HMC on the market? To perform pivotal Phase 3 studies, both funding and regulatory guidance is required to allow developers to appropriately evaluate longer term safety and efficacy. Surveys of men and women suggest a rapidly expanding desire for male contraceptive options and interest in sharing the burden of contraception [57]. Co-ordinated efforts between investigators, regulators, investors and the public are required to get male contraceptives to the market, a need that is increasingly urgent in the face of the economic and health impacts of unplanned pregnancies. Such efforts will hopefully result in novel, reversible male contraceptives in the next decade.
