Rising to the challenge of male hormonal contraception

More than a quarter of couples worldwide depend on male contraception.1 Yet, vasectomy aside, male contraceptives are not very reliable. The unintended pregnancy rate with condoms, for example, is 15% to 20% a year.2 This unreliability probably helps explain why more than half of men might try a male hormonal contraceptive (MHC).3 Indeed, new male contraceptives seem to be popular across all races, religions and ethnic backgrounds.1 Nevertheless, despite promising results in clinical studies dating back to the 1970s,1 a reversible MHC has not yet reached the market. “There are many challenges with MHC development,” says Stephanie Page, Robert G McMillen professor in lipid research at the University of Washington, Seattle. In particular, MHCs are not universally effective – for reasons no one really understands. There are lingering concerns over safety, and MHCs do not seem to be priorities for pharmaceutical companies or regulatory agencies. How MHC works In healthy men, the hypothalamus releases gonadotropin-releasing hormone (GnRH). The pulses of GnRH trigger, in turn, the pituitary gland to release pulses of the gonadotropins luteinising hormone (LH) and follicle stimulating hormone (FSH). LH stimulates testosterone production in the testes, while testosterone and FSH trigger spermatogenesis. Testosterone from the testes is released into the circulation and feeds back on the hypothalamus and pituitary gland, reducing production of GnRH, FSH and LH (see Figure 1).1,4 Clinical trials to develop a MHC based on testosterone began in the 1970s.1 The liver metabolises testosterone rapidly, particularly when the hormone is taken orally. So, most studies since the 1970s used longer-acting analogues, such as testosterone undecanoate, which can be administered by injection or implant. Init ial ly, researchers developing MHCs aimed to totally suppress Rising to the challenge of male hormonal contraception