Melatonin: a contraceptive for the nineties.

The hypothalamic GnRH pulse generator activates the pituitary-gonadal reproductive axis, and contraceptive techniques have advanced to the point where GnRH analogues can block this effect. However, nature has an even finer form of contraception, whereby the GnRH pulse generator is activated or inactivated at different seasons of the year. Darkness affects the retino-pineal nervous pathway to cause the synthesis and release of melatonin from the pineal gland at night. The duration of the night time release of melatonin is longer in winter than in summer; and it is the prolongation in the duration of the night time release of melatonin, with the change of season from summer to winter, which acts as the endocrine signal for inactivating the hypothalamic GnRH pulse generator. Humans are not seasonal breeders, and evidence is presented to indicate that this is due to an impairment of the retino-pineal pathway rather than an impairment of melatonin hypothalamic function. Thus the way is open for utilising melatonin as a human contraceptive, and a melatonin-based contraceptive is at present undergoing phase III clinical trials. The challenge is to develop more refined methods for administering (or releasing) melatonin, so that it has a night time amplitude and duration which mimics that seen in long day breeders.