Abstract

PIP: No contraceptive method which tricks nature by using nature's own method has yet been introduced. A prolonged release of melatonin from the pineal gland via the retina-pineal nervous pathway during the longer nighttime in winter operates as a signal to inactivate the hypothalamic gonadotropin releasing hormone (GnRH) pulse generator. Specifically, darkness activates the pathway. while light suppresses it. This process occurs in most mammals that are seasonal breeders. Yet, humans are not seasonal breeders. Scientists propose 2 possible reasons for the considerable variation in the nighttime release of melatonin in humans, which tends to be below the threshold needed to signal the GnRH pulse generator: an evolutionary phenomenon, or that humans are surrounded by artificial light. They have studied melatonin release in children before puberty and in women with functional hypothalamic amenorrhea to gain more insight. Increasing body mass and constant pineal production causes a reduced circulating level of melatonin to the point (during puberty) at which melatonin falls below a critical threshold and activates the GnRH pulse generator. Melatonin levels are significantly higher in functional hypothalamic amenorrheic patients than in normal controls. Phase III clinical trials of a melatonin-based contraceptive are occurring. At a dose of 75 mg melatonin, the maximum level of circulating melatonin is above 400,000 pmol/l, which maintains a nighttime level above the critical threshold for more than 12 hours. The strategies for developing more refined methods to mimic a nighttime amplitude and duration of long day breeders are likely a controlled release preparation or a method to activate N-acetyl transferase in the pineal body to synthesize and release melatonin at a sufficient level and duration.