Can melatonin cause infertility?/nA 37-year-old woman, with a two-year-old child has been using mel

Fråga: Can melatonin cause infertility?

A 37-year-old woman, with a two-year-old child has been using melatonin(non-prescribed, dose unknown) against insomnia for the past year. She has been trying to conceive for the past 10 months, without success.

Sammanfattning: Animal studies suggest that melatonin plays an important role in reproduction. The effect of melatonin on the reproductive system in humans is still unclear. In the present case, discontinuation of the drug is recommended, as the effects on fertility, as well as the teratogenic potential, have not yet been established.

Svar: Melatonin is an endogenous hormone produced from tryptophane in the pineal gland in mammals. The secretion increases during nighttime and decreases during exposure to light. It is implicated in the regulation of the circadian rhythm (sleep-wake rhythm) and possibly in the regulation of reproduction (1).

Melatonin has been classified as a drug in Sweden since 1995. It is not approved by the Swedish Medical Products Agency, but can be prescribed by a special licence. The main use is in the treatment of sleeping disturbances and jetlag (2).

There are no controlled clinical trials found in available literature evaluating the efficacy and safety of long-term use of melatonin in fertile women. There are reports of gynecomastia, decreased levels of lutenizing hormone (LH), and decreased body temperature, as a result of chronic melatonin use (3). There is one case report concerning amenorrhoea in the WHO:s adverse drug reactions database (4).

The exact mechanism of action of melatonin on the human reproduction system remains to be studied. Melatonin receptors have been demonstrated in the hypothalamus and the pituary in animals. Melatonin receptors have also been demonstrated in animal testis, epididymis, prostate, ovary and mammary glands (5) It has been suggested that melatonin could play an important role in both spermatogenesis and folliculogenesis The number of menstrual cycles with anovulation in women, have been shown to increase during the winter (6). Studies on human seminal plasma have demonstated higher levels of melatonin in oligospermic and azoospermic men (7,8). The effect of exogenous melatonin on the pituary hormones has been studied in a randomized controlled trial, where twelve sleep disorder patients who were given low doses of melatonin for a year, were compared to healthy volunteers. In this study, the levels of LH were higher in the sleep disorder patients. In all subjects, prolactine levels were increased by melatonin. There were no data concerning reported side effects in the study (7). 1 Wetterberg L. Melatonin - okritiskt bruk efter oseriös reklam. Läkartidningen 1996;93:3019-21. 2 Henningsson S. Förskrivning ex tempore av melatonin ersätts av licensförskrivning. Information från Läkemedelsverket 1999;10(7) 3 Micromedex(R) Healthcare Series: Micromedex Inc., Englewood, Colorado (Edition expires (3/2003)) 4 Intdis (International Drug Information System): WHO:s adverse drug reactions database (cited 2003-03-18) 5 Pang SF, Li L, Ayre EA, Pang CS, Lee PPN et al. Neuroendocrinology of melatonin in reproduction: recent developments. J Chem Neuroanat 1998;14:157-66. 6 Partonen T. Short note: melatonin-dependent infertility. Med Hypotheses 1999;52:487-8. 7 Ninomiya T, Iwatani N, Tomoda A, Miike T. Effects of exogenous melatonin on pituitary hormones in humans. Clin Physiol 2001;21:292-9. 8 Karasek M, Pawlikowski M, Nowakowska-Jankiewicz B, Kolodziej. Maciejewska H, Zieleniewski J, Cieslak D, et al. Circadian variations in plasma melatonin, FSH, LH, and prolactin and testosterone levels in infertile men. J Pineal Res 1990;9:149-57.