title: Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation.
abstract: Although melatonin (MEL) controls seasonal reproductive cyclicity in some mammalian species, its role in women is controversial. In this study data are presented related to the influence of MEL or MEL-progestin combinations on the pituitary-ovarian axis and ovulation in 32 women. MEL was administered in a dosage of 300 mg to 12 women for 4 months [to 8 women daily (days 1-30) and to 4 women on days 5-17 of the cycle]. MEL was also combined with the synthetic progestin norethisterone (NET) in an attempt to evaluate MEL's effect on a partially suppressed pituitary-ovarian axis. In 16 women, 4 combinations were tested on 4 women each on days 1-21: dosages of 300 mg MEL/0.75 mg NET, 75 mg MEL/0.75 mg NET, 7.5 mg MEL/0.75 mg NET, and 75 mg MEL/0.30 mg NET. In addition, 2 women were medicated with 300 mg MEL alone, and 2 were medicated with 300 mg MEL/0.15 mg NET on days 1-21 for 2 months. During the study, LH, FSH, estradiol (E2), and progesterone (P4) blood levels were determined at regular intervals. After a period of 4 months, daily administration of 300 mg MEL (days 1-30) caused significantly decreased mean LH levels compared to those in 8 nonmedicated controls (P less than 0.001). Also compared to nonmedicated control data, a significant inhibition of P4 in the first and fourth medication months (P less than 0.001) was observed. LH and E2 inhibition reached significance in the fourth medication month (P less than 0.005). Also, the treatments of 300 mg MEL (days 5-17) and 75 mg MEL combined with 0.3 mg NET caused a significant decrease in LH, E2, and P4 levels compared to those in the nonmedicated control group in the first and fourth medication months (P less than 0.05). The data further suggest an additive or synergistic effect between MEL and NET. The medications did not alter sleep-wake rhythms and were not complicated by any side-effects. The presented data suggest that MEL and MEL/NET combinations inhibit ovarian function in women, and that MEL/NET combinations can emerge as effective oral contraceptives.
authors.affiliation: Center for Reproductive Medicine and Breast Cancer Prevention, Dijkzigt University Hospital, Rotterdam, The Netherlands.
authors.forename: B C
authors.initials: BC
authors.lastname: Voordouw
authors.forename: R
authors.initials: R
authors.lastname: Euser
authors.forename: R E
authors.initials: RE
authors.lastname: Verdonk
authors.forename: B T
authors.initials: BT
authors.lastname: Alberda
authors.forename: F H
authors.initials: FH
authors.lastname: de Jong
authors.forename: A C
authors.initials: AC
authors.lastname: Drogendijk
authors.forename: B C
authors.initials: BC
authors.lastname: Fauser
authors.forename: M
authors.initials: M
authors.lastname: Cohen
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008597:Menstrual Cycle / Q000187:drug effects; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000494:pharmacology*; D010053:Ovary / Q000502:physiology*; D010060:Ovulation / Q000187:drug effects*; D010902:Pituitary Gland / Q000502:physiology*
chemical_list: D004338:Drug Combinations; D004958:Estradiol; D007986:Luteinizing Hormone; D008550:Melatonin; D009640:Norethindrone