Pii: S0531-5565(00)00217-5

In aging humans, night levels of melatonin (MEL) decline progressively. Also thyroid and gonadal functions decline during aging while gonadotropins (luteotropic hormone (LH) and follicle stimulating hormone (FSH)) steadily increase. A desynchronization of pineal circadian cyclicity as expressed by the progressive decrease of the MEL night peak may be permissively linked to the onset and progression of menopause. We studied the effects of exogenous, evening administration of MEL on the level of hormones which are known to be involved in the genesis and progression of menopause. Perimenopausal and menopausal women from 42 to 62 years of age with no pathology or medication were selected. MEL was measured in saliva to divide them into low, medium and high-MEL patients. Half of them took 3 mg MEL and half of them Placebo at bedtime (10±12 p.m.) in a fully randomized and double-blind fashion. Three and six months later blood was taken for determination of pituitary (LH, FSH), ovarian, and thyroid hormones I(T3 and T4). All women taking MEL with low basal level of MEL and/or Placebo for three and six months showed a signi®cant increase in levels of thyroid hormones. Before initiation of the study, a negative correlation was found in all women between LH, FSH and basal MEL levels. Within six months of treatment, MEL produced a signi®cant diminution of LH in the younger women (43 to 49 year-old), while no effect was seen in the older women (50±62 years old). A decrement of FSH was observed in MEL-treated women with low basal MEL levels. In addition, most MEL-treated women reported a general improvement of mood and a signi®cant mitigation of depression. MEL decline during aging may thus signal the derangement of pineal and pituitary-controlled ovarian cyclicity and the progressive quenching of G. Bellipanni et al. / Experimental Gerontology 36 (2001) 297±310 297 Experimental Gerontology 36 (2001) 297±310 www.elsevier.nl/locate/expgero 0531-5565/01/$ see front matter q 2001 Elsevier Science Inc. All rights reserved. PII: S0531-5565(00)00217-5 * Corresponding author. Tel.: 141-91-648-2440; fax: 141-91-648-3070. E-mail address: [email protected] (W. Pierpaoli). 1 Deceased on 15 October 1999. fertility in women. These ®ndings seem to show a recovery of pituitary and thyroid functions in MEL-treated women, towards a more juvenile pattern of regulation. q 2001 Elsevier Science Inc. All rights reserved.