Objectives: Melatonin levels decrease physiologically with age, and possibly with the transition to menopause. The plausible influence of hormone therapy (HT) on melatonin is poorly understood. The aim of this randomized, placebo-controlled, double-blind trial was to investigate the effect of HT administration on serum melatonin concentrations in late premenopausal and postmenopausal women. Study design: Analyses were carried out among 17 late premenopausal and 18 postmenopausal healthy women who participated in a prospective HT study in Finland. Serum melatonin was sampled at 20-min (21:00-24:00 h; 06:00-09:00 h) and 1-h (24:00-06:00 h) intervals at baseline and after 6 months with HT or placebo. Main outcome measures: Melatonin levels and secretion profile after 6 months of HT compared to placebo. Results: Mean melatonin levels, mean melatonin exposure level (area under curve, AUC) and mean duration of melatonin secretion did not differ after 6 months with HT vs. placebo, irrespectively of the reproductive state. However, in postmenopausal women the melatonin peak time (acrophase) was delayed by 2.4 h (2 h 21 min) on average after 6 months with HT vs. placebo (p<0.05). No interaction between time and group was detected when melatonin level was modelled before or after treatment. Conclusions: Administration of HT to postmenopausal women alters melatonin peak time, but not melatonin levels. Further research on larger clinical samples is needed to better understand the effects of HT on melatonin profile. (C) 2014 Elsevier Ireland Ltd. All rights reserved.