Defense Date


Graduation Date

Fall 2011


Immediate Access

Submission Type


Degree Name





School of Pharmacy

Committee Chair

Paula A. Witt-Enderby

Committee Member

Jane E. Cavanaugh

Committee Member

Frank D'Amico

Committee Member

David A. Johnson

Committee Member

Holly C. Lassila

Committee Member

Christine K. O'Neil


Bone, Bone turnover markers, Melatonin, Osteoporosis, Perimenopause


Objective: The purpose of this pilot study was to assess the effects of nightly melatonin supplementation on primary endpoints of bone health and secondary endpoints of quality of life in perimenopausal women.

Methods: A total of 18 perimenopausal women were randomized to receive melatonin, 3 mg p.o., (n=13) or placebo (n=5) nightly for six months. Bone density was measured by calcaneal ultrasound. Osteocalcin (OC), a bone formation marker, and amino-terminal cross-linking telopeptide of type I collagen (NTX), a bone resorption marker, were measured in serum samples taken bimonthly to assess changes in bone turnover. Participants completed the Menopause-Specific Quality of Life-Intervention (MENQOL) and Pittsburgh Sleep Quality Index (PSQI) questionnaires before treatment and after six months. Subjects kept daily diaries recording menstrual cycling, well-being, and sleep patterns.

Results: No significant differences in bone density or bone turnover markers were found with melatonin supplementation; however, there was a time-dependent trend in the melatonin group towards an NTX:OC ratio of 1:1. A ratio of 1:1 could be an indication of the ability of melatonin to balance bone resorption and bone formation to maintain bone mass. Melatonin had no effect on vasomotor, psychosocial, or sexual MENQOL domain scores after six months of nocturnal supplementation. However, women taking melatonin had significant improvement in physical MENQOL domain scores compared to placebo (-0.6 ± 0.8 and 0.1 ± 0.5, respectively). There were no significant changes in PSQI score or average number of hours slept with melatonin treatment. Analysis of menstrual cycling data showed women in the melatonin group had significantly fewer periods (4.3 ± 0.6, n = 10 melatonin; 6.5 ± 0.3, n =4 placebo; mean ± SEM) and longer days between periods (51.2 ± 11.4, n = 10 melatonin; 24.1 ± 0.9, n = 4 placebo) but showed no difference in duration of bleeding. Melatonin supplementation was well-tolerated.

Conclusions: Melatonin may have the ability to regulate serum markers of bone metabolism, indicating a potential role for melatonin in restoring imbalances in bone remodeling and prevention of bone loss. The improvement in quality of life with melatonin indicates supplementation may be beneficial for women experiencing physical symptoms of menopause. Further investigation into how melatonin impacts bone health and quality of life is warranted.