Melatonin supplementation therapy as a potent alternative to ERT in ovariectomized rats

Aim To evaluate the efficacy of melatonin supplementation therapy as an alternative to estrogen replacement therapy in an ovariectomized rat model and to assess diabetogenic metabolic dysregulation caused by estrogen deficiency in postmenopausal individuals. Methods Ovariectomized adult Wistar rats were treated with either estrogen/progesterone, melatonin or a combination of estrogen and melatonin. Body weight gain, feed efficiency, serum glucose, insulin, glucose tolerance and insulin response, serum and tissue lipids, tissue glycogen contents and activities of glycogen phosphorylase and glucose-6-phosphatase were analyzed in all the experimental groups. Results Ovariectomized animals showed increased body weight gain, feed efficiency, fasting insulin resistance, greater area under curve for the glucose tolerance test, higher serum and tissue lipids and reduced glycogen content and insulin sensitivity. A low dose of melatonin was more efficient than estrogen in reversing all the ovariectomy-induced changes. The combination of estrogen + melatonin was found to be best in correcting glycemic dysregulation while high doses of melatonin could effectively regulate dyslipidemia. Conclusion The present study provides strong evidence for melatonin supplementation therapy to be more potent and effective in comparison to estrogen replacement therapy due to its single-handed ability to revert all the ovariectomy-induced changes. No reported side-effect or long-term effect of melatonin, against the known effects of estrogen replacement therapy, make it more attractive as a candidate to treat postmenopausal symptoms.