Combination of Melatonin and Metformin Hydrochloride for Treatment Polycystic Ovarian in Female Rats

Ana Janaina Jeanine Martins de Lemos-Jordão, Fabiano Sellos Costa, Christina Alvez Peixoto, Álvaro Aguiar Coelho Teixeira, Solange Bezerra da Silva, Cintia Giselle Martins Ferreira, Anne Gabrielle Vasconcelos de Oliveira, Rayana Leal Luna, Eduardo Pereira Duarte Silva, Carolline Guimarães D’assunção, Valéria Wanderley-Teixeira


Background: Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder, results in menstrual abnormalities, androgynism and infertility. In the case of women or others animals with PCOS wishing to treat infertility with the aim of becoming pregnant, the most commonly used is metformin hydrochloride. Recent studies have analyzed the combination of metformin hydrochloride with melatonin in oncological treatment but not to treatment of polycystic ovary syndrome (PCOS). The aim of the present study was to analyze the effectiveness of the combination of metformin hydrochloride and melatonin in the treatment of PCOS to improve the fertility of rats and your hormonal alterations.

Materials, Methods & Results: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Federal Rural of Pernambuco (Permit Number: 23081.009130/2010). A total of 50 albino Wistar rats were used. The animal laboratory of an academic research environment, were randomly separated into five groups consisting of 10 females each. After inducing PCOS, the rats were treated with metformin hydrochloride, and/or melatonin, and the results compared with standard and ultrasound confirmed. The physiological similarities were confirmed by our academic researchers morphological science, and published to the association results of effects syndrome induction through constant lighting in reputable magazine recently. This article was analyzed histological of the implantation sites and ovaries, and the estradiol and progesterone levels on the seventh day of gestation, and the other rats for monitoring pregnancy and morphological identification of possible fetal abnormalities, weight measurement and quantification of offspring. The rats were anaesthetized with intraperitoneal injections of ketamine hydrochloride (80 mg/kg) and xylazine (6 mg/kg) to allow analysis of the reproductive organs. Main outcome measures: The study included histopathology, histochemical and quantitative (of the implantation sites) tests, ultrasound analysis, weight benchmarking and ovarian histology tests, as well as comparison of serum estradiol and progesterone levels, and the morphological assessment of offspring. Results paper shows pharmacological treatment reduced the time needed for pregnancy, increased the plasma progesterone levels, the number and weight of offspring, and reduced plasma estrogen levels and collagen fiber grade, improving blastocyst-endometrium interaction and fetal development.

Discussion: Our team of researchers confirmed in a previous paper; in addition, the main experimental model used in research about PCOS in recent years, and considered appropriate combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the POS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. The treatment with a combination of metformin hydrochloride and melatonin was more effective against hormonal alterations produced by PCOS, allowing a normalization of biochemical parameters during pregnancy, than monotherapeutic treatment with these drugs. In conclusion, proposed drug combination is a viable option to treatment of polycystic ovary syndrome and improved fetal development. This article allows suggest that further research should be conducted to examine effects associated with these drugs in the treatment of diseases of the female reproductive system experimentally. Only such treatment later in animals and humans suggest.


polycystic ovaries; metformin; melatonin; reproduction; estradiol; progesterone.

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