Effects Of Metformin On Estrous Cycle And Ovarian Hormones In Female Rats With Fructoseinduced Metabolic Syndrome

Over the last few decades, fructose consumption has dramatically increased in worldwide [1]. Growing evidence suggests that excessive fructose intake can also induce reproductive problems such as deterioration of oocyte quality and a decrease in estrogen level by disrupting follicular development and ovulation processes [2]. This study aimed to investigate the therapeutic effects of metformin on serum and ovarian reproductive hormone levels as well as ovarian cycle of rats with high-fructose diet induced metabolic syndrome. Female Wistar rats were divided into five groups as follows: control, carboxymethyl cellulose, metformin, fructose, fructose+metformin groups. 20% fructose was added to the drinking water of the rats in the fructose and fructose+metformin groups for 15 weeks, while the other groups were given tap water. Metformin was administered 200 mg/kg/day by gastric gavage after the 7th week. Vaginal cytology was stained with Giemsa and evaluated under a light microscope before and at the 7th and 15th weeks of the experiment. At the end of the experiment, rats were sacrificed by taking intracardiac blood, and ovarian tissues were removed. Although dietary high-fructose significantly increased serum glucose (147.00±3.00 mg/dL), insulin (362.00±21.00 pmol/L) and triglycerides (642.00±68.00 mg/dL) levels, these parameters were decreased with metformin treatment (fructose+metformin group) (p<0.05). Metformin caused a decrease in serum aromatase (11.27±2.39 ng/ml) and estrogen (15.47±5.06 pg/ml) levels in healthy rats compared to the other groups, while testosterone (0.72±0.35 pg/ml) level was the highest in the fructose group. However, when the serum aromatase, inhibin, estrogen, progesterone, and testosterone levels of the experimental groups were compared, no significant difference was observed among the groups. It was noted that the ovarian tissue aromatase level decreased in the fructose group compared to the other groups, while the testosterone level increased (p<0.05). Metformin treatment (fructose+metformin) was found to have a curative effect on these parameters. In vaginal cytology, it was observed that fructose disrupted the estrous cycle and the cycle started again with metformin treatment. Metformin contributed to restoring the estrous cycle's regularity, which was disrupted by highfructose diet. Our results suggest that metformin may improve the ovarian hormonal balance impaired by a high fructose diet. We also demonstrated that vaginal cytology may be useful for monitor ovarian activity in metabolic syndrome.