Effect of Sildenafil on Gonadotrophin and Sex Steroids in Fructose Induced Diabetes in Female Rats

Background: Diabetes is associated with increased risk of female reproductive problems. Although several studies have shown altered ovarian function in association with diabetes, the molecular alterations in ovarian steroid metabo-lism that could explain these reproductive dysfunctions remain to be elucidated. Sildenafil citrate is a PDE5 inhibitor (PDE-5i) selectively degrades cGMP and may affect gonadotrophin and sex hormone synthesis. This work was designed to study the effect of sildenafil on diabetic female rat serum LH, FSH, E2 and progesterone levels.Methods: 40 adult female albino rats were divided ran-domly into 4 groups; Group 1: Control group, Group 2: Sildenafil group, received sildenafil citrate at dose 5 mg/Kg BW/day for 3 consecutive days/week for 4 weeks, Group 3: Diabetic rats, administrated fructose dissolved in drinking water for 8 weeks, Group 4: Diabetic treated with sildenafil, administrated fructose dissolved in drinking water for 8 weeks and administered sildenafil citrate orally by gastric intubation at dose 5mg/Kg BW/day for 3 consecutive days/week for the last 4 weeks. All rats were sacrificed in the proestrous phase and FSH, LH, estrogen and progesterone were measured.Results: Fructose administration significantly increased blood glucose, insulin and HOMA-IR in diabetic rats (p 0.05) when compared to the control rats, while treatment with sildenafil resulted in significant decrease in blood glucose, insulin and HOMA-IR in group 4 when compared to diabetic group (p 0.05). Also, in diabetic rats, LH, estrogen and progesterone levels were significantly decreased (p 0.05) while FSH was insignificantly decreased (p 0.05) when compared to the control rats. Treatment with sildenafil significantly increased FSH, LH, estrogen and progesterone levels in treated diabetic rats (p 0.05) when compared un-treated diabetics.Conclusion: It can be concluded that treatment of the fructose-induced type 2 diabetic female rats with sildenafil citrate improved the altered glucose tolerance, had an insulin sensitizing action and improved the altered levels of FSH, LH, E2 and progesterone in diabetic female rats.