EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL

Abstract

OBJECTIVE: To evaluate the effect of canagliflozin and metformin on the estrous cycle and hormonal derangement of letrozole induced polycystic ovarian syndrome (PCOS) in Sprague Dawly rats. METHODS: Thirty six female adult non-pregnant Sprague Dawly rats were divided into six groups and all, except normal control (A), were treated with letrozole 1mg/kg daily for 21 days. Treatment was started to all rats except normal control (group-A) and disease control (group-B). Canagliflozin 10 mg/kg, metformin 100 mg/kg and their combinations in high and low doses were given daily to rats of groups-C (canagliflozin-alone), group-D (metformin-alone), group-E (high dose combination) and group-F (low dose combination) respectively. Vaginal smears were taken daily, to observe the estrous cycle, till the 48^th day of study. Blood samples were collected on the 22^nd and 48^th day for hormonal assay. RESULTS: Significant increase in serum estradiol levels (ηg/dl) [group-A=46.53±9.40, group-B=18.75±2.48, group-C=23.00±10.15, group-D=37.41±8.54, group-E=57.58±12.88, group-F=41.93±10.32] and Follicle Stimulating Hormone levels (IU) [group-A=22.90±5.98, group-B=9.30±2.88, group-C=25.73±6.70, group-D=17.60±4.89, group-E=27.36±4.12, group-F=16.11±3.56] and decrease in testosterone levels (ηg/dl) [group-A=4.48±1.21, group-B=10.12±2.90, group-C=2.85±1.00, group-D=4.41±2.30, group-E=2.50±1.28, group-F=4.15±0.79] and Luteinizing Hormone levels(ηg/dl) [group-A=24.55±7.07, group-B=31.25±12.88, group-C=7.71±2.89, group-D=11.43±7.17, group-E=6.98±2.28, group-F=15.86±16.35]. Number of estrous cycles were significantly less in group-B (3-4 cycles/rat). Group-E (10-11 cycles/rat) resulted in significantly high estrous cycles number as compared to group-C (8-9 cycles/rat), group-D and group-F (7-8 cycles/rat). CONCLUSION: Canagliflozin is effective alone and augment the effect of metformin for the regularization of estrous cycles and reversal of hormonal derangements in a rat model of PCOS.