EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL
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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 48th day of study. Blood samples were collected on the 22nd and 48th 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.
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