Endocrine Abstracts

Context: Metformin is an established therapy for women with PCOS and pre-diabetes or diabetes when lifestyle modification is insufficient. Metformin should also be considered in women with PCOS with BMI≥25 kg/m² independently of the presence of metabolic disturbances. However, its long-term efficacy in this subset of patients is inadequately studied.

Aim: We analyzed collection data of 10 years for the efficacy of metformin on body mass (BM), menstrual frequencies (MF), metabolic and hormonal outcomes in women with PCOS and BMI≥ 25 kg/m².

Methods: Collection data from endocrine outpatient clinic at the university medical centre for 10 years comprising 800 patients with PCOS defined by Rotterdam criteria including 180 patients with PCOS and BMI≥25 kg/m² (age 28.8±6.6 years, BM 96.4±18.7 kg, BMI 34.8±6.4 kg/m²) all receiving uniform monotherapy with metformin 1000 mg BID.

Results: The registry contained 7143 time-points with a subset of anthropometric, reproductive, hormonal and metabolic parameters. The drop out rate in the 1st year was 13%, in the 2nd 24%, in the 3rd 26%, in the 4th 32% and in the 5th year 40%. Only 18% of patients continued with metformin for 10 years. After the 1st year BM decreased for 4.2±1.1 kg (P<0.001) and remained in a steady state until the 10th year in those that continued with the therapy. MF increased from 7.5±3.8 to 10.7±2.9 bleeds/year (P<0.001) after 1st year to over 11 bleeds/year in the following years. The total testosterone and androstendione decerased for 25% after the 1st year, with further decrease in androstendione for 50% from the initial values within the 5 years. LH, FSH and fasting glucose did not changed significantly over the treatment period. Increased MF correlated with the decreases in BM and total testosterone, with no correlation with the change in LH/FSH ratio. Initially, 10% had pre-diabetes and 1.7% had diabetes. After the 1st year 5.7% had pre-diabtes and 1.9% diabetes, after 3rd year 2.2% of women that continued with metformin had pre-diabetes and none had diabetes. The remission rate from pre-diabetes to normal glucose homeostasis in the 1st year was 72%.

Conclusions: Long-term metformin treatment of women with PCOS and BMI≥ 25 kg/m² independently of their initial metabolic status resulted in maximum treatment response after the 1st year, with the improvements in BM, MF and androgen profile. A great drop out was seen after the 3rd year. In women that subsequently remained on therapy an overall beneficial steady state was observed up to the 10th year.