Effects of Low-Dose Spironolactone Combined with Metformin or Either Drug Alone on Insulin Resistance in Patients with Polycystic Ovary Syndrome: A Pilot Study

Metformin and spironolactone alone can be used for the management of polycystic ovarian syndrome (PCOS), and their combination could result in even better outcomes. To compare the effects and safety of low-dose spironolactone combined with metformin or either drug alone on insulin resistance (IR) and functional improvement in patients with PCOS, this was a single-center, randomized, open-label, pilot study of patients with PCOS at the Third Affiliated Hospital of Guangzhou Medical University between 01/2014 and 01/2016. The participants were randomized 1 : 1 : 1 to metformin, spironolactone, or metformin + spironolactone. The primary endpoint was the change in the homeostatic model assessment (HOMA)-IR after 12 weeks of treatment. A total of 189 participants were randomized (63 per group); 31 dropped out, and 54, 51, and 53 completed the 12-week treatment in the metformin, spironolactone, and combined groups, respectively. There were no differences in any parameters between the metformin and spironolactone groups (all P > 0.05). In the combined group, after 12 weeks of treatment, HOMA-IR (1.71 ± 0.91) was lower than in the metformin (1.92 ± 1.07, P < 0.05) and spironolactone (2.38 ± 1.14, P < 0.05) groups. In addition, total testosterone (TT), free androgen index (FAI), and area under the curve-insulin (AUCins) were lower in the combined group compared with the metformin group (all P < 0.05), while TT, FAI, HOMA-β, fasting plasma glucose, and AUCins were lower in the spironolactone group (all P < 0.05). Both metformin and spironolactone decreased HOMA-IR in patients with PCOS but without differences between the two monotherapies. The combined therapy decreased HOMA-IR to a greater extent than monotherapy.