Effect of pioglitazone on testosterone in eugonadal men with type 2 diabetes mellitus: a randomized double-blind placebo-controlled study

Objectives Pioglitazone is an insulin sensitizer used for the management of type 2 diabetes mellitus (T2DM). It has been shown to reduce testosterone level in patients with polycystic ovarian syndrome. However, its effect on testosterone in men has not been studied. Research design and methods A randomized, double-blind, placebo-controlled trial with 6 months follow-up. Fifty (25 in each group) eugonadal men (well virilized and total testosterone =12 nm) with T2DM, aged 3055 year and HbA1c of =7.5% were randomly assigned to receive pioglitazone 30 mg per day or placebo along with existing glimepiride and metformin therapy. Results As compared to placebo, 6 months of pioglitazone therapy in patients with T2DM resulted in significant reduction in mean total testosterone level (16.1 to 14.9 vs 17.1 to 17.0 nm; P = 0.031), calculated free testosterone (P = 0.001) and bioavailable testosterone (P = 0.000) despite significant increase in sex hormone-binding globulin (P = 0.000). Plasma androstenedione (4) level increased (1.5 to 1.9 vs 1.7 to 1.7 ng/ml; P = 0.051) following pioglitazone therapy. The decrease in testosterone was independent of change in body weight, body fat and HbA1c. Conclusion Pioglitazone therapy significantly decreases total, free and bioavailable testosterone in eugonadal men with T2DM. The effects of these alterations need to be determined by further long-term studies.