Long-term dutasteride therapy in men with benign prostatic hyperplasia alters glucose and lipid profiles and increases severity of erectile dysfunction

Background Dutasteride has been successfully used in treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, dutasteride inhibits 5α-reductase type 1 and type 2 enzymes and may compromises glucocorticoids and androgen metabolism and alters metabolic function resulting in undesirable metabolic and sexual adverse side effects. Aim The aim of this study was to investigate the long-term adverse effects of dutasteride therapy in men with BPH on: i) blood glucose, ii) glycated hemoglobin (HbA1c), iii) low density lipoprotein-cholesterol (LDL-C); high density lipoprotein-cholesterol (HDL-C) and total cholesterol (TC), iv) testosterone (T), v) liver alanine and aspartate aminotransferases (ALT and AST) and vi) erectile dysfunction (ED). Methods A retrospective registry study, with a cohort of 230 men aged between 47 and 68 years (mean 57.78 ± 4.81) were treated with dutasteride (0.5 mg/day) for LUTS, secondary to BPH. A second cohort of 230 men aged between 52 and 72 years (mean 62.62 ± 4.65) were treated with tamsulosin (0.4 mg). All men were followed up for 36-42 months. At intervals of 3-6 months, and at each visit, plasma glucose, HbA1c, TC, LDL-cholesterol, T levels and liver alanine amino transferase (ALT) and aspartate aminotransferase (AST) were determined. Further patient assessment was made by the International Index of Erectile Function (IIEF-EF) questionnaire, the Aging Male Symptom (AMS) and International Prostate Symptom Scores (IPSS). Results Long-term treatment with dutasteride therapy is associated with significant improvements in LUTS, as assessed by reduction in prostate volume, IPSS and prostate specific antigen (PSA). Long-term dutasteride therapy, however, resulted in increased blood glucose, HbA1c, TC and LDL levels, ALT and AST activities, AMS Score and reduced T levels and worsened ED as assessed by the IIEF-EF scores. No worsening of ED, glucose, HbA1c, ALT, AST, AMS were observed in men treated with tamsulosin. Most importantly, long-term dutasteride therapy resulted in reduction in total T levels, contributing to a state of hypogonadism. Conclusion Our findings suggest that long-term dutasteride therapy produces worsening of ED, reduced T levels and increased glucose, HbA1c and alters lipid profiles, suggesting induced imbalance in metabolic function. We strongly recommend that physicians discuss with their patients these potential serious adverse effects of long-term dutasteride therapy prior to instituting this form of treatment.

Hormone molecular biology and clinical investigation. 2017 Jun 21 [Epub ahead of print]

Abdulmaged Traish, Karim Sultan Haider, Gheorghe Doros, Ahmad Haider