Endocrine Abstracts

Introduction: Glucocorticoids (GC) are prescribed to 2–3% of the population of the UK and USA. Their use is associated with a significant side effect profile that includes the development of central obesity, insulin resistance and type 2 diabetes. 5α-reductase (5αR) inhibitors (Finasteride and Dutasteride) are also commonly prescribed in the context of prostate disease, where they inhibit the conversion of testosterone to dihydrotestosterone. Additionally, they have a role to inactivate and clear GC. We have therefore hypothesised that 5αR inhibitors have the potential to exacerbate the adverse metabolic effects of GC.

Methods: We conducted a prospective, randomised, study in 19 healthy male volunteers (age; 45±8.5 years, BMI; 27.1±3.1 kg/m²). Participants underwent detailed metabolic assessments including a 2-step hyperinsulinaemic euglycaemic clamp incorporating stable isotopes, adipose tissue microdialysis and biopsy. They were then randomised to receive either prednisolone (10 mg OD) or prednisolone (10 mg OD) and a 5αR inhibitor (finasteride 5 mg OD or dutasteride 0.5 mg OD) for 7 days, metabolic assessments were then repeated.

Results: We have previously shown that high dose parenteral GC administration decreases glucose utilization (M value; 3.1±0.4 vs 1.6±0.1 mg/kg per min, P=0.001) and 5αR inhibitors alone are without effect (M value; 3.5±0.4 vs 3.3±0.4 mg/kg per min, P=0.42). In this study, prednisolone only did not alter glucose utilization (M-value; 3.2±1.3 vs 2.8±1.6 mg/kg per min, P=0.37), however, co-administration of prednisolone and 5αR inhibitors significantly decreased it (M-value; 4.0±2.0 vs 2.6±1.3 mg/kg per min, P=0.02). Similarly, high dose GC, but not 5αR inhibitors alone, impair insulin-mediated suppression of circulating non-esterified fatty acids (NEFA). Prednisolone 10mg OD did not alter insulin-mediated suppression of NEFA (0.15±0.27 vs 0.13±0.13, P=0.88), however, co-administration with 5αR inhibitors impaired the ability of insulin to suppress NEFA (0.15±0.1 vs 0.29±0.18, P=0.01).

Conclusion: 5αR inhibitors exacerbate the adverse metabolic effects of prescribed GCs. This has significant translational implications, not only with regards to the need to consider steroid dose reductions, but also the necessity for increased vigilance for the development of adverse effects.