Co-administration of 5α-reductase Inhibitors Worsens the Adverse Metabolic Effects of Prescribed Glucocorticoids.
Othonos N., Marjot T., Woods C., Hazlehurst JM., Nikolaou N., Pofi R., White S., Bonaventura I., Webster C., Duffy J., Cornfield T., Moolla A., Isidori AM., Hodson L., Tomlinson JW.
CONTEXT: Glucocorticoids (GCs) are commonly prescribed, but their use is associated with adverse metabolic effects. 5α-reductase inhibitors (5α-RI) are also frequently prescribed, mainly to inhibit testosterone conversion to dihydrotestosterone. However, they also prevent the inactivation of GCs. OBJECTIVE: We hypothesized that 5α-RI may worsen the adverse effects of GCs. DESIGN: Prospective, randomized study. PATIENTS: A total of 19 healthy male volunteers (age 45 ± 2 years; body mass index 27.1 ± 0.7kg/m2). INTERVENTIONS: Participants underwent metabolic assessments; 2-step hyperinsulinemic, euglycemic clamp incorporating stable isotopes, adipose tissue microdialysis, and biopsy. Participants were then randomized to either prednisolone (10 mg daily) or prednisolone (10 mg daily) plus a 5α-RI (finasteride 5 mg daily or dutasteride 0.5 mg daily) for 7 days; metabolic assessments were then repeated. MAIN OUTCOME MEASURES: Ra glucose, glucose utilization (M-value), glucose oxidation, and nonesterified fatty acids (NEFA) levels. RESULTS: Co-administration of prednisolone with a 5α-RI increased circulating prednisolone levels (482 ± 96 vs 761 ± 57 nmol/L, P = 0.029). Prednisolone alone did not alter Ra glucose (2.55 ± 0.34 vs 2.62 ± 0.19 mg/kg/minute, P = 0.86), M-value (3.2 ± 0.5 vs 2.7 ± 0.7 mg/kg/minute, P = 0.37), or glucose oxidation (0.042 ± 0.007 vs 0.040 ± 0.004 mmol/hr/kg/minute, P = 0.79). However, co-administration with a 5α-RI increased Ra glucose (2.67 ± 0.16 vs 3.05 ± 0.18 mg/kg/minute, P