5α-reductase type 1 modulates insulin sensitivity in men

Area of Science:

• Endocrinology
• Metabolic Science
• Pharmacology

Background:

• 5α-Reductase (5αR) enzymes (types 1 and 2) are crucial for steroid A-ring reduction.
• Inhibitors like finasteride and dutasteride are used for benign prostatic hyperplasia, with dutasteride inhibiting both 5αR1 and 5αR2.
• Rodent studies indicate that 5αR1 deficiency is linked to fatty liver disease.

Purpose of the Study:

• To investigate the hypothesis that 5αR1 inhibition leads to metabolic dysfunction in humans.
• To compare the metabolic effects of dual 5αR inhibition (dutasteride) versus 5αR2 inhibition (finasteride).

Main Methods:

• A 3-month, double-blind, randomized controlled trial involving 46 men aged 20-85.
• Participants received oral dutasteride (0.5 mg/day), finasteride (5 mg/day), or tamsulosin (0.4 mg/day) as a control.
• Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, measuring glucose disposal and nonesterified fatty acid suppression.

Main Results:

• Dutasteride and finasteride similarly altered steroid profiles, reducing androgen/glucocorticoid metabolites and dihydrotestosterone (DHT).
• Only dutasteride significantly reduced insulin-stimulated glucose disposal and suppressed nonesterified fatty acids, indicating impaired insulin sensitivity in peripheral tissues.
• Dutasteride treatment led to a 1.6% increase in body fat, while finasteride and tamsulosin did not.

Conclusions:

• Dual 5αR inhibition, as with dutasteride, impacts insulin sensitivity in human peripheral tissues, not the liver.
• These findings suggest potential metabolic side effects for patients taking dutasteride for conditions like prostatic disease.
• Targeting 5αR1 may be a key factor in dutasteride's observed metabolic effects.