Finasteride, Dutasteride and Insulin Resistance

Do 5 alpha reductase inhibitors affect insulin sensitivity?

The topic of insulin resistance induced by 5 alpha reductase (5αR) inhibitors like finasteride and dutasteride is interesting.  Finasteride inhibits 5αR2 selectively, whereas dutasteride inhibits both 5αR1 and 5αR2. There is evidence that dutasteride has a more potent effect on insulin resistance than does finasteride. Finasteride may even reduce insulin resistance in some studies. 

It appears that the inhibition of 5αR1 is the relevant enzyme when discussing insulin resistance. Interestingly, Dowman and colleagues showed that increased liver fat and decreased insulin sensitivity are seen in mice with targeted disruption of 5αR1, but not 5αR2.

Upreti and colleagues performed a double-blind randomized controlled study of 46 men (20–85 years) with oral dutasteride (0.5 mg daily; n = 16), finasteride (5 mg daily; n = 16), or control (tamsulosin; 0.4 mg daily; n = 14) for 3 months. Dutasteride, but not finasteride, showed evidence of insulin resistance. There were no effects of dutasteride, finasteride or controls on BP, heart rate, body weight, BMI, or waist-to-hip ratio. However, there was an increase in body fat with dutasteride, but not finasteride. There were no differences in serum lipid profile

Hazlehurst and colleagues conducted a randomized study in 12 healthy male volunteers with detailed metabolic phenotyping performed before and after a 3-week treatment with finasteride (5 mg od) or dutasteride (0.5 mg od). Dutasteride, not finasteride, increased hepatic insulin resistance and hepatic lipid accumulation.

Clinical studies on Finasteride and Insulin Resistance

Duskova  and colleagues performed one of the most thorough studies examining the relationship between finasteride and insulin resistance. They examined 12 men with androgenetic alopecia who used finasteride for 12 months. Hormonal levels, metabolic parameters  and insulin tolerance tests performed for all individuals.  The authors observed an initial increase in total cholesterol and HDL- and LDL-cholesterol, which stabilized with prolonged treatment. However, they found a significant decrease in glycated hemoglobin HbA1c and decreased insulin resistance. The authors concluded that finasteride improves blood sugar parameters.

Conclusion

Dutasteride appears to have different effects on insulin sensitivity than finasteride likely due to its inhibitory effects on 5 alpha reductase type 1.  There are limited studies available on insulin resistance mediated by these drugs. However, the data would point to a slight insulin resistance effect with dutasteride and possibility slight improvement in insulin sensitivity with finasteride. 

References

Dowman et al. Loss of 5α-reductase type 1 accelerates the development of hepatic steatosis but protects against hepatocellular carcinoma in male mice. Endocrinology 2013; 154: 4536-4547

Duskova M, et al. Changes of metabolic profile in men treated for androgenetic alopecia with 1 mg finasteride. Endocr Regul. 2010.

Hazlehurst JM, et al. Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man. Randomized controlled trial. J Clin Endocrinol Metab. 2016.

Rita Upreti et al. 5α-Reductase Type 1 Modulates Insulin Sensitivity in Men. The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 8, 1 August 2014, Pages E1397–E1406,