Finasteride Pharmacogenomics & Genetic Variability: A Complete Clinical Guide

Does the finasteride label use genetic testing?

No. Propecia is one 1 mg tablet once daily, with or without food; three months or more is usually needed before benefit appears, and withdrawal reverses the effect within 12 months [1]. Proscar, the 5 mg product for benign prostatic hyperplasia, is a fixed 5 mg once daily [3]. Neither label keys its dose, indications or warnings to a genotype [1][3]. Finasteride is extensively metabolized in the liver, mainly by CYP3A4, but the interaction section reports no clinically important drug interactions and gives no genotype-based adjustment [1].

The gene finasteride acts on

Finasteride is a competitive, specific inhibitor of type II 5-alpha-reductase, which converts testosterone to DHT [1]. Type II is the main isozyme in prostate, seminal vesicles, epididymides and hair follicles and makes about two-thirds of circulating DHT; type I, predominant in sebaceous glands and liver, makes about one-third [1]. The type II enzyme complex turns over slowly, with a half-life of roughly 30 days, so finasteride's effect on DHT outlasts the drug's 5- to 6-hour plasma half-life [1]. The type II enzyme is encoded by SRD5A2, on chromosome band 2p23 [2].

What the variant experiments show

One in-vitro study expressed 10 naturally occurring missense substitutions and three double mutants of human 5-alpha-reductase type II [2]. Nine reduced enzyme activity (Vmax) by 20% or more, three increased it by more than 15%, and one was essentially neutral [2]. Tested against finasteride, dutasteride and PNU157706, the variants varied substantially in how well each drug blocked the enzyme [2]. That is a finding about enzyme molecules in a dish, not about men.

What the clinical trials reported

The pivotal hair-loss trials report outcomes for treated men as a group. In two 1-year placebo-controlled trials, 1,553 men aged 18 to 41 took finasteride 1 mg daily or placebo, and 1,215 continued into blinded second-year extensions [4]. Hair count in a 1-inch (5.1 cm2) circle of vertex scalp, from a baseline of 876 hairs, was 107 hairs higher than placebo at 1 year and 138 higher at 2 years (P<0.001) [4]. In three 12-month controlled trials (945 on finasteride, 934 on placebo), drug-related decreased libido was 1.8% versus 1.3%, erectile dysfunction 1.3% versus 0.7% and ejaculation disorder 1.2% versus 0.7% [1].

For male pattern hair loss, the labeled dose is one finasteride 1 mg tablet daily; the label gives no genotype-based adjustment [1].