Finasteride Off-Label Uses: Evidence Levels for Each Indication

What finasteride is actually approved for

Two tablets, two approvals. Finasteride 1 mg (Propecia) was approved on 19 December 1997 for male pattern hair loss in men only; the label states that efficacy in bitemporal recession has not been established and that the drug is not indicated for women [3][5]. Finasteride 5 mg (Proscar) was approved on 19 June 1992 for symptomatic benign prostatic hyperplasia in men with an enlarged prostate, to improve symptoms and reduce the risk of acute urinary retention and of surgery, and its label states plainly that it is not approved for the prevention of prostate cancer [4][1]. Oral tablets are the only FDA-approved form; no topical or injectable finasteride is approved [5]. HealthRX.com offers finasteride 1 mg tablets by prescription, the approved hair-loss form [3].

Finasteride competitively inhibits type II 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT). Type II produces about two-thirds of circulating DHT and is the main form in prostate, seminal vesicles, epididymides and hair follicles, and finasteride is roughly 100-fold selective for type II over type I [5]. A 1 mg tablet suppresses serum DHT by 65% within 24 hours; mean testosterone and estradiol rise by about 15% but remain within the normal range, and the drug has no affinity for the androgen receptor [5].

Prostate cancer risk reduction: the strongest evidence

The Prostate Cancer Prevention Trial randomized 18,882 men aged 55 or older with a normal digital rectal exam and a PSA of 3.0 ng/mL or lower to finasteride 5 mg daily or placebo for seven years [2]. Prostate cancer was detected in 803 of 4,368 men on finasteride (18.4%) and 1,147 of 4,692 on placebo (24.4%), a 24.8% relative reduction (95% CI 18.6 to 30.6; P<0.001) [2]. Gleason 7 to 10 tumors were more common on finasteride, 6.4% versus 5.1% of men [2]; the label reports Gleason 8 to 10 cancer in 1.8% versus 1.1% [1].

Longer follow-up did not show a survival difference. With up to 18 years of follow-up, prostate cancer was diagnosed in 10.5% of the finasteride group and 14.9% of the placebo group (relative risk 0.70, 95% CI 0.65 to 0.76), high-grade cancer in 3.5% versus 3.0% (relative risk 1.17, 95% CI 1.00 to 1.37), and 15-year survival was 78.0% versus 78.2% (hazard ratio for death 1.02, 95% CI 0.97 to 1.08) [10].

The ASCO and AUA joint guideline, published in 2009, concluded that asymptomatic men with a PSA of 3.0 ng/mL or less who are regularly screened may benefit from a discussion of seven years of 5-alpha reductase inhibitor use for prevention and of the potential risks, including possible high-grade cancer. It also notes that a PSA reduction of about 50% by 12 months is expected and that no specific PSA cut point for biopsy in men taking a 5-ARI has been prospectively validated [11].

The Proscar label states it is not approved to reduce the risk of developing prostate cancer [1]. Whether the reduced prostate volume or study-related factors drove the high-grade findings has not been established [1], and PSA performed better as a cancer detector in the finasteride arm of the trial, a bias expected to increase detection of all grades [12].

Female pattern hair loss: small studies, mixed results

Finasteride is not indicated for women, and pregnancy is a contraindication [5]. The published data are mostly uncontrolled. An open-label Korean study enrolled 87 normoandrogenic pre- and postmenopausal women with female pattern hair loss on finasteride 5 mg daily; 86 completed 12 months, hair density rose from 90 to 107 hairs per square centimeter (P<0.001) and hair thickness from 64 to 70 micrometers (P=0.02), and 70 of 86 patients (81.4%) were rated improved on global photographs. Four patients (4.6%) reported adverse events, including headache, menstrual irregularity, dizziness and increased body hair [6]. There was no placebo arm.

A second study treated 37 premenopausal women with 2.5 mg daily alongside an oral contraceptive containing drospirenone and ethinyl estradiol; 23 of 37 (62%) improved on global photography at 12 months, again with no control group, and the authors could not tell whether the higher finasteride dose or the antiandrogenic contraceptive explained the result [13].

The one randomized comparison was negative. In an unmasked randomized trial that assigned 36 hyperandrogenic women with alopecia to three treatments (with 12 more untreated observation patients), finasteride 5 mg daily for one year did not significantly change Ludwig scores, while flutamide 250 mg reduced them by 21% (2.3 to 1.8) [7]. Case reports describe improvement in women with hyperandrogenism, while the same authors note that finasteride has not improved hair growth in postmenopausal women with female pattern hair loss without hyperandrogenism [14].

Hirsutism: one randomized comparison

Forty hirsute women were randomized double-blind to spironolactone 100 mg, flutamide 250 mg, finasteride 5 mg, or placebo for six months. Mean Ferriman-Gallwey score fell 41.0% on spironolactone, 38.9% on flutamide and 31.6% on finasteride, with no statistically significant differences between the three active drugs; the placebo group rose 5.4%. Hair shaft diameter fell 11.7%, 18.0% and 12.6% respectively [8].

A Cochrane review of 157 randomized trials and 10,550 women with hirsutism found that few studies reported participant-rated improvement and that for most comparisons there was insufficient evidence to determine whether adverse events differed between drugs; known events include reduced libido and dry skin with finasteride and flutamide [15].

Frontal fibrosing alopecia: a single case report

A 2015 case report described hair regrowth and reversal of atrophy in one patient with frontal fibrosing alopecia [9].

Safety data at 1 mg and 5 mg

The studies summarized here used 2.5 mg or 5 mg in some women with hair loss and in women with hirsutism; separate 5 mg safety data come from men treated for BPH [6][13][8][7][1]. In the four-year PLESS trial of 5 mg in men aged 45 to 78, year-one rates were impotence 8.1% versus 3.7% on placebo, decreased libido 6.4% versus 3.4%, and decreased ejaculate volume 3.7% versus 0.8%; in years 2 to 4 there was no significant difference between groups for impotence, decreased libido or ejaculation disorder [1]. At 1 mg in the hair-loss trials, decreased libido was 1.8% versus 1.3%, erectile dysfunction 1.3% versus 0.7%, and ejaculation disorder 1.2% versus 0.7%, with 3.8% versus 2.1% reporting any of these (p=0.04) [5].

A meta-analysis of 15 placebo-controlled trials in 4,495 men with androgenetic alopecia found a 1.57-fold relative risk of sexual dysfunction overall (95% CI 1.19 to 2.08) and 1.66 (95% CI 1.20 to 2.30) for finasteride alone [16]. A separate review of 34 trials found that none had adequate safety reporting, 76% evaluated safety for a year or less, and funnel plots suggested under-detection of sexual adverse effects [17].

The Propecia and Proscar labels list postmarketing reports of sexual dysfunction that continued after stopping treatment and psychiatric events including depression and suicidal ideation and behavior; the labels state that causality cannot reliably be established from voluntary reports [5][18][1]. Neither the Propecia label nor the Proscar label has a boxed warning; these events appear in postmarketing sections instead [5][18][1].

The 5 mg label warns that 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer and states that the clinical significance of those findings for 1 mg users is unknown [5][1]. The label identifies pregnancy as a contraindication and warns of fetal risk from exposure to crushed or broken tablets; intact coated tablets prevent contact during normal handling [5].