Finasteride

Finasteride is used at 5 mg a day for an enlarged prostate and at 1 mg a day for male pattern hair loss [2][3]. Both conditions depend on DHT, the androgen that 5α-reductase makes from testosterone.

Hair loss. In two 1-year trials of 1,553 men aged 18–41, with a year of blinded extension, 1 mg a day increased hair counts in a 5 cm² area of the crown by 107 hairs over placebo at 1 year and 138 at 2 years, from a baseline of 876; men on placebo kept losing hair [1]. Over 5 years the improvement held, while placebo-treated men lost 239 hairs (26% of density) and 75% were rated as worse on photographs [2][8]. Finasteride cut the 5-year likelihood of further visible hair loss by 93% [9]. In a network meta-analysis of 23 studies, 0.5 mg dutasteride grew more hair than 1 mg finasteride at 24 weeks (7 more hairs/cm²), and 5 mg oral minoxidil gave more thick hairs than 1 mg finasteride [10]. A 2017 meta-analysis confirmed 1 mg finasteride beats placebo [11].

Topical finasteride. In a 24-week phase 3 trial of 458 men, a daily 0.25% spray increased hair count by 20.2 hairs against 6.7 on placebo, similar to oral finasteride. Peak blood levels were more than 100 times lower, and serum DHT fell 34.5% rather than 55.6% [12].

Women. In 137 postmenopausal women, 1 mg a day for a year did not increase hair growth or slow thinning [13].

Enlarged prostate. In the PLESS trial of 3,040 men with urinary symptoms, 5 mg a day for 4 years reduced the need for surgery from 10% to 5% and acute urinary retention from 7% to 3%, and shrank the prostate [3]. In the MTOPS trial of 3,047 men, it cut the risk of overall clinical progression by 34%, and by 66% combined with doxazosin [14]. A Cochrane review found it improves symptoms over more than a year, but less than the alpha-blockers doxazosin or terazosin [15].

Prostate cancer. In the Prostate Cancer Prevention Trial, 18,882 men aged 55 or over took 5 mg or placebo for 7 years. Prostate cancer was found in 18.4% vs 24.4% (a 24.8% reduction), but Gleason 7–10 tumours were found in 6.4% vs 5.1% [4]. Later analyses found finasteride shrinks the prostate and makes PSA and biopsy better at finding high-grade cancer, which accounts for at least part of that excess [16][17]. With up to 18 years of follow-up, overall survival was the same (78.0% vs 78.2% at 15 years) [18], and deaths from prostate cancer were 42 vs 56, a 25% reduction that was not statistically significant [19].

5α-reductase converts testosterone into DHT, which binds the androgen receptor more strongly. Finasteride inhibits the type 2 enzyme, lowering DHT in the scalp and in the blood [1]. In a 6-week dose-ranging study, scalp DHT fell by 57–69% on doses of 0.05–5 mg (13% on placebo) and serum DHT by 50–72%; doses as low as 0.2 mg a day gave near-maximal suppression [20]. Pattern hair loss is caused by androgen-dependent shrinking of scalp hair follicles, with scalp DHT implicated as a cause, so lowering it slows the process [1].

The prostate depends on DHT for growth, so 5 mg a day shrinks it and roughly halves PSA [3][21]. The effect on DHT outlasts the drug: a single dose suppresses serum DHT for up to 4 days [22].

The topical spray was developed to act on the scalp with less systemic exposure. In its phase 3 trial, plasma finasteride peaked at over 100 times lower concentrations than with the 1 mg tablet, and serum DHT fell by about a third rather than by half, with a similar hair response [12]. Different 5 mg tablet formulations were bioequivalent in healthy volunteers [23].

Sexual effects. In a meta-analysis of 15 placebo-controlled hair-loss trials, finasteride 1 mg raised the risk of sexual dysfunction by about two-thirds (relative risk 1.66) [5]. The Cochrane BPH review found more ejaculation disorders, erectile dysfunction and low libido at 5 mg [15]. In the Prostate Cancer Prevention Trial, the extra sexual dysfunction was small and shrank over time [24]. At 1 mg a day for 48 weeks, young men's sperm counts, motility and morphology did not change [21].

Mood. A WHO pharmacovigilance study found a signal for suicidality and psychological adverse events, mainly in men under 45 taking it for hair loss, and noted that reports rose after 2012, which may reflect stimulated reporting [6]. In a cohort of 93,197 older men, 5α-reductase inhibitors did not raise suicide risk, but self-harm was higher in the first 18 months and depression was higher throughout [25]. A Swedish cohort of 2.2 million men found higher depression (HR 1.61) but not suicide [26], and long-term follow-up of the prevention trial found a 10% higher rate of depression claims [27]. Some men report sexual, mental and physical symptoms that persist after stopping ("post-finasteride syndrome"); its existence and cause are debated [7].

Other. 5α-reductase inhibitors more than tripled the risk of breast enlargement in men treated for BPH, with no increase in male breast cancer; the risk was higher with dutasteride [28]. Because finasteride lowers PSA, results need adjusting when screening for prostate cancer [4][17]. In pregnant rats, finasteride caused hypospadias and other genital malformations in male offspring when given in late gestation [29].

Finasteride has been combined with doxazosin for an enlarged prostate, with a larger effect than either alone [14]. No interaction studies with compounds on this site were found.