Finasteride for Hirsutism: Off-Label Use, Evidence, and Monitoring

Is finasteride approved for hirsutism?

No. Propecia, the 1 mg tablet, is indicated for male pattern hair loss in men only; the label states it is not indicated for use in women and that efficacy in bitemporal recession has not been established [1][3]. Proscar, the 5 mg tablet, is indicated for symptomatic benign prostatic hyperplasia in men with an enlarged prostate [2].

Hirsutism is excessive terminal hair in androgen-sensitive areas of the female body. Prevalence is about 10% in most populations, lower in Far-East Asian women, and polycystic ovary syndrome is the most frequent cause [9]. PCOS and idiopathic hyperandrogenism together account for more than 85% of cases [7].

What finasteride does to androgen signalling

Finasteride is a competitive, specific inhibitor of type II 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT) [3]. Type II is found in prostate, seminal vesicles, epididymides, hair follicles and liver and is responsible for about two-thirds of circulating DHT; type I predominates in the sebaceous glands of most skin areas and in the liver and supplies about one-third [3]. Binding studies in scalp and prostate tissue show roughly 100-fold selectivity for type II over type I (IC50 4.2 nM vs 500 nM) [3]. A single 1 mg tablet suppresses serum DHT by 65% within 24 hours, and mean testosterone and estradiol rise by about 15% while staying within the normal range [3]. Finasteride has no affinity for the androgen receptor and no androgenic, antiandrogenic, estrogenic or progestational activity of its own [3].

What the trials in women with hirsutism found

A 2000 randomized trial. Forty hirsute women were randomly assigned, double-blind, to spironolactone 100 mg/day, flutamide 250 mg/day, finasteride 5 mg/day or placebo for 6 months. Ferriman-Gallwey scores fell by 41.0% with spironolactone, 38.9% with flutamide and 31.6% with finasteride, and rose 5.4% on placebo; the three active drugs did not differ significantly from one another [6].

A 2002 dose-comparison trial. Fifty-six women with moderate to severe hirsutism were randomized to finasteride 2.5 mg/day (n=29) or 5 mg/day (n=27) for one year. Hirsutism scores fell from 18.4 to 8.6 at 12 months on 2.5 mg and from 18.7 to 10.3 on 5 mg (P<0.001 for both). No serious side effects occurred in either group, and estradiol rose significantly at 6 and 12 months in the 5 mg group while the other hormones measured did not change significantly [5].

A 2002 trial of hyperandrogenic women. Forty-eight women were randomized for a year to two cyproterone acetate regimens, flutamide 250 mg daily or finasteride 5 mg daily. The measured outcome was acne severity (Cook score), not hair growth: finasteride lowered scores by 36%, less than the other agents, and all treatments were well tolerated [10]. That trial does not answer the hirsutism question.

The two hirsutism trials enrolled 40 and 56 women and ran for 6 to 12 months.

Where guidelines put finasteride

The Endocrine Society's 2018 guideline suggests testing for elevated androgen levels in every woman with an abnormal hirsutism score, and suggests against testing eumenorrheic women whose only complaint is unwanted local hair growth [4]. For most women with patient-important hirsutism despite cosmetic measures, it suggests starting pharmacological therapy and adding direct hair removal for those who want additional cosmetic benefit; for mild hirsutism with no evidence of an endocrine disorder, either approach is acceptable [4]. For pharmacological therapy it suggests combined oral estrogen-progestin contraceptives for most women, adding an antiandrogen after 6 months if the response is suboptimal, and it recommends against antiandrogen monotherapy unless adequate contraception is used [4]. It suggests against insulin-lowering drugs and suggests laser/photoepilation for women who choose hair removal [4].

A 2019 American Family Physician review lists combined oral contraceptives, finasteride, spironolactone and topical eflornithine as recommended pharmacological options, and notes that because of the length of the hair growth cycle a treatment should be tried for at least six months before switching [7].

A 2010 review of antiandrogen treatments placed combined estrogen-progestin contraceptives first-line for moderate hirsutism in women of childbearing age and spironolactone second-line when cyproterone acetate is not suitable. It reserved flutamide or finasteride, which have no market authorization in this indication, as third-line therapy under contraception, for severe hirsutism or when the other options cause side effects or are contraindicated [11].

Doses used off-label

Clinical trials studied finasteride at 2.5 mg/day and 5 mg/day [5][6]. The product labels identify 1 mg once daily for Propecia and 5 mg once daily for Proscar [3][8]. In the dose comparison both doses lowered hirsutism scores over 12 months, and the authors concluded that 2.5 mg is safe and cost-effective and may be used instead of 5 mg [5].

Pregnancy risk

Pregnancy is a contraindication to finasteride. Because type II 5-alpha-reductase inhibition blocks conversion of testosterone to DHT, a hormone needed for normal male genital development, finasteride may cause abnormalities of the external genitalia of a male fetus [3]. The Propecia label says women who are or may be pregnant should not handle crushed or broken tablets because of the risk to a male fetus; intact coated tablets prevent contact with the active ingredient during normal handling [3]. The 5 mg label carries the same contraindication and handling statement [8].

What monitoring the evidence supports

• Androgen testing at baseline. The guideline suggests checking androgen levels in every woman with an abnormal hirsutism score [4].
• Pregnancy status and contraception. Pregnancy is the contraindication that matters most [3].
• Response scoring at 6 and 12 months. The 2.5 mg versus 5 mg trial measured scores at baseline and at 6-month intervals through 12 months, while the 6-month four-arm trial measured scores at baseline and after 6 months [5][6], and the review advises at least 6 months before judging a treatment [7].
• Hormone panels, if following the trial protocol. The dose-comparison trial repeated FSH, LH, estradiol, androstenedione, testosterone, free testosterone, 17-hydroxyprogesterone, DHEAS and SHBG every 6 months; apart from estradiol in the 5 mg group, nothing changed significantly [5].

On drug interactions, section 7 of the Propecia label states that no drug interactions of clinical importance have been identified, that finasteride does not appear to affect the cytochrome P450 system, and that antipyrine, digoxin, propranolol, theophylline and warfarin were tested without clinically meaningful interactions [3]. That section does not address CYP3A4 inhibitors or inducers.

Side effects reported in women

In the 12-month dose comparison there were no serious side effects in either group [5], and the acne trial reported that all treatments were well tolerated [10].

The labels' adverse-reaction numbers come from men. In three 12-month trials of 1 mg in 945 men, decreased libido was reported by 1.8% (placebo 1.3%), erectile dysfunction by 1.3% (0.7%) and ejaculation disorder by 1.2% (0.7%), with 3.8% reporting at least one of these versus 2.1% on placebo [3]. Postmarketing reports in the same label include depression, suicidal ideation and behavior, and sexual dysfunction that continued after stopping; the label notes that these voluntary reports come from a population of uncertain size and that a causal relationship cannot reliably be established [3][12].