Finasteride Safety for Adults Ages 50 to 64: What the Evidence Shows

Is finasteride even studied in the 50-to-64 age band?

The 1 mg tablet (Propecia) is indicated for male pattern hair loss in men only, and efficacy in bitemporal recession has not been established [3]. The two pivotal hair-loss trials enrolled 1,553 men aged 18 to 41, and 1,215 of them continued into blinded one-year extensions [2]. The label's clinical studies section describes that same 18-to-41 population [3].

The 5 mg tablet (Proscar) is indicated for symptomatic BPH in men with an enlarged prostate [1]. PLESS, its 4-year placebo-controlled trial, enrolled 3,040 men aged 45 to 78 — 1,524 on finasteride and 1,516 on placebo — which includes the 50-to-64 range [1]. The Prostate Cancer Prevention Trial enrolled 18,882 men aged 55 or older [4]. Two large cohorts that examined psychiatric outcomes are covered below: one in men aged 66 and older, one in men aged 50 to 90 [5][6].

What the labels say about PSA on treatment

The Proscar label states that PSA falls by approximately 50% within six months, that a new PSA baseline should be established at least six months after starting, and that PSA should be monitored periodically after that [1]. For an isolated value in a man who has taken the drug six months or more, the label says PSA values should be doubled for comparison with normal ranges in untreated men [1]. The label says any confirmed increase from the lowest on-treatment value may signal prostate cancer and should be evaluated even if the number is still within the normal range for men not taking a 5-alpha reductase inhibitor [1]. It says percent free PSA remains constant, with no adjustment to it appearing necessary [1].

For the 1 mg dose, the Propecia label reports mean PSA going from 0.7 ng/mL at baseline to 0.5 ng/mL at month 12 in men aged 18 to 41 [3].

High-grade prostate cancer: what the PCPT found

In the Prostate Cancer Prevention Trial, 18,882 men aged 55 or older took finasteride 5 mg or placebo for seven years [4]. Among men with data for the final cancer analysis, prostate cancer was detected in 803 of 4,368 (18.4%) on finasteride and 1,147 of 4,692 (24.4%) on placebo, a 24.8% reduction (95% CI 18.6 to 30.6) [4]. Gleason 8 to 10 tumors were more frequent on finasteride, 1.8% versus 1.1% [1].

The labels state that 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer, and that whether the drugs' effect of reducing prostate volume, or study-related factors, influenced the results has not been established [1]. The label adds that the clinical significance of these findings for men taking Propecia is unknown [3]. Proscar is not approved to prevent prostate cancer [1].

A later bias-adjusted reanalysis of PCPT data estimated a non-significant 14% increase in high-grade cancer (relative risk 1.14, 95% CI 0.96 to 1.35), and after incorporating grading from radical prostatectomy specimens estimated high-grade rates of 8.2% on placebo versus 6.0% on finasteride (relative risk 0.73, 95% CI 0.56 to 0.96) [7].

Sexual side effects: the trial numbers by dose

In three 12-month controlled trials of Propecia in 945 men on drug and 934 on placebo, all aged 18 to 41, drug-related decreased libido was reported by 1.8% versus 1.3%, erectile dysfunction by 1.3% versus 0.7%, and ejaculation disorder by 1.2% versus 0.7% [3]. Overall, 36 of 945 men (3.8%) reported one or more of these events versus 20 of 934 (2.1%), p=0.04 [3]. Each individual rate fell to 0.3% or lower by year five, and a self-administered sexual function questionnaire at month 12 favored placebo in 3 of 4 domains [3].

In PLESS, the 5 mg trial in men aged 45 to 78, year-one rates were impotence 8.1% versus 3.7%, decreased libido 6.4% versus 3.4%, decreased ejaculate volume 3.7% versus 0.8%, and ejaculation disorder 0.8% versus 0.1% [1]. In years 2 to 4 there was no significant difference between groups for impotence (5.1% versus 5.1%) or decreased libido (2.6% versus 2.6%), and 3.7% on finasteride versus 2.1% on placebo discontinued for sexual adverse reactions [1]. The label cautions that adverse reaction rates from trials in different conditions cannot be directly compared [3].

A meta-analysis of 15 randomized placebo-controlled trials covering 4,495 men with androgenetic alopecia found a 1.57-fold relative risk of sexual dysfunction with 5-alpha reductase inhibitors (95% CI 1.19 to 2.08); for finasteride alone the relative risk was 1.66 (95% CI 1.20 to 2.30) [8]. A separate review of 34 finasteride hair-loss trials found that none had adequate safety reporting, 76% evaluated safety for one year or less, and funnel plots suggested systematic under-detection of sexual adverse effects [9].

On persistence, the Propecia label's postmarketing section lists sexual dysfunction that continued after discontinuation — erectile dysfunction, libido disorders, ejaculation disorders and orgasm disorders — and male infertility or poor seminal quality, with normalization reported after stopping [3]. The Proscar label says persistent sexual side effects were reported rarely in men taking 5 mg for BPH; most were older and taking other medicines, and Proscar's independent role is unknown [1].

One standardized-interview study of 71 otherwise healthy men aged 21 to 46 reported new sexual dysfunction lasting at least three months after stopping finasteride; mean use was 28 months and mean persistence 40 months [10]. The group was self-selected and the design cannot establish frequency or cause [10]. On semen, a 24-week study of healthy volunteers on 5 mg found no clinically meaningful effect on sperm concentration, motility or morphology, but median ejaculate volume fell 0.6 mL (22.1%), was reversible, and took an average of 84 weeks to return to baseline [1]. At 1 mg, median ejaculate volume changed by -0.3 mL (-11%) versus -0.2 mL (-8%) on placebo at 48 weeks [3].

Depression and suicidal ideation: what is and is not established

Neither the current Propecia nor Proscar label has a boxed warning. Both list depression and suicidal ideation as postmarketing reports whose causal relationship cannot reliably be established [3][1]. The Propecia label of June 2021 listed postmarketing depression; on May 31, 2022 the FDA issued a safety labeling change order under section 505(o)(4) citing suicidal ideation and behavior, additional sexual dysfunction and psychoneurocognitive events, and supplement S-030, approved 08/01/2022, changed the wording to depression, suicidal ideation and behavior [11]. The labels describe those reports as voluntary, from a population of uncertain size, and unable to reliably establish cause [3][1].

Two large cohort studies looked at this directly. In Ontario, 93,197 men aged 66 or older who started a 5-alpha reductase inhibitor, mostly for BPH, were matched to unexposed men: there was no increase in suicide (hazard ratio 0.88, 95% CI 0.53 to 1.45), self-harm was elevated only in the first 18 months (hazard ratio 1.88, 95% CI 1.34 to 2.64), and depression was elevated in the first 18 months (hazard ratio 1.94, 95% CI 1.73 to 2.16) and afterward (1.22, 95% CI 1.08 to 1.37) [5]. The absolute increases were 17 self-harm and 237 depression cases per 100,000 patient-years [5].

The Swedish register study covered 2,236,876 men aged 50 to 90, of whom 70,645 (3.2%) started finasteride [6]. Depression was more common on finasteride (hazard ratio 1.61, 95% CI 1.48 to 1.75) and the association stayed constant over time, while suicide was not clearly associated (hazard ratio 1.22, 95% CI 0.99 to 1.49) [6]. Median age at treatment start in that cohort was 73 (IQR 66 to 80), so its estimates largely describe older users [6].

A smaller cross-sectional study compared 61 former users with persistent sexual side effects to 29 men with hair loss who had never used finasteride: depressive symptoms (BDI-II score of 14 or more) were present in 75% (46 of 61) versus 10% (3 of 29), P<0.0001 [12]. It was small, self-selected and cannot prove cause [12].

Interactions with other medicines common in this age group

The 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 in humans with no clinically meaningful interactions [1][3]. In clinical studies finasteride was used alongside ACE inhibitors, alpha-blockers, beta blockers, calcium channel blockers, diuretics, NSAIDs, statins, benzodiazepines and quinolone anti-infectives without evidence of clinically significant adverse interactions [1]. The interaction section does not discuss CYP3A4 inhibitors or inducers, although finasteride is metabolized mainly by CYP3A4 [3].

In the MTOPS study of 3,047 men treated for 4 to 6 years, drug-related postural hypotension was reported by 8.0% on placebo, 16.7% on doxazosin, 9.1% on finasteride and 17.8% on the combination [1]. The label states that combination therapy with finasteride and doxazosin was associated with no new clinical adverse experience [1].

Does the 1 mg dose differ from 5 mg in safety terms?

The 1 mg tablet produces about 65% suppression of serum DHT within 24 hours of a dose, and 5 mg is five times the hair-loss dose [3]. Absolute sexual adverse event rates were lower in the 1 mg trials than in PLESS, but those trials enrolled men aged 18 to 41 versus 45 to 78, and the label warns against comparing rates across trials [3][1]. Mean terminal half-life is about 5 to 6 hours in men aged 18 to 60 and about 8 hours in men over 70 [3].

Breast changes and other reported events

In PLESS, drug-related breast enlargement was reported by 0.5% on finasteride versus 0.1% on placebo in year one, and 1.8% versus 1.1% in years 2 to 4; breast tenderness was 0.4% versus 0.1% and 0.7% versus 0.3% over the same periods [1]. In the Propecia trials, breast tenderness and enlargement rates were not different from placebo [3].

Male breast cancer appears in the postmarketing section, with the relationship to long-term finasteride use stated as unknown [1]. The label reports 4 cases in men on finasteride and none in untreated men during MTOPS, 2 cases in placebo-treated men and none on finasteride during PLESS, and 1 case in each group during PCPT [1]. Testicular pain, hematospermia and hypersensitivity reactions including rash, itching, hives and angioedema are also listed as postmarketing reports [3].

Women aged 50 to 64

Propecia is not indicated for women, is contraindicated in pregnancy, and the label carries a Pregnancy Category X designation [3]. Women who are or may be pregnant should not handle crushed or broken tablets because of the risk of abnormal external genitalia in a male fetus; the tablets are coated and prevent contact with the active ingredient when intact [3]. Use in postmenopausal women falls outside the approved labeling.