Finasteride Safety in Adults 65 and Older: Risks, Monitoring, and Deprescribing

Which product and which evidence base

Finasteride is sold as two oral tablets with separate approvals. Proscar, 5 mg, was approved 06/19/1992 [5] and treats symptomatic benign prostatic hyperplasia in men with an enlarged prostate; its approved uses include improving symptoms and reducing the risks of acute urinary retention and of surgery such as TURP [1]. Propecia, 1 mg, was approved 12/19/1997 [6] and treats male pattern hair loss in men only; it is not indicated for women [2]. No topical or injectable finasteride is FDA-approved [2].

The hair-loss trials that established the 1 mg dose enrolled men aged 18 to 41 [7], so nearly everything specific to men over 65 comes from BPH research at 5 mg.

PSA: the age-specific fact that changes decisions

Proscar's label states that it reduces serum PSA by approximately 50% within six months; that a new PSA baseline should be established at least six months after starting treatment and PSA monitored periodically after that; and that an isolated PSA value in a man treated for six months or more should be doubled for comparison with normal ranges in untreated men [1]. Any confirmed increase from the lowest PSA value while on treatment may signal prostate cancer and should be evaluated even if the value is still within the normal range for men not taking a 5-alpha reductase inhibitor [1]. Percent free PSA stays constant, so no adjustment to it appears necessary [1]. The label also notes that missed doses can affect PSA results [1].

At 1 mg, in Propecia's trials in men aged 18 to 41, mean PSA fell from 0.7 ng/mL at baseline to 0.5 ng/mL at month 12 [2]. The Propecia label gives the same instruction for any confirmed increase from the lowest value on treatment: it should be evaluated even if still within the normal range for men not taking a 5-alpha reductase inhibitor [2].

The prostate cancer question that shadows finasteride use in older men comes from the Prostate Cancer Prevention Trial: 18,882 men aged 55 or older took finasteride 5 mg daily or placebo for seven years. Prostate cancer was detected in 18.4% of evaluable men on finasteride (803 of 4,368) and 24.4% on placebo (1,147 of 4,692), a 24.8% relative reduction [8]. Gleason 8 to 10 tumors were more frequent on finasteride, 1.8% versus 1.1% [1]. Proscar is not approved to prevent prostate cancer [1], and the label says the clinical significance of the high-grade finding for men taking Propecia is unknown [2].

Sexual side effects: the BPH numbers

PLESS followed 1,524 men on Proscar 5 mg and 1,516 on placebo, aged 45 to 78, for four years. In year 1 the drug-related 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%; 3.7% versus 2.1% discontinued because of sexual adverse reactions [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 the label states there is no evidence of increased sexual adverse experiences with longer treatment [1].

For comparison, Propecia's three 12-month trials in men aged 18 to 41 (945 on 1 mg, 934 on placebo) reported decreased libido 1.8% versus 1.3%, erectile dysfunction 1.3% versus 0.7% and ejaculation disorder 1.2% versus 0.7% [2]. The 5 mg and 1 mg figures come from different populations and different doses, so they are not a like-for-like comparison.

Separately, a 24-week study of Proscar in healthy volunteers found no clinically meaningful effect on sperm concentration, motility, morphology or pH, with a median ejaculate volume decrease of 0.6 mL (22.1%) that was reversible, average time to return to baseline 84 weeks [1].

The label lists sexual dysfunction that continued after stopping treatment — erectile dysfunction, libido disorders, ejaculation disorders and orgasm disorders — as postmarketing reports. The label states these reports are voluntary, come from a population of uncertain size, and do not reliably establish a causal relationship [2][9]. A 2011 study of 71 men aged 21 to 46 described persistent symptoms after stopping finasteride, but the men were self-selected and the study cannot give a frequency [10].

Mood, self-harm and suicide in older men

Neither label has a boxed warning for psychiatric effects [2][1]. The Propecia label listed postmarketing depression by June 2021; on May 31, 2022 the FDA sent a safety labeling change order citing suicidal ideation and behavior, and supplement S-030, approved 08/01/2022, changed the wording to depression, suicidal ideation and behavior [9]. Those remain postmarketing listings, not numbered warnings, and the label states causality cannot reliably be established from them [2].

Two large cohorts looked at older men directly. In Ontario, 93,197 men aged 66 and older who started a 5-alpha reductase inhibitor, mostly for BPH, were matched to unexposed men: suicide hazard ratio 0.88 (95% CI 0.53 to 1.45); self-harm hazard ratio 1.88 (95% CI 1.34 to 2.64) in the first 18 months only; depression hazard ratio 1.94 (95% CI 1.73 to 2.16) in the first 18 months and 1.22 (95% CI 1.08 to 1.37) afterward. The absolute increases were 17 self-harm and 237 depression cases per 100,000 patient-years [3].

In Sweden, 70,645 men started finasteride among a cohort of 2,236,876 men aged 50 to 90, median age at treatment start 73. Depression was higher on finasteride, hazard ratio 1.61 (95% CI 1.48 to 1.75), and the excess was constant over time rather than concentrated at the start. Suicide was not significantly associated with finasteride (hazard ratio 1.22, 95% CI 0.99 to 1.49) or dutasteride (0.98, 95% CI 0.62 to 1.54) [4].

Dementia and cognition

The Swedish cohort also examined dementia. Finasteride was associated with all-cause dementia at a hazard ratio of 1.22, but the association faded over time, which the authors said may partly reflect more dementia detection in men who were also being seen for BPH [4]. That pattern is a caution about the finding, not a confirmation of it.

What did MTOPS show about dizziness and postural hypotension?

The MTOPS trial randomized 3,047 men with symptomatic BPH to Proscar 5 mg (768), doxazosin (756), both (786) or placebo (737) for four to six years. Among drug-related adverse experiences reported by at least 2% of any group, postural hypotension was reported in 8.0% on placebo, 16.7% on doxazosin, 9.1% on finasteride and 17.8% on the combination; dizziness was reported in 8.1%, 17.7%, 7.4% and 23.2% respectively [1]. The highest rates were in the arms that included the alpha-blocker, and combination therapy was associated with no new clinical adverse experience [1]. Four cases of male breast cancer occurred in MTOPS, three on finasteride alone and one on combination; the relationship between long-term finasteride use and male breast neoplasia is unknown [1].

Drug interactions and pill burden

The label states that no drug interactions of clinical importance have been identified and that finasteride does not appear to affect the cytochrome P450 system; antipyrine, digoxin, propranolol, theophylline and warfarin were tested in humans with no clinically meaningful interactions [2]. Finasteride was also used in clinical studies alongside ACE inhibitors, alpha-blockers, benzodiazepines, beta blockers, calcium channel blockers, diuretics, HMG-CoA reductase inhibitors, NSAIDs and quinolones without evidence of clinically significant adverse interactions [2]. Finasteride itself is metabolized mainly by CYP3A4 [2]; the interaction section does not address strong inhibitors or inducers of that enzyme.

Re-evaluating long-term use

The Propecia label recommends continued use to sustain benefit, with periodic re-evaluation, and states that withdrawal of treatment leads to reversal of effect within 12 months [2]. For BPH, Proscar's approved uses include improving symptoms and reducing the risk of acute urinary retention and of surgery such as TURP [1].