Finasteride Side Effects: Severity Distribution by Patient Phenotype

What do the controlled trials actually measure?

Both labels count adverse events that investigators judged possibly, probably or definitely drug related, not every symptom a participant happened to mention [1][2].

Finasteride 1 mg for hair loss

Three controlled 12-month trials enrolled 945 men on finasteride 1 mg and 934 on placebo, aged 18 to 41 [1]. 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% [1]. Counting all three sexual events together, 36 of 945 men on finasteride (3.8%) reported at least one, against 20 of 934 (2.1%) on placebo, a difference that reached P=0.04 [1]. Discontinuation for a drug-related sexual event was 1.2% versus 0.9%, and the incidence of each event fell to 0.3% or lower by the fifth year of treatment [1].

The finasteride 1 mg tablet is the dose studied in these trials. A self-administered sexual function questionnaire at month 12 found statistically significant differences favoring placebo in three of four domains — sexual interest, erections and perception of sexual problems — but not in overall satisfaction with sex life [1].

In the Propecia trials, the incidences of breast tenderness and enlargement, hypersensitivity reactions and testicular pain did not differ from placebo [1].

Finasteride 5 mg for BPH

PLESS followed 1,524 men on finasteride 5 mg and 1,516 on placebo, aged 45 to 78, for four years [2]. In year one, impotence was 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% [2]. In years two to four there was no significant difference between groups for impotence (5.1% versus 5.1%), decreased libido (2.6% versus 2.6%) or ejaculation disorder (0.2% versus 0.1%) [2]. Discontinuation for sexual adverse reactions across the four years was 3.7% versus 2.1% [2].

Breast enlargement in PLESS was 0.5% versus 0.1% in year one and 1.8% versus 1.1% in years two to four; breast tenderness was 0.4% versus 0.1% and 0.7% versus 0.3% [2]. In the MTOPS study of 3,047 men, gynecomastia was reported by 2.2% of men on finasteride alone versus 0.7% on placebo [2].

Is the gap between 1 mg and 5 mg about the dose or the men taking it?

The trials cannot separate the two. The 1 mg data come from men aged 18 to 41 with hair loss; PLESS enrolled men aged 45 to 78 with symptomatic BPH, and PCPT enrolled men 55 and older [1][2][5]. The labels caution that adverse reaction rates from one set of clinical trials cannot be directly compared with rates from another [1][2].

A pooled analysis of hair-loss trials covered 15 randomized placebo-controlled trials involving 4,495 men taking either finasteride 1 mg or dutasteride 0.5 mg, the relative risk of sexual dysfunction was 1.57 overall (95% CI 1.19 to 2.08). For finasteride alone, it was 1.66 (95% CI 1.20 to 2.30) [4]. How completely those events were captured is a separate question: a review of 34 finasteride trials for hair loss found that none had adequate safety reporting, 76% evaluated safety for one year or less, and funnel plots suggested under-detection of sexual adverse effects [6].

Does age change the distribution?

The labels describe different age groups rather than rates within an age group [1][2], so trial data do not answer the question directly. Observational cohorts in older men give the largest numbers. These cohorts mainly concern older men treated for prostate enlargement, so their findings do not directly describe younger men taking 1 mg for hair loss [7][8].

In Ontario, 93,197 men aged 66 or older starting a 5-alpha reductase inhibitor were compared with matched unexposed men: suicide HR 0.88 (95% CI 0.53 to 1.45), self-harm HR 1.88 (1.34 to 2.64) in the first 18 months only, and depression HR 1.94 (1.73 to 2.16) in the first 18 months, falling to 1.22 (1.08 to 1.37) afterward [7]. A Swedish register study of 2,236,876 men aged 50 to 90, including 70,645 finasteride starters with a median age of 73, found a depression HR of 1.61 (1.48 to 1.75) and a suicide HR of 1.22 (0.99 to 1.49) [8].

Smaller studies describe the opposite end of the age range. Interviews with 71 otherwise healthy men aged 21 to 46 who reported sexual symptoms lasting at least three months after stopping finasteride found a mean duration of use of 28 months and mean persistence of 40 months [9]. In a separate comparison, 75% of 61 former users with persistent sexual symptoms scored 14 or higher on the Beck Depression Inventory, versus 10% of 29 never-users with hair loss [10]. Both groups were self-selected, so neither can supply a frequency or a cause.

Does expectation change what men report?

One small trial tested this directly. A total of 120 men with BPH and good baseline erectile function were randomized to finasteride 5 mg with or without counseling that the drug may cause erectile dysfunction, decreased libido or ejaculation problems; 107 completed the year [3]. Among the 107 men who completed the year, 43.6% of the counseled group (N=55) reported one or more sexual side effects versus 15.3% of the uncounseled group (N=52), P=0.03; erectile dysfunction was reported by 30.9% versus 9.6% [3]. Both groups received the same tablet, and the authors described the difference as a nocebo effect.

What do the labels report about hormones?

The label reports few hormone findings. Mean circulating testosterone and estradiol rose by about 15% on finasteride 1 mg but stayed within the normal range, and finasteride has no affinity for the androgen receptor [1]. No clinically meaningful change in LH, FSH or prolactin was detected [1].

Which side effects are the serious ones?

Sexual dysfunction that continues after stopping

The Propecia label's postmarketing section lists sexual dysfunction that continued after discontinuation, including erectile dysfunction, libido disorders, ejaculation disorders and orgasm disorders, plus male infertility and poor seminal quality with reported normalization after stopping [1]. The Proscar label notes that these persistent events were reported rarely in men taking 5 mg for BPH, that most were older and on other medicines, and that the independent role of the drug is unknown [2]. The labels say these are voluntary reports from a population of uncertain size, and a causal relationship cannot reliably be established [1][2].

Mood and suicidal ideation

The current Propecia label lists depression and suicidal ideation and behavior in its postmarketing section; there is no boxed warning on Propecia or Proscar [1][2]. FDA ordered the wording change on May 31, 2022, citing new safety information on suicidal ideation and behavior, additional risk of sexual dysfunction and psychoneurocognitive adverse events, and the revised label was approved on 08/01/2022 [11]. The cohort data above are mixed on suicide, with no increase in either the Ontario or Swedish cohorts [7][8].

High-grade prostate cancer

In PCPT, Gleason 8 to 10 cancer was found in 1.8% of men on finasteride versus 1.1% on placebo; Gleason 7 to 10 tumors were also more common on finasteride, 6.4% versus 5.1% of men [2][5]. The authors of a bias-adjusted modeling analysis of the same trial concluded that the unadjusted excess high-grade rate appeared to result from improved detection with finasteride, with a non-significant 14% increase in high-grade cancer (RR 1.14, 95% CI 0.96 to 1.35) [12]. The label states that 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer, that whether reduced prostate volume or study factors affected the results has not been established, and that the clinical significance for men taking 1 mg is unknown [1]. Proscar is not approved to prevent prostate cancer [2].

Breast changes

The label reports 4 cases of male breast cancer 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 arm of PCPT; the relationship between long-term finasteride use and male breast neoplasia is unknown [2].

Semen and fertility

In healthy volunteers treated with Proscar for 24 weeks, there were no clinically meaningful effects on sperm concentration, motility, morphology or pH; median ejaculate volume fell 0.6 mL (22.1%), the values stayed within the normal range, and the change reversed after discontinuation with an average time to return to baseline of 84 weeks [2]. With Propecia 1 mg, median ejaculate volume fell 0.3 mL (11%) versus 0.2 mL (8%) on placebo at 48 weeks [1]. A separate double-blind study of 181 men aged 19 to 41, with 79 in the semen substudy, found no significant effect of 1 mg daily on sperm concentration, total sperm per ejaculate, motility or morphology [13].

What does the label say to watch for?

Proscar lowers serum PSA by approximately 50% within six months, and its label says a new PSA baseline should be established at least six months after starting treatment. For men who have taken Proscar for six months or more, the label says an isolated PSA result should be doubled for comparison with normal ranges, and that any confirmed rise from the lowest value on treatment should be evaluated [2]. Percent free PSA is unchanged [2]. With Propecia 1 mg, mean PSA fell from 0.7 to 0.5 ng/mL at month 12 in men aged 18 to 41, and the label says any confirmed increase from the lowest value while on treatment should be evaluated even if still within the normal range [1].

Pregnancy is a contraindication for both products, and the labels say women who are or may be pregnant should not handle crushed or broken tablets; intact coated tablets prevent contact with the active ingredient [1].