Finasteride Rebound Effects When Stopping: What the Evidence Actually Shows

What the Propecia label says about stopping

Propecia is finasteride 1 mg, one tablet once daily for male pattern hair loss in men only; efficacy in bitemporal recession has not been established [1]. Daily use for three months or more is usually needed before benefit appears, continued use is recommended to sustain benefit and should be re-evaluated periodically, and withdrawal of treatment leads to reversal of effect within 12 months [1]. In the trials, a change from Propecia to placebo (n=48) at the end of the first 12 months resulted in reversal of the hair-count increase 12 months later, at 24 months [1].

DHT after the last tablet

Finasteride is a competitive inhibitor of type II 5-alpha-reductase, the enzyme that converts testosterone to DHT and produces about two-thirds of circulating DHT [1]. A 1 mg tablet suppresses serum DHT by 65% within 24 hours [1]. Two clocks matter. The drug itself clears quickly, with a plasma half-life of about 5 to 6 hours in men aged 18 to 60 [1]. The type II enzyme complex turns over slowly, with a half-life of about 30 days, so the effect on DHT outlasts the plasma level [1]. The Proscar label reports that in healthy male volunteers treated with Proscar (5 mg) for 14 days, discontinuation resulted in a return of DHT levels to pretreatment levels in approximately 2 weeks [13]. That is a 5 mg study in volunteers, not a measurement in hair-loss patients on 1 mg.

Tissue measurements come from a 42-day study with scalp biopsies in 249 men with androgenetic alopecia: finasteride 1 mg lowered scalp DHT by 64.1% and serum DHT by 71.4% [4]. The authors concluded that doses as low as 0.2 mg per day maximally decreased both scalp and serum DHT [4].

Hair counts in the finasteride trials

The core dataset is two 1-year double-blind, placebo-controlled trials in 1,553 men aged 18 to 41 with male pattern hair loss [2]. Hair was counted in a 1-inch (5.1 cm2) circle of balding vertex scalp, starting from a baseline of 876 hairs. Finasteride 1 mg produced 107 more hairs than placebo at 1 year and 138 more at 2 years (P<0.001), and 1,215 men continued into blinded second-year extensions [2]. Placebo participants kept losing hair throughout [2].

In the five-year extension program, the same 1,553 men were randomized and 1,215 continued through up to four 1-year, placebo-controlled extensions. Finasteride produced durable improvements in scalp hair over five years (P<0.001 versus placebo on all endpoints), placebo led to progressive hair loss, and no new safety concerns emerged with long-term use [3].

Does hair loss overshoot after stopping?

The Propecia label describes reversal of effect within 12 months, and reports that the hair-count increase had reversed 12 months after 48 men were switched from finasteride to placebo [1]. It does not report a separate rebound phase. In the five-year extension studies, men assigned to placebo lost hair progressively while men on finasteride kept their gains [3].

Sexual side effects that continue after stopping

The current Propecia label lists, among postmarketing reports, sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, libido disorders, ejaculation disorders and orgasm disorders [1]. It also lists male infertility and poor seminal quality, with normalization or improvement reported after discontinuation [1]. These are voluntary reports from a population of uncertain size, and the label states a causal relationship cannot reliably be established [1]. There is no boxed warning [1].

In the three 12-month controlled trials (945 men on finasteride, 934 on placebo), drug-related decreased libido was 1.8% versus 1.3%, erectile dysfunction 1.3% versus 0.7%, and ejaculation disorder 1.2% versus 0.7%; 3.8% versus 2.1% reported one or more of these (p=0.04) [1]. Resolution occurred in the men who discontinued because of these effects and in most of those who continued, and the incidence of each fell to 0.3% or lower by year 5 [1].

Across 15 randomized placebo-controlled trials in 4,495 men treated for androgenetic alopecia, 5-alpha reductase inhibitors carried a relative risk of sexual dysfunction of 1.57 (95% CI 1.19 to 2.08), and 1.66 (1.20 to 2.30) for finasteride alone [6]. A separate 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 [7].

Smaller studies describe men whose symptoms persisted. Standardized interviews with 71 otherwise healthy men aged 21 to 46 who developed sexual dysfunction on finasteride that lasted at least three months after stopping found mean use of 28 months and mean persistence of 40 months; 94% reported low libido, 92% erectile dysfunction, 92% decreased arousal and 69% problems with orgasm [8]. In a related comparison, 61 former users with persistent sexual side effects and 29 men with hair loss who had never used finasteride were scored on the Beck Depression Inventory II: 75% versus 10% scored 14 or higher (P<0.0001) [9]. Both are small, self-selected studies: they cannot establish how often symptoms persist or whether finasteride caused them [8][9].

Depression and suicidal ideation: label and cohort data

The Propecia label of June 2021 listed postmarketing depression [5]. On May 31, 2022 the FDA sent a safety labeling change order citing new safety information on 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 [5]. The current label carries these as postmarketing reports that are voluntary, come from a population of uncertain size, and cannot reliably establish causality [1][5].

Two large cohorts looked at serious psychiatric outcomes, both in older men (median age 75 in Ontario; 73 at treatment start in Sweden). In Ontario, 93,197 men aged 66 or older starting a 5-alpha reductase inhibitor were compared with matched unexposed men: suicide was not increased (HR 0.88, 95% CI 0.53 to 1.45), self-harm was higher in the first 18 months only (HR 1.88, 1.34 to 2.64), and depression was higher in the first 18 months (HR 1.94, 1.73 to 2.16) and afterward (HR 1.22, 1.08 to 1.37) [10]. In a Swedish register cohort of 2,236,876 men aged 50 to 90, of whom 70,645 started finasteride at a median age of 73, depression was higher on finasteride (HR 1.61, 1.48 to 1.75) with no clear association for suicide (HR 1.22, 0.99 to 1.49) [11]. Neither cohort followed young men who stopped treatment for hair loss.

Neurosteroid measurements in three men

A study of three former finasteride users with persistent symptoms found differences in hormone-related substances in plasma and cerebrospinal fluid compared with five healthy men [12]. It cannot show whether finasteride caused those differences or the symptoms [12].