Avodart Side Effects: Withdrawal and Discontinuation Syndrome Explained

Is there such a thing as dutasteride withdrawal?

The label describes the period after the last capsule in terms of persistence and slow clearance, not withdrawal. Serum levels stay above 0.1 ng/mL for up to 4 to 6 months after stopping, and the label says men should not donate blood until at least 6 months after the last dose, to avoid giving dutasteride to a pregnant transfusion recipient [1]. In healthy men treated for 52 weeks, total sperm count was still 23% below baseline after 24 weeks off the drug [1].

What the label does count is men who stopped the drug because of side effects. In the pooled placebo-controlled BPH trials, 4% of men on dutasteride and 3% on placebo withdrew because of adverse reactions, most often impotence (1%) [1]. In the 4-year CombAT trial, withdrawal for adverse reactions was 6% on dutasteride plus tamsulosin versus 4% on either drug alone, most often erectile dysfunction (1% to 1.5%) [1]. Those numbers describe stopping because of symptoms, not symptoms caused by stopping.

Dutasteride leaves the body slowly

The terminal half-life at steady state is about 5 weeks [1]. After a month of daily dosing, serum levels are about 65% of steady state; after 3 months, about 90% [1]. The Avodart label gives no tapering schedule and no discontinuation protocol [1].

What happens to DHT on treatment

Dutasteride inhibits both type 1 and type 2 5-alpha reductase and does not bind the androgen receptor [1]. Median serum DHT fell 85% after 1 week and 90% after 2 weeks on 0.5 mg daily, then 94% at 1 year, 93% at 2 years and 95% at 3 and 4 years [1]. Median serum testosterone rose about 19% to 26% but stayed within the physiologic range [1].

Sexual side effects that continue after stopping

In the pooled 2-year trials (2,167 men on dutasteride, 2,158 on placebo, mean age 66), the label reports during months 0 to 6: impotence 4.7% vs 1.7%, decreased libido 3.0% vs 1.4%, ejaculation disorders 1.4% vs 0.5%, and breast disorders 0.5% vs 0.2% [1]. Rates fell after the first 6 months except breast disorders, which were 1.1% vs 0.3% at months 13 to 18 [1]. A footnote under that table says these sexual adverse reactions may persist after treatment discontinuation and that dutasteride's role in the persistence is unknown [1].

Over 52 weeks in healthy men, dutasteride reduced total sperm count by 23%, semen volume by 26% and sperm motility by 18% (placebo-adjusted); sperm concentration and morphology were unaffected and mean values stayed in the normal range. The label says the clinical significance for an individual's fertility is not known [1].

For hair-loss use, a meta-analysis of 15 randomized placebo-controlled trials (4,495 men) found a 1.57-fold relative risk of sexual dysfunction overall; for dutasteride 0.5 mg the relative risk was 1.37 (95% CI 0.81 to 2.32), which was not statistically significant, and the authors noted that dutasteride trials were few [2].

Mood and depression

The Avodart label lists depressed mood among its postmarketing reports, along with hypersensitivity reactions, male breast cancer, and testicular pain and swelling; it does not list suicidal ideation [1].

In a Swedish observational register cohort of 2,236,876 men aged 50 to 90, 8,774 started dutasteride; their hazard ratio for depression was 1.68 (95% CI 1.43 to 1.96) and stayed constant over time, while suicide was not associated (HR 0.98, 95% CI 0.62 to 1.54) [3]. Treatment started at a median age of 73, so these were mostly older men [3].

Hair after stopping: an off-label question

Dutasteride is not FDA-approved for hair loss; the approved use is symptomatic BPH, alone or with tamsulosin [1]. In a 24-week trial of 917 men aged 20 to 50 with androgenetic alopecia, dutasteride 0.5 mg daily increased hair count more than finasteride 1 mg (P=.003) and more than placebo (P<.001) [4]. With only 24 weeks of treatment, the trial does not show how quickly shedding resumes after the drug stops.

PSA interpretation on dutasteride

Dutasteride lowers serum PSA by about 50% within 3 to 6 months of starting [1]. For men taking dutasteride, the Avodart label calls for a new PSA baseline at least 3 months after starting and says an isolated PSA value after 3 or more months of treatment is doubled for comparison with untreated ranges; any confirmed rise from the lowest on-treatment value should be evaluated even if it is within the normal range [1]. Percent free PSA appears to need no adjustment, and the label notes that noncompliance can also affect PSA results [1].