Avodart Mental Health and Mood Impact: What the Evidence Actually Shows

What the Avodart label says about mood

Depressed mood appears on the Avodart label among adverse reactions reported after the drug reached the market [1]. It is not in the label's clinical-trial tables, which for the first six months of the pooled 2-year BPH trials (2,167 men on Avodart, 2,158 on placebo, mean age 66) list 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]. Apart from breast disorders, those rates fell after six months [1].

Suicidal ideation is not on the Avodart label's list, while the Propecia and Proscar labels do list it [1]. The label's postmarketing list names hypersensitivity reactions, male breast cancer, depressed mood, and testicular pain and swelling; anxiety is not among them [1].

The Swedish register cohort: 2.2 million men

Garcia-Argibay and colleagues followed 2,236,876 men aged 50 to 90 in Swedish national registers between 2005 and 2018 [2]. Of them, 8,774 (0.4%) started dutasteride and 70,645 (3.2%) started finasteride [2].

For dutasteride starters the hazard ratio for a diagnosis of depression was 1.68 (95% CI 1.43 to 1.96), and the excess was constant over time rather than concentrated in the first few months [2]. Completed suicide showed no association (HR 0.98, 95% CI 0.62 to 1.54) [2].

Two things limit how far this travels. The median age when treatment started was 73 (IQR 66 to 80), so the findings describe mostly older men treated for BPH, not men in their twenties and thirties taking dutasteride off-label for hair loss [2]. And a register cohort records who was diagnosed with depression, not why.

How dutasteride works

Dutasteride inhibits both type 1 and type 2 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, and it does not bind the androgen receptor [1]. Median serum DHT fell 85% after one week and 90% after two on 0.5 mg daily, 94% at one year and 95% at three and four years; median testosterone rose about 19% to 26% but stayed inside the physiologic range [1].

The label does not describe a mechanism for the depressed mood reported after marketing, and the Swedish cohort recorded diagnoses rather than hormone levels or scores on a mood scale [1] [2].

Sexual side effects

The label states that the sexual adverse reactions associated with dutasteride may persist after the drug is stopped, and that the role of dutasteride in that persistence is unknown [1].

Rates are highest early. In the 4-year CombAT trial over months 0 to 6, ejaculation disorders were 7.8% on dutasteride plus tamsulosin, 1.0% on dutasteride alone and 2.2% on tamsulosin alone; impotence 5.4%, 4.0% and 2.6%; decreased libido 4.5%, 3.1% and 2.0%; dizziness 1.1%, 0.5% and 0.9% [1]. Six percent of men on the combination withdrew because of adverse reactions, against 4% on either single drug, most often for erectile dysfunction (1% to 1.5%) [1].

In men treated for hair loss, Lee and colleagues pooled 15 randomized placebo-controlled trials covering 4,495 men and found a 1.57-fold relative risk of sexual dysfunction overall (95% CI 1.19 to 2.08), with a relative risk of 1.66 for finasteride 1 mg and 1.37 for dutasteride 0.5 mg (95% CI 0.81 to 2.32, not statistically significant, with few dutasteride trials) [3].

Dutasteride versus finasteride

Dutasteride inhibits both isoforms and pushes serum DHT down by roughly 90% or more; finasteride 1 mg inhibits mainly type 2 and suppresses serum DHT by about 65%. The half-life is about 5 weeks for dutasteride against about 5 to 6 hours for finasteride [1].

Men using it for hair loss

Avodart is not FDA-approved for hair loss; the approved use is symptomatic BPH, alone or with tamsulosin [1]. One trial randomized 917 men aged 20 to 50 to dutasteride 0.02, 0.1 or 0.5 mg, finasteride 1 mg or placebo for 24 weeks; dutasteride 0.5 mg increased hair count more than finasteride (P=.003) and placebo (P<.001), and the number and severity of adverse events were similar across groups [4]. An earlier placebo-controlled trial in 153 men aged 18 to 49 ran six months and reported no major difference in adverse events [5].

Cognitive changes and brain fog

Cognitive changes do not appear on the Avodart label's postmarketing list, which names depressed mood, male breast cancer, testicular pain and swelling, and hypersensitivity reactions [1]. The Swedish cohort looked at diagnoses of dementia, depression and suicide, not self-reported symptoms such as brain fog [2]. These data do not establish whether dutasteride causes everyday attention or memory complaints.