Avodart What to Expect: Week-by-Week First Month on Dutasteride

What changes in the first 30 days

Dutasteride is a competitive inhibitor of both type 1 and type 2 5-alpha-reductase, the enzyme that converts testosterone to DHT; finasteride mainly blocks type 2 [1]. Dutasteride does not bind the androgen receptor [1]. Its only approved use is symptomatic BPH in men with an enlarged prostate, alone or in combination with tamsulosin, and hair loss is off-label [1].

The label gives the dose as 0.5 mg once daily, with or without food. It says the capsule should be swallowed whole, not chewed or opened, because the contents can irritate the mouth and throat [1]. The label also notes that non-compliance can affect PSA test results [1].

In the first month the changes are chemical: DHT falls steeply, drug levels keep building toward steady state, and the common side effects can appear.

Week 1: DHT drops about 85%

Median serum DHT fell 85% after one week on 0.5 mg daily [1]. Median serum testosterone rose about 19% to 26% over treatment but stayed within the physiologic range [1]. Drug levels peak 2 to 3 hours after a dose [1].

Week 2: DHT suppression approaches its plateau

By two weeks, median DHT is down about 90% [1]. That is close to the suppression seen later: 94% at one year, 93% at two years, and 95% at three and four years [1].

Serum drug levels keep climbing long after that. The terminal half-life is about 5 weeks at steady state, and the label gives roughly 65% of steady state after one month and about 90% after three months [1].

Prostate volume changes more slowly. In CombAT, mean prostate volume of about 55 cc fell 28.0% on dutasteride and 26.9% on the combination at month 24, with no change (0%) on tamsulosin [1][2].

Weeks 3 and 4: the one-month checkpoint

By the end of the first month, DHT suppression is already near its later level, while serum dutasteride has reached about 65% of steady state [1].

For PSA, the label says dutasteride lowers it by about 50% within 3 to 6 months. It says a new PSA baseline should be established at least 3 months after starting, and that an isolated PSA value in a man treated for 3 months or more should be doubled for comparison with normal ranges in untreated men. It also says any confirmed rise from the lowest on-treatment value should be evaluated, even if the value is still inside the normal range, and that percent free PSA needs no adjustment [1].

The blood donation rule applies from the start of treatment. The label says men treated with Avodart should not donate blood until at least 6 months after the last dose, to prevent giving dutasteride to a pregnant transfusion recipient [1]. Serum levels stay detectable for up to 4 to 6 months after stopping [1].

Early side effects: what the label's numbers show

In the pooled 2-year BPH trials (2,167 men on Avodart, 2,158 on placebo, mean age 66), rates in months 0 to 6 were impotence 4.7% vs 1.7%, decreased libido 3.0% vs 1.4%, ejaculation disorders 1.4% vs 0.5%, and breast disorders (enlargement or tenderness) 0.5% vs 0.2% [1]. Rates fell after six months, except breast disorders, which were 1.1% vs 0.3% at months 13 to 18 [1]. The label states these sexual reactions may persist after the drug is stopped and that the role of dutasteride in that persistence is unknown [1].

In CombAT, months 0 to 6, ejaculation disorders were 7.8% on the combination vs 1.0% on dutasteride and 2.2% on tamsulosin; 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]. Withdrawal for adverse reactions was 6% on the combination vs 4% on either single drug, most often for erectile dysfunction [1].

Postmarketing reports in the Avodart label include hypersensitivity reactions (rash, itching, hives, localized edema, serious skin reactions, angioedema), male breast cancer, depressed mood, and testicular pain and swelling [1].

Hair loss: an off-label use on a 24-week clock

Avodart is not FDA-approved for hair loss [1]. In a 24-week trial of 917 men aged 20 to 50 with androgenetic alopecia, dutasteride 0.5 mg increased hair count more than finasteride 1 mg (P=.003) and more than placebo (P<.001), and adverse events were similar across groups [3]. Hair count was the 24-week primary end point, so a one-month change is not what that trial tested [3].

A 2019 meta-analysis of 15 randomized placebo-controlled trials (4,495 men treated for hair loss) found a relative risk of sexual dysfunction of 1.37 for dutasteride 0.5 mg (95% CI 0.81 to 2.32, not statistically significant, with few dutasteride trials) against 1.66 for finasteride 1 mg [4].

Beyond month one: later outcomes

• Month 24: in CombAT (4,844 men, baseline IPSS about 16.4), mean IPSS fell 4.9 points on dutasteride, 6.2 on the combination and 4.3 on tamsulosin. Prostate volume fell 28.0%, 26.9% and 0% respectively [1][2].
• Month 48: mean IPSS fell 5.3, 6.3 and 3.8 points. After 4 years, the combination gave no advantage over dutasteride alone in reducing acute urinary retention or BPH-related surgery [1][2].
• PSA: about a 50% reduction within 3 to 6 months [1].
• Prostate cancer: in REDUCE (4 years; men 50 to 75 with one prior negative biopsy and PSA 2.5 to 10 ng/mL), biopsy-detected cancer was 22.8% lower on dutasteride (659 of 3,305 vs 858 of 3,424) [5]. Gleason score 8 to 10 cancer occurred in 1.0% of men on Avodart and 0.5% on placebo. The label says 5-alpha-reductase inhibitors may increase the risk of high-grade prostate cancer and that Avodart is not approved for prevention [1].
• Sperm: over 52 weeks in healthy men, dutasteride lowered total sperm count by 23%, semen volume by 26% and sperm motility by 18% versus placebo. Sperm concentration and morphology were unaffected, and all values stayed in the normal range. Total sperm count was still 23% below baseline 24 weeks after stopping [1]. The label says the clinical significance for an individual man's fertility is not known [1].