FAQ

Both finasteride and dutasteride are FDA-approved for the treatment of benign prostatic hyperplasia, and finasteride is also approved for androgenetic alopecia.1-3 5-ARIs are not FDA-approved for the treatment of prostate cancer and are not currently included as a recommended treatment in U.S. clinical practice guidelines for prostate cancer.1,2,4 Outside the U.S., Cancer Care Ontario guidelines note that 5-ARIs may have a role in men on active surveillance.5

Studies in men with low-risk prostate cancer have used the FDA-approved dosages of 5-ARIs for benign prostatic hyperplasia: finasteride 5 mg once daily and dutasteride 0.5 mg once daily.1,2,6,7

Finasteride is also available in a 1 mg formulation, which is FDA-approved for androgenic alopecia and has not been comprehensively evaluated for use in patients with prostate cancer.3

An FDA warning states that 5-ARIs may increase the risk of high-grade prostate cancer, but research suggests it is unlikely that 5-ARIs increase the risk of developing high-grade prostate cancer. 8-11 While sometimes mischaracterized in communications, the safety statement is not an FDA-designated black-box warning.1,2,12  The warning, issued in 2011, is based on two early clinical trials that found an increase in the rate of high-grade disease in men receiving 5-ARIs for prostate cancer prevention.13-15

Multiple studies have shown that the association between 5-ARIs and high-grade prostate cancer is likely due to a detection bias: 5-ARIs shrink the prostate, making biopsies more likely to sample existing high-grade tumors.8-11 Long-term follow-up analysis suggests there is no increase in high-grade prostate cancer in patients receiving 5-ARIs.16

Most clinical evidence for 5-ARIs during active surveillance comes from men with Gleason score 6 prostate cancer. There is limited early data in Gleason score 7 (3+4). Moore et al., 2017, a small randomized trial (N = 40) including men with Gleason score 6–7 (3+4), reported reduced tumor volume with dutasteride versus placebo (36% reduction vs. 12% increase, p < 0.0001), and Kearns et al., 2019, a prospective cohort study (N = 1,009) that included some men with Gleason score 7 (3+4), found lower rates of transition to definitive treatment among 5-ARI users (19% vs. 24%, p = 0.04).17,18

Evidence on the duration that 5-ARIs delay radical therapy is limited. Studies suggest that 5-ARIs may delay radical therapy by several months to three years.6,19,20

In the REDEEM randomized controlled trial, men who received a 5-ARI (dutasteride) reported lower fear of cancer recurrence (p = 0.017) and lower overall prostate cancer anxiety (p = 0.036) compared with those who did not receive a 5-ARI.6

5-ARIs have been shown to reduce PSA levels by roughly 50%.15,21 In clinical practice, PSA values are often doubled to assist interpretation.15,21 Evidence also suggests that 5-ARIs may increase the sensitivity of PSA-based monitoring, which may enhance detection of disease.8,22

Evidence linking 5-ARIs to depression or suicidal ideation is inconclusive.23 Some data suggest a higher risk of suicide or self-harm among men with a history of mood disorders.24 Carefully assessing each individual’s mental health history may be beneficial.25

5-ARIs have been evaluated for prostate cancer prevention in two large randomized controlled trials.

• Thompson et al., 2003: The Prostate Cancer Prevention Trial (PCPT) was a multicenter, double-blind, randomized controlled study involving 18,882 healthy men followed over 7 years. Daily finasteride (5 mg) reduced the relative risk of prostate cancer by 24.8% compared with placebo (95% CI 18.6-30.6, p < 0.001).14

• Andriole et al., 2010: The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial was a multicenter, double-blind, randomized controlled study of 8,231 men aged 50 to 75 years with elevated PSA levels, followed over 4 years. Men who received dutasteride (0.5 mg daily) had a 22.8% lower relative risk of prostate cancer compared with placebo (95% CI 15.2-29.8, p < 0.001).15

Both finasteride and dutasteride inhibit the 5-alpha reductase enzyme, which converts testosterone to dihydrotestosterone. The key difference lies in their enzyme selectivity: dutasteride inhibits both type 1 and type 2 isoenzymes, whereas finasteride inhibits only type 2.21 Evidence suggests the two agents are clinically interchangeable.6,7