Reviews and evaluates published adverse effects associated with finasteride and dutasteride usage, both 5-Alpha Reductase Inhibitors (5ARIs). Finasteride is mentioned by the Royal College of Psychiatrists' Good practice guidelines for the assessment and treatment of adults with gender dysphoria as a potentially helpful drug for use by UK trans women who suffer from male-pattern baldness (androgenic alopecia), but it is also used in treatment of other conditions, including benign prostate hyperplasia. The review covers articles published from 1992-2012.

Abstract

Introduction.

5α-reductase inhibitors (5ARI) include finasteride and dutasteride, and are commonly prescribed in the treatment of benign prostatic hyperplasia and androgenic alopecia. 5ARIs are associated with several known adverse effects (AEs), with varying reported prevalence rates.

Aim.

The aim was to review and summarize findings from published literature detailing AEs associated with 5ARI use. A secondary aim was to review potential mechanisms of action, which may account for these observed and reported AEs.

Methods.

A PubMed search was conducted on articles published from 1992 to 2012, which reported AEs with 5ARIs. Priority was given to randomized, placebo-controlled trials. Studies investigating potential mechanisms of action for 5ARIs were included for review.

Main Outcome Measures.

AE data reported from available trials were summarized and reviewed.

Results.

Reported AEs with 5ARIs include sexual dysfunction, infertility, mood disorders, gynecomastia, high-grade prostate cancer, breast cancer, and cardiovascular morbidity/risk factors, although their true association, prevalence, causality, and clinical significance remain unclear. A pooled summary of all randomized, placebo-controlled trials evaluating 5ARIs (N = 62,827) revealed slightly increased rates over placebo for decreased libido (1.5%), erectile dysfunction (ED) (1.6%), ejaculatory dysfunction (EjD) (3.4%), and gynecomastia (1.3%). The limited data available on the impact of 5ARIs on mood disorders demonstrate statistically significant (although clinically minimal) differences in rates of depression and/or anxiety. Similarly, there are limited reports of reversible, diminished fertility among susceptible individuals. Post-marketing surveillance reports have questioned the actual prevalence of AEs associated with 5ARI use and suggest the possibility of persistent symptoms after drug discontinuation. Well-designed studies evaluating these reports are needed.

Conclusions.

5ARIs are associated with slightly increased rates of decreased libido, ED, EjD, gynecomastia, depression, and/or anxiety. Further studies directed at identifying prevalence rates and persistence of symptoms beyond drug discontinuation are required to assess causality.

Summary by Cate

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Reported adverse side effects of finasteride reviewed by the authors include depression, sexual dysfunction, infertility, breast cancer and high-grade prostate cancer.

(1) Depression. Limited data available, further study required. One study saw an increase in depressive symptoms in the short-term, but it is noted that, although ‘statistically significant’, there was only a slight increase and it was ‘clinically minimal’. A study that showed a much higher incidence of depressive symptoms amongst finasteride users is said to be ‘hindered by... a likely highly select and non-generalizable treatment population and non-standard methodology utilized’.

(2) Sexual Dysfunction. Pooled results from more than 62,000 patients show a slightly increased rate of sexual dysfunction on 5ARIs, but this varies depending upon age, time on the drug and so forth. On average, 1% more patients taking finasteride or dutasteride reported decreased libido compared to those on placebo; similarly, 1.6% more reported erectile dysfunction and 3.4% more reported ejaculatory dysfunction. However, erectile dysfunction and ejaculatory dysfunction were notably less common in younger, healthy patients (e.g. under 55: +0.6% difference from placebo in both cases)/patients who took the drug for androgenic alopecia, rather than for other reasons, such as prostate cancer. A higher rate of sexual dysfunction in the first 6–12 months of treatment is noted, apparently declining after this; also higher rates of sexual dysfunction have been reported with dutasteride rather than finasteride. The ‘significance, credibility and generalizability’ of recent claims that such sexual dysfunction may be permanent even after stopping 5ARIs for some patients is questioned, on the basis of the methodologies used in these studies, the atypicality of the study populations, and the results of other research that the authors review.

(3) Infertility. Unclear association; the impact is thought to be potentially greatest on those with an already low baseline fertility, although it is said to be ‘reversible’ in these cases by ceasing administration of 5ARIs . There is an observable reduction in semen volume and sperm count amongst healthy, non-infertile patients who take finasteride/dutasteride, but the effects don’t appear to be permanent on long term follow-up.

(4) Gynecomastia & Breast Cancer. Gynecomastia has a slightly increased rate of occurrence on these drugs: a pooled average of 2.8% occurrence amongst those taking finasteride/dutasteride vs. 1.6% amongst those taking placebo. In contrast, few studies report breast cancer developing amongst 5ARI users: e.g. there is a less than 0.1% incidence amongst both those on drug and those on placebo according to one large-scale study.

(5) Prostate Cancer. Finasteride 5mg daily is known to produce a c.25% reduction in prostate cancer in the treatment group vs. placebo over 7 years, but there has been a suggestion that it also leads to an increased rate of development of higher-grade prostate cancers. Multiple counterarguments have apparently been made in the medical literature against the latter being the case, however, with the result that the review article considers the risks to be ‘likely minimal’.