Finasteride is a synthetic 5a-reductase inhibitor (5a-RI) often used for the treatment of benign prostatic hyperplasia (BPH). 5a-RIs bind to their active sites with high affinity and have a slow rate of dissociation, leading to long-lasting effects which may be favorable for BPH, though serious and undesirable sexual and psychological adverse effects have also been described.¹ 5a-RIs are known to inhibit nitric oxide synthase leading to decreased erectile function.² Studies of post-finasteride syndrome have increased since 2012 and represent a myriad of symptoms, including sexual and physiological manifestations that may continue despite cessation of finasteride.³

Recent studies have investigated the use of finasteride in the management of alopecia and BPH in relation to attempted or completed suicide.^4,5 The authors utilized the World Health Organization’s global database of individual case safety reports, VigiBase, to explore the association of these adverse outcomes, comparing finasteride with other medical treatments (tamsulosin, minoxidil) for BPH and alopecia.⁵ They found an increased odds ratio for attempted or completed suicide (reporting odds ratio [ROR] 1.63; 95% CI, 1.47–1.81) and psychological adverse events (depression and anxiety) (ROR 4.33; 95% CI, 4.17–4.49) in users of finasteride versus other therapies. These findings were noted for younger patients (ages 18–44) and not older patients with BPH.

The authors extrapolated that a significant ROR of suicidality and psychological adverse events were associated with finasteride use in patients younger than 45 who used finasteride for alopecia. Additionally, a sensitivity analysis performed by the authors suggested the presence of a disproportional signal of adverse events attributable to younger patients being more vulnerable to finasteride’s adverse effects.

These findings, among others, have been used to substantiate the deterrence of using finasteride in the treatment of BPH and alopecia in a younger (<45 years) population. Interestingly, these practice patterns were instituted from a side effect database with neither a proper control population nor stratified for cofounding variables such as the demographics including hypogonadism, and more concerning, a lack of treatment for such.

In our present study, we sought to investigate the use of finasteride for indications, including alopecia and BPH, in the setting of patients treated for hypogonadism and sexual dysfunction with testosterone and PDE5i, respectively. Given an evaluation of this target population, we theoretically could more fully stratify for confounding variables such as a lack of treatment for hypogonadism or sexual dysfunction which could lead to an increased risk of suicidality or psychological adverse events.

Figure 1. Suicidal and self-injurious behavior in men with finasteride (606; ROR 1.89; 95% CI, 1.74–2.04), finasteride+testosterone therapy (6; ROR 0.80; 95% CI, 0.35–1.78), finasteride+sildenafil (2; ROR 0.23; 95% CI, 0.06–0.92), finasteride+tadalafil (8; ROR 1.34; 95% CI, 0.66–2.70), and finasteride+vardenafil (1; ROR 0.69; 95% CI, 0.10–4.98).

The data used in this study came from the VigiBase database, which collects data from 153 countries on all drug-adverse reactions. Four different populations of adverse drug reaction reports were examined for any indication, at any dose, and reporting an adverse drug event, including: 1) any adult receiving finasteride, 2) any adult receiving finasteride and a phosphodiesterase type 5 inhibitor (vardenafil, tadalafil, or sildenafil), 3) any adult receiving finasteride and testosterone for any indication, and 4) any adult receiving finasteride, testosterone, and a phosphodiesterase type 5 inhibitor. The primary end point was the quantitation of any adverse drug reaction-related suicidal and self-injurious reported behavior. Secondary endpoints were reported mood or behavior conditions reported as anxiety disorders and symptoms or depressed mood disorders and symptoms. Findings were reported as RORs.

VigiBase reported a total of 606 cases of suicidal behavior (ROR 1.89; 95% CI, 1.74–2.04; Fig. 1), 2,352 cases of anxiety disorders (ROR 2.51; 95% CI, 2.41–2.62; Fig. 2), and 2,392 cases of depressed mood disorders (ROR 4.6; 95% CI, 4.41–4.79; Fig. 3) related to finasteride use.

Figure 2. Anxiety disorders and symptoms in men with finasteride (2,352; ROR 2.51; 95% CI, 2.41–2.62), finasteride+testosterone therapy (366; ROR 1.25; 95% CI, 0.89–1.76), finasteride+sildenafil (36; ROR 1.08; 95% CI, 0.77–1.52), finasteride+tadalafil (21; ROR 0.89; 95% CI, 0.57–1.38), and finasteride+vardenafil (6; ROR 1.08; 95% CI, 0.47–2.46).

When VigiBase reports were examined for similar drug-adverse reactions in men with concomitant use of finasteride with testosterone, the ROR decreased with 6 cases of suicidal behavior (ROR 0.80; 95% CI, 0.35–1.78), 36 cases of anxiety disorders (ROR 1.25; 95% CI, 0.89–1.76), and 36 cases of depressed mood disorders (ROR 1.23; 95% CI, 0.88–1.73).

Similar reports of equivocal ROR for suicidality were noted with concomitant use of finasteride with sildenafil (ROR 0.23; 95% CI, 0.06–0.92), tadalafil (ROR 1.34; 95% CI, 0.66–2.70), and vardenafil (ROR 0.69; 95% CI, 0.10–4.98).

Figure 3. Depressed mood disorders and disturbances in men with finasteride (2,392; ROR 4.60; 95% CI, 4.41–4.79), finasteride+testosterone therapy (36; ROR 1.23; 95% CI, 0.88–1.73), finasteride+sildenafil (30; ROR 0.88; 95% CI, 0.61–1.27), finasteride+tadalafil (22; ROR 0.92; 95% CI, 0.60–1.41), and finasteride+vardenafil (3; ROR 0.52; 95% CI, 0.16–1.63).

There was a lower sample size for suicidality with concomitant testosterone or PDE5i use with finasteride, demonstrated by the larger error bars, though confidence interval crossed 1. Additional data analysis of primary patient data was limited as it was maintained and prepared through VigiBase.

The aim of this study was to evaluate for all adverse events of finasteride with concomitant testosterone and PDE5i use. Given the lower reported case numbers, the data presented weren’t sub-stratified by indication for finasteride, age, or additional medication.

The data presented suggest that men who take finasteride and are also treated with testosterone therapy or PDE5i use may have decreased rates of serious adverse psychological side effects associated with finasteride. Importantly, if men are treated with finasteride, they should be evaluated in a care capacity that will investigate and identify problems with a comprehensive evaluation of men’s health.