Why does finasteride (5-alpha-reductase inhibitor) cause a decrease in sexual function?

Mechanism of Finasteride-Induced Sexual Dysfunction

Finasteride causes sexual dysfunction primarily by inhibiting the 5-alpha-reductase enzyme, which blocks the conversion of testosterone to dihydrotestosterone (DHT), resulting in decreased libido, erectile dysfunction, and ejaculatory disorders due to DHT's critical role in normal male sexual function. 1

Hormonal Mechanisms

Finasteride's impact on sexual function occurs through several pathways:

1. DHT Reduction:

   • Finasteride inhibits 5-alpha-reductase, preventing conversion of testosterone to DHT
   • DHT is essential for normal erectile function and libido
   • Studies show finasteride reduces DHT levels by approximately 60% 2

2. Hormonal Alterations:

   • Testosterone levels increase by about 15% (compensatory mechanism)
   • FSH and LH levels decrease by 24% and 16% respectively 2
   • These hormonal changes disrupt normal sexual function signaling

3. Neurosteroid Effects:

   • Finasteride affects neurosteroid production, particularly allopregnanolone
   • Lower neurosteroid levels are associated with decreased libido and depression 3
   • These neurosteroids play important roles in sexual desire and function

Clinical Evidence of Sexual Dysfunction

The sexual side effects of finasteride are well-documented in clinical trials and include:

• Erectile dysfunction: Occurs in 18.5% of finasteride users compared to 12.2% with placebo 4
• Decreased libido: Affects 10.0% of users versus 5.7% with placebo 4
• Abnormal ejaculation: Reported in 7.2% of users versus 2.3% with placebo 4
• Sexual function abnormalities: Overall relative risk of 1.71 for erectile dysfunction 1

In long-term studies, these effects can persist:

• The PCPT trial showed 67.4% of finasteride users reported erectile dysfunction compared to 61.5% on placebo 1
• Decreased ejaculate volume was reported in 60.4% of finasteride users versus 47.3% on placebo 1

Persistence of Sexual Side Effects

An important clinical consideration is that sexual dysfunction may persist after discontinuation:

• FDA labeling notes "sexual dysfunction that continued after discontinuation of treatment" 4
• This includes erectile dysfunction, decreased libido, and ejaculation disorders
• Persistent effects may be related to long-term alterations in androgen receptor sensitivity or neurosteroid pathways 3

Risk Factors and Monitoring

Factors that may increase risk of sexual dysfunction with finasteride:

• Age (older patients experience more sexual side effects)
• Duration of treatment (effects may accumulate over time)
• Pre-existing sexual dysfunction
• Concurrent medications affecting sexual function

Clinical Implications

When prescribing finasteride, clinicians should:

1. Discuss sexual side effects with patients before initiating therapy
2. Monitor for sexual dysfunction during treatment
3. Consider that sexual side effects may persist even after discontinuation
4. Weigh benefits against risks, especially in younger men using finasteride for hair loss
5. Be aware that while sexual dysfunction often decreases over time during continued treatment, it typically remains statistically significant compared to placebo 1

The mechanism of finasteride-induced sexual dysfunction is complex and involves both peripheral effects (DHT reduction) and central effects (neurosteroid alterations), explaining why these effects can be persistent and impact multiple domains of sexual function.