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Author: Admin | 2025-04-28
They were thought to potentially increase the risk for higher-grade prostate cancers, but were later determined to be helpful in the process of detecting these cancers.5,16,22 These medications are regularly used and thought to be safe.Side effects of 5ARIs vary widely across research studies, but include bothersome symptoms related to testosterone deficiency including erectile dysfunction, ejaculatory dysfunction (reduced semen volume and thinned semen consistency), decreased libido, and possible fertility implications.5,24 Although a causal link between 5ARIs and infertility has yet to be elucidated, 5-alpha reductase is physiologically active in human testes, with dihydrotestosterone promoting expression of tight junction protein in Sertoli cells.24 Disruption of this process halts spermatogenesis.Two prospective randomized controlled trials that compared 5ARIs (dutasteride, finasteride) with placebo found statistically significant (P P 24–26 Because both trials studied healthy male populations (excluding patients with prior infertility), the impact on men with preexisting subfertility remains unknown. Beyond these findings, patients should also be informed of a small risk of gynecomastia and breast tenderness with 5ARI use.5 Finally, there are limited data in the recent literature suggesting a possible increased rate of depression in men using 5ARIs.24 Further study is needed to elucidate the mechanism behind these effects, as much of the data come from treatment with 5ARIs for androgenic alopecia where lower daily dosing of finasteride combats hair loss, making the results regarding depression unclear.24Phosphodiesterase-5 inhibitorsPhosphodiesterase-5 (PDE5) inhibitors increase intracellular cyclic guanosine monophosphate, causing nitric oxide-mediated relaxation of smooth muscle throughout the prostate, detrusor muscle (bladder), and urethra.27 It is thought that this is the beneficial mechanism of action of PDE5 inhibitors on patients with BPH and lower urinary tract symptoms. Tadalafil is the most-studied PDE5 inhibitor for patients with BPH and lower urinary tract symptoms, with an average improvement in International Prostate Symptom Score of 3 or more. Onset of effect is variable but usually within hours. Importantly, avanafil has the shortest onset of action (15–20 minutes) in this class but is not widely used for treatment of BPH.5,28PDE5 inhibitors are not titrated up or down in dose. They offer an alternative therapy for patients who cannot tolerate or prefer not to use alpha-blockers or 5ARIs.27 Additionally, a decrease in lower urinary tract symptoms, including overactive bladder symptoms such as urinary urgency and frequency, has been noted in patients taking PDE5 inhibitors.14 Once rather expensive, many of these medications are now available generically at low prices, can be purchased without insurance through self-pay, and are available at smaller, local pharmacies.29While the low daily dose of PDE5 inhibitors for BPH (such as US Food and Drug Administration-approved and guideline-based tadalafil 5 mg) can aid urinary symptoms, the benefit of such doses for erectile dysfunction is rather negligible.14 However, some patients report improvement in erectile dysfunction.30,31 For those without improvement, on-demand booster doses of PDE5 inhibitors can be administered with the low daily dose, although questions around precise timing, adjustments to daily dosing, and skipping of doses are debated and robust data for guidance are lacking. However, in general, the usual
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