5α-reductase inhibitors
The 5α-reductase inhibitors finasteride and dutasteride may also be used in men with BPH. These medications inhibit the 5α-reductase enzyme, which, in turn, inhibits production of DHT, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, no benefit was reported in short-term trials, but in a longer-term study (3–4 years) there was a greater reduction in BPH progression to acute urinary retention and surgery than with either agent alone, especially in people with more severe symptoms and larger prostates. Other trials have confirmed reductions in symptoms, within 6 months in one trial, an effect that was maintained after withdrawal of the alpha blocker. Side effects include decreased libido and ejaculatory or erectile dysfunction. The 5α-reductase inhibitors are contraindicated in pregnant women because of their teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets. Phosphodiesterase inhibitors (PDE)
A 2018 Cochrane review of studies on men over 60 with moderate to severe lower urinary tract symptoms analyzed the impacts of phosphodiesterase inhibitors (PDE) in comparison to other drugs. These drugs may improve urinary symptoms slightly and reduce urinary bother but may also cause more side effects compared to placebo. The evidence in this review found that there is probably no difference between PDE and alpha blockers, however when used in combination they may provide a greater improvement in symptoms (with more side effects).
They have a small to moderate benefit at improving symptoms. Selective alpha-1 blockers are similar in effectiveness but have slightly different side effect profiles. Alpha blockers relax smooth muscle in the prostate and the bladder neck, thus decreasing the blockage of urine flow. Common side effects of alpha blockers include orthostatic hypotension (a head rush or dizzy spell when standing up or stretching), ejaculation changes, erectile dysfunction, headaches, nasal congestion, and weakness. For men with LUTS due to an enlarged prostate, the effects of naftopidil, tamsulosin and silodosin on urinary symptoms and quality of life may be similar. Naftopidil and tamsulosin may have similar levels of unwanted sexual side effects but fewer unwanted side effects than silodosin.Tamsulosin and silodosin are selective α1 receptor blockers that preferentially bind to the α1A receptor in the prostate instead of the α1B receptor in the blood vessels. Less-selective α1 receptor blockers such as terazosin and doxazosin may lower blood pressure. The older, less selective α1-adrenergic blocker prazosin is not a first line choice for either high blood pressure or prostatic hyperplasia; it is a choice for patients who present with both problems at the same time. The older, broadly non-selective alpha blocker medications such as phenoxybenzamine are not recommended for control of BPH. Non-selective alpha blockers such as terazosin and doxazosin may also require slow dose adjustments as they can lower blood pressure and cause syncope (fainting) if the response to the medication is too strong.