5-Alpha-Reductase Inhibitors. The efficacy of 5-ARIs in preventing progression of LUTS secondary to BPH and their tolerability are well-established. Dutasteride was associated with a greater reduction in dihydrotestosterone in prostate tissues compared with finasteride (94% vs 80%, respectively) and has a longer elimination half-life.19 Finasteride was reported to be less effective than an AAB in improving LUTS. Dutasteride may have been more effective in reducing the relative risk for acute urinary retention and BPH-related surgery compared with tamsulosin over 4 years, but more research is needed.28 The 5-ARIs should not be used in men with LUTS secondary to BPH without prostatic enlargement, but may be used to prevent the progression of LUTS secondary to BPH and to reduce the risk for urinary retention and future prostate-related surgery.19 Prostate size ≥30 mL or PSA level ≥1.5 ng/dL is usually used as the threshold for considering 5-ARI therapy.19 As expected, because of the effects on dihydrotestosterone, AEs are primarily sexually related and include decreased libido, ejaculation disorders, and erectile dysfunction.19
Phosphodiesterase-5 Inhibitors. Approved by the FDA for erectile dysfunction, several observations led to the investigation of PDE-5Is for LUTS related to BPH.8,29 One was that the prevalences of BPH, LUTS, and erectile dysfunction increase as a man ages. Second was that LUTS have been identified as a risk factor for sexual dysfunction in aging men. Third was that limited evidence had suggested that PDE-5Is might be effective in treating LUTS and erectile dysfunction. Further investigation suggested beneficial effects on LUTS with each of the 3 PDE-5Is (ie, sildenafil, tadalafil, and vardenafil).30-32 Subsequent extensive investigation with tadalafil demonstrated its efficacy in reducing the storage and voiding symptoms of BPH and led to the approval by the FDA of tadalafil for symptoms of BPH alone or with erectile dysfunction.33-37
The clinical studies investigating the efficacy and tolerability of tadalafil for LUTS associated with BPH have included a 12-week study with a 1-year extension.38 Patients with BPH-associated LUTS (N = 1058) were randomized to tadalafil 2.5, 5, 10, or 20 mg/d or placebo once daily for 12 weeks. The total IPSS score was significantly improved at 12 weeks compared with baseline in each of the tadalafil groups relative to placebo (2.5 mg/d: –3.9, P = .015; 5 mg/d: –4.9, P < .001; 10 mg/d: –5.2, P < .001; 20 mg/d: –5.2, P < .001; placebo: –2.3). The use of tadalafil 5, 10, or 20 mg once daily was associated with significant improvements in the IPSS irritative (eg, frequency, nocturia, and urgency) and obstructive (eg, incomplete emptying, intermittency, slow stream, and straining) subscores, as well as scores on the IPSS quality-of-life measure, the BPH Impact Index (except 10 mg), and the LUTS Global Assessment Question. In sexually active men with erectile dysfunction, all doses of tadalafil were associated with significant improvements in scores on the International Index of Erectile Function–Erectile Function domain compared with placebo. Peak flow rate was not improved at any dose of tadalafil compared with placebo.
In total, 427 men who completed the 12-week study elected to receive tadalafil 5 mg once daily for an additional year.37 Patients who were switched from placebo or who had the dose increased from 2.5 mg/d had a significant reduction in total IPSS score from week 12 to week 16, and this change was maintained until the end of follow-up at week 64. Patients who had received tadalafil 5, 10, or 20 mg/d maintained the changes observed at the end of the 12-week study. Similarly, sexually active men with erectile dysfunction and who had a female partner maintained the improvements observed at the end of 12 weeks. The mean postvoid residual volume was decreased from 61 to 42 mL. At least 1 treatment-emergent AE (TEAE) was reported in 58% of patients, with 89% of events being either mild or moderate in severity. Treatment was discontinued in 5% due to a TEAE. The most common TEAEs were dyspepsia (4%), gastroesophageal reflux disease (4%), back pain (4%), headache (3%), sinusitis (3%), hypertension (3%), and cough (2%). In this study, the improvement in LUTS, sexual function, and quality of life observed after 12 weeks of tadalafil were maintained over the additional year with tadalafil 5 mg once daily.
Treatment options for RI are watchful waiting, an AAB with or without a PDE-5I, a 5-ARI, or tadalafil. RI indicates that he would rather not have his symptoms for the rest of his life, so watchful waiting is not appropriate. Because his prostate is only slightly enlarged, a 5-ARI is also not appropriate. An AAB or tadalafil should provide good relief to his LUTS within a few weeks. Tadalafil would also treat his erectile dysfunction. Alternatively, tadalafil or another PDE-5I could be combined with an AAB, which has been reported to provide added benefit in symptom improvement over an AAB alone.39
Plan
Following discussion of the benefits and risks of the different treatment options, RI elects to begin treatment with an AAB alone. For this reason, treatment with another antihypertensive to replace the diuretic will not be started. To promote self-management, educational materials and an action plan are reviewed with RI. Lifestyle management changes are discussed, including reducing his daily water intake by 25% to 2 quarts with no consumption of fluids within 3 to 4 hours of bedtime. He is assured that adjustments to his treatment plan will be made based on his symptoms and concerns.
3-Month Follow-Up
RI reports that his symptoms have improved, with a modest improvement of nocturia; he gets up once during the night 1 or 2 times every 2 weeks or so. He strains less frequently, but intermittency is unchanged. His IPSS is 7 (improved by 2 points vs before treatment). The findings on his physical examination are unchanged except that his BP has decreased slightly, to 124/72 mm Hg. He has noted 1 or 2 episodes of dizziness. Feeling better than 3 months ago, RI asks whether further improvement of his LUTS is possible. He wonders whether his erectile dysfunction can be treated.
The benefits and risks of each of the 3 PDE-5Is are reviewed with RI. He elects to begin treatment with tadalafil 5 mg once daily because it is the only agent that is approved for the treatment of LUTS associated with BPH. Lifestyle management and his action plan are reviewed.
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