A 62-Year-Old Male with Nocturia
A 62-year-old man presents with lower urinary tract symptoms. In the past year he has progressed from nocturia once nightly to 3-4 times currently. This symptom particularly prompted his wife to suggest he be evaluated. Further questioning reveals he also has significant urgency and hesitancy, as well as a diminished urinary stream. He has had no hematuria and has good sexual function.
History
He is otherwise a healthy man whose only major diagnosis is mild cholesterol elevation easily controlled with atorvastatin 10 mg/d.
Physical Examination
General physical examination is within normal limits. A rectal exam reveals a smooth but enlarged prostate gland. Ultrasound examination approximates the prostate gland at 80 gms.
Laboratory Results
PSA measurement is 2.2 ng/mL and urine analysis is negative for blood or WBC. Serum calcium and glucose levels are normal.
Which of the following is the least effective pharmacological intervention in this patient?
A. Administration of serenoa repens (saw palmetto) twice daily.
B. Initiation of tadalafil 5 mg daily.
C. A trial of terazosin 2 mg daily.
D. Initiation of dutasteride 0.5 mg/day.
(Answer and discussion on next page)
Correct Answer: A
The patient presented with a broad sampling of symptoms and findings consistent with lower urinary symptoms related to prostate gland enlargement. In fact, he probably has benign prostatic hyperplasia—but this is a histologic diagnosis that would require a prostate biopsy, which has not been performed in the presented data. He very likely would have that procedure if the urology service were consulted, but the data, indications, and controversies regarding if, when and who should have a biopsy continue to simmer, or even boil, are not the core topic of our case.
Our patient manifests both obstructive (hesitancy and diminished stream) and storage symptoms (nocturia and urgency), as well as evidence of enlargement of the gland on physical exam and ultrasound and an increased PSA >1.5 ngm/ml—all indications that are consistent with BPH. When his findings are applied to the American Urological Association Symptom Index (AUASI), point total accrues a value of at least “moderate” (score of 8-19) severity.1 This objective quantification, combined with the history of his symptoms clearly being bothersome and effecting quality of life, more than justify trying one of the pharmacological maneuvers available to relieve symptoms and/or shrink his prostate gland.
Treatment Options
There is currently a generous list of drugs that can help. These include:
• α adrenergic-receptor blockers, which block sympathetic adrenergic-receptor mediated contraction of prostatic smooth muscle cells and bladder neck.
• 5 α reductase inhibitors, which block testosterone conversion to its active metabolite, dihydrotestosterone and subsequently results in shrinkage and reduced growing of the prostate.
• Antimuscarinic therapy, which relaxes the detrusor muscle.
• Phosphodiesterase-5 inhibitors, which relax smooth muscle in the male GU tract and may also be antiproliferative to prostate and bladder smooth muscle.2
Management Strategies
Tadalafil (answer B) is a phosphodiesterase-5 inhibitor, which has a combined FDA indication for its most commonly used indication of erectile dysfunction as well as for BPH. In a placebo trial, tadelafil lowered the AUASI score by 3.8 points at 12 weeks.2 Terazosin (answer C) is also effective and quick acting (efficacy at 1 week) and randomized trials show AUASI score decreases of 4-6 points.2,3 Dutasteride is a 5 α reductase inhibitor (answer D) that has been shown to decrease prostate size by up to 25% and decrease AUASI scores by 4-5 points. It is long acting, taking 6 months or more for full effect, and works best in men with clear evidence on ultrasound or PSA (>1.5 ng/ml) of gland enlargement.2,4 Specifics of therapy, side effect profiles, and which agents to use in whom and when vary2,5, but any and all have been proven to be effective; thus, answers B, C, and D are correct.
What does not seem to work is saw palmetto (answer A), despite it being a major advertising force on radio and cable TV. A copious and thorough volume of double-blind, placebo-controlled studies available in the literature frankly do not support the efficacy of saw palmetto.2,6 Therefore, saw palmetto is the least effective of the options and A is the correct answer here. ■
Outcome of the Case
He was started on terazosin 2 mg/d and had initial improvement in symptoms that regressed within 3 months. Dose escalation did not help and postural hypotension ensued. He was started on dutasteride 0.5 mg/d and has significantly improved 3 months into that therapy.
References
1.Barry MJ, Fowler FJ Jr, O’Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol. 1992;148:1549-1557.
2.Samma AV, Wei JT. Benign prostatic hyperplasia and lower urinary tract symptoms. N Eng J Med. 2012;367:248-257.
3.McConnell ID, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin finasteride and combination therapy on the clinical progression of benign prostatic hypertrophy. N Eng J Med. 2003;349:2387-2398.
4.Crawford ED, Wilson SS, McConnel JD, et al. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol. 2006;175:1422-1427.
5.Lepor H. Long term efficacy and safety of terazosin in patients with benign prostatic hyperplasia. Urology. 1995;45:406-413.
6.Andreole GI, Bostwick DG, Brawley DW, et al. Effect of dutasteride on risk of prostate cancer. N Eng J Med. 2010;362:1192-2002.
7.Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Med Clin North Am. 2011;95:87-100.
8.Barry MJ, Meleth S, Lee JY, et al. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: A randomized trial. JAMA. 2011;306:1344-1351.
Ronald Rubin, MD is professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia.