Guidelines for the Treatment of Benign Prostatic Hyperplasia

Yunuo Wu, PharmD; Michael H. Davidian, MD, MS; Edward M. DeSimone II, RPh, PhD, FAPhA

US Pharmacist. 2016;41(8):36-41.

Pathophysiology

Prostatic enlargement with increased age is correlated with smooth muscle hyperplasia and may eventually lead to bladder outlet obstruction (BOO).^[2] The most common presentation of subjective BPH-associated symptoms is lower urinary tract symptoms (LUTS).^[3] LUTS may further be classified into obstructive and irritative symptoms. Examples of obstructive symptoms include urine hesitancy, straining, weak flow, prolonged voiding, partial or complete urinary retention, and urinary incontinence. Common irritative symptoms include urinary frequency, urgency, nocturia, dysuria, and decreased void volume.^[1]

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Table 1. Pharmacologic Treatment Options for BPH
Class	MOA	Drug (Brand)	Daily Dose (Oral)	Adverse Effects^a	30-Day AWP ($)^b
Alpha-blockers	Relax tension in the prostate smooth muscle by targeting alpha-receptors	Alfuzosin (Uroxatral) Doxazosin (Cardura) Tamsulosin (Flomax) Terazosin (Hytrin) Silodosin (Rapaflo)	10 mg 1–8 mg 0.4–0.8 mg 1–10 mg 8 mg	Erectile dysfunction, abnormal ejaculation, dizziness, headache, orthostatic hypotension, fatigue, infection, QT interval prolongation, polydipsia, IFIS	126.41 40.46 126.41 48.11 249.47
5ARIs	Block the growth of prostate cells by targeting the 5-alpha-reductase enzyme and decreasing concentrations of DHT	Dutasteride (Avodart) Finasteride (Proscar)	0.5 mg 5 mg	Libido impairment, abnormal ejaculation, erectile dysfunction, mastalgia, gynecomastia	181.50 93.80
MRAs	Decrease bladder smooth muscle cell contractions by inhibiting muscarinic receptors	Tolterodine (Detrol) Tolterodine (Detrol LA) Fesoterodine (Toviaz)	1–2 mg twice daily 4 mg 4–8 mg	Xerostomia (dry mouth)	198.55 365.69 297.36
PDE5 inhibitors	Decrease detrusor, prostate, and urethra smooth muscle tone via increase of intracellular cGMP	Tadalafil (Cialis)	5 mg	Back pain, dyspepsia, flushing, headache, infection, myalgia, nausea, pharyngitis	281.74
Combination product	Combined MOA from 5ARI and alpha-blocker (see above)	Dutasteride-tamsulosin (Jalyn)	0.5 mg/0.4 mg	See monotherapy agents above	181.52

^aMost common adverse effects (>1%) per drug package insert.
^bBased on least expensive available formulation (brand or generic) pricing for regular-release formulation of initial dosing from Lexicomp, calculated to 30-day supply based on per-unit pricing. https://online.lexi.com. Accessed April 23, 2016.
5ARI: 5-alpha-reductase inhibitor; AWP: average wholesale price; BPH: benign prostatic hyperplasia; cGMP: cyclic guanosine monophosphate; DHT: dihydrotestosterone; IFIS: intraoperative floppy iris syndrome; LA: long-acting; MOA: mechanism of action; MRA: muscarinic receptor antagonist; PDE5: phosphodiesterase 5. Source: References 5, 6, 8–12, 14–17, 19, 23.

Sidebar 1

BPH Case Report

Chief Complaint: LF is a 64-year-old white male presenting with fatigue and sleep pattern changes that have lasted over the past several years. He believes his poor sleep habits are due to frequent nighttime urination, occurring three to four times per night. He denies drinking any fluids in the evening. LF also complains of difficulty starting a stream, especially in public restrooms, and notes that this stream has become weaker over time. He also feels that it takes him longer to completely empty his bladder. He admits to "going a little in his shorts" after urinating and confirmed postvoid dribbling. He experiences some mild urgency but denies dysuria. He also confirms knowledge of all of the bathroom locations in his office building.

Past Medical History: LF denies blood in his urine, a past history of STDs, or other UTIs. He reluctantly reports difficulty keeping firm erections during sexual intercourse compared to when he was younger. However, he maintains that this issue is not one of his major concerns.

Family History: Negative family history of prostate cancer

Social History: Nonsmoker, no illicit drugs, mild alcohol consumption (2–3 beers per week)

Physical Examination: Male pattern baldness

Vital Signs: WNL

Genital Examination:

Circumcised penis without lesions
Two, nontender, normal-sized descended testicles

Digital Rectal Examination: Normal sphincter tone and hemoccult negative stool

Negative for masses in the rectal vault except for an enlarged, firm prostate without nodules or tenderness
Prostate size estimated to be 35 mL (normal size 20–25 mL)

Labs:

Total cholesterol: 230 (LDL: 165, HDL: 45, TG: 100)
PSA: 2.34 ng/mL (normal 0.0–4.0 ng/mL)
TSH: WNL
CMP/CBC: WNL

Prescription Medications: None

Nonprescription Medications:

Niacin 1,000 mg 1 daily
Cinnamon tablet 1 daily

Treatment: Therapy options were first discussed with LF, which included observation with lifestyle modifications and pharmacotherapy. Due to its invasive nature, surgical interventions should be discussed when there has been a failure of the less invasive treatments. Since LF's presentation was not suggestive of prostate cancer (e.g., an elevated PSA >4.0 or the presence of nodules on the prostate during the examination), a biopsy of the prostate was not indicated. LF was started on finasteride 5 mg once daily. After about 2 months, he reported improved urinary flow, less nocturia, and an improved sleep pattern with less daytime fatigue. His only side effects were a slightly diminished libido and an occasional retrograde ejaculation.

Discussion: Finasteride was indicated in LF due to its benefit of decreasing prostate size while improving maximum urinary flow rate and associated LUTS. In addition, it is also indicated for male pattern baldness. Alpha-blockers could also be considered in this patient, with the added benefit of a quicker response by dilating the prostatic urethra, although with the possible result of a higher prevalence of retrograde ejaculation. Another option discussed with LF was the use of tadalafil. However, he did not express significant interest regarding the need for improvement of erectile dysfunction. If LF does not respond to the currently prescribed therapy, urodynamic studies could be ordered, which would evaluate the actual flow kinetics of the urine through the prostate and also the amount of residual urine in the bladder after micturition. The results of these tests could then lead to a referral to a urologist in anticipation of one of the various surgical procedures such as TURP.

BPH: benign prostatic hyperplasia; CMP/CBC: complete metabolic profile/complete blood count; HDL: high-density lipoprotein; LDL: low-density lipoprotein; PSA: prostate-specific antigen; STD: sexually transmitted disease; TG: triglyceride; TSH: thyroid-stimulating hormone; TURP: transurethral resection of the prostate; UTI: urinary tract infection; WNL: within normal limits.