Category:BPH treatments

A BPH treatment is a medicine prescribed to relieve the lower-urinary-tract symptoms of benign prostatic hyperplasia, the non-malignant enlargement of the prostate gland that affects a large fraction of men over fifty. The category covers two principal pharmacological strategies: relaxation of the prostatic and bladder-neck smooth muscle by α1-adrenergic blockade, which provides symptomatic relief within days, and reduction of prostate volume by 5α-reductase inhibition, which acts more slowly but addresses the underlying gland enlargement. Adjunctive use of phosphodiesterase-5 inhibitors and bladder-selective antimuscarinics extends the pharmacological repertoire.

Benign prostatic hyperplasia is among the oldest documented conditions in surgery. Egyptian papyri and the Hippocratic corpus describe acute urinary retention; Roman and Byzantine surgeons performed perineal lithotomy for bladder stones formed behind enlarged prostates; the Persian polymath Avicenna in the eleventh century described the use of a hollow reed catheter to relieve obstruction. The first systematic anatomic study of the gland and its enlargement was published in 1786 by the London surgeon John Hunter, who recognised the role of the testes in maintaining the prostate and described atrophy of the gland after castration. Surgical management dominated the field until the late twentieth century: the suprapubic prostatectomy described by Eugene Fuller in 1895 and refined by Peter Freyer in London in 1900; the retropubic approach of Terence Millin in 1945; and the transurethral resection of the prostate (TURP) introduced by Maximilian Stern in 1926 and refined to its present form by Reed Nesbit at the University of Michigan in the 1940s, an operation that remained the standard treatment for medically significant BPH for sixty years.

The pharmacological era began with an observation in cardiovascular medicine. The selective α1-adrenergic blocker prazosin, introduced by Pfizer in 1974 as an antihypertensive, was found in case reports of the late 1970s to improve urinary flow and reduce post-void residual volume in men taking it for blood pressure. The Boston urologist Marco Caine in Israel formally tested the hypothesis in 1976, reporting that prazosin lowered intraurethral pressure in the prostatic urethra of men with bladder-outlet obstruction; subsequent work established that the prostatic and bladder-neck smooth muscle was richly innervated by sympathetic fibres acting on α1A and α1D receptors, and that pharmacological relaxation of these receptors lowered urethral resistance without affecting detrusor contractility.^[1] The longer-acting and more receptor-subtype-selective alpha-blockers followed: terazosin (Abbott, 1987), doxazosin (Pfizer, 1990), the α1A-selective tamsulosin (Yamanouchi, 1996, with substantially reduced postural-hypotension liability), alfuzosin (Sanofi, 2003), and silodosin (Kissei, 2008).

The second pharmacological strategy required a different physiological insight. In 1974 Julianne Imperato-McGinley reported a remarkable kindred from a village in the Dominican Republic in which children genetically male, with 46,XY karyotype, were born phenotypically female and raised as girls; at puberty, virilization occurred and the children developed a male phenotype.^[2] The investigators identified the genetic defect as inherited deficiency of 5α-reductase, the enzyme that converts testosterone to the more potent androgen dihydrotestosterone (DHT), and observed that the affected men, although fully virilized at puberty by direct testosterone action, never developed enlarged prostates or male-pattern baldness. The conclusion was immediate: a selective pharmacological inhibitor of 5α-reductase would replicate the favourable prostate-related and hairline-related effects of the natural mutation. Finasteride (Merck, 1992) was the first such inhibitor, selective for the type 2 isoform of the enzyme, and dutasteride (GlaxoSmithKline, 2002) followed with dual inhibition of types 1 and 2. The medicines reduce prostate volume by approximately one-quarter over six to twelve months and reduce the long-term risk of acute urinary retention and surgical intervention; their effect on day-to-day symptom score is modest, and they are most clinically useful in larger prostates and in combination with an alpha-blocker.

The combination strategy was formalised by the Medical Therapy of Prostatic Symptoms (MTOPS) trial in 2003, which randomised 3047 men with moderate-to-severe BPH symptoms to placebo, doxazosin, finasteride, or both, for an average of 4.5 years. Combination therapy was superior to either monotherapy for both symptom score and the long-term risk of clinical progression; alpha-blocker monotherapy improved symptoms but did not reduce progression, and 5α-reductase monotherapy reduced progression but improved symptoms modestly.^[3] Combination therapy has since been the standard for men with a large prostate (greater than 30 to 40 mL) or substantial elevation of prostate-specific antigen, where progression risk is highest.

Two additional pharmacological strategies have entered the BPH category in the last decade. The phosphodiesterase-5 inhibitor tadalafil, originally developed for erectile dysfunction, was approved in 2011 at a daily 5-milligram dose for the combined indication of lower-urinary-tract symptoms with or without concurrent erectile dysfunction; its mechanism is presumed to involve relaxation of the prostatic, bladder-neck, and pelvic-floor smooth musculature through cyclic-GMP. Beta-3 adrenergic agonists (mirabegron, 2012) and bladder-selective antimuscarinics have been added in combination with an alpha-blocker for men whose dominant symptom is urgency rather than obstructive flow. The newer agent vibegron (2020) extends the beta-3 class. The clinical decision between medicine and procedure has been progressively biased toward medicine over the last twenty years, although newer minimally invasive procedures (the prostatic urethral lift, water-vapour ablation, and prostatic artery embolisation) have entered the choice between long-term combination therapy and definitive intervention.

By mechanism:

• Alpha-1 adrenergic blockers (non-selective and α1A-selective): doxazosin, terazosin, tamsulosin (α1A-selective), alfuzosin, silodosin (α1A-selective)
• 5α-reductase inhibitors: finasteride (type 2 selective), dutasteride (dual type 1 and type 2)
• Phosphodiesterase-5 inhibitors (also indexed under erectile-dysfunction medicines): tadalafil (the only PDE5 inhibitor approved for BPH)
• Beta-3 adrenergic agonists (for the urgency-predominant phenotype, also indexed under overactive bladder medications): mirabegron, vibegron
• Bladder-selective antimuscarinics (in combination with an alpha-blocker for the urgency phenotype): listed under antimuscarinics and overactive bladder medications
• Plant-based (phytotherapy): saw palmetto (Serenoa repens), beta-sitosterol, pygeum (Prunus africana), used widely outside the United States; the controlled-trial evidence for symptom-score improvement is mixed

The boundary of this category is "medicine prescribed primarily for the relief of lower-urinary-tract symptoms attributed to benign prostatic hyperplasia." Medicines used in the management of prostate cancer (the antiandrogens, the gonadotropin-releasing hormone agonists and antagonists, the androgen-receptor-pathway inhibitors) are collected separately under their oncologic categories. The surgical and minimally invasive procedures for BPH (TURP, simple prostatectomy, prostatic urethral lift, water-vapour ablation, prostatic artery embolisation, laser enucleation and vapourisation, and the historically important transurethral microwave thermotherapy) are operative rather than pharmacological interventions and are described, briefly, on the medicine pages where they form part of the clinical-decision background.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.