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By Cydney E. McQueen, PharmD, and Kelly M. Shields, PharmD
Benign prostatic hyperplasia (BPH) is a non-cancerous increase in the tissue mass of the prostate, the muscular gland that produces seminal fluid. BPH is one of the most common medical conditions affecting older men. It may be diagnosed because of urinary symptoms, or identified when a large prostate is found during a routine screening rectal exam. Many men simply have a slow worsening of symptoms throughout their lifetimes, usually beginning in their 50s. Sub- clinical disease is very common: Approximately 80% of men older than age 60 will have histological changes indicative of BPH upon biopsy; by age 85, this percentage rises to 90%.1 Some of these patients have severe disease progression, which can lead to incontinence, formation of calculi, frequent urinary tract infections, or permanent urinary tract damage.
Despite the possibility of progression and the bothersome symptoms, many men—perhaps half of those with the condition—never seek medical advice or treatment for BPH symptoms, even when those symptoms are severe enough to warrant surgical intervention.2 Patients may believe that urinary symptoms are part of the normal aging process, that nothing that can be done, or that the available treatments have unacceptable side effects.Etiology/Pathophysiology
BPH is related to age-associated changes in the body’s hormone levels.3 Although the clinical ramifications of these hormone changes are not completely characterized, it is known that the levels of serum testosterone decrease while dihydrotestosterone (DHT), the principle androgen responsible for prostatic growth,4,5 accumulates. Until recently, it was believed that estradiol, converted from testosterone via the aromatase pathway, was implicated in initiating hyperplasia in the stroma and epithelium of the prostate.4 That now seems unlikely.6
Factors that may accelerate disease progression are not well enumerated. Diet is one factor that has been implicated in the development of BPH. A Western diet characterized by high fat intake appears to be linked to earlier onset of BPH.7,8 One study indicated that low intake of vegetables is positively associated with BPH risk,9 whereas another drew a correlation between alcohol consumption (more than 25 ounces/month) and BPH risk.10 However, each of these studies had limitations and did not demonstrate a clear, direct correlation. Symptoms may be worsened by various factors such as decongestant use, evening intake of liquids, or caffeine, alcohol, or spicy food intake.Symptoms
Urinary symptoms experienced by patients with BPH can be classified as obstructive or irritative (see Table 1). Obstructive symptoms, sometimes referred to as "voiding symptoms," include a decrease in the force of the urinary stream, difficulty in maintaining or initiating the stream, "dribbling" after ending the stream, or the inability to completely void the bladder. Although some obstructive symptoms can be directly correlated with restriction of urethral flow, others seem to be caused by a decrease in strength of the detrusor muscle or an increase in the excitability of the bladder muscle. Irritative symptoms of BPH also are referred to as "storage symptoms" and include dysuria, urge incontinence, urgency, nocturia, and increased frequency of urination during the day. These seem to be related to irritation of the epithelium of urethral and bladder structures.3,4
The International Prostate Symptom Score (IPSS) is a validated instrument that is widely accepted for staging the severity of the disease via scoring of subjective symptoms (see Table 2). It also is known as the American Urological Association Urinary Symptoms Index for Prostatism (AUA Index) and is a patient-completed instrument.4 Score ranges equate to "mild" (0-7), "moderate" (8-19), and "severe" (20-35) symptoms. The Boyarsky Index and the Madsen-Iversen Score are additional instruments that are physician-completed.11 Other instruments include the BPH Impact Index (BII), and various health-related quality of life (QOL) measurements. Interestingly, the severity of the symptoms experienced does not always correlate directly with the measured extent of glandular enlargement or with the objective measurements utilized to monitor disease progression.
Objective measurements include uroflowmetry, such as the maximum flow rate (MFR) in milliliters of urine passed per second (also termed peak urine flow rate) and post-void residual urine (PVR). Prostate volume usually is measured by transrectal ultrasonography.3,4 Normal MFR ranges decrease with age. Generally, rates of less than 15 mL/s are considered to be diagnostic of a urinary flow problem; however, because lower rates often are found in older men, MFR rates alone do not indicate the need for therapy. They must be correlated with other physical findings and symptoms.11Conventional Disease Management/Treatment
"Usual" disease management can differ significantly based on the stage of the disease and the impact of symptoms on the patient’s lifestyle. The emphasis of BPH treatment has changed over the last several years from surgical intervention to medical intervention.2,11 The first medical approach usually is "watchful waiting"—a recognition that the problem exists. Initiation of pharmacological treatment is delayed until symptoms become more bothersome to the patient. The next step generally involves a-1 blockers (doxazosin, tamsulosin, or terazosin). These agents relax muscles of the prostate and bladder neck, thus providing symptomatic relief. They are associated with side effects including hypotension, dizziness, fatigue, and changes in sleep patterns. Another drug treatment choice is finasteride (a 5-a-reductase inhibitor), which decreases the conversion of testosterone to the more active DHT. This agent has been associated with an increased incidence of sexual dysfunction.
A final choice for treatment is surgical intervention, which generally achieves the greatest degree of efficacy. Surgical options include: localized cryotherapy or thermal therapy, transurethral incision of the prostate (TUIP), transurethral resection of the prostate (TURP), electrovaporization (modified TURP), laser surgery, or open prostatectomy. These procedures are costly and confer an increased risk of complications, such as bleeding, infection, incontinence, and sexual dysfunction.3,4,11,12 All of the above treatment options, with the exception of watchful waiting, are associated with adverse effects and significant costs. For these and other reasons, patients and clinicians are beginning to consider the use of alternative therapies to treat BPH.
All of the treatments that will be discussed here are phytomedicinal in nature and are either whole extracts from botanical sources, or single extracted or manufactured constituents originally from botanical sources. Several of these treatments have been used in other parts of the world for many years. In fact, phytomedicinals are the initial treatments of choice in countries such as France and Germany. Many treatments show significant placebo effects in clinical trials; an examination of multiple BPH treatment trials provided estimates of this effect that ranged from 30% to 40%.2 The maximal placebo effect usually is seen in the first four to six months of therapy.2Pumpkin Seed
The use of pumpkin seed (Cucurbitae peponis) for treatment of symptoms associated with BPH has been approved by the Commission E, the German regulatory body responsible for phytomedicinals.
Pumpkin seed is theorized to act by displacing DHT from androgen receptors on human fibroblasts13 or by antiandrogenic/anti-inflammatory effects.14 Pumpkin seeds contain phytosterols and, therefore, may bind to androgen receptors. However, there are no human studies to support these proposed mechanisms. In addition, there have been a very limited number of clinical trials evaluating its efficacy, none of which are published in English.
Friederich et al evaluated the efficacy of 1-2 capsules of Prosta Fink Forte, a brand-name standardized extract, in the treatment of 2,245 patients who were classified as "Alken stage I or II" (this scale has not been equated to other standardized scales).15 The trial abstract reports that the results demonstrated a decrease in IPSS and quality of life improvement.
The average daily dose is 10 grams of the ground seeds in either single or divided doses.14,16,17 No adverse reactions or interactions with other drugs have been reported with the use of pumpkin seeds.