Clinical Practice Guideline

for

BENIGN PROSTATIC HYPERPLASIA

Developed for the

Aerospace Medical Association

by their constituent organization

American Society of Aerospace Medicine Specialists

Overview: Benign prostatic hyperplasia (BPH), one of the most common diseases of aging men, can be associated with bothersome lower urinary tract symptoms (LUTS) that include increased urinary frequency, nocturia, hesitancy, urgency and a weak urinary stream. Chronic inability to completely empty the bladder may cause bladder distension with hypertrophy and instability of the detrusor muscle. BPH can affect quality of life by interfering with normal daily activities and sleep patterns. The prevalence of histopathologic BPH is age-dependent, with initial development usually after 40 years of age. By age 60, its prevalence is greater than 50% and by age 85 it is as high as 90%. Similar to that of histologic evidence, the prevalence of bothersome symptoms also increases with age. Approximately one half of all men who have a histologic diagnosis have moderate to severe LUTS.

Diagnostically, BPH is defined as a patient with a score > 7 on the American Urological Association Symptom Index (AUASI) (see Table 1) and a peak urinary flow rate < 15 mL/s. It has also been defined as prostate enlargement from progressive hyperplasia of stromal and glandular prostatic cells. Clinical BPH refers to the LUTS associated with benign prostatic enlargement (BPE) causing bladder outlet obstruction (BOO). There is growing interest in the relationship of inflammation and BPH. In fact, inflammation of the prostate appears to be more closely related to BPH than the clinical syndrome chronic prostatitis. In the future, this may lead to treatment of BPH with therapies that target inflammation, but there is no good evidence at this time to support the treatment of BPH with antibiotics or anti-inflammatory medications such as NSAIDs. Large-scale studies of different populations have demonstrated consistent evidence of a relationship between LUTS symptoms and ejaculatory dysfunction that is independent of age and other comorbidities.

Because long-term data from population-based studies have only recently become available, the risks of developing complications and morbidities from untreated BPH are unclear. For example, despite recent evidence, there is still uncertainty regarding the likelihood that a patient with a specific symptom complex will develop acute urinary retention within a particular time frame. Nonetheless, BPH-associated mortality is rare in the United States, and serious complications are uncommon. In contrast, LUTS are bothersome to many patients, and the amount of bother may differ greatly among individuals with the same degree of symptom frequency and severity. Since the impact of LUTS on the patient's quality of life is highly variable and not directly related to any measurable physiological factors, the patient's perception of the severity of the condition, as well as the degree to which it interferes with his lifestyle or causes embarrassment, should be the primary consideration in choosing therapy.

The AUA recommends urinalysis for all men presenting with lower urinary symptoms to help rule out non-BPH causes of symptoms such as bladder cancer, bladder stones, infections, or urethral strictures. In addition, LUTS can be a presenting symptom of prostate cancer, and men with LUTS should undergo screening for prostate cancer with a digital rectal examination and serum Prostate Specific Antigen (PSA). Prostate cancer should be considered a diagnosis of exclusion in men with LUTS. PSA levels correlate with prostate volume and increased levels may direct particular forms of therapy. In addition, urine cytology should be obtained in men at risk of bladder cancer, particularly if they have associated irritative symptoms of urinary frequency and urgency or hematuria.

Treatment options for BPH include watchful waiting, medications and surgery. The decision to treat involves balancing the severity of the patient’s symptoms with potential side effects of therapy. Watchful waiting is recommended in men who have mild symptoms (AUASI of 6 or less) or who do not perceive their symptoms to be particularly bothersome. These men need to be monitored at least annually for symptom progression.

Treatment with medications is an increasingly popular choice. When selecting an agent one has to take into consideration the nature of the man’s disease, side effects of the selected agent and other medications utilized by the patient. The two major classes of medications act upon different components of the bladder outlet obstruction of BPH. The dynamic (physiologic, reversible) component is related to the tension of prostatic smooth muscle in the prostate, prostate capsule, and bladder neck. The fixed (structural) component is related to the bulk of the enlarged prostate impinging on the urethra. Two classes of drugs, alpha-adrenergic antagonists and 5-alpha-reductase inhibitors, act upon the dynamic and fixed components, respectively. Alpha-adrenergic antagonists (terazosin, doxazosin, tamsulosin, alfuzosin, and prazosin) appear to be more effective for short-term treatment of symptoms but do not appear to have an impact on reducing long-term complications such as urinary retention or the need for surgical intervention. Only 5-alpha-reductase inhibitors (finasteride and dutasteride) have demonstrated the potential for long-term reduction in prostate volume, which in turn reduces the long term risks of urinary retention and surgical intervention. The only current aeromedically approved medication therapy for BPH is the 5-alpha-reductase inhibitor finasteride. Regarding ED, the alpha-adrenergic antagonists appear to have a lower incidence of this potential side effect than do the 5-alpha-reductase inhibitors.

There is increased interest in “natural” remedies for BPH. The most popular such agent over the past few years has been saw palmetto, which is an extract of the saw palmetto berry. In 2001 it was estimated that 2.5 million adult Americans had reported using this product. A recent trial compared saw palmetto with placebo and found that there was no difference after one year in the two groups in AUASI scores, maximal urinary flow rates, prostate size, residual volume after voiding, quality of life, or PSA scores during the study. This study and others examining the efficacy of dietary supplement-like substances (including beta-sitosterol) raises questions about the variability of botanical products as well as their overall efficacy compared to their claims.

The most commonly performed surgical treatment for BPH is transurethral resection of the prostate (TURP). After this procedure, the patient is left with a wide open prostatic fossa bound by a denuded surgical capsule that will be lined by a newly regenerated epithelial surface in 6 to 12 weeks. Until this occurs, the patient is vulnerable to bleeding and most surgeons encourage him to avoid straining for at least six weeks. Most men note a marked decrease in symptom scores and a substantial increase in maximal urinary flow rates post-operatively. Side effects to this procedure include bleeding, incontinence and urethral strictures, each which is relatively uncommon. Most men will experience retrograde ejaculation after this procedure. Newer surgical options include several procedures with lasers, transurethral incision of the prostate, electrovaporization of prostate tissue, as well as several minimally invasive procedures such as transurethral needle ablation of the prostate and microwave thermotherapy have demonstrated efficacy as well, but are not appropriate for all TURP candidates. Urethral stents have been studied for BPH indications and are available, but have been abandoned by most urologists due to the tendency for tissue growth through stent fenestrations and encrustation of stent material.

Table 1 - AUA Urinary Symptom Index (AUASI)

Questions to be Answered	Not at all	Less than 1 time in 5	Less than half the time	About half the time	More than half the time	Almost always
Circle one number for each question
1. Over the past month, how often have you had a sensation of not emptying your bladder completely after you finished urinating?	0	1	2	3	4	5
2. Over the past month, how often have you had to urinate again less than 2 hours after you finished urinating?	0	1	2	3	4	5
3. Over the past month, how often have you found you stopped and started again several times when you urinated?	0	1	2	3	4	5
4. Over the past month, how often have you found it difficult to postpone urination?	0	1	2	3	4	5
5. Over the past month, how often have you had a weak urinary stream?	0	1	2	3	4	5
6. Over the past month, how often have you had to push or strain to begin urination?	0	1	2	3	4	5
7. Over the past month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?	0 (none)	1 (1 time)	2 (2 times)	3 (3 times)	4 (4 times)	5 (5 or more times)
Sum of circled numbers (AUA symptom score): _______
0 to 7: Mild symptoms
8 to 19: Moderate symptoms
20 to 35: Severe symptoms

Aeromedical Concerns: The presence of BPH symptoms alone is not automatically disqualifying for flying duties. The primary aeromedical and operational concern with BPH relates to the potential for urinary obstruction/retention. The symptoms of acute urinary retention include severe lower abdominal pain, a distended abdomen, and the sudden inability to pass urine.

Operationally, urinary frequency can be disruptive, and nocturia can result in sleep disruption and fatigue. The tendency to delay bladder emptying while in-flight can lead to excessive bladder distention and acute urinary retention. As such, judgment should be used in determining the aeromedical significance of reported symptoms.

Regarding medication therapy, the most important side effects of the alpha-1-adrenergic antagonist class are orthostatic hypotension, dizziness, and somnolence. As such, alpha-blockers are not acceptable for use in the aerospace environment at this time. Alfuzosin may be reviewed in the next year for consideration. Regarding the 5-alpha-reductase inhibitors, specifically finasteride, a detailed aeromedical medication review in Sep 04 concluded it to be both effective and safe in the aerospace environment.⁹ Surgical treatment for BPH should only result in grounding for several weeks and a later return to flying as long as the symptoms are relieved with the procedure. Furthermore, “natural” products such as saw palmetto and beta-sitosterol should be considered cautiously, with the knowledge and approval of the flight surgeon, due to big questions regarding efficacy, side effect profile, and the lack of regulation regarding contents and purity of these over-the-counter supplements.

Medical Work-up: The evaluation needs to include a complete symptom history to include feelings of incomplete emptying of the bladder, urinary frequency, stopping and starting of urinary stream, urinary urgency, weak stream, difficulty initiating stream and nocturia. The history also needs to discuss all attempted treatments/medications to include results and side effects. The exam needs to include, at a minimum a digital rectal exam. Laboratory evaluation should consist of: urinalysis, PSA, urine flow rate, and post-void residual. Some cases may require a more detailed evaluation to include cystoscopy, 24-hour urine for creatinine clearance and protein, IVP, renal/prostate ultrasound, and serum creatinine. And finally, a urology evaluation if surgery performed or symptoms severe, otherwise, a report from the treating physician will suffice if treated medically.

Aeromedical Disposition:

Air Force: Symptomatic BPH (AUASI score of seven or greater) is disqualifying for all classes of flying in the Air Force per AFI 48-123. Asymptomatic BPH, and history of invasive surgical therapy such as TURP are not disqualifying, and do not require waiver submission if the obstructive symptoms are relieved, urinary continence is maintained, and healing is complete. Of note, it is recommended that after invasive surgery the aviator remain DNIF for a minimum of 3 weeks to heal due to the risk for acute bleeding and post-operative urgency. Furthermore, DNIF is required if the patient’s symptoms remain operationally significant, regardless of the treatment course.

Army: A prostate exam is required on all flight physicals, and BPH is not an infrequent finding, but BPH is not a disqualifying condition in the Army. When BPH requires medical treatment, the alpha blockers used, (prazosin (Minipress), doxazosin (Cardura), and terazosin (Hytrin), require waiver in that they are considered Army Class 3 chronic use medications. Tamsulosin (Flomax) and alfuzosin (Uroxatrol), being more prostate selective alpha blockers, have a lower incidence of side effects and are also waiverable. The 5-alpha-reductase inhibitor Finasteride is waiverable and requires documentation of objective and subjective signs of prostatic hyperplasia on periodic health exams as an annual waiver requirement.

Navy: BPH and use of finasteride for management is routinely waivered after two week grounding. A Local Board of Flight Surgeons can issue an “upchit” provided aviator remains asymptomatic.

Civilian: The FAA has allowed benign prostatic hyperplasia as a chronic medical condition. An authorization for special issuance is not required. They have permitted the surgeries to correct the symptoms of BPH. Standard recovery times are acceptable. The FAA has been accepting the use of the alpha-1 blocking agents but is currently re-evaluating its policies on their use.

Waiver Experience:

Air Force: AIMWTS review revealed 19 cases submitted with a diagnosis of BPH. Of the total, there were 0 FC I/IA cases, 12 FC II cases, and 7 FC III cases. There were two disqualifications; one was a FC II flight surgeon disqualified for another medical problem and the other was an initial FC III case who was disqualified as he was on a medication (tamsulosin) that is not approved for flying in the Air Force. Interestingly, there were three aviators waived on different alpha-1 receptor antagonists (these medications are not approved for aviation duties in the US Air Force.); one each for doxazosin, terazosin and alfuzosin. Two of these cases were FC III aviators and the other was a pilot (FC II). It is important that all waived medications are on the current approved medication list.

Army: The Aeromedical Epidemiological Data Repository (AEDR) catalogs all Army flight physicals since 1960. There have been approximately 160,000 individual aircrew entered in this database. During this period of time, there have been 35 aeromedical summaries requesting waiver for BPH. Of those 26 were rated aviators, 5 were non-rated and 2 were applicants. Waivers were granted to all 35. This does not represent all cases since BPH is usually an incidental finding or submitted for information only and not considered in the waiver process.

Navy: Not available at this time.

Civilian: See above.

ICD 9 code Benign Prostatic Hyperplasia
600	Hyperplasia of prostate

====================================================================================================================

References:

Cunningham GR and Kadmon D. Clinical manifestations and diagnosis of benign prostatic hyperplasia. UpToDate. Online version 17.1.; 1 January 2009.

Edwards JL. Diagnosis and Management of Benign Prostatic Hyperplasia. Am Fam Physician, 2008; 77:1403-10.

Roehrborn CG, McConnell JD, Barry MJ, et al. Guideline on the Management of Benign Prostatic Hyperplasic (BPH). American Urological Association, 2003.

Jacobsen SJ, Girman CJ, and Lieber MM. Natural History of Benign Prostatic Hyperplasia. Urology, 2001; 58(Suppl 6A):5-16.

Nickel JC. Inflammation and Benign Prostatic Hyperplasia. Urol Clin N Am, 2007; 35:109-15.

Hellstrom WJG, Giuliano F, and Rosen RC. Ejaculatory Dysfunction and Its Association with Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia and BPH Treatment. Urology, 2009; 74:15-21.

Cunningham GR and Kadmon D. Epidemiology and pathogenesis of benign prostatic hyperplasia. UpToDate. Online version 17.1.; 1 January 2009.

Cunningham GR and Kadmon D. Medical treatment of benign prostatic hyperplasia. UpToDate. Online version 17.1.; 1 January 2009.

Pickard JS. Finasteride Memorandum for HQ AFMSA/SGPA, Sep 2004.

Bent S, Kane C, Katsuto S, et al. Saw Palmetto for Benign Prostatic Hyperplasia. N Engl J Med, 2006; 354:557-66.

DiPaola RS and Morton RA. Proven and Unproven Therapy for Benign Prostatic Hyperplasia. N Engl J Med, 2006; 354:632-34.

Cunningham GR and Kadmon D. Surgical and other invasive therapies of benign prostatic hyperplasia. UpToDate. Online version 17.1.; 1 January 2009.

Prepared by Dr. Dan Van Syoc

Date: September 26, 2010