BPH

 

Edward Lichten, M.D.,PC
555 South Old Woodward Suite #700
Birmingham, MI 48009 
248.593.9999

BILATERAL PROSTATIC HYPERPLASIA

OVERVIEW: Benign prostatic hyperplasia (BPH),  benign prostatic hypertrophy or, benign enlargement of the prostate (BEP), and adenofibromyomatous hyperplasia, are descriptive terms for the enlargement of the prostate that men develop with aging.  Technically, the cells that line the urethra multiply (hyperplasia) not enlarge (hypertrophy), but the result is the same[1]:

When the nodules enlarge enough there is a relative to complete obstruction of urine flow. The process begins in the 30's and by age 80, 75% of men have symptoms. For half, the symptoms are significant enough to take medication or have surgery[.]2

 

Men experience voiding symptoms including:

  •  hesitancy (needing to wait for the stream to begin),

  • intermittency (when the stream starts and stops intermittently), straining to void, and dribbling.

  • Pain and dysuria are usually not present. These storage and voiding symptoms are evaluated using the

  • International Prostate Symptom Score (IPSS) questionnaire, designed to assess the severity of BPH.[3]

CAUSE: [from Wikipedia]

A study published in 2008 in the journal of andrology "Andrologia"[4] reports on a newly discovered venous route by which free (active) testosterone reaches the prostate in extremely high concentrations, promoting the accelerated proliferation of prostate cells, leading to the gland's enlargement. The study suggests that BPH is caused by malfunction of the valves in the internal Spermatic veins manifesting as varicocele, a phenomenon which has been shown to increase rapidly with age,[5][6] roughly equal to the 10% per year increasing prevalence of BPH. The 6- to 8-fold elevated hydrostatic pressure then leads to retrograde venous drainage, allowing free communication with the prostatic circulation. Having measured a concentration of free testosterone of some 130-fold above serum level in the internal spermatic vein (the testes being the main source and the blood being undiluted in systemic circulation), the authors conclude that the elevated venous pressure causes hypertrophy and exposure to high concentrations of free testosterone causes hyperplasia in the prostate. The study also proposes a treatment method (Gat–Goren Technique) similar to that used in treating varicocele, which restores normal pressure in the venous drainage system, effectively reducing the volume of the prostate and clinical manifestation of BPH.

Androgens (testosterone and related hormones) are considered to play a permissive role in BPH by most experts. This means that androgens have to be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by the fact that castrated boys do not develop BPH when they age. On the other hand, administering exogenous testosterone is not associated with a significant increase in the risk of BPH symptoms. Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. DHT is synthesized in the prostate from circulating testosterone by the action of the enzyme 5α-reductase, type 2. This enzyme is localized principally in the stromal cells; hence, those cells are the main site for the synthesis of DHT.

DHT can act in an autocrine fashion on the stromal cells or in paracrine fashion by diffusing into nearby epithelial cells. In both of these cell types, DHT binds to nuclear androgen receptors and signals the transcription of growth factors that are mitogenic to the epithelial and stromal cells. DHT is 10 times more potent than testosterone because it dissociates from the androgen receptor more slowly. The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5α-reductase is given to men with this condition. Therapy with 5α-reductase inhibitor markedly reduces the DHT content of the prostate and, in turn, reduces prostate volume and, in many cases, BPH symptoms.PMID: 18318566]

Testosterone promotes prostate cell proliferation,[7] but relatively low levels of serum testosterone are found in patients with BPH.[8][9] One small study has shown that that medical castration lowers the serum and prostate hormone levels unevenly, having less effect on testosterone and dihydrotestosterone levels in the prostate.[10]

While there is some evidence that estrogen may play a role in the etiology of BPH, this effect appears to be mediated mainly through local conversion of estrogen to androgens in the prostate tissue rather than a direct effect of estrogen itself.[11] In canine in vivo studies castration, which significantly reduced androgen levels but left estrogen levels unchanged, caused significant atrophy of the prostate.[12] Studies looking for a correlation between prostatic hyperplasia and serum estrogen levels in humans have generally shown none.[9][13]

On a microscopic level, BPH can be seen in the vast majority of men as they age, in particular over the age of 70 years, around the world. However, rates of clinically significant, symptomatic BPH vary dramatically depending on lifestyle. Men that lead a western lifestyle have a much higher incidence of symptomatic BPH than men that lead a traditional or rural lifestyle. This is confirmed by research in China showing that men in rural areas have very low rates of clinical BPH, while men living in cities adopting a western lifestyle have a skyrocketing incidence of this condition, though it is still below rates seen in the West.

Much work remains to be done to completely clarify the causes of BPH.

TREATMENT:

The initial medical treatmente, if symptomatic, is a 5-alpha reductase medication, whether Flomax™ or Avadart™.   Flomax™ is associated with a 20% incidence of arthralgia (muscle aches and pains) and headaches. Avadart™ interferes with blood donations.  When medication fails, there are a number of office/ out-patient surgial procedures that apply heat/radiation to the prostatic tissue that surrounds the urethra. The resulting  tissue damage causes shrinkage of the BPH and relief of symptoms, although a urethral catheter or similar device may be necessary for a number of days.  If this fails, the 'tired-and-true" surgery called TURP (Transurethral Resection of the Prostate) can be performed in an outpatient setting.

 

SCIENTIFIC THESIS:

If BPH is caused by the local effects of testosterone or testosterone's conversion to either estrogen or dihydro-testosterone, then changing the principal androgen from testosterone to nandrolone should relieve symptoms while lowering estradiol and DHT levels.  Although spirolactone is a 5-alpha reductase, it's use in BPH has not been documented.

While no clinical studies have been performed to date, personal experience has found this to be at least temporarily helpful and discontinuation of 5-alpha reductase medications was well tolerated.

 

CLINICALLY, TESTOSTERONE REPLACEMENT CAN BE BENEFICIAL.

Purpose. We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH). Methods. Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment. Results. Forty-six patients (ART group, n = 23; control, n = 23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7 ± 8.7 vs. 12.5 ± 9.5; p < 0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p < 0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p < 0.05), whereas no significant changes were seen in the controls. Conclusion. ART improved LUTS in hypogonadal men with mild BPH.[15]

 

 

INTERNATIONAL PROSTATE SYMPTOM SCORE QUESTIONNAIRE

During the last month or so how often have you...

Not at all Less than 1 time in 5 Less than 1/2 the time About 1/2 the time More than 1/2 the time Almost always
1. had a sensation of not emptying your bladder completely after urinating?
0
1
2
3
4
5

2. had to urinate again less than two hours after you have urinated?
0
1
2
3
4
5

3. how often have you stopped and started, several times when you urinated?
0
1
2
3
4
5

4. found it difficult to postpone urination?
0
1
2
3
4
5

5. had a weak urinary stream?
0
1
2
3
4
5

6. had to push or stain to urinate?
0
1
2
3
4
5
During the last month...
None 1 time 2 times 3 times 4 times 5 times or more
7. 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
1
2
3
4
5
 Maximum score is 7 x5 = 35. Any score over 20 is considered significant.

ICD 9 CPT CODE  600.

REFERENCES:

  1. Bostwick, D. G. (2002). "The Pathology of Benign Prostatic Hyperplasia". In Kirby, Peter; McConnell, John D.; Fitzpatrick, John M. et al.. Textbook of Benign Prostatic Hyperplasia. London: Isis Medical Media. ISBN 978-1-901865-55-4.

  2. Rubenstein, Jonathan; McVary, Kevin T. (February 6, 2008). "Transurethral Microwave Thermotherapy of the Prostate (TUMT)". eMedicine

  3. Barry MJ, Fowler FJ, O'Leary MP, et al. (November 1992). "The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association". The Journal of Urology 148 (5): 1549–57; discussion 1564. PMID: 1279218.

  4. Gat, Y.; Gornish, M.; Heiblum, M.; Joshua, S. (2008). "Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatment". Andrologia 40 (5): 273–81. doi10.1111/j.1439-0272.2008.00883.x. PMID: 18811916.

  5. Canales, B; Zapzalka, D; Ercole, C; Carey, P; Haus, E; Aeppli, D; Pryor, J (2005). "Prevalence and effect of varicoceles in an elderly population". Urology 66 (3): 627–31. doi.10.1016/j.urology.2005.03.062. PMID: 16140091.

  6. Levinger, U.; Gornish, M.; Gat, Y.; Bachar, G. N. (2007). "Is varicocele prevalence increasing with age?". Andrologia 39 (3): 77–80. doi: 10.1111/j.1439-0272.2007.00766.x. PMID:17683466.

  7. Feldman, Brian J.; Feldman, David (2001). "The development of androgen-independent prostate cancer". Nature Reviews Cancer 1 (1): 34–45. doi:10.1038/35094009. PMID:  11900250.

  8. Lagiou, Pagona; Mantzoros, Christos S.; Tzonou, Anastasia; Signorello, Lisa B.; Lipworth, Loren; Trichopoubs, Dimitrios (1997). "Serum Steroids in Relation to Benign Prostatic Hyperplasia". Oncology 54 (6): 497–501. doi:10.1159/000227609.PMID: 9394847.

  9. Roberts, Rosebud O.; Jacobson, Debra J.; Rhodes, Thomas; Klee, George G.; Leiber, Michael M.; Jacobsen, Steven J. (2004). "Serum sex hormones and measures of benign prostatic hyperplasia". The Prostate 61 (2): 124–31.doi::10.1002/pros.20080. PMID: 15305335.

  10.  Page, S. T.; Lin, D. W.; Mostaghel, E. A.; Hess, D. L.; True, L. D.; Amory, J. K.; Nelson, P. S.; Matsumoto, A. M. et al. (2006). "Persistent Intraprostatic Androgen Concentrations after Medical Castration in Healthy Men". Journal of Clinical Endocrinology & Metabolism 91 (10): 3850–6. doi: 10.1210/jc.2006-0968. PMID: 16882745.

  11. Ho, C. K M; Nanda, J.; Chapman, K. E; Habib, F. K (2008). "Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen". Journal of Endocrinology 197 (3): 483–91. doi:10.1677/JOE-07-0470.PMID 18492814.

  12. Niu, YJ; Ma, TX; Zhang, J; Xu, Y; Han, RF; Sun, G (2003). "Androgen and prostatic stroma". Asian journal of andrology 5 (1): 19–26. PMID 12646998.

  13. Ansari, Mohammad Abduljalil; Begum, Dilruba; Islam, Fakhrul (2008). "Serum sex steroids, gonadotrophins and sex hormone-binding globulin in prostatic hyperplasia". Annals of Saudi Medicine 28 (3): 174–8. doi:10.4103/0256-4947.51727.PMID: 18500180.

  14. Mendosa P et al. Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma. Int J Androl. 2009 Dec;32(6):607-15. Epub 2008 Jul 9. PMID: 18637152

    15. Shigehara K. Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study. Aging Male. 2010 Dec 21. [Epub ahead of print] PMID: 21171937