Lifestyle changes and pharmacological treatment of Benign Prostate Hyperplasia (BPH)

This article is the first one from a short series of 3 articles on Benign Prostate Hyperplasia. In the first one we talk about what is Benign Prostate Hyperplasia or BPH and I recommend reading it before this one. This is the second article and the third talks about the surgical treatment for BPH

In this article we will review:

  1. Conservative treatment (lifestyle changes).
  2. Medical treatment or Pharmacotherapy:
    • Alpha-blockers.
    • 5-alpha-reductase inhibitors (5ARIs).
    • Antimuscarinics and Beta-3 agonists.
    • Phosphodiesterase 5 inhibitors (IPDE5).
    • Phytotherapy – Plant extracts.
    • Combined treatment.
    • What happens when medical treatment fails?

Conservative treatment: lifestyle changes.

Many people with BPH do not exhibit a level of discomfort that warrants treatment with prescription medicine. Your doctor should rule out possible complications of BPH, such as the risk of suddenly not being able to urinate (acute urinary retention), kidney functionality issues, bladder stones, or urine infections, among others.

Many individuals with BPH who have only mild symptoms will not need treatment for years to come (1). In these cases, it would be advisable to simply start monitoring or consider certain lifestyle changes (2) such as:

  • Reduce the amount of liquids that are ingested at certain times, for example, before going to sleep or before making a long trip.
  • Avoid or moderate your intake of alcohol or caffeine, as they have a diuretic and irritating effect and can increase the amount of urine produced and the frequency with which you urinate.
  • Review the background medication to improve the type of medications and the time of day they are taken (for example, treatment with diuretics will aggravate voiding symptoms).
  • Treat constipation, as it can worsen urinary symptoms.

Applying these recommendations, alone or in addition to treatment with prescription drugs, has been shown to help ameliorate symptoms and also help prevent the progression of the disease (3).


Pharmacotherapy

In the event that the symptoms or the risk of complications cannot be controlled with changes in lifestyle, pharmacological treatment should be started, that is, prescribing medicine. The different treatments will be differentiated by the type of symptoms to be treated and their origin, as well as by the size of the prostate and the characteristics and preferences of each patient.

1. Alpha-blockers (or alpha-adrenergic blockers) 
  • The main ones are: Alfuzosin, Doxazosin, Terazonsin, Tamsulosin, and Silodosin.
  • Its function is to relax the muscles of the prostate and allow urine to flow more easily. (4)
  • They do not reduce the size of the prostate.
  • They are more effective in small prostates (<40 cc) (5).
  • In long-term studies, they do not reduce the risk of developing acute urinary retention, the likelihood of needing surgery later in life. (5)
  • No differences in effectiveness have been observed between the different types of alpha-blockers, so it is not recommended to switch from one type to another if the first has not been effective. (7)
  • Adverse effects:  
    • The most common are dizziness, orthostatic hypotension (dizziness when standing up), and tiredness. (8)
    • Normally they do not affect sexual function (erections, sexual appetite), but they do produce an alteration in ejaculation that consists of no semen coming out when ejaculating. Semen usually goes into the bladder and then comes out with urine. This is known as retrograde ejaculation. (9)
2. 5-alpha-reductase inhibitors (5ARIs)
  • There are 2 types of 5ARIs: finasteride and dutasteride.
  • They exert their effect by reducing the size of the prostate.
  • 5ARIs reduce the level of prostate specific antigen (PSA) in the blood by approximately 50% after 6 months of treatment. Thus, when performing a prostate cancer screening on a patient taking 5ARIs, doctors must double the recorded PSA level in the test, otherwise the results could be misleading.
  • Because the drug’s effects are incremental, the maximum impact on the pattern of urination will be seen after 6 months of treatment. (5)
  • They are more effective in prostates of more than 40cc. (11) (11). 
  • 5ARIs reduce the risk of acute urinary retention and reduce the need for long-term prostate surgery.
  • Adverse effects:
    • The most common adverse effects are: decreased sexual appetite, erectile dysfunction and, to a lesser extent, ejaculation disorders.
    • In a few cases, swelling of the breasts (gynaecomastia) may also occur. (13)
3. Antimuscarinics (Anticholinergics) and Beta-3 agonists
  • They are medications aimed at the so-called symptoms of bladder filling, which we explained above.
  • They act by controlling the contraction of the bladder, they do not act on the prostate.
  • The most common side effects of antimuscarinics are dry mouth, constipation, and difficulty urinating.
  • Beta3-agonists produce less dry mouth and constipation compared to patients treated with muscarinic receptor antagonists, but are contraindicated in patients with severe and poorly controlled hypertension. (16)
4. Phosphodiesterase 5 inhibitors (IPDE5)
  • The most famous of this family is Viagra, but the only one accepted, at the moment, for the treatment of lower urinary tract symptoms secondary to BPH is Tadalafil.
  • They improve urinary symptoms and erectile function. (17)
  • These drugs are a good option in patients with BPH and ED, but they are more expensive and are not usually covered by social security.
  • Side effects:
    • The main ones are facial flushing, headache and gastric discomfort. (18)
    • They are contraindicated in patients with severe heart problems, among others.
5. Phytotherapy – Plant extracts
  • Phytotherapy or herbal medicines include roots, seeds, pollen, bark, or fruits.
  • The mechanism of action in the patient (in vivo) of this type of preparation is not entirely clear.
  • Extracts of the same plant produced by different companies and even different batches from the same company may contain different concentrations of the active ingredient. Therefore, the effect of treatment can be difficult to predict. (19)
  • Only Serenoa repens extracted with hexane has been recommended for well-established use by the European Medicines Agency. (20)
6. Combined treatment

Depending on the patient's symptoms or response to initial treatment, a combination of medications may be offered. The most studied and most frequently used combinations are:

a. Combination of alpha-blocker and 5ARI: has been shown to be superior to each of these drugs individually, whenever indicated. (21, 22)

b. Combination of alpha blocker and anticholinergic:  it has been shown to be effective and safe in the treatment of patients with symptoms of bladder filling and emptying, that is, who present both an obstruction to the outflow of urine caused by the prostate and an excess of bladder activity. (23)

There are other drug combinations that do not have as much scientific evidence and their use is at the discretion of each urologist and the patient's preferences.

7. What happens when medical treatment fails?

If medical treatment is not effective from the start, if it loses effectiveness over time, or if the side effects are not well tolerated by the patient, surgical treatment should be considered, which we will discuss in the next article.



If you have any doubts about the treatment you are following, discuss it with your doctor and NEVER make changes to your medication on your own initiative.


Bibliography

1.        BALL AJ, FENELEY RCL, ABRAMS PH. The Natural History of Untreated “Prostatism.” Br J Urol [Internet]. 1981 [cited 2020 May 25];53(6):613–6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/6172172

2.        Yap TL, Brown C, Cromwell DA, Van Der Meulen J, Emberton M. The impact of self-management of lower urinary tract symptoms on frequency-volume chart measures. BJU Int [Internet]. 2009 Oct [cited 2020 May 25];104(8):1104–8. Available from: https://pubmed.ncbi.nlm.nih.gov/19485993/

3.        Brown CT, Yap T, Cromwell DA, Rixon L, Steed L, Mulligan K, et al. Self management for men with lower urinary tract symptoms: Randomised controlled trial. Br Med J [Internet]. 2007 Jan 6 [cited 2020 May 25];334(7583):25–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17118949

4.        Michel MC, Vrydag W. α 1-, α 2- and β-adrenoceptors in the urinary bladder, urethra and prostate. In: British Journal of Pharmacology. Br J Pharmacol; 2006.

5.        Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Nandy I, et al. The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study. Eur Urol [Internet]. 2010 Jan [cited 2020 May 25];57(1):123–31. Available from: https://pubmed.ncbi.nlm.nih.gov/19825505/

6.        Roehrborn CG. Three months’ treatment with the α1-blocker alfuzosin does not affect total or transition zone volume of the prostate. Prostate Cancer Prostatic Dis. 2006 Jun;9(2):121–5.

7.        Djavan B, Chapple C, Milani S, Marberger M. State of the art on the efficacy and tolerability of alpha 1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia [Internet]. Vol. 64, Urology. Urology; 2004 [cited 2020 May 25]. p. 1081–8. Available from: https://pubmed.ncbi.nlm.nih.gov/15596173/

8.        Nickel JC, Sander S, Moon TD. A meta-analysis of the vascular-related safety profile and efficacy of α-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract [Internet]. 2008 Oct [cited 2020 May 25];62(10):1547–59. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18822025

9.        Gacci M, Ficarra V, Sebastianelli A, Corona G, Serni S, Shariat SF, et al. Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: A systematic review and meta-analysis. J Sex Med [Internet]. 2014 [cited 2020 May 25];11(6):1554–66. Available from: https://pubmed.ncbi.nlm.nih.gov/24708055/

10.      Naslund MJ, Miner M. A review of the clinical efficacy and safety of 5α-reductase inhibitors for the enlarged prostate. Clin Ther [Internet]. 2007 Jan [cited 2020 Jun 3];29(1):17–25. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17379044

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13.      Corona G, Tirabassi G, Santi D, Maseroli E, Gacci M, Dicuio M, et al. Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis [Internet]. Vol. 5, Andrology. Blackwell Publishing Ltd; 2017 [cited 2020 Jun 3]. p. 671–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28453908

14.      Ichihara K, Masumori N, Fukuta F, Tsukamoto T, Iwasawa A, Tanaka Y. A randomized controlled study of the efficacy of tamsulosin monotherapy and its combination with mirabegron for overactive bladder induced by benign prostatic obstruction. J Urol [Internet]. 2015 Mar 1 [cited 2020 Jun 4];193(3):921–6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25254938

15.      Taneja SS, Morton R, Barnette G, Sieber P, Hancock ML, Steiner M. Prostate Cancer Diagnosis Among Men With Isolated High-Grade Intraepithelial Neoplasia Enrolled Onto a 3-Year Prospective Phase III Clinical Trial of Oral Toremifene. J Clin Oncol [Internet]. 2013 Feb 10 [cited 2017 Sep 21];31(5):523–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23295793

16.      Chapple CR, Kaplan SA, Mitcheson D, Klecka J, Cummings J, Drogendijk T, et al. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β3-adrenoceptor agonist, in overactive bladder. Eur Urol [Internet]. 2013 Feb [cited 2020 Jun 4];63(2):296–305. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23195283

17.      Wang Y, Bao Y, Liu J, Duan L, Cui Y. Tadalafil 5 mg Once Daily Improves Lower Urinary Tract Symptoms and Erectile Dysfunction: A Systematic Review and Meta-analysis. LUTS Low Urin Tract Symptoms [Internet]. 2018 Jan 1 [cited 2020 Jun 4];10(1):84–92. Available from: https://pubmed.ncbi.nlm.nih.gov/29341503/

18.      Porst H, Oelke M, Goldfischer ER, Cox D, Watts S, Dey D, et al. Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: Subgroup analyses of pooled data from 4 multinational, randomized, placebo-controlled clinical studies. Urology [Internet]. 2013 Sep [cited 2020 Jun 4];82(3):667–73. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23876588

19.      Habib FK, Wyllie MG. Not all brands are created equal: A comparison of selected components of different brands of Serenoa repens extract [Internet]. Vol. 7, Prostate Cancer and Prostatic Diseases. Prostate Cancer Prostatic Dis; 2004 [cited 2020 Jun 28]. p. 195–200. Available from: https://pubmed.ncbi.nlm.nih.gov/15289814/

20.      Medicines Agency E. European Union herbal monograph on Serenoa repens (W. Bartram) Small, fructus [Internet]. [cited 2020 Jun 28]. Available from: https://www.ema.europa.eu/en/documents/herbal-monograph/draft-european-union-herbal-monograph-serenoa-repens-w-bartram-small-fructus_en.pdf

21.      McConnell JD, Roehrborn CG, Bautista OM, Andriole GL, Dixon CM, Kusek JW, et al. The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia. N Engl J Med [Internet]. 2003 Dec 18 [cited 2018 Mar 15];349(25):2387–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14681504

22.      Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Nandy I, et al. The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study. Eur Urol [Internet]. 2010 Jan [cited 2019 Feb 28];57(1):123–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19825505

23.  Kaplan SA, He W, Koltun WD, Cummings J, Schneider T, Fakhoury A. Solifenacin plus tamsulosin combination treatment in men with lower urinary tract symptoms and bladder outlet obstruction: A randomized controlled trial. Eur Urol [Internet]. 2013 Jan [cited 2020 Jul 29];63(1):158–65. Available from: https://pubmed.ncbi.nlm.nih.gov/22831853/

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