Benign Prostatic Hyperplasia

What is benign prostatic hyperplasia (BPH)?

Benign prostatic hyperplasia is one of the most common diseases in older men. Before age 40, a man’s prostate gland normally remains the same size. After age 40, the prostate may begin to enlarge. BPH prevalence is roughly 30 to 40% in men in their forties. By age 80, roughly 70 to 80% of men will have developed BPH (1). 

The prostate is a ping pong ball-sized gland that plays a key role in male reproduction, as it helps to make semen. It is located between the penis and the rectum and below the bladder. The prostate is near the urethra, the channel through which urine is carried out of the bladder and into the penis. BPH refers to when the prostate becomes enlarged.

With the enlargement of the prostate comes a few problems. First, a large prostate can affect how you can urinate. In this instance, the bladder must work harder to overpower the prostate. This causes blockage and resistance to urinary flow. If the prostate continues to grow and create a blockage, you may find it difficult to empty your bladder fully. This condition is called urinary retention (2).

What causes BPH?

The exact causes of BPH are unknown, but we do know that BPH occurs with increased age in men. Experts think that hormones in the testes may be involved, particularly testosterone and dihydrotestosterone (DHT). Testosterone is a male sex hormone produced in the testicles. It is a hormone critical to male sexual development and function. As men age, the amount of testosterone in their blood decreases. 

Another possibility involves the role of DHT. DHT is another male hormone, and it is a key player in the development of the prostate. Some studies have suggested that older males have increased DHT levels (1,3). Other causes may include:

• Bladder cancer
• Congestive heart failure
• Diabetes
• Parkinson’s disease
• Prostate cancer

Who is at greatest risk for BPH?

Multiple risk factors may predispose someone to BPH. Those at an increased risk of BPH include men who:

• Are over the age of 50. As men age, their risk for BPH increases.
• Have fathers with BPH
• Are not physically active
• Are overweight or obese
• Have erectile dysfunction (ED)

There is no way to completely prevent BPH. However, certain lifestyle modifications can help decrease your risk of developing BPH. For example, being overweight or obese is a risk factor for BPH. This is because excess body fat can increase certain hormone levels and disrupt processes related to prostate cell growth. Therefore, maintaining a healthy weight with proper diet and exercise can help keep hormone levels in check and reduce your risk of BPH (3).

What are the signs and symptoms of BPH?

Common symptoms of BPH include:

• Difficulty initiating a stream of urine, oftentimes only being able to make a dribble
• Feeling as if the bladder is not fully empty
• Urinating frequently, specifically at night
• Having to stop and start a stream multiple times while urinating
• Feelings of urgency to urinate
• A weakened or slowed urine stream
• Straining to urinate 
• Pain while urinating or after ejaculation 
• Urine with an abnormal appearance (e.g., color) or smell (2,4)

Earlier symptoms of BPH may not affect your daily function or quality of life. However, if you start to experience one or more of these symptoms, you should alert your doctor of what is happening. If BPH is not treated, urethra blockage may worsen symptoms and cause:

• Bladder infection
• Bladder stones
• Blood in the urine
• Kidney damage due to the buildup of urine in the bladder
• Erectile dysfunction

Therefore, if you experience any common symptoms above, you should contact your doctor. Additionally, if you experience any of the following symptoms, you should seek medical attention right away:

• Pain while urinating
• Inability to urinate
• Blood in the urine (4)

How is BPH diagnosed?

Your physician will review your medical history, physical examination, and various tests to check for signs and symptoms of BPH. These tests may include:

A rectal exam

If your doctor suspects BPH, they will do a rectal exam. A rectal exam involves the provider placing a lubricated, gloved finger into the rectum. In this exam, they can feel the prostate and its size. Your doctor will see if any hard portions could potentially be cancerous. This exam typically lasts between 10 to 15 seconds.

Urine test

Your doctor will usually also perform some urine tests to see if you have urination abnormalities. These tests will analyze if your urethra (the tube that carries urine out of the body) is blocked. There are a few methods to test this, some of which include:

• A urinalysis. This test checks to see what is in your urine. It looks for blood, sugar, protein, or any signs of infection. Depending on the results, a urinalysis can indicate signs of BPH or other conditions.
• A uroflowmetry test. This test measures the rate at which you urinate. 
• A post-void residual volume (PVR) test. A PVR test sees how much urine you have left in your bladder after you urinate.
• Urodynamic pressure-flow study tests. These analyze the amount of pressure in the bladder while urinating.

 Scans

 Your doctor may also do certain scans to aid in diagnosis. These include:

• An ultrasound to determine the shape and size of the prostate
• A cytoscopy, which looks inside the bladder
• Magnetic resonance imaging (MRI) and computed tomography (CT) to obtain a better picture and understanding of the prostate, especially if surgery is involved 

Blood tests

BPH is not cancerous, nor does it cause cancer. However, your doctor may screen you for prostate cancer by doing a blood test. This blood test looks at prostate-specific antigen (PSA), a protein produced by the prostate gland. With a healthy prostate, the blood will have minimal PSA levels. However, a rapid increase in PSA could indicate certain conditions, such as BPH or cancer (3).

Treatment

After being diagnosed with BPH, you and your provider will discuss your treatment options. Depending on your symptoms and how far the BPH has progressed, you may require medication or surgery. Your doctor will discuss the benefits and risks associated with each of your options. The treatment goals are to relieve bothersome BPH symptoms and reduce the risk of disease complications. Treatment is guided by the American Urological Association (AUA) Symptom Index.

AUA Symptom Index

The AUA created a survey to assess BPH symptoms and determine treatment. It considers how much your urinary symptoms affect your quality of life (5). Depending on your score, the AUA recommends treatment as described in the following table:

Watchful Waiting

Not everyone who has BPH will require immediate treatment. In this instance, providers will do “watchful waiting”. Watchful waiting is for men with only mild BPH symptoms that have not begun to affect their quality of life and who do not have bladder obstruction. This method is when your BPH is managed through active and frequent surveillance. You may also be advised to implement lifestyle changes to improve your quality of life. To lessen symptoms and risk factors for BPH, you may be told to:

• Implement a healthy diet and exercise regimen to lose weight
• Avoid constipation
• Lessen caffeine intake
• Lessen fluid intake at night
• Avoid alcohol and spicy foods
• Avoid medications that may worsen symptoms

Some medications may worsen your BPH symptoms. If you are on these medications, talk to your doctor about the risk and benefits of that medication and consider switching therapy. These medications include:

• Antihistamines (e.g., Benadryl)
• Decongestants
• Diuretics (“water pills”)
• Opioids
• Certain antidepressants

Your doctor might also recommend something called “timed bladder voiding”. This refers to urinating depending on the time of day and not how you feel. Providers may also recommend that you urinate frequently during waking hours. Another method you may try is known as double voiding, which is a technique aimed at more effectively emptying the bladder. During double voiding, you should urinate, relax for a few moments, and then try to urinate again. 

These lifestyle changes and techniques will help to improve symptoms. Additionally, they should help to slow symptom progression and avoid the need for medication and surgery. While watchful waiting, it is important to understand the chance of disease progression. One study found that approximately 31% of individuals with BPH had disease progression (6,7).

Can BPH increase the risk of cancer?

BPH is an abbreviation for benign prostatic hyperplasia. “Benign” means not harmful. “Prostatic hyperplasia” means an enlarged prostate. Therefore, BPH does not elevate your risk of getting cancer and will not progress to cancer. However, the symptoms of prostate cancer and BPH are similar (2).

Medication

For those that cannot manage their BPH with watchful waiting and lifestyle changes alone, there are multiple medications available to help with symptoms. Medications are a great option for those who need to manage their disease but whose disease has not progressed far enough to require surgery.  There are two main medication classes used in BPH: 

1. Alpha-adrenergic antagonists (alpha-blockers)
2. 5α-reductase inhibitors (5ARIs)

Other oral medication options include muscarinic receptor antagonists (MRAs) and phosphodiesterase 5 (PDE5) inhibitors. A summary of these four medications is included below:

Medications for BPH

Alpha-blockers

Alpha-blockers are indicated for patients that have moderate-to-severe BPH with symptoms. They function by inhibiting receptors in the prostate, urethra, and bladder. All the medications in the alpha-blocker class have relatively similar efficacy. They can help to better urinary flow after just a few doses, and symptoms should resolve within two to four weeks. In one study, alpha-blockers were shown to be more effective than placebo in decreasing symptoms and disease progression (7).

Mechanism

Alpha-blockers relax the muscle in the bladder and prostate, thereby decreasing the amount of obstruction in the bladder. This mechanism increases your urinary flow rate and decreases your PVR volume (7).

Adverse events

One adverse event that can occur while taking an alpha-blocker includes intraoperative floppy iris syndrome (IFIS). This condition occurs when you are on an alpha-blocker while undergoing cataract surgery. The pupil suddenly constricts and has poor dilation. Therefore, you should stop an alpha-blocker before undergoing cataract surgery.

Orthostatic hypotension is a sudden drop in blood pressure that can cause you to feel dizzy or faint. This can also happen with alpha-blockers, as this class can widen the blood vessels, thus decreasing blood pressure. Therefore, if you take alpha-blockers, you should use caution when taking medications for high blood pressure or if you have a cardiovascular condition. Additionally, you should use caution with these agents if you are at high risk of falling. This effect is seen more in doxazosin and terazosin (7). 

Important things to remember

If you take alfuzosin, tamsulosin, or silodosin, you should take these medications with or right after the same meal every day. Make sure not to crush or chew the capsule, and swallow the capsule whole. Tamsulosin capsules can be opened and sprinkled into soft food or fruit juice. Silodosin capsules can be opened and mixed only with applesauce. Doxazosin and terazosin need not be taken with meals (7). 

You should be careful when moving suddenly to avoid orthostatic hypotension. Your risk of orthostatic hypotension is greater if you also take drugs for erectile dysfunction. In this instance, space your BPH and ED drugs by four hours. Additionally, make sure to stop your alpha-blocker before cataract surgery. Other drug-specific points are included in the table below.

5α-reductase inhibitors

5α-reductase inhibitors, known as dutasteride and finasteride, are also used in those with moderate-to-severe BPH with symptoms. They should be used in individuals that have an enlarged prostate. An enlarged prostate is larger than 40 mL or where PSA levels are greater than 1.5 ng/mL. 5α-reductase inhibitors are preferred in patients who could not tolerate alpha-blockers because of their effects on the heart. Symptom improvement can normally be seen within two to six weeks. (7)

Mechanism

In the body, two substances known as testosterone and androstenedione are converted to DHT. DHT plays a role in the growth and development of the prostate. 5α-reductase inhibitors block this conversion, decreasing the levels of DHT in the body. This leads to decreased prostate size, increased urinary flow, decreased PSA, and improvement in voiding symptoms (7).

Adverse effects

The major difference between dutasteride and finasteride is their half-life, which refers to how long they stay in the body. Finasteride has a half-life of a few hours, while dutasteride has a half-life of a few weeks. This can cause the two medications to differ in how long an adverse effect lasts and medication adherence.

5ARIs can cause sexual dysfunction, including erectile dysfunction and decreased sex drive. Other side effects include nausea, abdominal pain, and male breast enlargement. Dutasteride must be swallowed whole to avoid throat irritation. Additionally, both medications are pregnancy category X, meaning that taking these medications during pregnancy can cause fetal abnormalities (7).

Important things to remember

Both medications can be taken with or without regard to food. While taking a 5ARI, you should have annual physicals where your doctor checks the PSA level in your blood.

Finasteride is also indicated for male pattern hair loss. Dutasteride can also be used for this reason, however, it is an off-label use (7). Other drug-specific points are included in the table below.

Phosphodiesterase 5 inhibitors

PDE5 inhibitors have historically been used to treat erectile dysfunction. The most updated AUA guidelines for BPH treatment do not discuss PDE5 inhibitors, however, the 2013 European Association of Urology (EAU) guidelines mention their utility in relieving urinary symptoms. That is why tadalafil has been approved for BPH. PDE5 inhibitors should be used in those with mild-to-moderate BPH symptoms (7).

Mechanism

PDE5 inhibitors work by relaxing the bladder and prostate’s smooth muscle fibers. Additional research indicates that PDE5 inhibitors may also work by anti-inflammatory effects, as inflammation is a major mechanism underlying BPH progression (8).

Adverse effects

The most common side effects associated with PDE5 inhibitors include headache, nasal congestion, indigestion, flushing, and cold symptoms. A rare side effect includes prolonged erections lasting more than four hours or priapism (a painful erection lasting greater than 6 hours). If you experience this, you should seek medical attention right away. If left untreated, you could have permanent penile tissue damage.

Vision problems have also been reported with PDE5 inhibitors. Post-marketing studies have also seen hearing loss associated with this class of medications (9).

Muscarinic receptor antagonists

Muscarinic receptor antagonists are normally used to treat symptoms of overactive bladder. However, recent research suggests a potential role in helping with BPH symptoms, as the bladder contributes to lower urinary tract symptoms. MRAs, therefore, can be used as an add-on therapy for those experiencing symptoms of overactive bladder. These symptoms can include urgency or frequent urination during the night. As for side effects, one of the most common side effects of MRAs is dry mouth. If you take an MRA, be sure to swallow the medication whole. You do not need to take an MRA with regard to meals (10).

Combination therapy

One product on the market, known as Jaylyn, contains a 5ARI (dutasteride) and an alpha-blocker (tamsulosin). These two medications work together to provide significantly better symptom improvement and reduction in disease progression than with either agent alone. AUA guidelines recommend that combination therapy be used in those with moderate-to-severe BPH, reduced urinary flow, and an enlarged prostate. The side effects of this combination therapy are similar to when each drug is used alone (7,11)

Surgery

Some individuals may need or opt for surgery to manage their BPH. Surgery is for patients who:

• Have BPH that does not respond to medication and lifestyle changes
• Have problems with their kidneys due to BPH
• Have urinary retention (inability to fully empty bladder) due to BPH
• Have recurring urinary tract infections (UTI)
• Have recurring hematuria (urine in the blood) or bladder stones due to BPH 

Surgery is the most invasive option when it comes to treating BPH. Therefore, patients usually try lifestyle changes and medication first before undergoing surgery. Surgery is an option, but you should discuss the benefits and risks with your doctor before deciding (12).

References

1. https://pubmed.ncbi.nlm.nih.gov/30943489/
2. https://www.cancer.gov/types/prostate/understanding-prostate-changes
3. https://www.urologyhealth.org/urology-a-z/b/benign-prostatic-hyperplasia-(bph)
4. https://my.clevelandclinic.org/health/diseases/9100-benign-prostatic-enlargement-bph
5. https://www.mottchildren.org/health-library/ug1952
6. https://www.ncbi.nlm.nih.gov/books/NBK558920/
7. https://www.uspharmacist.com/article/guidelines-for-the-treatment-of-benign-prostatic-hyperplasia
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570643/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776492/
10. https://www.nature.com/articles/srep03948
11. https://pubmed.ncbi.nlm.nih.gov/17577460/
12. https://pubmed.ncbi.nlm.nih.gov/29775639/