Benign prostatic hyperplasia (BPH) is a condition that affects a significant number of men globally once they reach the age of 40 (and occasionally even earlier). It is estimated to occur to some degree in about a quarter of men by age 50, a third of men in their 60s, and increasing to somewhere around 80% by age 90. While these numbers are approximate, there is a reasonable chance that if you are a male reader you will personally be dealing with this at some point (or now). So I’m going to provide some basic information about it.
The prostate gland releases prostate fluid, one of the ingredients that go into making semen. It is an exocrine gland, meaning that it secretes the fluid into tiny ducts that lead into the urethra, and the gland itself has histological structures known as acini, similar in several respects to those found in mammary gland, pancreas, sweat glands and salivary glands. The prostate gland contains so-called stromal structures that include contractile smooth muscle, nerve, and blood vessels. When the prostate smooth muscle contracts (during ejaculation), the fluid is essentially squirted into the urethra. The gland itself is located at the intersection of the bladder and the urethra. From a topological perspective you can think of it as approximately like a fat rounded horseshoe that wraps around the urethra with right, left, and medial lobes. It is worth noting that the rectum passes immediately by that area, nearly touching the bladder-urethra-prostate junction.
Hyperplasia means excessive growth. As men age, the prostate grows larger, sometimes in the just the lateral lobes, sometimes in all three. The effect of this is to impinge on the urethra, making it increasingly difficult for the bladder to squeeze urine through the urethra, leading to a series of lower urinary tract symptoms (LUTS). These typically include difficulty in starting or maintaining a stream of urine, and frequent “urges to go”, which are especially disruptive at night when people are trying to sleep. Often there is dribbling of urine after the bladder has stopped contracting. Eventually, the muscles in the bladder find it difficult to contract and they literally degenerate, meaning symptoms can worsen quickly, and may require catheterization in an ER. It is best to do something about BPH well before that happens. You should not ignore these symptoms! Because the prostate gland lies immediately adjacent to the rectum, a physician can get a rough estimate of the size of the prostate by palpating it through the wall of the rectum. This is not very pleasant but only takes a second.
Cancers of the prostate are very common in men, and outcomes vary considerably depending on when it is detected, the types of cells involved, etc. Many of the molecular processes that lead to cancers in the prostate are similar to those that occur in the breast, but I’m not going to write about prostate cancers here, other than to say that what needs to be done with prostate cancer depends critically on the pathological classification of the cancer cells. One sign of prostate problems is an increase in blood levels of something called the prostate serum antigen (PSA). PSA levels are often somewhat elevated in BPH but most typically not as high as they would be in most prostate cancers (but PSA levels can be distorted if you are taking certain drugs as noted below).
So let’s say you have LUTS and your doctor palpates the prostate and decides it is enlarged. What happens next? Well this all depends on whether or not you have access to healthcare. In the US, too many people don’t. It is a national embarrassment. But let’s say you do, in which case hopefully you would be referred to a urologist. The urologist will often order an ultrasound exam of the prostate, using a probe inserted into the rectum. It doesn’t hurt and it only takes a few minutes. From that, the urologist will have an idea of the size of the prostate, and probably which of the three lobes are affected (and maybe all three if you are unlucky). What then?
Often if it is fairly early in the course of BPH, based on severity of LUTS and size of prostate, treatment will be done with drugs. There are two widely used classes of drugs for BPH. The first are so-called alpha-adrenoceptor blockers, such as tamsulosin, alfuzosin, terazosin, and others. These all work by relaxing the muscles of the bladder where the urethra emerges, and in the prostate itself. They inhibit actions of the neurotransmitter norepinephrine on those cells (and wherever else sensitive forms of alpha receptors occur, which is actually lots of places, and depends a bit on which drug you use). This improves the flow of urine but does nothing to stop the growth of the prostate. They are usually reasonably well tolerated but can cause dizziness upon standing (postural hypotension) and general light-headedness. Those symptoms usually subside after a few days. Tamsulosin can have a weird effect of making men ejaculate into the bladder (retrograde) instead of out the urethra, and for some reason alfuzosin is less likely to do this. These drugs can be used for years and they remain the front-line therapy, although I will mention one potential issue further below. Some relief can also be had by using so-called phosphodiesterase-5 inhibitors like Cialis and Viagra but they are less effective than alpha blockers. Finally, I will mention a class of drugs known as 5-alpha-reductase inhibitors, which actually reduce the progression of prostate growth but which have some really awful side-effects. The one most commonly used is called finasteride, another is called duasteride.
Finasteride works as an anti-androgen by blocking the production of dihydrotestosterone from its precursor (and it has been marketed as an anti-baldness medication under the brand name Propecia). Finasteride can be very bad news. There is now clear evidence that it can produce a “post-finasteride syndrome”. This syndrome includes a host of sexual and neurological issues, one of the most severe being depression and anxiety, cognitive impairment and suicidal thoughts [1]. Importantly, these effects do not necessarily go away after people stop taking the drug. Finasteride can also mask the presence of high grade prostate cancers by reducing PSA production (the drug now has an FSDA Black Box warning about this). There are scandals surrounding these effects, in particular what did Merck known about all of this (including cognitive effects) and when did they know it. Evidence suggests they knew this was going on during their initial clinical trials and hid these data [2].
In many men there will come a time when the drugs are not working well enough anymore and then it is common to do a surgical procedure. What can be done depends a lot on how big the prostate gland is and which lobes are involved. The urologist will probably carry out imaging based again on ultrasound and using cystoscopy to visualize more of what is going on. (In cystoscopy a fiber-optic device is inserted into the urethra up to bladder-prostate interface). If it is just the lateral lobes they may be able to simply stitch the lobes out of the way, which is essentially an out-patient procedure. But in a lot of men that won’t solve the problem, mainly if there is extensive medial lobe involvement, and then it will be necessary to actually remove some of the prostate. This is usually done by inserting a laser or some other device through the urethra and blasting away a portion of the prostate that is impinging on the urethra (transurethral resection of the prostate, or TURP). This will require one or two days and nights in the hospital. The recovery time afterword is a couple of months while all the inflammation subsides and the urethra, prostate and bladder heal. During that time patients need to curtail their physical activities, including sex. In some men after the surgery they will experience the weird retrograde ejaculation that also occurs with tamsulosin.
A very recent study has suggested that prolonged use of alpha blockers is associated with greater risk of heart failure [3]. The so-called hazard ratio for this effect was between 1.18 and 1.26. This is an issue that has come up before in the history of these drugs (they were originally developed to treat high blood pressure but are largely worthless for that). Not every study has seen an increase in heart failure due to alpha blockers [4]. Although this most recent study attempted to account for many potential confounding factors, a major weakness is that all of the patients studied were 66 years of age and older [3]. In any case, the study authors suggested that one might at least consider that an earlier surgical intervention might be a better option, and their data also suggested that more selective inhibitor like tamsulosin might be better than a less selective one like alfuzosin.
It is not entirely clear what causes this in the first place. There is almost certainly a heavy genetic element to this. There are also reports that diet and lifestyle can play a role in progression of BPH [5]. I should mention that herbal remedies such as saw palmetto have been used for BPH for a long time but the most carefully done clinical trials have provided no evidence that it works [6]. As with all herbal remedies, it may depend a great deal on how the plant extract is prepared [7], and since supplements are not regulated by anyone you have no idea what you are buying.
The last important thing is that prostate cancer and BPH can occur together, so anyone with LUTS needs to get it checked out.
1. https://www.researchgate.net/publication/326574804_Post-finasteride_Syndrome_A_Review_of_Current_Literature
2. https://www.reuters.com/investigates/special-report/usa-courts-secrecy-propecia/
3. https://www.urologytimes.com/view/alpha-blockers-and-5-alpha-reductase-inhibitors-raise-cardiac-failure-risk
4. https://www.sciencedirect.com/science/article/pii/S2213177918304712
5. https://pubmed.ncbi.nlm.nih.gov/23202286/
6. https://pubmed.ncbi.nlm.nih.gov/16467543/
7. https://pubmed.ncbi.nlm.nih.gov/31807332/
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