BPH Medications and Possible Long-Term Side Effects

February 27, 2024

BPH, or benign prostatic hyperplasia, is the medical term used to describe the enlargement of the prostate gland that occurs as most men age. This prostate enlargement or prostatic hyperplasia is benign (non-cancerous) and isn’t known to cause prostate cancer, but it can still be problematic for many men as they age into their 50s, 60s and beyond. One way to address BPH is through medication. However, all medication can cause side effects.¹ This includes BPH medication or hormone therapy that addresses BPH Symptoms. BPH drug regimens can produce side effects, and some of these side effects may last long-term.² Benign prostatic hyperplasia is a very common disease that affects the prostate of most men as they get older. From a histologically diagnosed BPH incidence of 8% in men aged 31 to 40 years of age to over 80% of men over the age of 80, BPH occurs frequently.³ Even though the majority of older men will be diagnosed with BPH or prostatic hyperplasia, not all of these men will experience lower urinary tract symptoms (LUTS) brought on by BPH. For those men who do realize urinary symptoms caused by benign prostatic hyperplasia, they may be able to rely on watchful waiting (monitoring symptoms and instituting simple lifestyle changes) or BPH medication to deal with their LUTS without electing to have surgery, but recently released studies have come out showing some BPH medications can have significant neurocognitive, psychiatric, and sexual side effects, including dementia and depression.²

Possible Long-Term Side Effects of Using BPH Drugs

There are numerous prostate therapies that men have tried over the decades for dealing with LUTS brought on by benign prostatic hyperplasia, however, only three avenues have proven successful: lifestyle modifications, prescription medicine, and surgery, each dependent on the severity and progression of BPH. Several avenues are non-invasive, including watchful waiting and BPH medication. Additionally, there are minimally invasive office-based procedures and hospital-based surgical therapies for treating prostatic hyperplasia. However, some men with BPH-induced LUTS may not be good candidates for surgery or they may choose to forgo a surgical procedure and opt for medication to control their LUTS. Medical therapy (drugs) for the treatment of benign prostatic hyperplasia with LUTS has exploded in the past 20 years and is a feasible alternative to lifestyle modifications or surgery. Major clinical trials showed evidence that these medications are acceptable treatment alternatives and that the medications were well tolerated with relatively few adverse effects.² The only known drawback to the clinical evidence was that the initial follow-up period for the time patients were on these medications was relatively short.² Throughout the entire field of medicine, new information is emerging about potential unintended consequences of some common BPH medicines when taken for an extended period.² Recently, research has suggested that the long-term use of commonly prescribed BPH medications, including alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and anticholinergics, could have negative neurocognitive and psychiatric consequences, amongst others.² A scientific review paper by Bornick EM, Simma-Chiang V and Kaplan SA (2019) summarizes this emerging information and provides their expert perspective on the potential long-term side effects. These long-term side effects can include:

Dementia

Further research into BPH medications such as alpha-blockers, 5-ARIs, and anticholinergics, has found that they may have neurocognitive side effects that could lead to an increased risk of dementia, according to the view of the authors Bortnick EM, Simma-Chiang V and Kaplan SA (2019). Tamsulosin (Flomax) is one of the most selective alpha-1A antagonists of the alpha-blockers, and since alpha-1A receptors are present in both the brain and prostate, using this antagonist against those receptors could have adverse effects. Using Medicare data, a study comparing 253,136 men over the age of 65 who were diagnosed with benign prostatic hyperplasia and taking tamsulosin was compared to a propensity-matched group of men who were either using no BPH medication or a different BPH medication. The study showed after a follow-up period of 19.8 months, that men who had used tamsulosin had an incidence of dementia of 31.3/1000 person-years compared with only 25.9/1000 person-years for men taking no BPH medication.⁴ The overall risk of dementia was significantly higher in the group taking tamsulosin compared to the groups taking no BPH medication or alternative BPH medication groups taking doxazosin (Cardura), terazosin, alfuzosin (Uroxatral), dutasteride (Avodart) and finasteride (Proscar and Propecia)², however questions are ongoing as to the possible causal explanation for these findings. There may also be a risk of neurocognitive deficit in men taking anticholinergic medications – and, in particular, less selective anticholinergic medications, such as oxybutynin – since the cholinergic system in the brain plays an important role in attention, memory, awareness, psychomotor speed, and selection of relevant stimuli from the environment, according to Bortnick EM, Simma-Chiang V and Kaplan SA (2019). When anticholinergic medication blocks this pathway in the central nervous system, it can impair cognitive functions. “A 10-year cumulative dose-response relationship of anticholinergic intake was monitored for dementia and Alzheimer’s disease, showing that higher cumulative anticholinergic use is associated with increased risk of dementia.”⁵ Similarly, there are some findings that suggest a potential increased risk of neurocognitive effects with 5-ARIs: “Given the effects of testosterone and 5-ARIs on the brain, it was also a concern that 5-ARIs may lead to an increased risk of dementia if taken for an extended period.”² A study that included 81,162 men who started taking a 5-ARI, compared to an equal number of men who didn’t, found that there was an increased risk of dementia during the first 2 years of taking a 5-

Depression

Together with the neurocognitive effects of dementia, per Bortnick EM, Simma-Chiang V, and Kaplan SA (2019), there is also evidence that benign prostatic hyperplasia medications in the form of 5-ARIs could be associated with depression. “As 5-ARIs reduce the synthesis of several neuroactive steroids, the modulation of the neuroendocrine stress response may lead to depression.” “Many studies have shown correlations between 5-ARIs and depression.” Some of the first studies linking 5-ARIs to depression were found in men taking low-dose finasteride for male pattern baldness according to Bortnick EM, Simma-Chiang V, and Kaplan SA (2019). “Rates of depressive symptoms were significantly higher in former finasteride users as compared to the control group.”⁷ Studies specific to men with benign prostatic hyperplasia taking 5-ARIs have found similar results. A study of 93,197 men older than 66 years of age on 5-ARIs for a median duration of 1.57 years by Welk and colleagues found that depression risk was elevated during the initial 18 months after starting a 5-ARI and remained elevated, although to a lesser extent, throughout the remainder of the study period.⁶ The risk of self-harm was also significantly elevated during the initial 18 months on a 5-ARI, although there was no increased risk of suicide⁶

Sexual Function

In addition to dementia and depression, another topic of concern regarding the use of BPH medications is sexual function. It is well known in the medical community and among men who use alpha-blockers to address their BPH symptoms, that these medications can include ejaculatory dysfunction as a possible side effect.² However, according to Bortnick EM, Simma-Chiang V, and Kaplan SA (2019), there has more recently been added concern with some sexual side effects presenting later and potentially becoming permanent. Known in the medical community as post-finasteride syndrome (PFS), studies show that sexual dysfunction can continue even after the medication is halted. “In a single-group study of 11,909 men that had previously taken 5-ARIs, duration of 5-ARI exposure was associated with persistent erectile dysfunction (ED) after stopping the 5-ARI with a persistent median of 1348 days.”^{9 “}Anticholinergic drugs presumably cause erectile dysfunction by inhibiting preganglionic cholinergic receptors.”⁸

Miscellaneous

Potentially undesirable side effects of extended dutasteride BPH medication usage go beyond the dementia, depression, and sexual function effects per Bortnick EM, Simma-Chiang V, and Kaplan SA (2019). “A 2017 retrospective study of 460 men compared long-term dutasteride to tamsulosin for benign prostatic hyperplasia. Although dutasteride was associated with significant improvement of LUTS, there were also significant increases in blood glucose, glycated hemoglobin, total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, and liver enzymes, along with a reduction in total testosterone.”² “No changes were seen in the cohort of men taking tamsulosin. Overall, the study suggests that dutasteride may induce a negative imbalance of metabolic function.”² In Conclusion BPH, or prostatic hyperplasia, is a benign enlargement of the prostate that is not prostate cancer and isn’t known to cause prostate cancer. BPH medication can be both a short-term and long-term solution to addressing BPH symptoms if surgical therapy is not yet desired. However, as benign prostatic hyperplasia therapies, in the form of BPH medications, have increased rapidly and become popular in the last couple of decades, the urological profession is grappling with how to interpret and react to new information that is emerging on their potential adverse side-effects.² “In fact, recent studies suggest that alpha-blockers, 5-ARIs, and anticholinergics may negatively affect mental and psychological status, sexual function and overall health”.² Since men who choose medication therapy to address their BPH symptoms will likely need to take these BPH medications long-term, it is important for doctors and patients to discuss the potential risks and benefits before these drugs are prescribed. References:

All surgical treatments have inherent and associated side effects. Individual’s outcomes may depend on a number of factors, including but not limited to patient characteristics, disease characteristics and/or surgeon experience. The most common side effects are mild and transient and may include mild pain or difficulty when urinating, discomfort in the pelvis, blood in the urine, inability to empty the bladder or a frequent and/or urgent need to urinate, and bladder or urinary tract infection. Other risks include ejaculatory dysfunction and a low risk of injury to the urethra or rectum where the devices gain access to the body for treatment. Further, there may be other risks as in other urological surgery, such as anesthesia risk or the risk of infection, including the potential transmission of blood borne pathogens. For more information about potential side effects and risks associated with Aquablation therapy for Benign Prostatic Hyperplasia (BPH) treatment, speak with your urologist or surgeon. Prior to using our products, please review the Instructions for Use, Operator’s Manual or User Manual, as applicable, and any accompanying documentation for a complete listing of indications, contraindications, warnings, precautions and potential adverse events. No claim is made that the AquaBeam Robotic System will cure any medical condition, or entirely eliminate the diseased entity. Repeated treatment or alternative therapies may sometimes be required.

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BPH Medications and Possible Long-Term Side Effects

Possible Long-Term Side Effects of Using BPH Drugs

Dementia

Depression

Sexual Function

Miscellaneous

Important Safety Information

Benign Prostatic Hyperplasia (BPH) Signs and Symptoms

BPH Treatment Options

BPH Causes, Complications, and Who is Affected