As men begin to gain more years, something strange begins to happen. Sometimes, it is that the previously simple act of urinating now takes more time, effort, and concentration than it used to. Sometimes, it is that feeling of incomplete emptying. Other times, it might be those stubborn extra drops that cling to your member and stain your underwear. These changes, more often than not, are due to benign prostatic hyperplasia.
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What is benign prostatic hyperplasia?
Table of Contents
Benign prostatic hyperplasia (BPH) is a benign disease characterized by abnormal hyperplasia of the smooth muscle and stroma cells located in the transitional zone of the prostate gland. It is one of the most common diseases of the urinary system noted to occur more frequently in middle-aged and elderly men. The disease manifests with several lower urinary tract symptoms which could be classified into voiding symptoms such as urinary hesitancy, straining, weak urine stream, etc, and storage symptoms which include; dysuria, frequency, nocturia, and urinary urgency. Other symptoms of BPH may affect sexual function and the disease could progress to complications affecting the kidneys.
It is quite important to differentiate the mass of BPH from that of prostate cancer as they sometimes might present with similar symptoms. A visit to the doctor can help identify the exact pathology being dealt with.
In the treatment of BPH, emphasis is placed on improving the quality of life of patients and preventing progression into more serious complications of the disease. Medications as well as surgery play a role in the management of BPH. The major classes of drugs used in the treatment of BPH include; Alpha-Blockers, 5 Alpha-reductase inhibitors, and Phosphodiesterase inhibitors. Over the years, the side effects of these medications such as sexual dysfunction have grown to become a major challenge in their use and several studies have explored therapeutic approaches to minimize these side effects during the treatment process.
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Mechanism of Action and Side Effects of Common BPH Medications
Alpha-Blockers
Drugs like Terazosin, Doxazosin, Tamsulosin, Alfuzosin, and Silodosin belong to this class. These drugs have been proven to be effective in achieving better urine flow in patients with BPH. They act by blocking Alpha 1a adrenergic receptors and relaxing the smooth muscles around the prostate and bladder neck. This minimizes the constriction of the urinary channel and improves urinary outflow. The side effects noticed with the use of these medications include; headaches, lightheadedness, retrograde ejaculation, and orthostatic hypotension. Alpha-blockers only improve urine flow but do not reduce the risk of acute urinary retention or the need for surgery in the future.
5 Alpha-reductase Inhibitors
Drugs in this group include; Finasteride (Proscar) and Dutasteride (Avodart). They prevent the conversion of testosterone to dihydrotestosterone by inhibiting the rate-limiting enzyme known as 5-Alpha-reductase. This results in shrinkage of the prostate and effectively slows down prostate growth. They have been found to reduce the risk of acute urinary retention and the need for BPH-related surgery in patients. Major side effects of these drugs include; decreased libido, erectile dysfunction, ejaculatory dysfunction, and depression.
Phosphodiesterase 5 Inhibitors
These include drugs like Tadalafil, Vardenafil, and Sildenafil which improve erections and smooth muscle relaxation in patients with BPH by inhibiting the degradation of PDE-5; an enzyme that promotes smooth muscle contraction.
Alpha Blockers and 5 Alpha Reductase Inhibitors Affect Sexual Function
Several studies have demonstrated a strong association between alpha-blockers, 5 ARIs, and sexual dysfunction in patients with BPH. These studies have identified retrograde ejaculation, erectile dysfunction, and decreased libido as adverse effects to expect while using drugs like Tamsulosin, Finasteride, or Dutasteride. As is to be expected, these side effects could be downright devastating for any man experiencing them.
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The link between the use of 5 ARIs and erectile dysfunction could be a result of androgen deficiency caused by the inhibition of testosterone conversion to dihydrotestosterone by 5 ARIs like Finasteride. Reduction in dihydrotestosterone production also leads to decreased libido which results in erectile dysfunction (Shin, Karna, Choi, and Park, 2019). A study that reviewed literature findings on the sexual side effects of 5 ARI therapy found an increased incidence of decreased libido, ejaculatory dysfunction, and impotence in patients who were treated with Finasteride and Dutasteride with Dutasteride showing a greater risk of sexual side effects than Finasteride (Fertig, Gamret, Darwin & Gaudi, 2017).
The association between these drugs and depression was also examined and findings suggested an increased risk for depression and suicidal ideation in patients using 5 ARIs. 5 Alpha-reductase inhibitors are believed to cause these psychiatric adverse effects by reducing androgen levels as well as the synthesis of neurosteroids believed to have antidepressant, anxiolytic, and memory-enhancing effects.
Minimizing the Side Effects of Common BPH Medications
Considering how severe the impact of the BPH medication side effects is, they could be a factor in reducing compliance with these medications. It is then important that for any progress to be made with these drugs, attempts should be made to either eliminate or at the very least drastically reduce these side effects.
Sexual side effects and depression are the most worrisome adverse effects reported by patients receiving pharmacological therapy for Benign Prostatic Hyperplasia. The little information available on the pathophysiology of these side effects remains the major obstacle to developing effective therapeutic interventions to minimize these side effects.
A number of studies have explored the possible benefits of combination therapies in improving treatment outcomes and minimizing the sexual side effects of common BPH medications like 5 ARIs and Alpha-blockers. Tadalafil; a phosphodiesterase inhibitor has been included in combination therapies and used for clinical trials. It is taken orally and acts by selectively inhibiting phosphodiesterase 5-mediated degradation of cGMP in the corpora cavernosa of the penis. This promotes smooth muscle relaxation, vasodilation, blood engorgement of the corpora cavernosa, and prolonged erection as well as improved urine outflow in patients. Several clinical trials have reported the use of Tadalafil and Finasteride as a safe and effective combination therapy that improves urinary symptoms and reduces the sexual adverse effects of pharmacological therapy in patients with BPH.
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A study carried out in 2014 in which the subjects were divided into Tadalafil/Finasteride and Placebo/Finasteride groups reported improved IPSS total scores, sexual function, and lower urinary tract symptoms in the Tadalafil/Finasteride group when compared to the Placebo/Finasteride group. several other clinical trials carried out after that have pointed out that the use of Tadalafil and Finasteride reduces the risk of sexual dysfunction in patients, reduces the risk of BPH-related surgery, and improves the overall quality of life in BPH patients (Olesovsky and Kapoor, 2016).
According to the findings of a study by Casabe et al, patients who have moderate to severe lower urinary tract symptoms, a prostate volume > 30g, and want to avoid the surgical intervention or the sexual side effects of alpha-blockers are ideal candidates for combination therapy using Tadalafil and Finasteride (Elkelany, Owen, Kim, 2015). This therapy can also be used for patients who are responding well to 5 Alpha-reductase inhibitors but with sexual dysfunction. The use of Tadalafil and Finasteride in the treatment of BPH has also been approved and is gradually overthrowing other known therapies.
How About Estrogen Levels?
At standard doses, both finasteride and dutasteride can raise estrogen levels by around 15% (possibly from 35 ng/L to 40 ng/L). For most men, this rise is of negligible significance. The odds are improved even more with Tadalafil combination therapy. Studies also show that concurrently taking a Selective Estrogen Receptor Modulator like tamoxifen can further drop the chances of developing gynecomastia. For the few men who go ahead to develop these estrogen-linked side effects, stopping the drug in most cases will reverse the side effects. This is because the inhibition from 5 ARIs is reversible and concentration-dependent. In the rare cases where these side effects do not disappear with cessation of the drugs, once again tamoxifen or aromatase inhibitors like anastrozole are very helpful in reversing the undesired changes. Aromatase inhibitors are known to cause osteoporosis, so it is advisable that you inform your doctor before you commence them.
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Conclusion
For many who are scheduled to start receiving medications for BPH, the adverse effects might be foremost on their minds. Retrograde ejaculation, erectile dysfunction, decreased libido and depression are the commonest side effects of BPH medications. They are considered a major challenge in the pharmacological treatment of the disease. In fact, many might consider this a situation where the cure is worse than the disease. It is believed that a better understanding of their pathophysiology will pave the way for the development of effective therapies to minimize these side effects and improve the quality of life of patients. In the grand scheme of events, the use of combination therapies like Tadalafil and Finasteride may be new discoveries, but they hold great promise and have demonstrated impressive results.
References
Elkelany, O., Owen, R., & Kim, E. (2015). Combination of tadalafil and finasteride for improving the symptoms of benign prostatic hyperplasia: critical appraisal and patient focus. Therapeutics and Clinical Risk Management, 11, 507-513. https://doi.org/10.2147/TCRM.S80353
Fertig, R. M., Gamret, A. C., Darwin, E., & Gaudi, S. (2017). Sexual side effects of 5-α-reductase inhibitors finasteride and dutasteride: A comprehensive review. Dermatology Online Journal, 23(11). https://doi.org/10.5070/D32311037240
Olesovsky, C., & Kapoor, A. (2016). Evidence for the efficacy and safety of tadalafil and finasteride in combination for the treatment of lower urinary tract symptoms and erectile dysfunction in men with benign prostatic hyperplasia. Therapeutic Advances in Urology. https://doi.org/10.1177/1756287216650132
Shin, Y. S., Karna, K. K., Choi, B. R., & Park, J. K. (2019). Finasteride and Erectile Dysfunction in Patients with Benign Prostatic Hyperplasia or Male Androgenetic Alopecia. World Journal of Men’s Health, 37(2), 157-165. https://doi.org/10.5534/wjmh.180029
Kunath, F., Keck, B., Antes, G. et al. Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review. BMC Med 10, 96 (2012). https://doi.org/10.1186/1741-7015-10-96
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