Benign Prostatic Hyperplasia and the Medication Management of Associated Lower Urinary Tract Symptoms

Emily L. Knezevich, PharmD, BCPS, CDE; Jon T. Knezevich, PharmD, BCPS; Mikayla L. Spangler, PharmD, BCPS

Disclosures

US Pharmacist 

In This Article

5-alpha-reductase Inhibitors

The 5-alpha-reductase inhibitor class has been shown to improve LUTS in the presence of BPH.[4] Two drugs currently available within this class are finasteride and dutasteride (Table 2). These medications differ in the extent that they are able to block the 5-alpha-reducatase conversion of testosterone to dihydrotestosterone (DHT) within the body. By inhibiting the formation of DHT, 5-alpha-reducatase inhibitors are able to mitigate the effects that androgens have on the prostate. Androgenic effects include proliferation of prostate cells, decrease in prostate cell apoptosis, and elevation of rate of angio-genesis within the prostate.[3] Finasteride works solely on the 5-alpha-reductase type II enzyme by inhibiting about 70% of the conversion of testosterone to DHT within the body, while dutasteride has been shown to inhibit both 5-alpha-reductase type I and type II, preventing 95% conversion of testosterone to DHT.[4] As a result of the high prevalence of 5-alpha-reductase type II enzymes present within the prostate and genital tissue, any clinical benefits seen from dutasteride's inhibition of both 5-alpha-reductase enzymes have not been evident. However, no comparative trials have been reported.[20]

Meta-analyses have demonstrated an improved IPSS and peak urinary flow rate in patients who have prostate volumes ≥30 mL upon initiating therapy.[21] Individuals with lower prostate volumes have not shown statistically significant improvement in their symptom scores or peak urinary flow rates and will most likely not benefit from a 5-alpha-reductase inhibitor.[21] Additionally, when using an agent in this class, if prostate specific antigen (PSA) levels are monitored for the detection of prostate cancer, one must understand that 5-alpha-reductase inhibitors typically decrease a patient's PSA by about 50%.[4] Because of delayed prostatic response to this class of medications, after 3 to 6 months of therapy practitioners should double the PSA level drawn if a patient is on a 5-alphareductase inhibitor in order to appropriately assess the patient's true level.[2] If PSA levels increase or do not follow this trend, further urologic workup is warranted.[4] In addition, dutasteride dosage reductions may be warranted in patients concurrently taking CYP3A4 and CYP3A5 inhibitors.[22]

It should also be noted that 5-alpha-reductase inhibitors differ in their reported length of activity, with finasteride's half-life estimated to be around 6 to 8 hours while dutasteride's is estimated to be 5 weeks.[20] Appropriate treatment duration of at least 6 months should be allowed before a response is evaluated. Clinically important adverse effects in this class are decreased libido, decreased semen quantity during ejaculation, and impotence.[21] Furthermore, gynecomastia is reported as a potential, though infrequent, adverse event. Finally, it should be noted that all adverse effects have been shown to diminish after the first year of treatment.[20]

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