A 64-year-old man comes to the office due to a 6-month history of difficulty urinating, with frequent straining and dribbling. His symptoms have increased over time and affect his quality of life significantly. The physician prescribes a drug that gives the patient moderate symptomatic relief. However, he also experiences a decrease in libido and impaired erectile function. Which of the following is the most likely mechanism of action of this patient's medication?

Question

A 64-year-old man comes to the office due to a 6-month history of difficulty urinating, with frequent straining and dribbling.  His symptoms have increased over time and affect his quality of life significantly.  The physician prescribes a drug that gives the patient moderate symptomatic relief.  However, he also experiences a decrease in libido and impaired erectile function.  Which of the following is the most likely mechanism of action of this patient's medication?

Quizplus · Accepted Answer

11ec160b_3baa_994d_9249_a39685e495e8_MD0001_00 This patient has benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (eg, hesitancy, dribbling). BPH is characterized by an increase in glandular volume, which obstructs urine flow in the prostatic urethra. Prostate enlargement in BPH is driven primarily by dihydrotestosterone (DHT), which is derived from testosterone by 5-alpha-reductase (5AR) in peripheral tissues. DHT has a much higher affinity than testosterone for the androgen receptor and mediates the majority of testosterone effects. 5AR inhibitors (eg, finasteride) are antiandrogen agents that reduce conversion of testosterone to DHT. In men with BPH, 5AR inhibitors induce a gradual reduction in prostate volume, improving urinary flow. However, they are associated with significant androgen-deficiency effects, including decreased libido, erectile dysfunction, and decreased ejaculate volume. In addition, the residual testosterone is available for conversion by aromatase to estradiol, leading to gynecomastia. (Choices B and C) Long-acting gonadotropin-releasing hormone (GnRH) analogues (eg, leuprolide) suppress pituitary LH secretion, leading to decreased testosterone production in Leydig cells. Steroid synthesis inhibitors (eg, ketoconazole) directly reduce testosterone production in the testes. However, 5AR inhibitors affect peripheral testosterone metabolism, not testosterone production. (Choice D) Aromatase inhibitors (eg, anastrozole) decrease conversion of androgens to the corresponding estrogens and are primarily used in treatment of hormone receptor-positive breast cancer in women. These agents are not used for BPH. (Choice E) The interaction of testosterone and DHT with the androgen receptor is inhibited by flutamide and spironolactone. These agents have significant feminizing effects (eg, gynecomastia) and are not used in BPH. (Choice F) The androgen receptor primarily acts as a DNA-binding transcription factor and does not require second messenger action. 5AR inhibitors do not have a significant effect on second messenger systems. Educational objective: 5-alpha-reductase inhibitors (eg, finasteride) reduce conversion of testosterone to dihydrotestosterone. In men with benign prostatic hyperplasia, these agents reduce prostate volume and alleviate obstruction of urinary flow. However, they are associated with androgen-deficiency effects, including decreased libido, erectile dysfunction, and decreased ejaculate volume.

A 64-Year-Old Man Comes to the Office Due to a 6-Month