A 65-year-old man with benign prostatic hyperplasia comes to the office for a follow-up appointment. He has a history of obstructive urinary symptoms that were unrelieved with tamsulosin, and a new medication was prescribed at his last visit 8 months ago. Since starting the new medication, the patient has experienced gradual improvement in urinary hesitancy and strength of urinary stream. However, he also has noticed a significant increase in the size of his breasts. The patient reports no pain or changes in weight. Glandular tissue, approximately 2 cm in diameter, is palpated under the nipples and is mildly tender to palpation. There is no nipple discharge, breast asymmetry, or rash. This patient's breast findings are most likely due to which of the following drug effects?

Question

A 65-year-old man with benign prostatic hyperplasia comes to the office for a follow-up appointment.  He has a history of obstructive urinary symptoms that were unrelieved with tamsulosin, and a new medication was prescribed at his last visit 8 months ago.  Since starting the new medication, the patient has experienced gradual improvement in urinary hesitancy and strength of urinary stream.  However, he also has noticed a significant increase in the size of his breasts.  The patient reports no pain or changes in weight.  Glandular tissue, approximately 2 cm in diameter, is palpated under the nipples and is mildly tender to palpation.  There is no nipple discharge, breast asymmetry, or rash.  This patient's breast findings are most likely due to which of the following drug effects?

Quizplus · Accepted Answer

11ec160b_3ab7_fc1b_9249_35f9fd5c5774_MD0001_00 Gynecomastia is the abnormal development of glandular breast tissue in males. It is characterized by ductal epithelial hyperplasia with fibrosis of the surrounding stroma. Breast growth is inhibited by androgens and promoted by estrogens; conditions that cause increased estrogen/androgen ratio can lead to gynecomastia. This patient, who did not respond to first-line therapy (ie, tamsulosin, an alpha-adrenergic antagonist) for benign prostatic hyperplasia, has likely been prescribed a 5-alpha reductase inhibitor (eg, finasteride, dutasteride). These medications block conversion of testosterone to dihydrotestosterone, which has a higher affinity for the testosterone receptor and mediates most testosterone effects (including prostatic hyperplasia). However, the excess testosterone is then converted to estrogen (eg, estradiol) by aromatase in various tissues (eg, adipose, bone), leading to gynecomastia. Both the beneficial effects and potential gynecomastia of 5-alpha reductase inhibitors develop slowly and are generally not apparent in the first several months of therapy. (Choice A) Androgen receptor antagonists (eg, flutamide, bicalutamide) are competitive inhibitors that block the binding of androgens in target tissues; these agents are widely used in metastatic prostate cancer but not for treating BPH. (Choices B and C) Ketoconazole is an antifungal agent that inhibits enzymes in the steroid hormone biosynthetic pathway, reducing testosterone synthesis. Spironolactone is an aldosterone receptor antagonist that also decreases testosterone synthesis in addition to cross-inhibition of the androgen receptor. Both drugs also can displace estrogen from plasma binding proteins and raise free estrogen levels, but neither is used in BPH. (Choice E) Pituitary prolactin secretion is under negative regulation by dopamine. Dopamine receptor antagonists (eg, antipsychotic medications) facilitate increased prolactin release and can occasionally cause galactorrhea. The resulting hyperprolactinemia can also suppress release of FSH and LH, leading to central hypogonadism (and rarely gynecomastia). Educational objective: 5-alpha reductase inhibitors (eg, finasteride, dutasteride) are used in the treatment of benign prostatic hyperplasia. They block the conversion of testosterone to dihydrotestosterone; the excess testosterone is then available for conversion to estrogens (eg, estradiol) by aromatase, which can lead to gynecomastia. __________ References: Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia. (http://www.ncbi.nlm.nih.gov/pubmed/28228662)

A 65-Year-Old Man with Benign Prostatic Hyperplasia Comes to the Office