WBR0339

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Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [1])]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology
Sub Category SubCategory::Oncology
Prompt [[Prompt::Androstenedione, an androgen formed by theca cells and transported to granulosa cells, is converted to estrogen by the action of enzyme X under the positive hormonal effect of follicle-stimulating hormone (FSH). On enzyme X, FSH's activity is demonstrated to be time- and dose-dependent. The illustration below demonstrates the enzymatic conversion of androstenedione to estrogen. Pharmacological inhibition of enzyme X is most likely prescribed in which of the following conditions?

]]

Answer A AnswerA::Benign prostate hyperplasia (BPH)
Answer A Explanation AnswerAExp::Patients with BPH are often prescribed alpha-1-antagonists, such as tamsulosin, or 5-alpha-reductase inhibitors, such as finasteride.
Answer B AnswerB::Prostate adenocarcinoma
Answer B Explanation AnswerBExp::Anti-androgens, such as flutamide, are typically prescribed to patients with prostate adenocarcinoma.
Answer C AnswerC::Breast cancer among post-menopausal women
Answer C Explanation [[AnswerCExp::Aromatase inhibitors are often prescribed to post-menopausal women with breast cancer in order to decrease the peripheral production of estrogen.]]
Answer D AnswerD::Contraception
Answer D Explanation AnswerDExp::Hormone replacement therapy, such as progestin and estrogen, may be used for contraception.
Answer E AnswerE::Triple negative breast cancer
Answer E Explanation [[AnswerEExp::Patients with triple negative breast cancer, defined as breast cancers that do not express estrogen receptors (ER), progesterone receptors (PR), and Her2/neu, do not benefit from hormonal therapy, such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors.]]
Right Answer RightAnswer::C
Explanation [[Explanation::The enzyme described above is aromatase. FSH has a time- and dose-dependent mechanism for the activation of aromatase. In granulosa cells, aromatase is responsible for the conversion of androstenedione to estrogen. Inhibition of aromatase by pharmacological therapy (aromatase inhibitors), such as anastrozole and exemestane, is particularly beneficial for post-menopausal women with breast cancer. In these patients, inhibition of peripheral estrogen production is essential for targeted therapy.

Educational Objective: Aromatase, an enzyme stimulated by FSH, is responsible for the conversion of androstenedione to estrogen. Aromatase inhibitors, such as anastrozole and exemestane, are clinically beneficial among post-menopausal women with breast cancer.
References: First Aid 2014 page 590]]

Approved Approved::Yes
Keyword WBRKeyword::Aromatase, WBRKeyword::Aromatase inhibitor, WBRKeyword::Anastrozole, WBRKeyword::Enzyme, WBRKeyword::Enzyme X, WBRKeyword::Exemestane, WBRKeyword::Postmenopausal women, WBRKeyword::Menopause, WBRKeyword::Breast cancer, WBRKeyword::Estrogen, WBRKeyword::Androstenedione, WBRKeyword::Receptor, WBRKeyword::Granulosa cell, WBRKeyword::FSH, WBRKeyword::Hormone
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