Hormonal Therapy for Prostate Cancer Flashcards
Clinical Vignette: A 58-year-old male with prostate cancer undergoes castration as a part of his treatment. Which androgen is insufficient to maintain prostate epithelium in castrated men?
Options:
A. Testosterone
B. Dihydrotestosterone
C. Androstenedione
D. Dehydroepiandrosterone
Correct Answer: D. Dehydroepiandrosterone
Explanation:
A: Testosterone, produced mainly by the testes, is one of the potent androgens that maintains prostate epithelium. It’s not the answer.
B: Dihydrotestosterone (DHT) is converted from testosterone and has a potency between 160-190, making it quite effective in maintaining prostate epithelium.
C: Androstenedione, although weaker compared to testosterone, still has a relative potency of 39, which isn’t insufficient for maintaining the prostate epithelium.
D: Dehydroepiandrosterone (DHEA) is produced in the adrenal glands and has a relative potency of just 15, making it insufficient for maintaining prostate epithelium in castrated men, according to Walsh and Siiteri, 1975.
Memory Tool: “D-Efficient: DHEA is deficient for the prostate.”
Reference: Paragraph 2, Walsh and Siiteri, 1975.
Rationale for Question: The importance of knowing the relative potency and sources of different androgens is crucial for understanding the pathophysiology and treatment options for conditions like prostate cancer.
Clinical Vignette: A 35-year-old male athlete is seeking advice to improve his muscle performance. Which enzyme converts testosterone to DHT, potentially affecting muscle tissue?
Options:
A. Aromatase
B. 5α-reductase
C. Cytochrome P450
D. Lactase
Correct Answer: B. 5α-reductase
Explanation:
A: Aromatase converts androgens to estrogens and is not involved in converting testosterone to DHT.
B: 5α-reductase is the enzyme that converts testosterone to DHT. DHT is even more potent than testosterone and can affect tissues like muscles that express androgen receptors.
C: Cytochrome P450 is involved in the metabolism of various substances but not in the specific conversion of testosterone to DHT.
D: Lactase is an enzyme that breaks down lactose and is unrelated to androgen conversion.
Memory Tool: “5α-Reds lift: 5α-reductase helps muscles get a lift from DHT.”
Reference: Paragraph 1, Montgomery et al., 2008.
Rationale for Question: Understanding the role of enzymes in androgen biochemistry is essential for understanding their tissue-specific effects and can be important in cases like enhancing athletic performance or managing conditions like prostate cancer.
Clinical Vignette: A laboratory report indicates elevated levels of an androgen with the highest potency per amount produced. Which androgen is it likely to be?
Options:
A. Testosterone
B. Dihydrotestosterone
C. Androstenedione
D. Dehydroepiandrosterone
Correct Answer: B. Dihydrotestosterone
Explanation:
A: Testosterone has a relative potency of 100, and its potency per amount produced is 15.2, which is not the highest.
B: Dihydrotestosterone (DHT) has a relative potency between 160–190, and its potency per amount produced is 533–633, making it the most potent per amount produced.
C: Androstenedione has a relative potency of 39, and its potency per amount produced is 27.9, which is not the highest.
D: Dehydroepiandrosterone (DHEA) has a relative potency of 15, and its potency per amount produced is 0.5, which is the lowest.
Memory Tool: “DHT: ‘D’ for Dominant in potency.”
Reference: Table 161.2
Rationale for Question: This question emphasizes the need to understand the potency per amount produced for different androgens, which can be critical in diagnosis and treatment planning.
Clinical Vignette: A 44-year-old male has recently been diagnosed with prostate cancer. A biopsy shows elevated androgen receptors (AR) in his prostate cells. What is the function of AR when engaged by DHT?
Options:
A. Converts DHT back to testosterone
B. Translocates into the nucleus to regulate gene expression
C. Increases the expression of 5α-reductase
D. Exits the cell to bind with circulating androgens
Correct Answer: B. Translocates into the nucleus to regulate gene expression
Explanation:
A: Conversion of DHT back to testosterone is not a function of AR.
B: When engaged by DHT, AR translocates into the nucleus, where it binds with androgen response elements (AREs) in gene promoters to regulate gene expression.
C: AR itself doesn’t increase the expression of 5α-reductase; it regulates genes once it’s in the nucleus.
D: AR does not exit the cell to bind with circulating androgens; it works within the cell nucleus.
Memory Tool: “AR Trans: AR Translocates to the Nucleus with DHT.”
Reference: Key Points, 2nd Bullet Point.
Rationale for Question: Knowing the function of AR when engaged by DHT is crucial for understanding how prostate cancer cells might behave.
Clinical Vignette: A research team is studying muscle cells to determine how they respond to androgens. What enzyme should they focus on that converts testosterone to DHT in muscle cells?
Options:
A. Cytochrome P450
B. Aromatase
C. 5α-reductase
D. Amylase
Correct Answer: C. 5α-reductase
Explanation:
A: Cytochrome P450 is a general enzyme involved in the metabolism of various substances but is not specific for the conversion of testosterone to DHT.
B: Aromatase converts androgens to estrogens; it doesn’t convert testosterone to DHT.
C: 5α-reductase is the enzyme that converts testosterone to DHT, and cells like muscle cells that are responsive to testosterone express this enzyme.
D: Amylase is involved in carbohydrate metabolism and is not relevant to androgen biochemistry.
Memory Tool: “Muscle Memory: Remember 5α-reductase for muscles.”
Reference: Paragraph 1 and Key Points, 1st Bullet Point.
Rationale for Question: Understanding which enzymes are involved in specific tissues, like muscles, helps in both clinical and research settings.
Clinical Vignette: A 55-year-old woman with adrenal tumors has an imbalance of androgens. Which adrenal androgen has the lowest relative potency per amount produced?
Options:
A. Androstenedione
B. Dehydroepiandrosterone
C. Dihydrotestosterone
D. Testosterone
Correct Answer: B. Dehydroepiandrosterone
Explanation:
A: Androstenedione has a relative potency of 39 and a potency per amount produced of 27.9, which isn’t the lowest.
B: Dehydroepiandrosterone (DHEA) has a relative potency of 15 and a potency per amount produced of 0.5, making it the lowest in relative potency per amount produced.
C: Dihydrotestosterone is not produced by the adrenal glands.
D: Testosterone is not exclusively produced by the adrenal glands.
Memory Tool: “Low DHEA: DHEA has the lowest punch per pinch.”
Reference: Table 161.2
Rationale for Question: Understanding the potency of adrenal androgens is crucial for managing conditions like adrenal tumors.
Clinical Vignette: A 29-year-old male bodybuilder is considering androgen supplementation. Which cells are primed to respond to testosterone?
Options:
A. Liver cells
B. Prostate and muscle cells
C. Neurons
D. Kidney cells
Correct Answer: B. Prostate and muscle cells
Explanation:
A: Liver cells are involved in metabolism but are not specifically primed to respond to testosterone.
B: Prostate and muscle cells express AR and the enzyme 5α-reductase, making them primed to respond to testosterone.
C: Neurons are not specifically primed to respond to testosterone.
D: Kidney cells are more involved in filtration and electrolyte balance and are not specifically primed to respond to testosterone.
Memory Tool: “Pro-Muscle: Prostate and Muscle are Pro-Testosterone.”
Reference: Paragraph 1.
Rationale for Question: Understanding which cells are responsive to androgens like testosterone is important for targeting interventions, like androgen supplementation.
Clinical Vignette: A 63-year-old man is diagnosed with advanced prostate cancer, and genomic analysis shows altered androgen response elements (AREs). What is the role of AREs in androgen action?
Options:
A. Convert DHT back to testosterone
B. Regulate gene expression when bound by AR
C. Act as an external ligand for AR
D. Facilitate the export of AR from the nucleus
Correct Answer: B. Regulate gene expression when bound by AR
Explanation:
A: Conversion of DHT back to testosterone is not the role of AREs.
B: AREs are bound by AR in the nucleus, which then regulates gene expression.
C: AREs are not external ligands for AR; they act as gene promoters.
D: AREs don’t facilitate the export of AR; they are involved in gene regulation within the nucleus.
Memory Tool: “A-REady to Regulate: AREs are ready to regulate genes when bound by AR.”
Reference: Key Points, 2nd Bullet Point.
Rationale for Question: Understanding the genetic mechanisms by which androgens exert their effects is crucial, especially in conditions like advanced prostate cancer where genomic alterations could play a role.
Clinical Vignette: A 68-year-old male patient with metastatic prostate cancer is being considered for hormonal therapy. You opt for a GnRH agonist.
Multiple-Choice Options:
A. Triptorelin
B. Ketoconazole
C. Flutamide
D. Enzalutamide
Correct Answer: A. Triptorelin
In-Depth Explanation:
A: Triptorelin is a GnRH agonist that stimulates the release of LH from the pituitary gland. It is the mainstay of therapy for metastatic prostate cancer (Paragraph 1).
B: Ketoconazole is an adrenal-targeting drug, not a GnRH agonist (Paragraph 3).
C: Flutamide is a first-generation AR antagonist, not a GnRH agonist (Paragraph 5).
D: Enzalutamide is a second-generation AR antagonist, not a GnRH agonist (Paragraph 7).
Memory Tool: “Tri” as in “Triple action” for LH release, decrease in LH production, and treatment of metastatic disease.
Reference Citation: Table 161.1, Paragraph 1.
Rationale: GnRH agonists like Triptorelin are foundational for managing metastatic prostate cancer. Understanding their role is essential for board exams and patient care.
Clinical Vignette: You prescribe a GnRH antagonist to a 65-year-old patient to treat his prostate cancer. What side effect should you specifically caution him about?
Multiple-Choice Options:
A. Gynecomastia
B. Increased FSH levels
C. Fatigue
D. Considerable side effects
Correct Answer: D. Considerable side effects
In-Depth Explanation:
A: Gynecomastia is associated with first-generation AR antagonists like Flutamide (Paragraph 5).
B: Increased FSH levels are associated with GnRH agonists like Leuprolide (Paragraph 1).
C: Fatigue is associated with second-generation AR antagonists like Enzalutamide (Paragraph 7).
D: Considerable side effects are associated with both GnRH agonists and antagonists (Paragraph 2).
Memory Tool: “Antagonists are Antagonistic” - they have considerable side effects.
Reference Citation: Table 161.1, Paragraph 2.
Rationale: Knowing the range of side effects for different hormonal interventions is crucial for patient safety and effective treatment.
Clinical Vignette: A 70-year-old male with hypertension is under your care for prostate cancer treatment. You’re considering an adrenal-targeting drug. Which side effect should you monitor?
Multiple-Choice Options:
A. Hypertension
B. Gynecomastia
C. Decreased appetite
D. Increased FSH levels
Correct Answer: A. Hypertension
In-Depth Explanation:
A: Hypertension is a side effect of adrenal-targeting drugs like Ketoconazole (Paragraph 3).
B: Gynecomastia is associated with first-generation AR antagonists (Paragraph 5).
C: Decreased appetite is a side effect of second-generation AR antagonists (Paragraph 7).
D: Increased FSH levels are associated with GnRH agonists (Paragraph 1).
Memory Tool: “Adrenaline Rush” for Adrenal-targeting drugs elevating blood pressure.
Reference Citation: Table 161.1, Paragraph 3.
Rationale: Being aware of drug-specific side effects, especially when a patient already has a comorbidity like hypertension, is essential for quality care.
Clinical Vignette: A patient is recommended a GnRH antagonist as part of prostate cancer therapy. How do these agents typically work?
Multiple-Choice Options:
A. Stimulate release of LH
B. Bind to receptors and block release of GnRH
C. Decrease androgen production from steroid precursors
D. Inhibit the conversion of testosterone to DHT
Correct Answer: B. Bind to receptors and block release of GnRH
In-Depth Explanation:
A: Stimulate release of LH is a mechanism of GnRH agonists (Paragraph 1).
B: Bind to receptors and block release of GnRH is the specific mechanism for GnRH antagonists like Degarelix (Paragraph 2).
C: Decrease androgen production from steroid precursors is the mechanism of adrenal-targeting drugs (Paragraph 3).
D: Inhibit the conversion of testosterone to DHT is the mechanism of 5α-Reductase inhibitors (Paragraph 7).
Memory Tool: Antagonists “Block and Lock” GnRH.
Reference Citation: Table 161.1, Paragraph 2.
Rationale: Understanding the exact mechanism of action for different drug classes is critical for appropriate prescription and patient care.
Clinical Vignette: A 50-year-old patient comes to your clinic with symptoms of gynecomastia. You find out he is on a drug for prostate cancer. What is he most likely taking?
Multiple-Choice Options:
A. Ketoconazole
B. Leuprolide
C. Flutamide
D. Enzalutamide
Correct Answer: C. Flutamide
In-Depth Explanation:
A: Ketoconazole is an adrenal-targeting drug (Paragraph 3).
B: Leuprolide is a GnRH agonist (Paragraph 1).
C: Flutamide is a first-generation AR antagonist, associated with gynecomastia (Paragraph 5).
D: Enzalutamide is a second-generation AR antagonist (Paragraph 7).
Memory Tool: “First-gen, First problem” to remember that the first-gen AR antagonists cause gynecomastia.
Reference Citation: Table 161.1, Paragraph 5.
Rationale: Recognizing drug-related side effects is key for differential diagnosis and subsequent management.
Clinical Vignette: You are considering prescribing a 5α-Reductase inhibitor for a patient’s BPH. Where is the primary site of action for this class of drugs?
Multiple-Choice Options:
A. Pituitary gland
B. Adrenal gland
C. Prostate
D. Prostate cancer
Correct Answer: C. Prostate
In-Depth Explanation:
A: Pituitary gland is the site of action for GnRH agonists and antagonists (Paragraph 1, 2).
B: Adrenal gland is the site of action for adrenal-targeting drugs (Paragraph 3).
C: Prostate is the primary site of action for 5α-Reductase inhibitors like Finasteride (Paragraph 7).
D: Prostate cancer is not the primary site for 5α-Reductase inhibitors; they are not indicated for prostate cancer management (Paragraph 7).
Memory Tool: 5α-Reductase inhibitors: “Five-Star Pro-state Agents.”
Reference Citation: Table 161.1, Paragraph 7.
Rationale: Knowing the site of action for drugs, especially when not indicated for cancer, is essential to avoid therapeutic missteps.
Clinical Vignette: A 60-year-old male patient with prostate cancer complains of fatigue and frequent falls after starting a new medication. What drug is he likely taking?
Multiple-Choice Options:
A. Ketoconazole
B. Abarelix
C. Flutamide
D. Enzalutamide
Correct Answer: D. Enzalutamide
In-Depth Explanation:
A: Ketoconazole is an adrenal-targeting drug associated with hypertension, not fatigue or falls (Paragraph 3).
B: Abarelix is a GnRH antagonist, not linked to falls or fatigue (Paragraph 2).
C: Flutamide is a first-generation AR antagonist mainly associated with gynecomastia (Paragraph 5).
D: Enzalutamide is a second-generation AR antagonist associated with falls and fatigue (Paragraph 7).
Memory Tool: “Second-Gen, Second Wind” to remember that second-generation AR antagonists can lead to fatigue.
Reference Citation: Table 161.1, Paragraph 7.
Rationale: Side effect profiles differ among drug classes, and recognizing this can inform patient care and symptom management.
Clinical Vignette: A patient with prostate cancer is prescribed a medication that acts by inhibiting cytochrome P450 enzymes. Which class of drugs does this medication belong to?
Multiple-Choice Options:
A. GnRH agonists
B. GnRH antagonists
C. Adrenal-targeting drugs
D. Second-generation AR antagonists
Correct Answer: C. Adrenal-targeting drugs
In-Depth Explanation:
A: GnRH agonists act by stimulating the release of LH (Paragraph 1).
B: GnRH antagonists bind to receptors and block the release of GnRH (Paragraph 2).
C: Adrenal-targeting drugs act by blocking cytochrome P450 enzymes to decrease androgen production (Paragraph 3).
D: Second-generation AR antagonists block AR and diminish AR-mediated transcription (Paragraph 7).
Memory Tool: “Adrenaline Drop” to remember that adrenal-targeting drugs drop androgen levels by inhibiting enzymes.
Reference Citation: Table 161.1, Paragraph 3.
Rationale: Knowing the mechanisms of different drug classes can help guide appropriate medication choices and improve patient outcomes.
Clinical Vignette: You have a 55-year-old male patient with benign prostatic hyperplasia (BPH). Which class of drug could be administered for his condition?
Multiple-Choice Options:
A. GnRH agonists
B. First-generation AR antagonists
C. Adrenal-targeting drugs
D. 5α-Reductase inhibitors
orrect Answer: D. 5α-Reductase inhibitors
In-Depth Explanation:
A: GnRH agonists are primarily indicated for metastatic prostate cancer, not BPH (Paragraph 1).
B: First-generation AR antagonists are not indicated as monotherapy (Paragraph 5).
C: Adrenal-targeting drugs mainly treat prostate cancer (Paragraph 3).
D: 5α-Reductase inhibitors like Finasteride are commonly administered for BPH (Paragraph 7).
Memory Tool: “5α for 55” to remember that 5α-Reductase inhibitors can be used for a 55-year-old patient with BPH.
Reference Citation: Table 161.1, Paragraph 7.
Rationale: Tailoring drug prescriptions to specific conditions like BPH is crucial for optimal treatment.
Clinical Vignette: A patient with prostate cancer reports hypertension, edema, and hypokalemia after starting a new medication. What class of drugs could be causing these side effects?
Multiple-Choice Options:
A. GnRH agonists
B. GnRH antagonists
C. Adrenal-targeting drugs
D. Second-generation AR antagonists
Correct Answer: C. Adrenal-targeting drugs
In-Depth Explanation:
A: GnRH agonists are associated with considerable side effects but not specifically hypertension, edema, and hypokalemia (Paragraph 1).
B: GnRH antagonists also have considerable side effects, but not these specific ones (Paragraph 2).
C: Adrenal-targeting drugs like Ketoconazole and Abiraterone can lead to hypertension, edema, and hypokalemia (Paragraph 3).
D: Second-generation AR antagonists are mainly associated with falls, fatigue, and decreased appetite (Paragraph 7).
Memory Tool: “Adrenal Ailments: H-E-H” for Hypertension, Edema, Hypokalemia.
Reference Citation: Table 161.1, Paragraph 3.
Rationale: Being aware of the side-effect profiles of each class of drugs is essential for correct diagnosis and patient management.
Clinical Vignette: A 67-year-old male is being treated for metastatic prostate cancer. He’s given a medication that ultimately decreases LH production. What class of drugs has he likely been prescribed?
Multiple-Choice Options:
A. GnRH agonists
B. GnRH antagonists
C. Adrenal-targeting drugs
D. 5α-Reductase inhibitors
Correct Answer: A. GnRH agonists
In-Depth Explanation:
A: GnRH agonists like Leuprolide stimulate the release of LH initially but then ultimately decrease LH production (Paragraph 1).
B: GnRH antagonists bind to receptors and block the release of GnRH (Paragraph 2).
C: Adrenal-targeting drugs act by inhibiting cytochrome P450 enzymes (Paragraph 3).
D: 5α-Reductase inhibitors inhibit the conversion of testosterone to DHT (Paragraph 7).
Memory Tool: “Agonists Act, Then Attract Less” to remember that GnRH agonists initially act by releasing LH, then reduce it.
Reference Citation: Table 161.1, Paragraph 1.
Rationale: Differentiating drug classes by their mechanisms is crucial, especially for conditions like metastatic cancer where specific interventions are needed.
Clinical Vignette: You are considering medication options for a 49-year-old man newly diagnosed with prostate cancer. Which of the following is NOT indicated for managing his prostate cancer?
Multiple-Choice Options:
A. Leuprolide
B. Flutamide
C. Finasteride
D. Enzalutamide
Correct Answer: C. Finasteride
In-Depth Explanation:
A: Leuprolide is a GnRH agonist indicated for metastatic prostate cancer (Paragraph 1).
B: Flutamide is a first-generation AR antagonist used for prostate cancer, though not as monotherapy (Paragraph 5).
C: Finasteride is a 5α-Reductase inhibitor and is not indicated for prostate cancer management (Paragraph 7).
D: Enzalutamide is a second-generation AR antagonist used for prostate cancer (Paragraph 7).
Memory Tool: “Fine, No Cancer” to remember that Finasteride is not fine for treating prostate cancer.
Reference Citation: Table 161.1, Paragraph 7.
Rationale: Knowing what NOT to prescribe is just as important as knowing what to prescribe for effective patient care.
Clinical Vignette: A 72-year-old male is diagnosed with metastatic prostate cancer. What is considered the mainstay of therapy for his condition?
Multiple-Choice Options:
A. GnRH agonists
B. GnRH antagonists
C. Adrenal-targeting drugs
D. First-generation AR antagonists
Correct Answer: A. GnRH agonists
In-Depth Explanation:
A: GnRH agonists like Leuprolide and Goserelin are considered the mainstay of therapy for metastatic prostate cancer (Paragraph 1).
B: GnRH antagonists, while effective, are not considered the mainstay of therapy for metastatic disease (Paragraph 2).
C: Adrenal-targeting drugs are not the mainstay therapy for metastatic prostate cancer (Paragraph 3).
D: First-generation AR antagonists are not considered the mainstay and are not indicated as monotherapy (Paragraph 5).
Memory Tool: “A-Gone: Metastatic Gone” to remember that GnRH agonists are the mainstay for metastatic prostate cancer.
Reference Citation: Table 161.1, Paragraph 1.
Rationale: Knowing the first-line treatment for conditions like metastatic prostate cancer is crucial for providing optimal care.
Clinical Vignette: A 58-year-old man with prostate cancer is started on a new medication to prevent a testosterone surge. Which class of drugs is he likely taking?
Multiple-Choice Options:
A. GnRH agonists
B. GnRH antagonists
C. Adrenal-targeting drugs
D. 5α-Reductase inhibitors
Correct Answer: B. GnRH antagonists
In-Depth Explanation:
A: GnRH agonists initially stimulate the release of LH and are not used to prevent a testosterone surge (Paragraph 1).
B: GnRH antagonists like Degarelix and Abarelix prevent a testosterone surge by blocking the release of GnRH (Paragraph 2).
C: Adrenal-targeting drugs inhibit cytochrome P450 enzymes and are not used for preventing testosterone surges (Paragraph 3).
D: 5α-Reductase inhibitors are not used to prevent testosterone surges; they inhibit the conversion of testosterone to DHT (Paragraph 7).
Memory Tool: “Antagonize to Neutralize Surge” to remember that GnRH antagonists prevent testosterone surges.
Reference Citation: Table 161.1, Paragraph 2.
Rationale: Accurate understanding of drug mechanisms allows you to select the appropriate medication for specific patient needs.