Androgens Flashcards
What is the indication for testosterone?
Male hypogonadism
What are the adverse effects of testosterone?
Acne Increased risk prostate cancer Increased risk BPH Worsening of sleep apnea Erythrocytosis -> increased risk VTE Increased risk CVD (vHDL, ^LDL) Hepatic dysfunction (oral derivatives) Suppression of spermatogenesis
What are the contraindications for testosterone?
Prostate cancer
High level PSA
Untreated sleep apnea
Name the 4 androgen receptor antagonists that we have to know.
Flutamide
Bicalutamide
Nilutamide
Enzalutamide (2nd gen)
“Lutamides antagonize androgens”
What is the MoA for androgen receptor antagonists?
For testosterone?
ARA: Directly inhibits action of testosterone and DHT at the AR
T: Direct agonism of AR to restore T to nl level.
What are the indications for flutamide, bicalutamide, nilutamide, and enzalutamide? (androgen-receptor antagonists)
What are they used in combination w/?
Which of them can women use, and as tx for what?
Tx of advanced prostate cancer.
Used in combination with androgen deprivation therapy (e.g. GnRH agonist/antagonist)
Flutamide also used for tx of hyperandrogenism in women (King Fish’s sister plays the flute)
What are the adverse effects of androgen receptor antagonists?
What about rare SE’s?
Men- typical effects of androgen deprivation. (e.g. sexual dysfunction, gynecomastia, vasomotor responses)
Rare side effects:
1st Gen- Hepatotoxicity
2nd Gen (Enzalutamide) - increased seizure risk
Which of the androgen-receptor antagonists is most potent?
Enzalutamide (2nd gen)
Recall: list the GnRH agonists.
What is their MoA?
Leuprolide, Goserlin, Buserelin, Triptorelin, Naferelin (Lewd Pro [Jeremy] Lin agonizes the pussy)
Sustained activation of GnRH receptor inhibits release of gonadotropins (even though they’re agonists)
What are Leuprolide, Goserlin, Buserelin, Triptorelin, Naferelin (GnRH agonists) indicated for in males?
Advanced prostate cancer
Recall, in females: Controlled ovarian stimulation.
Palliative therapy of hormone-dependent tumors.
Suppression of inappropriate growth of hormone-dependent tissues (e.g. endometriosis & fibroids).
Tx of precocious puberty.
Suppression of endogenous puberty in gender dysmorphic adolescents.
Which GnRH antagonist is used in the tx of advanced prostate cancer?
Recall: what is the MoA?
Degarelix
Antagonize GnRH receptors, reduce gonadotropin release.
What are the adverse effects of both GnRH agonists and antagonists in males?
Sexual dysfunction Osteoporosis & bone fractures Vasomotor responses (hot flashes) Loss of lean body mass & increased fat mass Fatigue Anemia (>90%) Gynecomastia Decreased penis and testicular size Emotional & cognitive changes
(basically makes you more like a woman)
Recall: what are the adverse effects of GnRH agonists and antagonists in females?
Side effects associated with gonadal hormone deprivation, e.g.: Hot flashes Decreased bone density Vaginal dryness/atrophy Erectile dysfunction.
What type of drug is abiraterone?
What is its MoA?
Therefore, what are its adverse effects?
Androgen synthesis inhibitor
Inhibition of CYP17A1. Inhibits synthesis of testosterone (also affects cortisol, but not aldosterone)
Adrenocorticol insufficiency
Mineralocorticoid excess
Indications for abiraterone?
Hormone-resistant prostate cancer not responding to androgen deprivation therapy
What is the MoA for spironolactone?
Antagonist/weak partial agonist of androgen receptor
Also mineralocorticoid receptor antagonist- used as diuretic to treat HF
What are indications for spironolactone?
Treatment of women with acne, hirsutism, or androgenic alopecia
What are the adverse affects a/w spironolactone?
Menstrual irregularities
Breast tenderness
Orthostatic hypertension
Who is contraindicated in the use of spironolactone?
Should not be used in men w/prostate cancer
Name the 2 drugs that are 5alpha-reductase inhibitors.
What does this enzyme normally convert ?(inhibited by these drugs)
Finasteride
Dutasteride
Inhibits peripheral conversion of testosterone to DHT
What are the indications for 5alpha-reductase inhibitors?
BPH
Male pattern baldness
Female hirsutism
(those w/hair loss use sterides)
What is the adverse effect a/w dutasteride and finasteride?
Male sexual dysfunction
When are 5alpha-reductase inhibitors contraindicated?
Pregnancy
