Pharmacology of Androgens (Exam 1) Flashcards
GnRH is released by the ______, which stimulates release of _____ and _____ from the ant. pituitary.
Hypothalamus
LH and FSH
LH stimulates ____ cells to produce testosterone.
Leydig cells
Testosterone promotes production of _____ by sertolli cells.
Sperm
Testosterone is converted to DHT by?
5 alpha reductase
Testosterone is converted to estradiol by?
aromatase
Testosterone and DHT work on what receptors?
Androgen receptors
Estradiol works on what receptors?
Estrogen receptors
Testosterone is the most important androgen in _____ and _____.
Muscle and liver
Testosterone levels peak at what time?
8-10 am
Normal testosterone levels are between ____ and ____ at their peak.
500-700 ng/dl
Hypogonadism is marked by testosterone levels of _____.
<200ng/dl
DHT is the predominant androgen in ____ and _____.
Prostate and reproductive tissue.
T/F? DHT can be converted to estradiol by aromatase.
False - only testosterone is the only substrate for aromatase.
The most significant action mediated by estrogen receptors occurs in ______.
Bone
What are the clinical uses for androgens?
Hypogonadal men/boys
Osteoporosis
Muscle wasting in AIDS pts
Hormone replacement therapy in aging men
What are symptoms of androgen deficiency?
Low libido
Low bone mineral density
Gynecomastia
T/F? Testosterone can help treat impaired spermatogenesis.
False - Testosterone suppression of gonadotropin secretion would further impair spermatogenesis
What should be recommended to patients with low normal T levels?
Diet, lifestyle changes, and weight loss
IM dosing of testosterone provides what benefits?
Drawbacks?
Less frequent injections but higher fluctuation in T levels.
Oral testosterone is hardly ever used do to what side effects?
Hepatic side effects
What adverse effect of a testosterone patch requires discontinuance in up to 1/3 of patients trying the patch?
Severe skin rash
List the adverse effects of testosterone.
Decreased HDL and increased LDL
Hypomania (roid rage)
Cardiovascular risks
T/F? All anabolic hormones also have androgenic side effects.
True
Pulsatile administration of GnRH ______ (increases/decreases) LH and FSH release.
Continuous administration of GnRH _______ LH and FSH release.
Increases
Blocks
Targets for Anti-Androgen drug action include?
GnRH receptors
CYP17 (testosterone synthesis)
5 alpha reductase
Androgen receptors
Give an example of a CYP17 inhibitor.
Ketoconazole
Give an example of a 5 alpha reductase inhibitor.
Finasteride
Give an example of an androgen receptor inhibitor.
Flutamide
Spironolactone
List the clinical uses of anti-androgens.
BPH
Androgenic alopecia
Prostate cancer
Hirsutism of polycystic ovarian syndrome
List 3 alpha blockers for BPH treatment.
Tamsulosin (flomax) - uroselective
Silodosin (rapaflo) - uroselective
Doxazosin - non selective.
Common side effect of alpha blockers?
Orthostatic hypotension
For BPH patients who cannot tolerate alpha blockers, what medications would you recommend?
5 alpha reductase inhibitors
FInasteride
Dutasteride
Adverse effects of 5 alpha reductase inhibitors?
decreased libido
ejaculatory or erectile dysfunction
weakness
What oral medication is available for treatment for androgenic alopecia?
Finasteride
Is there a difference in dose of finasteride for treatment of BPH vs androgenic alopecia?
Yes
BPH - 1mg
Androgenic alopecia - 5mg
What topical medication is available for androgenic alopecia?
Minoxidil (Rogaine)
What class of medications used to treat prostate cancer is associated with an initial flare of bone pain and urinary tract symptoms?
GnRH agonists
What medications are examples of GnRH agonists used to treat prostate cancer?
Leuprolide (Lupron)
Histrelin (Supprelin)
What is the preferred androgen receptor blocker used for prostate cancer?
Bicalutamide
Role of bicalutamide in prostate cancer?
Reduces flare symptoms
When are GnRH antagonists indicated for prostate cancer?
Advanced prostate cancer
T/F? GnRH antagonists are associated with flare symptoms.
False
First line treatment for hirsutism of PCOS?
Combined oral contraceptive.
Your patient you are treating for hirsutism of PCOS has had a suboptimal response to a COC. What medication would you consider adding?
Spironolactone