Androgens

Question 1

Testosterone synthesized where?

Can also be synthesized?

Answer 1

Leydig cells of testes, and in ovaries

in peripheral tissues and testes from low potency androgens from the adrenal cortex

Question 2

HPG Axis

Answer 2

Hypothalamus releases GnRH

GnRH acts on Pituitary to release gonadotropes LH AND FSH

LH acts on Leydig cells to produce TESTOSTERONE

FSH acts on Sertoli cell to produce ABP and INHIBIN

Testosterone negative feedback inhibits hypothalamic release of GnRH

Inhibin negative feedback on pituitary gonadotropes release

Question 3

Prominent pathway of testosterone synthesis in human testis

Answer 3

Cholesterol to pregnenolone (cholesterol desmolase)

Pregnenolone to 17-a-pregnenolone (17-a hydroxylase)

17-a-pregnenolone to DHEA (17-a-hydroxylase)

DHEA to Androstenedione (3-beta-HSD)

Androstenedione to Testosterone (17-BETA-hydroxylase)

Testosterone to Dihydrotestosterone (5-a-reductase) in some tissues

Question 4

Forms of testosterone in the blood

Answer 4

albumin bound - physiologically active

SHBG bound - not physiologically active

Free

Question 5

Testosterone MOA (3 paths)

Answer 5

Testosterone
Estradiol
DHT

All act on respective receptor to pass into nucleus

Then bind respective receptors again to ALTER TRANSCRIPTION

Question 6

Androgen effects on skeleton

Answer 6

reduces bone reabsorption, enhances formation

estradiol facilitates closure of growth plates at puberty

Question 7

Androgen general effects

Answer 7

increases resting metabolic rate

inhibits lipid accumulation

lower blood glucose

Question 8

Androgen effects on RBC’s

Answer 8

increases EPO

Question 9

Androgen effects on muscle

Answer 9

increase protein synthesis, inhibits protein breakdown

Question 10

Primary hypogonadism

Answer 10

loss of negative feedback causes HYPERGONADOTROPIC HYPOGONADISM

Cryptorchidism
Klinefelter
Medications

Question 11

Secondary hypogonadism causes

Answer 11

hypothalamus/pituitary
morbid obesity
decrease in gonadotropins
low testosterone with low LH and FSH

Question 12

Therapeutic androgen preps and route of admin

Answer 12

Methyltestosterone - oral/sublingual

Testosterone enanthate - intramuscular

Testosterone - transdermal, topical

Question 13

Testosterone esters (1)

Used for

Characteristics

Answer 13

Testosterone enanthate

Replacement in hypogonadal men

longer duration, slower metabolism

Question 14

17-alkylated derivatives (1)

characteristics

Answer 14

methyltestosterone

significantly slower liver metabolism

liver toxicity and hepatic cancer

Question 15

Therapeutic Uses of anti-androgens

Answer 15

hirsutism in females

precocious puberty
BPH
Prostate cancer
Alopecia

Question 16

4 types of anti-androgens

Answer 16

Androgen receptor inhibitor
GnRH agonists
GnRH antagonists
Steroid synthesis inhibitors

Question 17

Non-steroidal anti-androgens (3)

MOA

Answer 17

Flutamide, Bicalutamide, Enzalutamide

competiive ANTAGONIST AT ANDROGEN RECEPTOR

prostate cancer

mild gynecomastia, reversible liver toxicity

Question 18

Enzalutamide important differences

Answer 18

ADDITIONAL EFFECTS

inhibits nuclear translocation of AR

blocks DNA binding

Blocks co-activator recruitment

Question 19

GnRH Receptor Agonists (2)

MOA

Answer 19

Leuprolide, Goserelin

initially INCREASES LH AND TESTOSTERONE PRODUCTION

OVER TIME LEADS TO DESENSITIZATION AND DOWN-REGULATION OF GnRH receptors on pituitary gonadotropes

Question 20

Side Effects of GnRH Agonists

Answer 20

sexual dysfunction

bone mineral density loss

anemia

fatigue

prostate cancer growth

Question 21

GnRH Receptor Antagonists

Answer 21

Degarelix

BLOCKS RECEPTOR

faster onset
no LH/Testosterone surge

Question 22

Androgen Biosynthetic inhibitor

Answer 22

ABIRATERONE

BLOCKS 17-ALPHA-HYDROXYLASE

metastatic prostate cancer

combo with prednisone

adrenal insufficiency, hepatic toxicity, HTN, hypokalemia, fluid retention

Question 23

5-alpha reductase inhibitors (2)

clinical

adverse

Answer 23

finasteride, dutasteride

BPH, androgenic alopecia

reduce overall cases of prostate cancer, but increase grades of prostate cancer, impotence, gynecomastia, lowers PSA levels

Question 24

major causes of erectile dysfunction (2)

name some others

Answer 24

vasculogenic
drug-induced

psychogenic, neurogenic, hormonal

Question 25

PDE5 INhibitors (3)

adverse effects

Answer 25

Sildenafil, Vardenafil, Tadalafil

serious cardiac effects, dangerously low BP with nitrates, priapism