Androgen Pharmacology

Question 1

T secretion is high in three phases of life

Answer 1

1. Fetal phase (male differentiation)
2. Neonatal phase
3. Puberty (secondary sex characteristics, spermatogenesis, anabolic effects, libido)

Question 2

Location of DHT receptors

Answer 2

Sebaceous glands, prostate, scrotum, penis, hair, and skin

Question 3

Genomic and non-genomic actions of androgens

Answer 3

Genomic: bind to nuclear androgen receptors to affect transcription of target genes

Non-genomic: intracellular ion concentration changes and membrane fluidity

Question 4

Therapeutic uses of androgens

Answer 4

1. Primary causes- Klinefelter, congenital, Leydig cell dysfunction, trauma, radiation, tumor
2. Secondary causes (hypogonadotropic hypogonadism)- pituitary dysfuntion (e.g. tumor) causing decreased release of FSH/LH
3. Tertiary causes- Hypothalamic dysfunction, extreme stress, Kallman’s syndrome
4. Post-pubertal testicular failure (low libido, prostate, and seminal vesicle regress, low semen volume, decreased bone mass)
5. Delayed puberty (age 15-17)
6. Osteoporosis (due to androgen deficiency)
7. Muscle wasting (associated with AIDS)
8. HRT in aging men (low T)– assess prostate risk before initiating therapy

Question 5

Pros and cons of HRT

Answer 5

Pros: more energy, better libido, and less mood fluctuation

Cons: may be hepatotoxic (HCC), sustained erections, decreased sperm count, testicular atrophy (decreased LH/FSH), mild gynecomastia, edema, increased LDL, polycythemia, sleep apnea, BPH, possible prostate cancer

Question 6

Name the uses, method of intake, mechanisms, and adverse effects of the following drugs:

Methyltestosterone, testosterone

Answer 6

Mechanism:

MT, T: agonist at androgen receptors; oral intake

Use: tx for hypogonadism and promote development of secondary sex characteristics; stimulate anabolism after burn or injury

Adverse effects: masculinization in females, gonadal atrophy, leukopenia, increase LDL, decrease HDL

Question 7

Other forms of testosterone

Answer 7

Testosterone enanthate (parenteral)- can cause more variation of serum T levels

Transdermal gel or patch (better at regulating serum T levels)

CHECK PSA before starting any testosterone therapy

Question 8

Use of anti-androgens

Answer 8

Prostate cancer
BPH (largely DHT driven)
Male baldness
Hirsuitism
Precocious puberty
Acne

Question 9

Name the uses, method of intake, mechanisms, and adverse effects of the following drugs:

Leuprolide (-relins: e.g. Buscerelin)

Answer 9

MOA: GnRH agonist;
Pulsatile- agonist
Continuous- antagonist properties (inhibits FSH/LH release –> decreases testosterone synthesis and secretion)

Uses: Prostate cancer, precocious puberty, uterine fibroids, infertility

Adverse effects: osteoporosis and pseudo-menopause

Notes: causes initial surge in GnRH release

Question 10

GnRH antagonist (-relix: cetrorelix)

Answer 10

MOA: Inhibits GnRH signal (therefore decreasing testosterone synthesis and secretion)

Uses: prostate CA

Notes: no initial surge of GnRH; administer by injection, IP, and IM

Question 11

Ketoconazole

Answer 11

CYP450 inhibitor (remember what AAA RACKS in GQ Magazine stands for?)

MOA: inhibits steroid synthesis (17, 20 desmolase) –> decreases testosterone synthesis

Uses: PCOS, anti-fungal

Adverse SE: gynecomastia and amenorrhea

Question 12

Finasteride

Answer 12

5 alpha reductase inhibitor

Uses: BPH, male-pattern baldness

Notes: increased risk of undetected high grade prostate cancer

Question 13

Spironolactone, Cyproterone, and Flutamide/ Biscalutamide

Answer 13

Androgen receptor inhibitor

Uses: prostate CA

Notes: flutamide/ biscalutamide given with GnRH agonist

Question 14

General side effects

Answer 14

decreased muscle strength, impotence, decreased libido, osteoporosis, gynecomastia, hot flashes and sweating