Androgens

Question 1

Regulation of testosterone synthesis

Answer 1

1) Hypothalamus releases GnRH (suppresses LH/FSH)
2) GnRH receptors + gonadotrophs bind (anterior pituitary gland releases LH + FSH)
3) LH stimulates Leydig cells in testes (Gs activated -> cholesterol in mitochondria)
4) Intratesticular steroidogenesis (cholesterol -> testosterone)
5) FSH + Sertoli cells INDIRECT (ensures high test content is available)
6) Negative feedback by test and estradiol
7) inhibin B feedback on FSH (sertoli cells secrete inhibin B in response to FSH)

Question 2

Role of LH and FSH in testosterone synthesis + spermatogenesis

Answer 2

LH: stimulates Leydig cells in testes, promotes testosterone synthesis, Leydig cells respond by converting cholesterol -> testosterone
FSH: stimulates sertoli cells to produce ABP, support sperm development, release inhibin

Question 3

Role of 5a-reductase in testosterone action

Answer 3

Converts testosterone into a stronger hormone called DHT (dihydrotestosterone)
3x more potent

Question 4

What are the physiological effects of testosterone? (5)

Answer 4

• changes during puberty
• growth promoting properties (penile growth, change in skin, hair, deepening of voice, increase in mass)
• stimulation and maintenance of sexual function
• stimulation of erythrocyte production
• decrease in HDL levels

Question 5

What are the effects of structural modifications in synthetic androgens?

Answer 5

• 17-a-alkylation = makes drug more orally potent
• Esters + long side chains (test cyp/test enan) = slows metabolism
• Ester at C17 = longer injectable forms

Question 6

What are the adverse effects of androgens? (5)

Answer 6

1) not for infants/pregnant women (disturbances in sexual development)
2) sodium retention + edema (cross reactivity with aldosterone receptor
3) hepatic dysfunction in case of 17-alkyl steroids
4) in women: hirsutism, acne, amenorrhea, clitoral enlargement, deepening of voice
5) in men: acne, sleep apnea, erythrocytosis, gynecomastia, azoospermia, testicular atrophy, increase aggression + psychotic sx

Question 7

What are the pharmacological uses for antiandrogens? (4)

Answer 7

1) Androgen replacement therapy in men
- male hypogonadism (test deficiency)
- hypopituitarism
2) Gynecologic disorders
- must be used with great caution due to adverse effects
- endometriosis
3) Protein anabolic agents
- reverses protein loss after trauma, surgery, or prolonger immobilization
4) Andropause

Question 8

What are the types of antiandrogens? (2)

Answer 8

1) 5a-reductase inhibitors
- block conversion from test -> 5a-dihydrotest
2) androgen receptor antagonists
- block binding of endogenous androgens to receptor or inhibit activation of receptors
- steroidal inhibitors
- non-steroidal inhibitors

Question 9

5a-reductase inhibitors

Answer 9

1) Finasteride
uses: BPH, baldness in men, hirsutism in women
2) Dutasteride
uses: BPH, baldness in men

Question 10

Steroidal androgen receptor antagonists

Answer 10

1) Cyproterone acetate
- androgen antagonist
- suppresses release of LH and FSH
- used to treat hirsutism in women and excessive sexual drive in men
2) Spironolactone
- androgen + aldosterone antagonist (may cause polyurea)
- used to treat acne and hirsutism in women
- may cause feminization in men

Question 11

Non-steroidal androgen receptor inhibitors

Answer 11

1) Flutamide
- non-steroidal antiandrogen
- prostate cancer
2) Enzalutamide
- non-steroidal antiandrogen
- metastatic castration resistant prostate cancer

Question 12

Synthetic Androgens (3)

Answer 12

**17-alkyl form: more orally active
1) Methyltestosterone
**ester forms: prolonged absorption time + greater activity for IM admin
2) testosterone enanthate
3) testosterone cypionate