Pharmacology of Gonadal Hormones 4

Question 1

What are the therapeutic uses of androgens?

Answer 1

• Replacement
  
  • pre- and post-pubertal hypogonadism
  • some cases of cryptorchidism
• Anabolic
  
  • premature infants
  • postoperative
  • anemia
• Palliative
  
  • hormone-dependent breast cancer
  • fibrocystic breast disease
  • endometriosis
• Treatment
  
  • hereditary angioneurotic edema
    
    • inhibitor of complement deficient
    • androgens decrease the abnormal capillary permeability

Question 2

What are the non-therapeutic (ab)uses of androgens?

Answer 2

• Used at ~100x replacement dose
• Post-pubertal males, effects mediated through receptors are limited because they may be saturated
• more marked in prepubertal males or elderly males with lower androgens, and females
• Antagonism of anti-anabolic effects of glucocorticoids
  
  • provide androgen-receptor independent effects

Question 3

What are the major side effects of androgens?

Answer 3

• Adult male
  
  • infertility
    
    • excessive feedback inhibition leads to impotence and sterility
    • azoospermia
• Prepubertal male
  
  • precocious puberty
  • premature epiphyseal closure
• Female
  
  • masculinization
    
    • muscle
    • voice
    • hair
    • clitoral enlargement
• Other
  
  • promote growth of prostatic tumors
  • decreases HDL
  • increases LDL
  • acne
  • jaundice, possibly hepatocellular carcinoma (methyltestosterone)
  • CV effects
    
    • MI
    • stroke

Question 4

What are the major uses of estrogen?

Answer 4

• Replacement therapy for ovarian or pituitary failure
• With SERM for menopausal symptoms
• As androgen antagonist
  
  • prostate cancer
  • acne
  • hirsutism
• Contraception

Question 5

What are the major uses of progestin by itself?

Answer 5

• Dysfunctional uterine bleeding
• Endometriosis
• Endometrial cancer
• Prevention of premature labor
• Some types of oral contraceptives

Question 6

What are the major uses of progesterone combined with estrogen?

Answer 6

• Hormonal replacement therapy (HRT) for menopausal symptoms
• Treat dysmenorrhea
• Suppress lactation
• Limit excessive growth
• Contraception

Question 7

What are the major adverse effects of estrogens?

Answer 7

• Nausea
• Na retention, edema
• Weight gain
• Breast tenderness
• Endometrial hyperplasia
• Thromboembolism
• Hypertension
• Decreased glucose tolerance
• Increased breast cancer risk in post-menopausal women

Question 8

What are the representative progestins?

Answer 8

• Progesterone
  
  • physiological progestin
  • first pass metabolism
  • effective orally when micronized
• Medroxyprogesterone
  
  • orally effective synthetic analog
  • also used as depot
• Norethindrone, levonorgestrel
  
  • synthetic
  • orally effective
  • 19-nortestosterone derivatives (gonanes)

Question 9

What are the major adverse effects of progestins?

Answer 9

• Na retention, edema
• Weight gain
• Depression

Question 10

What agents are used to induce ovulation?

Answer 10

• GnRH
• Gonadotropins
• Clomiphene
  
  • selective estrogen receptor modulator (SERM)
  • selectively blocks estrogen feedback inhibition
  • promotes ovulation

Question 11

What agents are used for breast cancer chemoterapy, especially ER+ breast cancer?

Answer 11

• Tamoxifen
  
  • SERM that acts as an antiestrogen on the mammary gland
    
    • also has estrogen agonist activity on bone and uterus
  • approved as breast cancer preventative
  • can have initial stimulatory effects
• Fulvestrant
  
  • SERM that is a pure estrogen antagonist
  • lacks the initial stimulatory effects elicited by tamoxifen
• Anastrozole
  
  • aromatase inhibitor, blocks estrogen synthesis
  • used for ovarian and prostate cancer
  • used in sequence with tamoxifen to prevent breast cancer recurrence

Question 12

What agents are used for endometriosis?

Answer 12

• Danazole
  
  • weak androgen that binds progestin receptors
  • also used for fibrocystic breast disease
• Leuprolide