Pharmacology of Gonadal Hormones 4 Flashcards
Describe the relationship of the psychological effects of androgens, estrogens, and progestins to their therapeutic applications and side effects.
1
Q
What are the therapeutic uses of androgens?
A
-
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
- hereditary angioneurotic edema
2
Q
What are the non-therapeutic (ab)uses of androgens?
A
- 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
3
Q
What are the major side effects of androgens?
A
-
Adult male
- infertility
- excessive feedback inhibition leads to impotence and sterility
- azoospermia
- infertility
-
Prepubertal male
- precocious puberty
- premature epiphyseal closure
-
Female
- masculinization
- muscle
- voice
- hair
- clitoral enlargement
- masculinization
-
Other
- promote growth of prostatic tumors
- decreases HDL
- increases LDL
- acne
- jaundice, possibly hepatocellular carcinoma (methyltestosterone)
- CV effects
- MI
- stroke
4
Q
What are the major uses of estrogen?
A
- Replacement therapy for ovarian or pituitary failure
- With SERM for menopausal symptoms
- As androgen antagonist
- prostate cancer
- acne
- hirsutism
- Contraception
5
Q
What are the major uses of progestin by itself?
A
- Dysfunctional uterine bleeding
- Endometriosis
- Endometrial cancer
- Prevention of premature labor
- Some types of oral contraceptives
6
Q
What are the major uses of progesterone combined with estrogen?
A
- Hormonal replacement therapy (HRT) for menopausal symptoms
- Treat dysmenorrhea
- Suppress lactation
- Limit excessive growth
- Contraception
7
Q
What are the major adverse effects of estrogens?
A
- Nausea
- Na retention, edema
- Weight gain
- Breast tenderness
- Endometrial hyperplasia
- Thromboembolism
- Hypertension
- Decreased glucose tolerance
- Increased breast cancer risk in post-menopausal women
8
Q
What are the representative progestins?
A
-
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)
9
Q
What are the major adverse effects of progestins?
A
- Na retention, edema
- Weight gain
- Depression
10
Q
What agents are used to induce ovulation?
A
- GnRH
- Gonadotropins
-
Clomiphene
- selective estrogen receptor modulator (SERM)
- selectively blocks estrogen feedback inhibition
- promotes ovulation
11
Q
What agents are used for breast cancer chemoterapy, especially ER+ breast cancer?
A
-
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
- SERM that acts as an antiestrogen on the mammary gland
-
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
12
Q
What agents are used for endometriosis?
A
-
Danazole
- weak androgen that binds progestin receptors
- also used for fibrocystic breast disease
- Leuprolide