Estrogen-Progestin Inhibitors

Question 1

Compare mechanisms for:
SERMS:
Antagonists:
Partial Agonists:

Answer 1

SERMS: do different things in diff tissues: IE Bone is an agonist, Endometrium is a partial agonist, and breast/pituitary is an antagonist
Antagonists: Inhibit activity
Partial Agonists: stimulate a less than normal response

Question 2

What are tissue specific effects of SERMS?

Answer 2

Bone: Suppress Resorption
Endometrium: Proliferation
Pituitary: Hot flashes
Breast: Inhibit Proliferation

Question 3

What is the physiological and molecular MOA for estrogen and Progesterone inhibitors?

Answer 3

Estrogen Inhibitors:
-Clompiphene: Partial agonist, Give before ovulation if pnt has low LH/FSH levels, will increase, interrupt neg feedback!
- Tamoxifen: SERM, agonist in BONE, Partial agonist in ENDOMETRIUM, antagonist in BREAST/HPG axis.
- Raloxifene: SERM, agonist in BONE, NOT partial agonist, antagonist in BREAST/UTERUS/HPG axis
- Danazol: Estrogen Inhibitor, inhibit gonadal function/inc clearance of steroids
- Anastrozole: Aromatase Inhibitor, less estrogen production
Letrozole: Aromatase Inhibitor, Less estrogen

Progesterone Inhibitors:

• Mifepristone: Antiprogesterone, abortion, first give alone, then with misoprostol
• Ulipristal: Partial agonist, Emergency contraceptive
• these
  1. Inhibit Progesterone receptors which causes
  2. Uterine Contractions and leads to
  3. Shedding of uterine lining and
  4. Opens Cervix

Question 4

What are the adverse effects of each of the Estrogen and Progesterone inhibitors?

Answer 4

Estrogen Inhibitors:
- Clomiphene: Multi Births, Hot Flashes, Ovary enlargement
- Tamoxifen: Hot flashes, Endometrial CA
- Raloxifene: Hot flashes, N/V
- Danazol: Wt Gain, Edema, Oily Skin, Acne, Hirsutism, HOT FLASHES
Anastrazole: Hot flashes, GI disturb
Letrozole: Hot flashes, GI

Progesterone Inhibitors:

• Mifepristone
• Ulipristal

Question 5

What are the therapeutic uses for Estrogen and Progesterone Inhibitors?

Answer 5

Estrogen Inhibitors:
- Clomiphene: Fertility Drug
- Tamoxifen: ER+ Breast CA
- Raloxifene: CA, Post menopausal bone loss
- Danazol: Endometriosis, Breast Fibrocystic disease
Anastrazole: Breast CA
Letrozole: Breast CA

Progesterone Inhibitors:

• Mifepristone
• Ulipristal
  1. Contraceptive - disrupt ovulation
  2. Anticancer - breast, endometrial
  3. Induce delivery after fetal death
  4. Induce labor