B / 15 : Estrogens And Antiestrogens

Question 1

What are the natural estrogens and where are they produced?

Answer 1

• Estradiol : produced in ovary
• Estrone and estriol formed in the liver from estradiol, or in the peripheral tissues from androgens

Question 2

Pharmacological effects of estrogen (6)

Answer 2

• Promotes proliferation (breast, endometrium)
• Female sexual maturation + growth, secondary sex characteristics
• Metabolic and cardiovascular effects
• Enhance blood coagulation
• Activation of stress and SYM systems
• Na retention, edema

Question 3

Contraindications for estrogens

Answer 3

• Patients with estrogen dependant neoplasms
• Patients with undiagnosed genital bleeding
• Severe liver disease
• Heavy smokers
• History of thromboembolic disorder

Question 4

Side effects of estrogens (4)

Answer 4

• Increased risk of endometrial carcinoma, breast cancer
• Postmenopausal uterine bleeding
• Increase in migraine frequency
• Cholestasis, gallbladder disease

Question 5

Estradiol
- MOA
- Effect
- Indication
- Extra
- ROA

Answer 5

• Natural estrogen
• Promote female maturation + decreased bone resorption + increased blood coagulation
• Hormone replacement (hypogonadism, post-menopause), ovarian suppression (contraception, menstrual problems)
• High first pass metabolism
• Oral, transdermal patch, IM, vaginal creams

Question 6

Ethinylestradiol
- MOA
- Effect
- Extra
- ROA

Answer 6

• Synthetic estrogen
• Accelerate growth, stimulate secondary sex characteristics
• Good oral bioavailability
• Oral, transdermal patch, IM, vaginal cream

(Everything else is same as estrogens)

Question 7

What are the anti-estrogens? (3)

Answer 7

• Clomifen (SERM)
• Tamoxifen (SERM)
• Raloxifene (SERM)

Question 8

What does SERM stand for?

Answer 8

Selective estrogen receptor modulator

Question 9

Clomifen
- MOA
- Effect
- Indication
- SE
- ROA

Answer 9

• Estrogen receptor antagonist in pituitary gland
• Prevents normal negative feedback : increase FSH + LH -> stimulate ovulation
• To induce ovulation and treat infertility
• Hot flashes, ovarian enlargement, multiple pregnancies
• Oral

Question 10

Tamoxifen
- MOA
- Effect / indication
- SE
- ROA

(- Extra)

Answer 10

• Estrogen receptor ANTAGONIST in breast tissue, but AGONIST in endometrium and bones
• Prophylaxis treatment of breast cancer in post-menopausal women
• Hot flashes, endometrial hyperplasia, polyps, increased risk of endometrial cancer
• Oral

(- can now be replaced by anastrozole, better results)

Question 11

Raloxifene
- MOA
- Effect
- Indication
- SE
- Extra
- ROA

Answer 11

• Estrogen receptor ANTAGONIST in breast, estrogen receptor AGONIST in bones
• Inhibits osteoclast differentiation
• First line prevention of postmenopausal osteoporosis
• Hot flashes + increased risk of thromboembolic events
• No effect on endometrium : no increased cancer risk
• Oral

Question 12

What is an example of an estrogen synthesis inhibitor?

Answer 12

Anastrozole

Question 13

Anastrozole
- MOA
- Effect
- Indication
- SE
- ROA

Answer 13

• Aromatase (non-steroidal) inhibitor
• Prevents conversion of testosterone to estrogen
• Hormone dependant breast cancer in postmenopausal women
• Hot flashes, vaginal dryness, increased risk of osteoporosis, cardiovascular diseases
• Oral