Pharmacology-Estrogen Therapy

Question 1

What causes the ovaries to produce small amounts of estrogen for the first time at puberty?

Answer 1

GnRH pulse stimulate FSH/LH release. LH stimulates theca cell androgen production. FSH stimulates conversion of androgen to estrogen. This causes breast enlargement, altered fat distribution and after a year or so menstruation begins.

Question 2

What is the main form of estrogen produced in females? How is it altered by the liver?

Answer 2

17beta-estradiol is the main one. The liver can convert it to weaker estrogens estrone and estriol.

Question 3

How does estrogen accomplish cell signaling?

Answer 3

It binds two nuclear estrogen receptors that dimerize and bind to activator complexes on DNA to initate gene transcription.

Question 4

What does estrogen do for the fetus?

Answer 4

Stimulates formation of the vagina, uterus and fallopian tubes

Question 5

Why is estrogen prothrombotic?

Answer 5

Decreases anti-thrombin III and increases clotting factors

Question 6

Why is estrogen important for bone growth?

Answer 6

It stimulates closure of the epiphyseal plates

Question 7

Why might women have less CVD than men?

Answer 7

It increases HDL and decreases LDL

Question 8

Pharmacologists render estrogen orally active by adding a 17alpha group to form what drugs?

Answer 8

Ethinyl estradiol and mestanol

Question 9

What estrogen preparations are from horses and are conjugated with SO4 and C3?

Answer 9

Equilenin and equilin (Premarin). These are a little weaker than ethinyl estradiol, but avoid 1st pass metabolism by the liver because the SO4 is removed lower in the intestine.

Question 10

Therapeutic uses of estrogen

Answer 10

Hypogonadism (begin estrogen at age 11-13, start with a low dose and increase gradually, when they are done growing add progestin to second half of cycle), Menopause

Question 11

Pros of using estrogen in menopause

Answer 11

Prevents osteoporosis, hot flashes and vaginal dryness. Improved choesterol levels.

Question 12

Cons of using estrogen in menopause

Answer 12

Increased risk for thrombosis (less when used w/progestin), endometrial carcinoma (except when used w/progestin) and breast cancer.

Question 13

Main drug for treating osteoporosis in post-menopausal women?

Answer 13

Bisphosphonate (alendronate)

Question 14

Actions of tamoxifen

Answer 14

It is a SERM that antagonizes breast (decreased risk of breast cancer) and hypothalamus (increased hot flashes). It agonizes receptors in endometrium (increased risk for endometrial cancer), bone and liver (increased risk of thrombosis).

Question 15

Actions of raloxifene

Answer 15

It is a SERM that antagonizes breast (decreased risk of breast cancer) and hypothalamus (increased hot flashes). It also partially antagonizes the endometrium. It agonizes bone (protects against osteoporosis) and liver (increased risk for thrombosis).

Question 16

Actions of ospemifen

Answer 16

It is the only SERM that is an agonist on vaginal epithelium and can be used to treat dyspareunia. It agonizes bone and endometrium. It antagonizes breast and hypothalamus.

Question 17

Actions of clomiphene citrate

Answer 17

It is an estrogen antagonist in the hypothalamus and pituitary gland. This is used to induce ovulation in premenopausal women by blocking estrogen negative feedback at the hypothalamus and anterior pituitary = increased FSH/LH release which stimulates ovulation.

Question 18

How is it possible that tamoxifen can act as an agonist in bone but an antagonist in the breast?

Answer 18

In breast, co-activators that recognize estrogen do not recognize tamoxifen. Co-repressors recognize tamoxifen and it antagonizes breast tissue. In bone, different co-activators recognize tamoxifen and turns on gene transcription.