Lecture 7 - Estrogen and Progestin

Question 1

What are the indications of estrogen?

Answer 1

Contraception (NOT as single agent) 
HRT 
Hirsutism (suppresses ovarian androgen production) 
Amenorrhea
dysfunctional uterine bleeding
dysmenorrhea

Question 2

How does estrogen production differ before and after ovulation?

Answer 2

Before ovulation - produced in follicle by theca and granulosa cells

After ovulation - estrogen and progesterone produced by luteinized granulosa and theca cells of the corpus leuteum

Question 3

Estradiol

Answer 3

ovary, major secretory product
binds sex hormone-binding globulin (SHBG) (and to albumin to a lesser extent) in blood

only free estrogen are active

Question 4

Estrone

Answer 4

(E1) Estriol (E3)
synthesized in liver (from E2)
peripheral tissues (made from androgen)
weaker binding to the estrogen receptor (ER)

Question 5

What are the effects on exogenous progestins?

Answer 5

endometrial regression: impairs implantation
thickens cervical mucus
prevents ovulation by decreasing frequency of GnRH

Question 6

What are the toxicities of progestin only preparations?

Answer 6

androgenic effects (acne, hirsutism) 
menstrual bleeding
delayed return to ovulatory function

Question 7

What are the contraindications of progestins?

Answer 7

PERSONAL hx of breast cancer
undx vaginal bleeding
active thrombeombolic disease within last 6 months

Question 8

“Big picture” concept: how do contraceptives with estrogen and progesterone work?

Answer 8

preventing ovulation by suppressing plasma levels of LH and FSH which decreases follicular development

P - no LH surge d/t decrease in GnRH pulses
Thickening of cervical mucus
Atrophic decidulaized endometreium

Question 9

What is the MOA for mifespristone?

Answer 9

progesterone-receptor modulator (PRM): competitive antagonist

blocks uterine progesterone receptors —- decidual breakdown — blastcocyst detachment (decrease hCG)

Question 10

What are the contraindications of combo E/P?

Answer 10

CV disease, stroke, HTN 
TVE
Abnormal liver function
Hx of breast cancer 
Smoker >35 
Migraine with neuro sxs 
Vaginal bleeding of unknown cause 
Pregnancy 
Breastfeeding

Question 11

Why is there no increase in endometrial cancer with combo pills?

Answer 11

Progestin counteracts estrogen-induced proliferative changes on endometrium

Question 12

What is the major hormone produced from the ovaries?

Answer 12

Estradiol (E2)

This is only active when free

Binds stronger to estrogen receptor than estrone (E1)/estriol(E3) that is produced in the liver

Question 13

Aromatase

Answer 13

CYP19A1

Enzyme used to convert testosterone into estrogen (estradiol)

Question 14

What are estrogens general effects?

Answer 14

Favorable effects on plasma lipids

Increase clotting factors and plaminogen
Decrease antithrombin 3

Question 15

Why don’t we use estrogen in pregnancy?

Answer 15

Risk of genital cancers/growths

Question 16

Progestins general effect

Answer 16

Negative feedback on LH production by blocking GnRH pulses from hypothalamus

Suppress LH

Supports luteal phase of menstrual cycle

Exogenous:
Endometrial regression
Creates thick cervical mucus
Prevents ovulation (decrease GnRH pulses)

Question 17

What are the toxicities (or SE) of progestin only preps?

Answer 17

Menstrual bleeding/irregularities

Unfavorable lipid changes (this is the opp of estrogen)

Androgenic effects (acne, hirsutism)

Question 18

What are the contraindications of progestins?

Answer 18

Pregnancy (not breast feeding)
PERSONAL hx of breast cancer
Undx vaginal bleeding
Active TVE within last 6 months