Female Sex Hormones

Question 1

How does GnRH lead to stimulation of the pituitary

Answer 1

GPCRs- GPCR’s are in the cell’s membrane, triggering reactions inside the cell by increasing intracellular signaling molecules like cAMP, IP3/DAG

Question 2

What happens in GnRH disensitization

Answer 2

sustained GnRH will not cause LH/FSH release because the GnRH recceptor will be desensitized. Pulsatile GnRH release will continuously activate the GnRH receptor.

Question 3

Tolerance vs desensitization vs downregulating

Answer 3

Question 4

Function of FSH and how it achieves this

Answer 4

FSH stimulates ovarian follicular development, estrogen secretion, and promotes maturation of the ovum.

works by binding G-protein Coupled Receptors (GPCRs) to produce cAMP

Question 5

Function of LH

Answer 5

LH supports corpus luteal function and the mid-cycle surge in LH leads to ovulation.

Question 6

What do estrogens do in female reproduction

Answer 6

primarily estradiol from follicle and corpus luteum. Estrogen drives proliferation of the endometrial lining

Question 7

Function of progesterone in repro

Answer 7

primary hormone that ensures survival of the pregnancy after implantation

Question 8

Primary androgen of female repro

Answer 8

primarily androstenedione, testosterone from stroma

Question 9

Effects of estrogen

Answer 9

growth, development and maintenance of feminine primary and secondary sex characteristics

proliferation of the endometrium

uterine and tubal motility

watery cervical secretions

Question 10

How are natural estrogenic steroids and their derivatives modified to avoid first pass metabolism

Answer 10

ethinylation of C17

Question 11

What is the most potent synthetic estrogen

Answer 11

Diethylstilbestrol (DES)

Question 12

When is DES used and when is it contraindicated

Answer 12

Used for inoperable prostate cancer

Contraindicated in pregnancy - teratogen

Question 13

What are the semi-synthetic estrogen receptor agonists

Answer 13

Question 14

What are the natural estrogen receptor agonists

Answer 14

Question 15

What are the synthetic estrogen receptor agonists

Answer 15

Question 16

What are xenoestrogens

Answer 16

xenohormone that imitates estrogen. Typically, refers to compounds that are absorbed without a pharmacological purpose

Question 17

What are the xenoestrogens

Answer 17

Question 18

Side effects of all estrogens

Answer 18

Sodium and water retention, which can also increase blood pressure

Increase in synthesis of clotting factors [especially if p.o. (orally)]. This risk is particularly increased in patients with a positive family history of thrombosis, patients > 35 years old, or patients who smoke.

Unfavorable lipid alterations that increase risk for cardiovascular disease.

Some increased risk for breast cancer when used for HRT (not OCPs), especially when combined with progesterone.

Question 19

How do SERMs work

Answer 19

Selective Estrogen Receptor Modifiers. These are drugs that have a selective affinity for subclasses of estrogen receptors, and block the effects of estrogen by blocking the target organ receptor. The selectivity of the drug dictates the clinical utility.

Question 20

What do SERMs end in

Answer 20

All drugs ending in fene, -fen, or -phene are SERMs

Question 21

What is Clomiphene (Clomid) and what is it used for

Answer 21

Partial agonsit of estrogen receptor

Irregular ovulation

“male factor” fertility problems

Unexplained infertility

Question 22

What is tamoxifen

Answer 22

ER antagonist

useful for the management of estrogen dependent cancer as it blocks estrogen receptors. It will block estrogen in breast cancer cells as well as in other cells with estrogen receptors, and is famous for causing symptoms of menopause as a result.

Question 23

What is Raloxifene

Answer 23

ER Antagonist

useful for maintaining bone mass post-menopausally without extreme stimulation of breast or uterine tissue. It has selective agonist activity in one tissue (bone) with antagonist activity in another (breast) - it is useful in the treatment of osteoporosis without increasing the risk of breast cancer.

Question 24

Action of aromatase inhibitors

Answer 24

enzymes block the formation of the aromatic “A” ring in the synthesis of estrogens and thus block the production of estrogen by the ovary and peripheral tissues

Question 25

Examples of aromatase inhibitors

Answer 25

Anastrozole

Exemestane

Question 26

What are progestins

Answer 26

class of compounds that has effects like progesterone - optimize implantation and maintain pregnancy

Question 27

What are the progesterone receptor agonists

Answer 27

Question 28

What are progesterone receptor antagonists used for

Answer 28

induce abortion or passing the products of conception after an intrauterine demise (miscarriage).

Question 29

Examnple of progesterone receptor antagonist

Answer 29

Mifepristone [RU486]

Question 30

What is a major limitation of estrogen and progesterone administration

Answer 30

first pass metabolism following oral administration. Chemical modification of estrogen (ethinylation at C-17) and progesterone (ethinylation at C-17) allows them to be taken orally.

Question 31

Mechanism of Danazol

Answer 31

It is an anti-gonadotropin that is an adrogen agonist. It exerts negative feedback on the pituitary without estrogenic effects.

The state induced is called psuedomenopause. The 17-ethinyl group makes this an orally useful steroid.

Question 32

Side effects of Danazol

Answer 32

There are still some virilizing side effects. One common use is for endometriosis, which causes painful, abnormal periods.

Question 33

Mechanism of Sustained release GnRH analogs

Answer 33

The goal of these drugs is to decrease pituitary gonadotropin secretions by causing desensitization of the GnRH receptor, thus they have to be given in constant doses rather than pulsatile or intermittent doses. So, the continuous administration acts as an antagonist, but they technically are not antagonists in the sense they do not compete for agonist binding.

Question 34

Uses of sustained release GnRH analogs

Answer 34

The GnRH analogs are usually administered as a depot injection (s.c., i.m.) or as a nasal spray as a result. This is used in the treatment of endometriosis and prostatic cancer by suppressing the production of either estrogen or potent androgens, respectively.

Question 35

Examples of sustained release GnRH analogs

Answer 35

Gonadorelin, Leuprolide, Nafarelin, Goserelin

Question 36

Estrogenic agents are used for:

Answer 36

Dysmennorhea

Contraception

Menopausal symptoms

Not Used in Pregnancy!

Question 37

Uses for anti-estrogens

Answer 37

Hormone responsive tumors

Endometriosis

Question 38

Uses for progestins

Answer 38

Contraception

Dysfunctional uterine bleeding

Threatened or habitual abortion

Question 39

Most common reason for a missed period

Answer 39

Pregnancy