Female Sex Hormones Flashcards
How does GnRH lead to stimulation of the pituitary
GPCRs- GPCR’s are in the cell’s membrane, triggering reactions inside the cell by increasing intracellular signaling molecules like cAMP, IP3/DAG
What happens in GnRH disensitization
sustained GnRH will not cause LH/FSH release because the GnRH recceptor will be desensitized. Pulsatile GnRH release will continuously activate the GnRH receptor.
Tolerance vs desensitization vs downregulating
Function of FSH and how it achieves this
FSH stimulates ovarian follicular development, estrogen secretion, and promotes maturation of the ovum.
works by binding G-protein Coupled Receptors (GPCRs) to produce cAMP
Function of LH
LH supports corpus luteal function and the mid-cycle surge in LH leads to ovulation.
What do estrogens do in female reproduction
primarily estradiol from follicle and corpus luteum. Estrogen drives proliferation of the endometrial lining
Function of progesterone in repro
primary hormone that ensures survival of the pregnancy after implantation
Primary androgen of female repro
primarily androstenedione, testosterone from stroma
Effects of estrogen
growth, development and maintenance of feminine primary and secondary sex characteristics
proliferation of the endometrium
uterine and tubal motility
watery cervical secretions
How are natural estrogenic steroids and their derivatives modified to avoid first pass metabolism
ethinylation of C17
What is the most potent synthetic estrogen
Diethylstilbestrol (DES)
When is DES used and when is it contraindicated
Used for inoperable prostate cancer
Contraindicated in pregnancy - teratogen
What are the semi-synthetic estrogen receptor agonists
What are the natural estrogen receptor agonists
What are the synthetic estrogen receptor agonists
What are xenoestrogens
xenohormone that imitates estrogen. Typically, refers to compounds that are absorbed without a pharmacological purpose
What are the xenoestrogens
Side effects of all estrogens
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.
How do SERMs work
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.
What do SERMs end in
All drugs ending in fene, -fen, or -phene are SERMs
What is Clomiphene (Clomid) and what is it used for
Partial agonsit of estrogen receptor
Irregular ovulation
“male factor” fertility problems
Unexplained infertility
What is tamoxifen
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.
What is Raloxifene
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.
Action of aromatase inhibitors
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
Examples of aromatase inhibitors
Anastrozole
Exemestane
What are progestins
class of compounds that has effects like progesterone - optimize implantation and maintain pregnancy
What are the progesterone receptor agonists
What are progesterone receptor antagonists used for
induce abortion or passing the products of conception after an intrauterine demise (miscarriage).
Examnple of progesterone receptor antagonist
Mifepristone [RU486]
What is a major limitation of estrogen and progesterone administration
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.
Mechanism of Danazol
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.
Side effects of Danazol
There are still some virilizing side effects. One common use is for endometriosis, which causes painful, abnormal periods.
Mechanism of Sustained release GnRH analogs
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.
Uses of sustained release GnRH analogs
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.
Examples of sustained release GnRH analogs
Gonadorelin, Leuprolide, Nafarelin, Goserelin
Estrogenic agents are used for:
Dysmennorhea
Contraception
Menopausal symptoms
Not Used in Pregnancy!
Uses for anti-estrogens
Hormone responsive tumors
Endometriosis
Uses for progestins
Contraception
Dysfunctional uterine bleeding
Threatened or habitual abortion
Most common reason for a missed period
Pregnancy
