Khan Endocrine Exam 3

What are the structural requirements of Estradiol for estrogenic action?

What are the structural requirements of Estradiol for estrogenic action?

-OH group on Carbon 3

-Aromatic A RIng

Estradiol cannot be administered orally because…

It is metabolized and conjugated, which decreases the therapeutic efficacy, and oral bioavailability.

What are the benefits of introducing an alkyne group in estradiol?

It increases half life and decreases metabolic alteration/degradation

How is mestranol metabolized?

Metabolized to EE via Hepatic O-demethylation

How is ethinyl estradiol metabolized?

Ethinyl Estradiol is metabolized into

-3-O-Glucuronide

-3-O-Sulfate

Why EE plus an antibiotic combination decreases efficacy of an oral contraceptive?

Because the antibiotic blocks the bacteria in the GI tract from hydrolyzing the glucuronide and the sulfate conjugate → antibiotic stops the reabosorption of the EE

At which position of Estradiol is an ester group added?

At position 17

Why is esterification needed for estradiol?

It prolongs the duration of action.

What are the common ADR’s of Estrogen use?

-Hypertension

-Increased risk of clotting

-Nausea

-Weight gain

-Bloating

What is the first boxed warnings of estrogen use?

Unopposed estrogen increases risk of endometrial carcinoma

What is the second boxed warning of estrogen use?

Estrogen with or without Progesterone should not be used in CV prevention.

List the Contraindications of Estrogen use?

-Endometrial carcinoma

-Breast Carcinoma

-Undiagnosed Genital bleeding

-Thromboembolic Disroders.

Moa of Clomiphene

-Antagonizes estrogen receptors in the hypothalamic-pituitary-ovarian axis

It inhibits the release of estrogen and progesterone, allowing us to produce more LH and FSH because their isn’t negative feedback → more folicle production and ovulation

MOA of fulvestrant

Estrogen receptor antagonist: Competitive

What is aromatase?

An enzyme that converts androgens to estrogen.

What are the substrates of the of aromatase?

Androstenedione and Testosterone

What are the products of the of aromatase?

Estrone and Estradiol

What are the names of the competitive inhibitors of Aromatase?

Anastrazole and Letrozle

What are the names of the Irreversible inhibitors of aromatase?

Exemastane (Aromasin)

Why does progesterone cause acne, hirstuism?

Progesterone binds to androgen receptors.

How is norgestrel different than progesterone?

It has carbon removed removed, becomes 19-nor progesterone derivative

What is the role of progesterone in contraception?

-GnRH suppression
-decreased release of LH
-inhibits ovulation

What are the CNS effects of progesterone?

1) Increases body temperature from mid-cycle to onset of menstruation

2) Depressant and Hypnotic actions

Effects of progesterone on endometrial proliferation

-binds to nuclear PR and modulates gene transcription

-decreases estrogen driven endometrial proliferation

-leads to development of a secretory endometrium

-abrupt decline in release of progesterone from the corpus luteum at the end of the cycle

--onset of menstruation