Pharmacology of Estrogens, Progestins, & Androgens

5a reductase

What enzyme is responsible for the conversion of testosterone to DHT?

17b Hydroxysteroid dehydrogeanse (17b HSD)

What enzyme is responsible for the converison of androstenediol to testosterone?

Aromatase (Bonus: Sertoli cells)

What enzyme is responsible for the conversion of testosterone to estrogen? (Bonus: Where does this happen in males?)

Estradiol (E2) and estrone (E1)

What estrogens are produced by the ovary?

Estriol (E3)

What estrogen(s) are produced by the fetoplacental unit during pregnancy?

Reduces first pass effect, increases bioavailability

Why is an ethinyl group added to estradiol for synthetic estrogens?

Development of female sex organs and secondary sex characteristics, breast duct development, grows endometrium, inhibits osteoclasts

What are some of the important physiological effects of estrogens?

Increases SHBG, TBG, transferrin

What important effects does estrogen have in the liver?

Maturation of endometrium

What are the physiological effects of progesterone?

Progesterone, metabolites like allopregnanolone

Which is more likely to cause depressant effects (like sedative/hypnotic effects): estrogen or progesterone? Why?

Desogestrel, norethindrone, norgestimate, norgestrel

What are the 19 nortestosterone derivatives?

Drospirenone

Which clinically used progestin has anti-androgenic properties and can be given orally or as an implant?

SHBG or albumin

Most of the testosterone in the body is bound to:

Erythropoetin

Androgens stimulate secretion of ______

Decreases SHBG

Unlike estrogen, androgens cause what effect in the liver?

Intracellular/nuclear receptors

Genomic effects are mediated by what receptors?

G proteins

Some progesterone receptors are on the membrane and may be coupled to:

Tamoxifen

What medication is an estrogen antagonist in the breast, but agonist in the endometrium?

Clomiphene

What medication competes with estrogen to reduce negative feedback on gonadotropins?

Faslodex

What medication is a "pure" anti-estrogen?

Aromatase inhibitors

What is the MOA of testolactone and anastrozole?

5a reductase inhibitors

What is the MOA of finasteride and dutasteride?

Androgen receptor antagonists

What is the MOA of flutamide, nilutamide, bicalutamide, and cyproterone?

Transdermal

Which route of administration is best for post-menopausal women?

Override normal ovarian steroid regulation of reproductive function, exert negative feedback on hypothalamus and pituitary to reduce LH and block ovulation

How do OCPs work?

Desogestrel

Which progestin has the highest progestagenic potency?

Norgestrel

Which progestin has the highest androgenicity?

Medroxyprogesterone (depot)

Which contraceptive is given in an IM injection?

Progestin only OCPs

What oral contraceptive is indicated in women at higher risk of estrogen dependent cancers or coagulopathy?

Thromboembolism, CV events, HTN, nausea, HA, cervical/liver cancer

What are possible side effects associated with the estrogen in OCPs?

Increased appetite, weight gain, depression, acne (if androgenic)

What are possible side effects associated with the progestin in OCPs?

Phenytoin, rifampin

What drugs can lead to lower efficacy of OCPs?

Pregnancy, h/o estrogen dependent cancer or breast cancer, thromboembolism, liver disease, heavy smokers >35 years old

What are the most important contraindications of OCPs?

Levonorgestrel

What is "plan B"?

Hormone therapy with estrogen/progesterone combo, transdermal estrogen, CEEs

How can you help treat a menopausal woman with terrible hot flashes that are interfering with her life and osteopenia?

Azoospermia, hepatic dysfunction, acne, gynecomastia, urinary retention

What adverse effects might you see in a man abusing exogenous androgens?

Estrogen + drospirenone

A young woman on a combination OCP develops facial hair and definitely doesn't want to keep it. What OCP combination would be best to switch her to?

Raloxifene

A woman with a family history of breast cancer develops osteoporosis. What drug would be best to help reduce the risk of fracture?

Anastrozole or testolactone

A 42 year old male with BRCA2 develops breast cancer. It is ER+. What treatment would be best without disrupting his ability to reproduce?