steroidal sex hormones gavande

what is the structure of the steroid core

17C atoms with 3 cyclohexanes and 1 cyclopentane

what is the pathway of cholesterol breaking down into other hormones and how many carbons are in each

cholesterol-> progesterone (21C)-> androgens (19C)-> estrogens (18Cs)

how can you distinguish progesterones, androgens, and estrogens structurally

progesterone= has an acetyl group on cyclopentane

androgens= have ketone or hydroxyl group on cyclopentane

estrogens= have aromatic ring to replace cyclohexane

testosterone

type and C:

action:

uses:

androgen 19Cs

muscle growth, bone closure, stimulates EPO

uses: hypogonadism, anemia, osteoporosis

what are some barriers to testosterone administration?

high oral absorption BUT has high first pass metabolism (need to change structure or route)

what are the 2 testosterone derivatives and what are their differences

1. 17 alpha esters

- esterification makes it more lipophilic= dissolves in oil

- give IM q1-2 weeks

sx= cough, pain at injection site, sx fluctuations (high/low bp...)

2. 17 alpha alkyls

-methyl makes it more lipophilic

- oral qday (short acting)

NOT RECOMMENDED (liver toxicity)

Testred/ Android

methyltestosterone (17 alpha alkyl testosterone derivative)

-oral and short acting

-not recommended bc of potential liver toxicity

oxandrolone

17a methyl testosterone derivative

-BEST ratio of protein anabolic effects to virilizing (baldness, facial hair)

-offsets protein catabolism (helps muscles)

-helps with osteoporosis bone pain

why arent 17a methyl testosterone derivatives recommended

potential liver toxicity

out of IM, patch, and gel, which has the steadiest delivery over 24hrs

gel

3 common strategies for anabolic steroid abuse

- stacking

- cycling

- pyramiding

what is "stacking"

taking DIFF TYPES or formulas of steroids at ONCE to increase results

what is "cycling"

taking multiple doses of same steroid for weeks, stop for weeks, and restart again

- break allows body to produce its own testosterone and reduce damage to internal organs

t/f: in "cycling" no testosterone is produced as you cycle between different types of steroids

false. in cycling you take multiple doses for weeks, then stop for weeks, then start again. break allows body to form its own testosterone and limit organ damage

what is "pyramiding"

taking low dose of steroid then building up to max dose then slowly tapering down dose

compare the MOA of GnRH receptor agonists and antagonists

GnRH agonist: causes big initial surge in testosterone which will cause receptor downregulation via feedback= lowered testosterone

GnRH antagonist= blocks receptor right away= lowered testosterone AND NO SX FLUCTUATION

what are GnRH receptor agonists/antagonists used for

lower testerone

prostate cancer, breast cancer, endometriosis, uterine bleeding, fibroids, precocious puberty

examples of GnRH receptor AGonists

leuprolide

goserelin

triptorelin

= all are GnRH analogues

= all are INJECTABLE

what are leuprolide, goserelin, and triptorelin used for

used to lower testerone (after initial spike)

these are GnRH receptor agonists (injections)

ex: prostate cancer, breast cancer, endometriosis, etc

examples of GnRH receptor ANTAGonists?

moa?

uses?

ganirelix, cetrorelix

block receptor= less LH and FSH released= prevents testosterone release

for prostate cancer, breast cancer

nonsteroidal androgen receptor antagonists

moa?

examples?

use?

block testosterone from binding to receptor= stop signal

flutamide (Eulexin)

nilutamide (Nilandron)

bicalutamide (Casodex)

enzalutamide (Xtandi)

for: prostate cancer

5-alpha reductase inhibitors

MOA?

examples?

blocks conversion of testosterone to DHT by blocking enzyme 5-a-reductase. stops DHT from acting on prostate/hair follicles/etc

NEEDS CONTINUOUS TX

finasteride (Proscar,Propecia)

dutasteride (Avodart)

finasteride

5-alpha reductase inhibitor (no DHT)

Proscar, Propecia

for BPH, male pattern baldness

dutasteride

5-alpha reductase inhibitor (no DHT)

Avodart

for BPH, male pattern baldness

5-alpha reductase inhibitors

indications?

benign prostatic hyperplasia (BPH)

androgenic alopecia (male pattern baldness)

adverse effects of 5-alpha reductase inhibitors (finasteride, dutasteride)

pregnant women: genital abnormalities in baby boy

decreased libido, sexual dysfunction

5-alpha-reductase inhibitors counseling points (finasteride, dutasteride)

- used for BPH or baldness

- must be used continuously

- abnormalities in baby boy if pregnant

- decreased libido and sexual dysfunction

abiraterone

brand?

MOA?

Zytiga

inhibits CYP17 lyase in adrenal, testicular, and prostate cancer tissue

blocking the lyase enzyme stops progesterone-> androgen conversion. so no test is formed.

used in prostate cancer resistant to hormone blockers. must combine with prednisone

why must Zytiga be combined with prednisone

Zytiga blocks CYP17 enzyme that converts progesterone to testosterone. this also blocks cortisol synthesis so must give prednisone.

which combination drugs is given to maintain mineralocorticoid levels in prostate cancer resistant to hormone blockers

abiraterone (Zytiga) + prednisone

which hormone is ketoconazole most likely to inhibit

androgens (testosterone) and glucocorticoids

what can spironolactone be used for/ moa

competitive androgen receptor antagonist

female hirsutism, PCOS

which enzyme is needed to convert testosterone to estradiol? where does this take place?

aromatase

this is endoplasmic reticulum enzyme found in ovary and other tissues

follicular phase:

_____ stimulates ______ cells to make estradiol and estrone which elevates _________ levels

FSH-> granulosa

estrogen

luteal phase:

___ stimulates _______ cells to produce ______

LH->>> Theca

progesterone

t/f: FSH and LH reach 0 at the start of menses

false. never 0

which functional groups do naturally occurring estrogens have on C-17

hydroxyl or ketone (just like test. but estrogens also have aromatic ring)

which functional group on estrogen has the highest affinity to binding to the estrogen receptor

aromatic ring with hydroxyl on it

what is the bioavailability of estrogen? how is it eliminated?

- rapid absorption via GI, skin, mucus

- short half life orally

- renally eliminated metabolites

- bypasses first pass metabolism via C17 modification (OH)

how does synthetic estrogen bypass first pass effect

by adding OH to C17= increases lipophilicity and tissue distribution

examples of estrogen derivatives modified at C17

Mestranol (prodrug of ethinyl estrogen)

Ethinyl estrogen

what are phytoestrogens

derived from plants and do not have steroid backbone

-can act as estrogen agonist OR anti-estrogen

ex: soy

examples of phytoestrogens

soy isoflavones

ex:

daidzein

genistein

glycitein

what are progestins?

examples?

synthetic forms of progesterone

norethindrone, medroxyprogesterone

what are progestins (ex: norethindrone, medroxyprogesterone) used for

- develop endometrium

- maintain pregnancy

- suppress menstruation and uterine contractions

which hormone should be maintained at a high level to maximize egg maturation, maintain the endometrium, and maintain pregnancy

progesterone

which progestin is most specific at the progestrin receptor

a. norethindrone

b. levonorgestrel

c. norgestimate

d. drospirenone

d. drospirenone (4th gen)

a. norethindrone= 1st

b. levonorgestrel= 2nd

c. norgestimate= 3rd

d. drospirenone= 4th

tamoxifen

estrogen agonist/ antagonist

used for breast cancer

clomiphene citrate MOA and use

estrogen agonist/antagonist

-bind to estrogen receptor in hypothalamus, blocking neg feedback

-hypothalamus thinks theres not enough estrogen-> increased GnRH output= more FSH= more estradiol

triggers ovulation, increases estrogen, helps with fertility issues

what are triphenylethylene derivatives

nonsteroidal compounds that can be both estrogen agonist and antagonist

ex: tamoxifen (antagonist in breast, for cancer)

ex: clomiphene citrate (antagonist in hypothalamus= induces ovulation)

what are aromatase inhibitors? examples?

inhibit enzyme aromatase from converting test to estradiol (anti estrogen)

for breast cancer

ex: letrozole, anastrozole, exemestane

what are the steroidal aromatase inhibitors? non-steroidal?

steroidal= exemestane

non= letrozole, anastrozole

anastrozole

aromatase inhibitor, anti-estrogen, breast cancer

roles of estrogen

- reproduction

- lipid and carb metabolism

- cardiovasc

-CNS

- skeletal homeostasis

what are hormone disruptors

chemicals that mimic hormones and interfere with endocrine system

BPA

bisphenol A

this mimics estrogen. carcinogen.

diethylstilbestrol (DES)

a fertility agent that resulted in genetic defects in baby girls

dioxins

hormone disruptors found in manufacturing, forest fires, volcanic eruptions

t/f: compounded hormones are clinically preferred due to their higher accuracy and efficacy

false, conventional preferred over compounded.

lack safety tests, effectiveness, and dosing consistency, limited evidence about side effects.

hormone level monitoring does not correlate to symptom relief