Gonadal Steroids Flashcards
metabolism of natural estrogen
more rapid inactivation in liver
oral estrogen forms
ESTRADIOL
ETHYNIL ESTRADIOL
CONJ EQUINE ESTRADIOL
synthetic estrogen metabolism
less rapid degradation
binds mainly to SHBG
less to albumin
ESTRADIOL
bind extensively to albumin
ETHYNIL ESTRADIOL
distribution of oral estrogen
rapidly and extensively
responsible for the unwanted effects of estrogen such as increase in clotting factors and inc in plasma Triglycerides
ENTEROHEPATIC CIRCULATION
intramuscular estrogen
ESTRADIOL VALERATE
estrogen + straight chain fa
intramuscular estrogen advantage
prolonged half life
can be given on a weekly or monthly basis
lesser hepatic effects compared to orally admin
transdermal patch
greater systemic absorption which can produce systemic effects
vaginal administration
effects of estrogen on endometrium
proliferatove -> endometrial hyperplasia
effects of estrogen on cervical mucus
watery, mucoid, stretchable -Spinbarkeit
estrogen on mammary glands
stromal and ductal devt
pigmentation of nipples and areola
estrogen on adipose tissue
female distribution pattern
estrogen on bones
pubertal linear growth
epiphyseal closure
estrogen on liver
inc coagulation factors 2,7,9,10
dec protein C, S, antithrombin
inc binding proteins SHBG,TBG,CBG
estrogen on bile
inc cholesterol secretion
dec bile acid secretion
-inc formation of gallstones
estrogen on plasma lipids
⬆HDL
⬇️LDL
slight decrease in total serum cholesterol
inc TAG
estrogen on kidneys
Sodium and water retention
use of estrogen
replacement therapy
- hypogonadism
- menopause
contraception
deficiency in sex hormones and the ovaries are non functioning
Turner’s syndrome
most important progestin in humans
precursor of estrogens, androgens, adrenocortical steroids
PROGESTERONE
absorption of PROGESTERONE
rapid
hepatic metabolism of PROGESTERONE to
PREGNANEDIOL
PROGESTERONE is conjugated with
GLUCORONIC acid
effect of progesterone on reproductive tract
secretory endometrium
⬇️uterine contractility
thick, scanty cervical mucus
progesterone on breast
proliferation in acini
vs ESTROGEN on stroma and ducts
PROGESTERONE on plasma lipids
⬆️LDL
slight ⬇️HDL
PROGESTERONE on brain
resets hypothalamic thermostat- increase heat production
PROGESTERONE on HP function
⬇️GNRH pulse frequency➡️suppressed Gn release
synthetic progestins
C21 progestins- PREGNANES
19-nortestosterone derivatives- ESTRANES
19-nortestosterone derivatives- GONANES
spironolactone analog- DROSPIRENONE
most chemically and pharmacologically related to progesterone
C21 progestins - PREGNANES
pregnanes- HYDROXYPOGESTERONE CAPROATE admin
IM due to first pass hepatic metabolism
MPA MEDROXYPROGESTERONE ACETATE admin
oral- HRT
IM- every 3 months for contraception
SC- for contraception
19 NT derivatives- ESTRANES
NORETHINDRONE
major effect of NORETHINDRONE
from androgenic to progestational
- removal of carbon at position 19
strong antigonadotropic activity of NORETHINDRONE
⬆️ affinity to testosterone
suppress gonadotropin release
contraceptive effect
norethindrone AE
acne
hirsutism
19nt derivatives GONANES
a further modification of testosterone
LEVONORGESTREL
LEVONORGESTREL androgen activity
minimal or absent
LEVANOGESTREL moa
potent gonadotropin inhibitor
antimineralocorticoid
androgen receptor antagonist
spironolactone analog- DROSPIRENONE
effects on DROSPIRENONE
⬇️water retention and breast tenderness : bloated and painful
improves skin appearance
uses of progestins
hormone replacement therapy
❤️contraception-⬇️GnRH
endometriosis, dysmenorrhea tx
relief of hot flushes when estrogen is CI
WHI estrogen + progestin tx
higher incidence of
breast CA
heart attack, stroke, thromboembolism
WHI estrogen + progestin tx
lower incidence of
fracture
colorectal cancer
US FDA approved indications for estrogen-progestin therapy
treat vasomotor symptoms
menopausal genital atrophy- topical
prevention of osteoporosis- consider non estrogen tx
EP replacement therapy CI
thromboembolic disorders breast or endometrial neoplasms hepatic or gallbladder disease undiagnosed genital bleeding DM HPN migraine
HRT regimens: cyclic
1st half: estrogen
2nd half: estrogen + progestin
drug free: menstrual bleeding
HRT regimen: Continuous
if symptomatic during estrogen free days
(-) uterus: estrogen only
(+) uterus: estrogen + progestin
oral contraceptive types
combined estrogen + progestin
progestin only
emergency contraception
COC mechanism of contraception
prevent ovulation-synergystic actions
progestin in COC effect on hypothalamus
⬇️frequency of GnRH pulses
effect of COC estrogen on pituitary
suppression of FSH release
-no maturation of graafian follicle
COC progestin effect on pituitary
inhibition of estrogen- induced LH surge
COC combo on pituitary
⬇️pituitary responsiveness to GnRH
COC effects
prevent ovulation
produce thick cervical mucus
endometrial atrophy
altered tubal support
high dose COC
> or equal to 50mcg ETHYNIL estradiol
low dose COC
30-35 mcg
very low dose COC
20-25 mcg
monthly cycle COC
- 21 days active pills + 7 days active pills
* 24 days active pills + 4 days inactive pills
extended cycle COC
84 days active pills + 7 days inactive- quarterly menstrual periods
no period COC
28 active pills per pack, no inactive pills
continuous intake
fixed amount of estrogen and progestin
monophasic COC
more closely approximates the estrogen progestin ratios that occur during the menstrual cycle
biphasic COC
three dosage formulation that also mimics the menstrual cycle
triphasic COC
doses vary 4x each 28 day treatment cycle
quadriphasic COC
mild AE of COC
nausea mastalgia edema breakthrough bleeding headache
moderate COC AE
weight gain
hirsutism
amenorrhea
prolactinemia or prolactinoma
severe COC AE
venous thromboembolism MI-obese, HPN, smokers ⬆️risk of stroke: women >35 hepatic adenoma gallbladder disease breast cancer
absolute CI to COC
history carcinoma of the breast, female repro tract abnormal undiagnosed vaginal bleeding liver tumors or impaired fxn pregnancy
relative CI to COC
migraine
HPN
DM
cholestatic jaundice of pregnancy
PROGESTIN only dose
28 day packs all active
PROGESTIN only oral contraceptive effect
⬇️menstrual blood loss and cramps
uses of PROGESTIN only
breastfeeding
CI estrogen- smokers,HPN,migraine
PROGESTIN only AE
acne
irregular bleeding
not recommended for long term contraception
EMERGENCY CONTRACEPTIVE PILLS
emergency contraceptive forms
PROGESTIN only
SPRM- selective progesterone receptor modulator
Yuzpe regimen
emergency contraceptive pill that contaisn LEVONORGESTEL
progestin only pills
progestin only pills must be talen
within 72 hours of unprotected sex
PLAN b otc dose
2 pills taken 12 hours apart within 3 days
plan B one step OTC dose
single dose, greater compliance
SPRM - Ella contains
ullipristal : partial agonist
SPRM is effective for
5 days (120hours) after coitus
SPRM dose
1 tab single dose
YUZPE regimen contain
high dose estrogen + progestin pills : COC
yuzpe regimen taken within
72 hours of unprotected coitus
yuzpe regimen dose
2 doses 12 hours apart
inge table contraceptives
MPA or medroxyprogesterone acetate
MPA dosing
IM or SC. every 3 months
MPA ae
irregular spotting or bleeding ⬆️LDL ⬇️HDL ⬇️bone density delayed return of ovulation
transdermal contraceptive releases estrogen and progestin for
7 days
transdermal contraceptive dosing
one patch per week for 3 weeks
no patch for 1 week»_space; menstrual period
subdermal implant : IMPLANON form
single 4 cm rod releases progestin
IMPLANON is removed after
3 years
intrauterine contraceptive MIRENA releases
LEVONORGESTREL for 5 years
CVR: NUVARING contains
estrogen and progestin
NUVARING is left in place for
3 weeks
most of circulating testosterone is bound to
Sex hormone binding globulin or SHBG
5 alpha reductase converts testosterone to
DHT
aromatase converts testosterone to
ESTRADIOL
adipose tissues, liver hypothalamus
DHT in males is responsible for
puberty inc activity of sebaceous glands inc lean body mass inc skeletal muscle growth closure of epiphysis
androgens stimulate the secretion of
erythropoietin for rbC production
Androgens decrease HDL levels, favoring
atherosclerosis
oral androgens
ESTER FORM TESTOSTERONE UNDECANOATE
ALKYKL DERIVATIVE STANOZOLE
parenteral androgen
ester form TESTOSTERONE CYPLONATE
alkyl derivative NANDROLONE
preparation of androgen that exhibit prolonged absorption can be administered weekly
parenteral form of Androgen
androgen prep that bypass first pass effect
trandermal Androgen
by pass first effect,tablet is placed at incisor
Transbucca androgen
transbuccal androgen is taken
12 hours apart
uses of androgen
replacement therapy for male hypogonadism
protein anabolic agent
gynecologic disorders
androgen abuse in sports
androgen in male hypogonadism
preferred prep is testosterone
restores or induces virillization
DANAZOL causes
atrophy of lesion in endometriosis
increases strength, aggressiveness, competitive edge are seen on
androgen use in sports
ANDROGENS AE
masculinizing effects
hepatic
prostatic enlargement
decrease HDL, increased LDL
selective estrogen receptor modulators have tissue selective effects
agonist - bone, liver
antagonist- breast and endometrium
has both agonist and antagonist action
RALOXIFENE
RALOXIfene use
prevent or treat osteoporosis
breast cancer prophylaxis
RALPXIFENE
hot flushes
leg cramps
DVt
ANASTROZOLE MOA
aromatase inhibitor
FULVESTRANT MOA
estrogen receptor antagonist
used for TAMOXIFEN resistant breast tumors
ANASTROZOLE
FULVESTRANT
5 alpha reductase inhibitors
FINASTERIDE : type 2
DUTASTERIDE : type 1,2
FINASTERIDE and DUTASTERIDE are used for
BPH
androgenic alopesia- FINASTERIDE
moa of FLUTAMIDE
andorgen receptor antagonist
FLUTAMIDE use
treatment of prostatic cancer