Hormones Flashcards
classical pathway of hormones
released from cells then circulate the blood bound to sex hormone binding globulin. unbound enter cytoplasm of target tissue cells where they ind to the hormone recept which translocates to the nucleus and changes gene trasncription
potency of estrogen
E2 > E1 > E3
estrogen effects
sexual maturation and growth development of endometrial lining maintain skin and blood vessels decrease bone reabsorption alters liver enhances coagulability of blood induces synthesis of estrogen and progesterone receptors
progesterone is a precursor to
estrogens
androgens
adrenocortical steroids
progesterone effects
downregulat estrogen receptor and suppresses estrogenic stimulation of endometrium
induce maturation adn secretory changes in endometrium
what effects does progesterone metabolites have on the brain
anxiolytic and hypnotic effect
what receptor does progesterone antagonize and result
mineralcorticoid receptor
decrease sodium resorption and water retention
what is the hypothalamic pituitary gonadal axis responsible for in men and women
female - regulates menstrual cycle
male - regulate testosterone production and spermatogenesis
role of gonadotropin releasing hormone secreted from the hypothalmus
stimulates anterior pituitary to secrete LH and FSH which stimulate E and P formation in females and spermatogenesis and testosterone production in males
estrogen containing contraceptives are contraindicated in
over 35 who smoke hypertension diabetes with severe vascular disease history of stroke migraines risk factors for CVD breast, cervical, ovarian,endometrial cancer active liver disease thromboembolic disorder pregnancy
what is the most important mecahnism of action of HC
suppression of gonadotropin secretion
dose dependent inhibition of ovulation
MOA of HC
inhibits development of dominant follicle by suppressing FSH
endometrail less suitable
thickening of cervical mucus
impair tube motility
reason for ethinyl sub to estradiol
inhibits first pass metabolism and increases potency
describe first generation progestins
affinity for progesterone androgen receptors
medium androgen activity
describe second generation progestins
increeased affinity for progestine and androgen receptors
strong androgen and anti-estrogen activity increases acne and weight gain
lower VTE risk?
describe third generation progestins
greater affinity for progesterone receptors
low androgen activity
higher VTE risk?
describe unclassfied progestins
bind primarly to progesterone receptors
anti-androgenic
higher VTE risk
first gen progestin example
norethindrone
ethynodiol diacetate
second gen progestin example
levonorgestrel
norgestrel
third gen progestin example
norgestimate
desogestrel
unclassified progestin example
ddrospirenone
cyproterone acetate
metabolism of ethinyl estradiol and progestins
first pass hepatic metabolism by CYP 3A4
benefits of oral contraceptives that arent well none
treat PCOS reduce pelvic inflammatory disease reduce ectopic pregnancoes improve endometriosis reduce risk of ovarian and endometrial cancer reduce benign breast disease prtective against colon cancer maintain bone mineral density decrease risk of fibroids
too much estrogen effects
nausea
breast tenderness
headache
bloatin
too little estrogen effects
spotting
breakthrough bleeding early cycle
too much progestin effects
breast tenderness headache fatigue mood changes bloating
too little progestin effects
breakthrough bleeding late cycle
too much androgen effects
weight gain acne hhirsutism increased LDL decreased HDL
what is chloasma
irreversible darkening/pigmentation of facial skin exacerbated by sunlight
risks with hormonal contraception
venous thromboembolism MI stroke gallbladder disease breast cancer
medications which may cause contraceptive failure dur to induction of CYP enzymes
anticonvulsants antifungals antibiotics HIV meds st johns wort bile acid sequestrants
medications which may increase OC activity
CYP 3A4 inhibitors: fluconazole, grapefruit juice
vitamin C
what is effective birth control in obese women
ring
depo-provera
progestin on pill should be used in
over 35 smokers obese migraine thromboembolic or CV disease history post partum breast feeding endometriosis
MOA of mini pill
thicken cervial mucus
lower FSH and LH peaks
alter endometrium
impair sperm motility
depo provera MOA
suppresses ovulation
increase cervical mucus atrophy of endometrium
side effect of depo provera
headache weight gain decreased libido mood changes decreased BMD delay of ovulation 9 months after last dose
do progestin products increase CV, stroke, MI, or VTE risk
no
progestin only IUS MOA
decrease estrogen and progestron receptors and strong antiproliferative effect
weak foreign bod reaction
thickens cervical mucus
drug interactiosn with IUS
no becuase local action
side effecs of IUS
mood change
decreased libido
become amenorrheic
when is fertility restored in IUS
after removal
emergency contraception MOA
thickens cervical mucus
inhibits ovulation
alters endometrium
mifepristone MOA
competitively binds to both progesterone receptors blocking the effects
combo of misoprostol and mifepristone effective how many days after pregnnacy
50 days
mistoprostol MOA
prostaglandin analogue
promotes contractions
effects of mifepristone
degenerates endometrium decrease embryo support soften and dilate crevix promote release of prostaglandins increase uterine contractions
adverse effects of mifepristone
vaginal bleeding abdominal pain cramping nausea vomiting diarrhea
what is methotrexate used for in canada
ectopic pregnancies
what are ovulation inducers and what are they used for
anti-estrogens
women with anovulatory cycles and polycystic ovarian syndrome
what is clomiphene citrate
selective estrogen receptor modulator
clomiphene citrate MOA
competitive inhibitor of estrogen receptors in hypothalamus
agonist and antagonist depending on target tissue
what does clomiphene citrate do in the hypothalamus
inhibits negative estrogenic feedback, increases GnRH release causes growth of ovarian follicles with subsequent ovulation
what is letrozole
an aromatase inhibitor
letrozole MOA
blocks conversion of testosterone and androsteinedione to E2/E1 decreasing the negative estrogenic feedback at pituitary resulting in increased FSH output
example of a gonadotropin releasing hormone agonist
leuprolide acetate
uses of leuprolide acetate
endometriosis
uterine fibroids
advanced prostate cancer
leuprolide MOA
interrupts normal pulsatile stimulation of GnRH receptors inhibiting FSH and Lh secretion thereby suppressing the production of estrogen and testosterone
adverse effects of leuprolide acetate
menopausal symptoms
hot flashes
define final menstrual period
12 months of amennorhea in women with a uterus that occurs between 45-58 years old
abrupt menopause cause by
oophorectomy (remove ovaries)
radiation to pelvis
chemo
premature menopause requires
hormone therapy until age 51
when does perimenopause occur
2-8 years prior to final menstrual period
what is the hypothesis of thermoregulatory dysfunction in menopause
disturbance in thermoneutral zone in hypothalamus
increased sensitivity to core body temp changes causes vasomotor symptoms
cause of the narrowing of thermoneutral zone
elevated sympathetic activation through alpha 2 adrenergic receptors
best treatment for menopausal symptoms
exogenous estrogen widens the thermoneutral zone
common combo with systemic estrogen if uterus intact
progestogens to prevent hyperplasia and possible uterine cancer
continuous regimen for menopause
estrogen and progestogen continuously
causes unpredictable bleeding
sequential regimen for menopause
estrogen continuous
progestogen pulses for 10 days per month
causes predictable bleeding
two types of progestogen used in post menopause
micronized progesterone or
medroxyprogesterone acetate
what are vaginal estrogen therapries
local treatment of urogenital atrophy due to low estrogen levels that restores urogenital health in 3 months
examples of selective estrogen receptor modulators
tamoxifen - breast cancer
raloxifene - osteoporosis
where does tamoxifen act
antagonist in breast
agonist in endometrium and bone
where does raloxifene act
antagonist at breast and endometrium
agonist at bone
what does clomiphene do
ovulation inducer in fertility treatment
ER antagonist in hypothalamus
partial agonist in ovaries
example of a selective progestin receptor modulator
ulipristal acetate
use of selective progestin receptor modulator
treatment of moderat to severe signs of uterine fibroids in women eligible for surgery
selective progestin receptor modulator MOA
prevents progesterone from binding to the PR
direct effect of endometrium and fibroids
effect of selective progestin receptor modulator
reduces the size of uterine firoids by inhibiting cell proliferation adn inducing apoptosis
decreased bleeding
improved Hgb
decrease pain
LH purpose in men
interacts with receptors on leydig cells in the testes to enhance testosterone synthesis
FSH purpose in men
act on receptors in the sertoli cells in testes to regulate spermatogenesis
enhances synthesis of aromatase enzymes that converts testosterone to E2
why do they say testosteron acts as 3 hormones
direct action affects lean muscle mass and strength
conversion to DHT amplifies action on external genitalia and sexual ahir
conversion to estradiol acts on bone, stimulates sexual function and decreases body fat
symptoms of androgen deficiency
low libido decreased morning erections loss of body hair low bone mineral density gynecomastia small testes
