estrogen Flashcards
where are GnRH neurons
in the hypothalamus
what is GnRH
gonadotrophin releasing hormone
when do GnRH neurons fire
at hourly intervals
where does the GnRH act
on anterior pituitary gland (gonadotropes)
where are gonadotropes
anterior pituitary gland
what do the gonadotropes release
gonadotrophins
what are the 2 gonadotrophins
luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
where does LH and FSH act
on the ovary
what does the ovary release
estrogen and progesterone
when in the menstrual cycle does LH peak
right before ovulation
when in the menstrual cycle does FSH peak
right before ovulation
when in the menstrual cycle does estradiol peak
before ovulation, then a bit more later in the cycle
when in the menstrual cycle does progesterone peak
later in the cycle, day 21
what causes LH and FSH peak in the menstrual cycle
estrogen acting as a positive regulator on the gonadotrophins until the ovum is released
what does estrogen do to the gonadotropes usually
inhibit
what does progesterone do to the gonadotropes
inhibit
what does progesterone do to the hypothalamic GnRH neurons
inhibit
where does estrogen inhibit
anterior pituitary gonadotrope glands
where does progesterone inhibit
anterior pituitary gonadotrope glands and hypothalamic GnRH neurons
what is E2
estradiol
what is another name for estradiol (2)
E2 or estradiol-17β
what are the 3 types of estrogens
E1 - estrone
E2 - estradiol
E3 - estriol
which estrogen is the most potent
E2
which estrogen is the main endogenous estrogen
E2
where is E2 synthesized in females
in the ovary and placenta
where is E2 synthesized in males
testis and adrenal cortex
what is the name for E1
estrone
what is the name for E2
estradiol
what is the name for E3
estriol
how potent is E1
not, low binding affinity for estrogen receptors
how potent is E3
not, low binding affinity for estrogen receptors
where is E1 synthesized
in liver from estradiol
in peripheral tissues from androstenedione and other androgens
where is E3 synthesized
in liver from estradiol
in peripheral tissues from androstenedione and other androgens
which E is made in the ovaries
E2
which E is made in the liver
E1 and E3
where is estradiol metabolized
into the liver
what is estradiol metabolized into
estrone, estriol, conjugated metabolites
what is estradiols binding to albumin like
weak
how long is the half life for estradiol
short, only minutes
what is SHBG
sex hormone binding globulin
what is estradiols binding to SHBG like
stronger
where does estradiols bind weak
albumin
where does estradiols bind strong
SHBG (sex hormone binding globulin)
what increases sex hormone binding globulin
estrogen and thyroid hormone
what decreases sex hormone binding globulin
androgen and growth hormone
where are estradiol conjugated metabolites excreted
in bile then GI tract
what happens with estradiol conjugated metabolites in the GI tract
they may be hydrolyzed to active estrogen in GI tract and reabsorbed (via bacteria)
what can antibiotics do to birth control efficacy and why
decrease cause less estrogen can be made in GI from the estradiol conjugated metabolites
how do non genomic actions of estrogen work
rapid effects via plasma membrane estrogen receptors
what does estrogen do to acute blood vessel diameter
acute vasodilation
how do genomic actions of estrogen work
intracellular estrogen receptors, ERα and ERβ
where are ERα and ERβ
in female reproductive tract, breast, pit, hypo, bone, liver, etc
what does ERα and ERβ receptor activation cause
changes in gene transcription
how are synthetic estrogens made (what are 2 types)
- chemical alternations to the estrogen molecule
- non-steroidal compounds with estrogenic activity
why do we make synthetic estrogens from chemical alternations to the estrogen molecule
to increase the effectiveness of oral administration
what are non-steroidal compounds with estrogenic activity structurally like
presence of phenolic A ring which is important for binding to ER
what does estrogen do to growth spurt
helps with the long bones and epiphyseal closure
what does estrogen do to female maturation
- growth of vagina uterus fallopian tubes
- secondary sex characteristics
what are 3 female secondary sex characteristics
- enlargement of breasts
- changes in distribution of body fat
- growth of axillary and pubic hair
what does estrogen do to endometrium
increase in thickness and vascularity of endometrium
what does estrogen do to regulation of menstrual cycle
brief positive feedback on the pituitary to stimulate pre-ovulatory LH and FSH surge mid cycle
what does estrogen do to progesterone receptors + where
increases progesterone receptor synthesis in uterus vagina pituitary and hypothalamus
what does estrogen do to blood + how
increase coagulation - decrease in anticoagulation factors
what does estrogen do to bone
decrease in resorption by increase osteoclast apoptosis and decreasing the maturation of osteoclasts
what does estrogen do to osteoclast
increase apoptosis and decrease maturation
what does estrogen do to binding proteins
increase levels of corticosteroid-binding globulin, sex steroid-binding globulin and thyroxine-binding globulin
what does estrogen do to plasma lipids (3)
increase HDL (good) decrease LDL (bad) small increase in triglycerides
what does estrogen do to HDL
increase
what does estrogen do to LDL
decrease
what does estrogen do to triglycerides
small increase
what does estrogen do to salt and water intension and how
increase likely by ADH release
what are 4 therapeutic uses of estrogen
- primary hypogonadism
- amenorrhea
- birth control
- postmenopausal hormonal therapy
what is estrogen often combined with therapeutically
progesterone
what is primary hypogonadism
failure of ovarian development
what are 3 uses of postmenopausal hormonal therapy
decrease vasomotor symptoms
reduce genitourinary syndrome
reduce osteoporosis
what are 4 vasomotor symptoms of menopause
- hot flashes
- inappropriate sweating
- irritability, difficulty concentration, mood changes
- insomnia
what are 3 genitourinary symptoms of menopause
- genital dry/burn/irritation
- sexual pain / less lubrication
- urinary urgency, dysuria, UTIs
what is dysuria
painful or difficult urination
what are 2 main untoward effects of estrogen
cancer (breast and endometrial)
embolisms
what kinds of cancer are common with estrogen
breast and endometrial
how can you reduce the risk of endometrial carcinoma with estrogen
progesterone supplement (prevents proliferation caused by E)
what does estrogen do to embolisms
small increase risk of pulmonary embolism and venous thromboembolism
what are 4 contraindications for estrogen
- estrogen dependent cancer
- undiagnosed genital bleeding
- history of thromboembolic disorders
- liver disease
what was the point of the womens health initiative
assess the major health benefits and risks associated with the use of estrogen or combined estrogen/progestin preparation in hormone replacement therapy
what is the most effective treatment for vasomotor symptoms and genito-urinary syndrome
hormone therapy
what can hormone therapy do to bone loss and fracture
prevent
who is hormone therapy most beneficial for
women under 60 or within 10 years of menopause with VMS and high risk for bone loss/fracture
who is hormone therapy least beneficial for
women over 60 or more than 10 years of menopause due to coronary heart disease, stroke, thromboembolism, and dementia risk
what was the conclusion of womens health initiative
therapy with estrogen/progestin or 5.6 years or estrogen for 7.2 years was not associated with all-cause, cardiovascular or cancer mortality during cumulative follow-up of 18 years
what do anti-estrogen drugs do / mechanism of action (tamoxifen)
partial agonist inhibitor of estrogen receptor
what is tamoxifen
anti-estrogen
what is mechanism of action of tamoxifen
partial agonist inhibitor of estrogen receptor
what does tamoxifen have estrogenic effects on (4)
- bone (less osteoporosis)
- plasma lipids (more HDL good)
- endometrium (cancer!)
- blood coagulation (clot!)
what does tamoxifen have anti-estrogenic effects on (1)
breast tissue
what are non estrogen receptor mediated actions if tamoxifen
modulation of signalling proteins and activation of apoptosis
what can be a good use of tamoxifen and why
breast cancer because it has anti-estrogenic effects on breast tissue
what are 2 types of aromatase inhibitors
steroidal or non steroidal inhibitor of aromatase
what do aromatase inhibitors do
selective inhibition of estrogen synthesis
what are aromatase inhibitors used for
breast cancer
what does aromatase inhibitors do to estrogen synthesis
reduce
do aromatase inhibitors stimulate endometrial tissue
no
do aromatase inhibitors increase risk of uterine cancer
no
do aromatase inhibitors increase risk of venous thromboembolism
no
do aromatase inhibitors have a beneficial effect on bone
no
what is the mechanism of action of clomiphene
anti-estrogen : reduces estrogen binding in gonadotropes, decrease in negative feedback
what does anti-estrogen clomiphene do to gonadotrophins
increase secretion of them (LH FSH)
what does anti-estrogen clomiphene do to estrogen secretion
increase
what does anti-estrogen clomiphene do to ovulation
increase
what is the use of anti-estrogen clomiphene
treatment of infertility and amenorrhea
what are 5 unwanted effects of anti-estrogen clomiphene
- ovarian enlargement
- ovarian cysts
- hot flashes
- blurred vision
- multiple births
