Menopausal Hormone Therapy; Selective Estrogen Modulators and Tissue Selective Estrogen Complexes Flashcards
what are the symptoms of menopause
hot flashes, night sweats, vaginal dryness (painful intercourse) , sleep disturbances, mood disorders, urinary incontinence
anybody who wants MHT needs 1 or more of these signs
what disorders have an increased prevelance in menopause
cardiovascular effects (ACS, MI)
bone effects (osteoporosis, osteopenia)
when a premenopausal/menopausal patient presents to you, you should be asking about these things
the primary therapy for menopausal symptoms is _
estrogen
with or without the addition of progestin
women with an intact uterus must also be on a _ along with the estrogen)
progestin
why do women with an intact uterus going through menopause need to be on both estrogen and progestin?
because unapposed estrogen increases the risk of endometrial hyperplasia/carcinoma
pharmacotherapy during peri-menopause can also commonly consist og _ therapy
combinedation hormonal contraceptives
combined hormone contraceptive therapy provides _ regulation and _ protection
hormone regulation
pregnancy protection
available formed of estrogen (4)
- estradiol
- conjugated estrogens
- esterified estrogens
- estropipate
estradiol is in _ form in the tablet/vaginal ring and _ form in the injectable version
acetate
cypionate
conjugated estrogens are a blend of many _ derivatives that are derived from estrogens found in the _
estrogen
urine
esterified estrogens are a combination of _ and _
Na+ estrone sulfate (majority)
Na+ equillin sulfate (minority)
estropipate is a cyrstalline estrone solubilized sulfate and stabilized with?
piperazine
progesting _ (enhance/oppose) estrogen effects
oppose
what are the avaibale progestenic components
medroxyprogesterone MPA
methytestosterone
Progesterone
medroxyprogesterone MPA is given with what estrogen?
CE: conjugated estrogens
methyltestosterone is given with what estrogen?
EE: esterified estrogens
what is the MOA of exogenous estrogen?
bind to the estrogen receptors in various tissues and is transferred to the nucleus which results in increase gene and protein expression that give the physiological responses of estrogen
estrogen effect on the endometrium
proliferation
increased risk of hyperplasia and carcinoma this is why this is not given alone in someone who still has their uterus
estrogen effects on lab results:
cholesterol
antithrombin III
osteoclastic bone activity
triglycerides
clooting factoris
platelet aggregation
sodium/fluid retention
thyroid binding TBG
estrogen will work to decrease cholesterol LDL/TC (this is good)
it will decrease antithrombin III activity (break up a clot)
will decrease osteoclastic acivity
will increase HDL and triglycerides (good)
will increase clotting factors and platelet aggregation (higher chance of clotting-not good)
increase sodium and fluid rentention (bloating and puffy)
increase thyroid binding globulin (TBG)
womens health initiative study said that MHTs are benifical or preventative effects are on ? and risks of various _
preventative effects on heart disease, osteoposis related fractures
risk of various cancers though
what are the benefits of both combined MHT and estrogen only MHT (people with no uterus)
benefits are a decrease in diabetes and fractures
what is a benefit singular to combined MHT (estrogen and progestin in a patient with a uterus)
decerase in colorectal cancer
what is a benefit to just estrogen MHT
decrease in invasive breast cancer
what are some harms associated with both combination MHT and estrogen only MHT
dementia
gall bladder disease
stroke
VTE
urinary incontience
what are some harms associated with just combined MHT
increased risk of breast cancer (invasive) and increased risk of coronoary heart disease
MHT very effectively minimizes/treates _ symptoms and _ changes
vasomotor symptoms
and vaginal changes
MHT should not be used to prevent _ or _
CVD or dementia
MHT benefit on bone and colon cancer are outweighed by _
all the other risks
for younger women with menopausal symptoms can you give them MHT?
yes, it can treat troubling menopausal symptoms in the relatively young and within 10 years of menopause
you can individualize this to your patients
they dont have to be on it forevere
start with patch over oral therapy
for women with vaginal symptoms only the preffered treatment is?
low dose vaginal estrogen topicals
both estrogen alone therapy and estrogen with progestin increases risk of _
blood clots
counsel your patients
alhtough risks of blood clots and stroke increase with either MHT, risk is less in _ year old age group
50-59 year old
there is an increased risk of _ cancer seen within 2-4 uears of continuous estrogen with progestin therapy
breast
for women at risk for breast cancer, maybe shouldnt give them this
MHT take home messages
use the _ (lowest/highest) dose possible to control symptoms
treat for the _ (shortest/longest) duration possible and re-evaluate at least yearly )
lowest
shortest
make sure you document everything
risks and benefits of MHT are essentially eliminated several years after MHT is stopped
what are SERMS
selective estrogen receptor modulators
what is the goal of a SERM
to be proestrogenic at select tissues like the bone, vagina, and hotflashes
but to be anti estrogenic at other sites like the breast or the endometrium
whar are TSECS
tissue selective estrogen complexes
what is the goal of TSECs
to combine the unique elements of a SERM with an estrogen compound
SERMs are replacing progestin actions of traditional progestin- inclusive
MHT
what are the SERMs we need to know?
ospemifene
clomiphene
what is a TSEC we need to know about?
Bazedoxifene
this is a combo with conjugated estrogen and selective receptor modulator
not available in a single ingredient compound
OSpemifene indications (serm)
dypareunia (symptom of menopause due to vaginal atropy)
vaginal dryness
if vaginal dryness is the only issue maybe just topical
MOA of ospemifene (SERM)
functions as an estrogen agonist by binding to ER in the vagina but anti- estrogenic at the breast
increases vaginal secretions, decreases vaginal pH, reduces pain during intercourse, increase superifical cell growth
side effects of ospemifene
hot flashes, estrogenic effects of coagulation/endometrial thickening and hyperplasia
contrainications of ospemifene
AUB, thromboembolic events, estrogen related neoplasia
bazedoxifen is used in women with a _ uterus
intact
bazedoxifence with a conjugate estrogen is used for?
menopausal symptoms in women with a uterus
prevention of post menopausal osteoporosis in women with a uterus
MOA of bazedoxifene (TSEC)
antagonistic affect in the endometrium (prelaces the progestin concept in tradiational MHT) and in breast tissue
agonist/estrogenic physioloigcal effect in bone
does not stimulate endometrial proliferation
destroys HER2 malignant cells
TSECS with Conjugated estrogen have replaced what
traditional MHT therapy with progestin
this is because they are anti-estrogenic at the places where unapposed estrogen could create problems
less vaginal bleeding compared to progestin therapy
side effects of bazedoxifene
all estrogen related side effects: DVT, dementia, stoke, gall bladder disease, urinary incontinence
specific: worsening of hot flashes
contraindicated in all estrogen situations
what is clomiphene
an anti estrogen SERM that is used in infertility and anovulatory women, irregular ovulation, luteal phase defects, PCOS
used in infertility !
MOA of clomiphene
blocks inhibitory/negative feedback actions of estrogen oon the hypothalamus preventing estrogen from lowering GNRH on the pituitary gonadotropin release (LH and FSH)
increases gonadotropin (LH and FSH) secretion to help stimulate ovaries to develop oocyte follicles
given orally between cycle days 5 and 9
side effects of clomiphene used in infertility
- multiple gestations
- ovarian cysts
- hot flashes
- luteal-phase dysfunction (inadequate progesterone production)
