Menopause, Infertility, PCOS Flashcards
what is the definition of menopause?
permanent cessation of menstruation
defined retrospectively after 1 year of amenorrhea without any other pathological cause
what is the range of menopause years?
45-55 y/o (mean 51)
what is the biggest factor affecting menopause? others?
GENETICS - biggest
others: tobacco use, chemo, radiation, hysterectomy
how does tobacco affect menopause?
tobacco use decreases age of menopause by 2 years
what is primary ovarian insufficiency/premature ovarian failure?
premature menopause (before the age of 40)
at what age is premature menopause?
40 y/o
what are the stages of menopause?
(1) peri-menopause (menopausal transition)
(2) menopause
(3) post-menopause
at how many years does peri-menopause (menopausal transition) occur?
47 y/o - 4 years before menopause
when is peri-menopause? what’s happening in it?
right before menopause occurs
at this stage egg viability declines before there is any measurable hormonal decrease (ex: FSH, LH)
QUALITY OF EGGS GO DOWN
are hormones recommended at peri-menopause?
NO!!!
what is peri-menopause a sign of?
ovarian decline
what is happening to the menstrual cycle length in peri-menopause?
menstrual cycle length increases and then gets shorter closer to menopause
what is the pathophysiology of menopause?
decline in quantity and quality of follicles and oocytes
granulosa cells in follicles stop making estrogen and inhibin
loss of inhibin means loss of negative feedback loop to hypothalamus and pituitary -> thus, FSH and LH increase in production by pituitary
ovary can’t respond to FSH
permanent amenorrhea once all follicles are depleted
what does the loss of inhibin in menopause cause? and what does this lead to?
causes loss of negative feedback loop to hypothalamus and pituitary -> thus, FSH and LH increase in production by pituitary
menopause is what type of dx?
clinical dx
if <40 y/o and have menopause what must be done? why?
complete evaluation b/c not normal age for menopause
if 40-45 y/o and have menopause, what must be done? what must be ruled out?
evaluation similar to workup of oligo/amenorrhea
other causes of menstrual dysfunction must be ruled out
if >45 y/o and have menopause what is not recommended?
diagnostic testing is not recommended
what other considerations/situations do you need to work up for dx of menopause?
underlying menstrual disorders (ex: PCOS need FSH work-up)
OCPs (if taking them late in age b/c suppresses HPO axis)
Hysterectomy (won’t be able to tell menopause based on irregular cycle b/c there’s no uterus -> need FSH measurement)
if menopause and had hysterectomy what labs do you need?
FSH levels b/c won’t be able to tell menopause based on irregular cycles since no uterus
what is the HALLMARK sx of menopause?
hot flashes
-get sudden sensation of heat in upper chest and face and then centralizes throughout the body
other sx’s of menopause?
sleep disturbances, mood changes (depressed, anxiety), cognitive changes, vaginal dryness, decreased sexual function/activity, breast pain and tenderness, joint pain and aches
dyspareunia (b/c of vaginal atrophy/dryness)
DECREASE IN BONE DENSITY
why does vaginal dryness occur in menopause?
b/c epithelial lining of vagina and urethra are estrogen dependent tissues and in menopause have decline of estrogen
urinary sx’s of menopause?
incontinence, urgency, recurrent UTIs
recurrent UTIs can be fixed with estrogen replacement b/c related to estrogen deficiency
what is the MAIN INDICATION for HRT in menopause?
hot flashes
PE findings of labia minora in menopause?
fusion or resorption
PE findings of vagina in menopause?
atrophy and thin mucosa, pale, lack of rugae (becomes smooth), less elasticity and tutor, shorter and narrower
PE findings of cervix in menopause?
atrophy, decreases in size, can become stenosis
what happens to the uterus and ovaries in menopause?
they shrink
what happens to the breast in menopause?
decrease in size
what happens to skin/hair in menopause?
thinning of skin with decreased elasticity
loss of pubic and axillary hair
hirsutism due to increased androgen (b/c ovaries still producing androgens)
what are the long-term effects of menopause?
dementia, CV disease, osteoporosis
when is the highest loss of bone mass and osteoporosis in menopause?
at 1 year before final menstrual period and 2 years after
what do you counsel menopausal pts on?
to stop smoking, do weight bearing exercises, Ca and vitamin D supplementation
may give them bisphosphonates to prevent osteoporosis
important lifestyle modifications for menopause management?
avoid triggers that cause hot flashes like spicy foods
smoking cessation
exercise, weight loss
lubricants, vaginal dilators or intercourse
who are HRTs indicated for in menopause?
women whose sx’s can’t be controlled by lifestyle modifcations
what are HRT’s NOT indicated for? why?
NOT indicated for long-term use and prevention of disease
what can long-term use of HRT’s put you at risk for?
long-term use can put you at risk for breast cancer, uterine cancer (b/c of unopposed estrogen)
C/I’s for HRT tx for menopause?
coronary heart disease, VTE, stroke, TIA, liver disease, gallbladder disease, breast cancer, unexplained vaginal bleeding, endometrial cancer, high triglycerides, thrombophilias
what must be calculated before initiating HRT tx for menopause?
calculate risk before initiating tx
after what age does risk outweighs benefits for use of HRTs?
after 60 y/0
what is the duration of therapy for HRTs?
2-3 year; max is 5 years or don’t use after 60 y/o
when does risk of breast cancer increase when using HRTs?
after 4th year of use of HRT
how do you discontinue HRT tx?
use a taper
all routes of estrogen administration are what for symptom relief?
equally effective for symptom relief
how do you start dose of HRT?
start with lower dose and titrate up if needed
lower doses of HRT have fewer effects of what?
fewer effects on coagulation and inflammatory markers, possible lower risk of stroke and VTE
what drugs increase estrogen clearance and what will you need to do to the dose HRT with these drugs?
anticonvulsants and thyroid meds increase estrogen clearance so will need to increase dose of HRT
what does alcohol do to exogenous estrogen? limit alcohol use to how many drinks/day?
alcohol slow metabolism of exogenous estrogen, so if active heavy drinker should cut down to 1-2 drinks/day
what are the HRT medications?
oral 17-beta estradiol
transdermal 17-beta estradiol
progesterone (oral micronized)
topical vaginal estrogen replacement
SERMs
OCPs
what is the oral estrogen HRT?
oral 17-beta estradiol
what does oral 17-beta estradiol have a more favorable effect on?
lipid profiles (but unknown if long-term benefit)
risk of what with oral 17-beta estradiol? higher risk than what other HRT?
risk of VTE and stroker (higher risk than transdermal)
oral 17-beta estradiol has lower free ___?
lower free testosterone
transdermal17-beta estradiol has lower risk of what vs oral 17-beta estradiol? therefore which one is used more?
lower risk of VTE and stroke
transdermal patch used more
what is the progesterone HRT that is FIRST LINE?
oral micronized progesterone
all women in menopause with a uterus MUST have what added to their estrogen HRT? to prevent what?
a progestin added to prevent endometrial hyperplasia
what are the side effects of progesterone HRT?
mood changes, bloating
what helps to relieve the side effects of progesterone HRT?
continuous administration
if menopausal pt is not tolerating progesterone for HRT, what can you give them that is off-label use?
lower dose leveonorgestrel IUD
what is the difference in what systemic HRT treats and what topical HRT treats?
system HRT treats hot flashes
topical HRT can be used indefinitely but doesn’t treat hot flashes -> only treats local symptoms like atrophy
what do topical HRTs (topical vaginal estrogen replacement) treat?
vaginal atrophy
is progestin needed for topical vaginal estrogen replacement?
probably don’t need progestin, but if use vaginal creams you may need progestin b/c higher systemic absorption
what are the formulations of topical vaginal estrogen replacement?
vaginal ring (string)
vaginal tablet (vagifem)
vaginal cream (Premarin or estrace)
what HRT is NOT first line?
SERMs - Bazedoxifen
when would menopausal pt be put on SERM?
if can’t tolerate oral HRT or IUD
have moderate-to-severe hot flashes who have breast tenderness w/estrogen-progestin therapy or women who can’t tolerate any type of progestin therapy b/c of adrs
Bazedoxifen (SERM) use in addition to what?
estrogen
what is Bazedoxifen (SERM) used for the tx of?
tx of menopausal vasomotor sx’s and osteoporosis prevention
what does Bazedoxifen (SERM) prevent and as a result what is not necessary to administer?
Bazedoxifen (SERM) prevents estrogen-induced endometrial hyperplasia so that administering a progestin is NOT necessary
what does Bazedoxifen (SERM) increase your risk of?
VTEs
when can OCPs be used for menopause?
used in perimenopausal women who also desire contraception and for women who need control of heavy bleeding
if woman is perimenopausal and desires contraception and/or may need control of heavy bleeding, what can you give them?
OCPs
what is the OCP used for perimenopausal women? used at what age?
20mcg ethanol estradiol
used at ages 40-50
at what age do you not want to use OCPs for perimenopuase?
> 50 b/c high doses of estrogen so increases clot risk
OCPs should be avoided in who?
obese women d/t risk of VTE as well as hx/o smoking, HTN, or migraine HA’s
stop OCPs how?
by 1 pill a week (taper) otherwise get abrupt hot flashes
what are the most effective non-hormonal therapies for menopause?
SSRIs - paroxetine, fluoxetine (Prozac)
do the alternative therapies for menopause work? what should women be aware of?
NO - women should be area of safety and efficacy of many alternative therapies b/c they are unproven
what is infertility based on?
based on fecundability - probability of pregnancy with each menstrual cycle
what is primary infertility?
inability to conceive in a couple who never has been pregnant (man or woman)
what is secondary infertility?
inability to conceive in a couple with a history of prior pregnancy (man or woman)
does age play a role in infertility of men?
unclear if age plays any role in men for infertility
does age play a role in infertility of women? increased rate of what?
YES!!!
increased miscarriage rate with increased age
-damage to eggs -> get chromosomal abnormalities
when do you evaluate/refer patients for infertility?
under 35 y/o attempts for 12 months
over 35 y/o attempts for 6 months
female causes of infertility?
tubal obstruction or damage, PID, ovulatory dysfunction, uterine anomalies/adhesions, fibroids, endometriosis, cervical factors, premature ovarian failure
male causes of infertility?
varicocele, ED, testicular trauma or infection, hypogonadism, oligospermia, azoospermia, cryptorchidism
female evaluation work-up for infertility includes?
ovarian evaluation, uterine evaluation, labs, genetic testing
female PE work-up for infertility includes?
BMI, breast exam (galactorrhea), pelvic exam, skin exam (hirsutism, acne), thyroid exam
labs to obtain for female infertility work-up?
TSH (want to be < 3)
Prolactin
STI testing
Prenatal screening
Genetic testing
what is involved in ovarian evaluation for infertility?
confirm ovulation and ovarian reserve testing
how can you confirm ovulation?
use ovulation predictor kit
Can also do progesterone labs during mid-luteal phase -> if >3 then the patient ovulated
if progesterone level during mid-luteal phase >3, what does that mean?
pt ovulated
what is the MOST COMMON ovarian reserve testing for ovarian evaluation for infertility?
Day 3 labs - FSH and Estradiol
what are the ovarian reserve tests for ovarian evaluation for infertility??
Day 3 labs (M/C) - FSH and estradiol
Clomiphene Citrate Challenge Test (CCCT)
Anti-mullerian Hormones (AMH)
Antral Follicle Count (AFC)
what labs are in Day 3 ovarian reserve testing?
FSH and estradiol
what do you want FSH level to be? borderline? abnormal?
- Want <10
- 10-15 is borderline
- > 15 abnormal
what should the ovaries be doing to FSH?
suppressing FSH
why check estradiol levels in day 3 labs?
to make sure they area actually cycle day 3
also check for any abnormalities
what level should anti-mullerian hormone (AMH) for ovarian evaluation in infertility?
> 1
what is FIRST LINE uterine evaluation for infertility?
Hysterosalpingogram
what’s good about hysteroscopy for uterine evaluation in infertility?
good if only care about uterus, can also treat with it (remove polyps)
what analysis for male evaluation in infertility? when collected?
semen analysis
-collected 2-7 days after abstinence
oligospermia is most frequent cause of what in men? what does it mean?
most frequent cause of infertility; low concentration of sperm in ejaculate and may be associated with ejaculatory dysfunction
what is azoospermia? results from/
complete absence of sperm
results from congenital absence or bilateral obstruction of the vas deference or ejaculatory dcts
what is asthenospermia?
abnormal sperm motility
what is teratospermia?
abnormal morphology
what is the tx for male infertility?
based on underlying pathology
smoking cessation
what do all therapies for infertility center on?
manipulation of the physiologic HPO axis in 2 ways:
(1) ovulation induction
(2) controlled ovarian stimulation - use gonadotropins
most common ovulation induction agents?
Clomid -> SERM
Letrozole -> aromatase inhibitors
what is the end result of how clomid works?
makes higher plasma levels of FSH and LH which stimulate ovarian follicular growth
tricks brain into thinking estrogen is low so secretes a lot of FSH -> follicles grow -> egg
whats the FIRST LINE tx for ovulation induction for infertility?
Clomid
side effects of Clomid?
typical menopause sx’s
- vasomotor symptoms
- mood swings
- visual sx’s -> D/C med
when do you D/C Clomid?
when visual sx’s occur (blurred or double vision)
main adr of Clomid?
ovarian cancer if used >12 months/cycles
what is Preimplantation genetic screening (PGS)? reason to do it?
genetic testing for embryo - both parents are chromosomal normal so screen embryos for aneuploidy
recurrent pregnancy loss
what is preimplantation genetic dx (PGD)?
one or both parents carry a specific known genetic mutation or defect
screens embryos for that defect
what is PCOS characterized by?
amenorrhea, obesity, hirsutism
PCOS is due to?
insulin resistance
PCOS risk factor for?
CVD, obesity, DM
endometrial hyperplasia and endometrial cancer
why PCOS at risk for endometrial cancer?
b/c of unopposed estrogen exposure
dx of PCOS? what criteria?
Rotterdam criteria - 2/3 of following:
(1) ovulatory dysfunction (oligo and/or an ovulation)
(2) chemical and/or biochemical signs of hyperandrogenism
(3) polycystic ovaries on US
main tx for PCOS if not pursuing pregnancy?
OCPs
main tx for PCOS if pursuing pregnancy?
Letrozole
