Flashcards in CM- Menopause Deck (37):
What are the STRAW classification stages based on?
What are the 3 major categories?
Menstrual cycle patterns divide menopause into the following 3 cycles:
2. perimenopausal/ menopause transition
3. post menopause
According to STRAW classification, what are the somatic and hormonal changes that occur in late reproduction stage -3b? -3a?
In -3b, the menstrual cycle is still regular but the hormone levels of FSH, AMH are low and the antral follicle count is low.
In -3a, there are subtle changes in flow and length. The FSH is variable, while AMH, inhibin and the number of antral reproductive follicles are low.
A women is experiencing a variable menstrual cycle where there are persistent differences of over 7 days between days of consecutive cycles.
When you measure her hormones, you note a variable increase in FSH, with low AMH, inhibin, and decreased number of antral follicles.
Aside from the irregularity of the period, she is showing no symptoms. What STRAW stage is she most likely in?
How long does this stage usually last?
Early menopausal transition [early perimenopause]
Stage length is variable
A woman is experiencing intervals of amenorrhea where periods are over 60 days apart.
Her FSH level is over 25 and her AMH, inhibin, and antral follicle number are low.
She has started experiencing vasomotor symptoms [hot flashes].
What stage of the STRAW classification is she most likely in?
Late menopausal transition [late perimenopause]
A womans FMP occurred over 12 months ago. Her FSH is variably increased with low AMH, inhibin and very low antral follicle count.
She is experiencing vasomotor symptoms [hot flashes] regularly. What stage of STRAW classification is she most likely in?
How long does this stage tend to last?
early post menopause because FSH is still moderately elevated, but she has no period
Early post menopause usually lasts 2 +/- 1 year
A woman has not experienced a period for 10 years.
Her labs show stabilized FSH, low AMH, inhibin and VERY low antral follicle number.
She has started experiencing vaginal atrophy noted by increased pain with sex. What STRAW stage is she most likely in?
Late menopause due to the the vaginal atrophy
What is the exact definition of menopause [as we currently understand it]?
It is a retrograde diagnosis because it is defined as a specific point in time secondary to:
1. genetically programmed follicle loss
2. surgical excision of the ovaries
This specific point in time is the FMP. This is denoted as the last menses before 12 months of amenorrhea
What is menopausal transition?
Stage -2 to stage-1 where menstrual cycle changes and endocrine changes are observed. It begins with varying menstrual cycle length and the rise of FSH and ends with the FMP.
What is postmenopausal?
The time period from FMP to death.
+1 = early--> 5 years after FMP [dampening of hormone function is still occuring, time of increased bone loss]
+2 = late
What are the 4 major factors affecting the age of menopause?
1. smoking bumps it up by 1-2 years
2. genetic - daughters will start menopause around the same time their mothers did
3. Chemotherapy and pelvic irradiation can abruptly lead to menopause or advance the age depending on the duration bc they destroy rapidly dividing germ cells
4. procedures that alter ovarian blood flow like Uterine artery embolization (UAE) used to treat fibroids or bilateral tubal ligation may advance the age of menopause
_____________________ is generally considered to be the primary event defining menopause, but recent studies suggest that __________ precede overt ovarian failure and may contribute to the rapid decline of ovarian function with aging.
Depletion of the # of oocytes is generally considered the primary event
Neuroendocrine changes precede overt ovarian failure
What are the early symptoms of postmenopausal women?
1. VMS -hot flashes
2. menstrual irregularity
3. night sweats
6. mood disturbances
What are the intermediate physical changes associated with postmenopausal women?
1. vaginal atrophy
2. loss of urogenital integrity [freq, incontinence]
3. loss of skin elasticity
What are the late diseases associated with postmenopausal women?
3. alzheimer's and memory and cong. decline
5. macular degeneration
6. hearing loss
7. decreased balance
8. decreased quality of life
Chronic anovulation and deficient progesterone lead to intermittent amenorrhea followed by long, heavy anovulatory bleeding.
What STRAW stage does this occur in?
What must you do for these women?
Late menopausal transition.
The irregular bleeding shows that estrogen is still present but is most likely unopposed by progesterone [hence anovulatory cycle]
Therefore women with >7 days and/or heavy perimenopausal bleeding should get an endometrial biopsy to rule out endometrial hyperplasia [which leads to cancer]
A woman comes in complaining of a prodrome headache, followed by a sensation of heat in the face, neck and chest that travels cranial to caudal.
It lasts for 1-5 minutes and can repeat up to 20x a day.
After the heat passes, she experiences perspiration, palpitations and then chills.
This happens more frequently at night and she wakes up with drenched sheets.
What is she experiencing? What is the physiological cause?
What is the most effective treatment?
This is a hot flash and affects 75% of postmenopausal women [including those with surgically induced menopause].
They result from a decline in estrogen.
It is likely mediated by CNS site and is caused by a sudden lowering of the hypothalamic thermoregulatory set point.
The core temperature must be reduced by vasodilation causing increased cutaneous blood flow and heat loss.
HT [ET, EPT] is the most effective treatment for hot flashes
What are the 3 main genitourinary changes associated with menopause?
1. vaginal dryness- lack of estrogen leads to atrophy, thinning, dryness. this causes spotting, burning, dyspareunia, itching and irritation
2. Sexual dysfunction - decreased lubrication due to estrogen deficiency and decreased vaginal flow-->dyspareunia. Reverse with topical estrogen
3. Urinary urgency, frequency, dysuria and stress incontinence. Estrogen has no benefit for incontinence but because transitional epithelium of the vagina is estrogen sensitive, it can help with the frequency, dysuria
What is the impetus for the HP axis changes that occur during menopause?
The depletion of ovarian follicles leads to estrogen deficiency [<20] so there is less negative feedback on the HP axis. This leads to an increase in GnRH and FSH/LH [rise from 3.5 to 40]
What are the 2 current markers of "ovarian reserve"?
AMH and inhibin will reduce even before FSH increases.
AMH is the most sensitive indicator of ovarian reserve and ovarian failure
What is osteoporosis?
When in the postmenopausal cycle is it most accelerated?
What is the physiological cause for the acceleration?
1. decreased bone mass
2. disturbed skeletal architecture [reduced trabeculae]
In the first 5-7 years after menopause, 20% of the bone loss will occur.
After that, 1-2% a year is lost
Estrogen usually decreases osteoclast activity so after menopause the decrease in estrogen leads to unbalanced resorption of bone exceeding formation. 80% is in trabecular bone so vertebrae and femoral bones are affected the most
What factors are known to increase the risk of osteoporosis in post menopausal women?
1. white or asian
2. low body weight
3. positive family history
4. low Ca and vit D diets
5. caffeine, protein
7. sedentary lifestyle
After menopause, the incidence of CHD in women increases drastically and is the leading cause of death. Why does the incidence increase?
Lack of estrogen leads to:
1. increased total cholesterol
2. increased LDL, decreased HDL
3. decreased prostacyclin
4. increased proinflammatory cytokines
5. decreased NO synthase
6. increased endothelin
What was the difference between the observational study with women on HRT and the WHI that may account for why the observational studies found a decreased risk of CHD, while the WHI found an increased risk of CHD?
Observational studies were of younger [50s] women that were experiencing hot flashes.
The WHI/RCT was done in older women[avg 63] and any women having hotflashes were excluded because they would know if they had HRT vs. placebo
How is the diagnosis of menopause made?
How does diagnosis differ in a woman who has had a hysterectomy but not an oophorectomy?
Diagnosis is usually clinical based on symptoms of amenorrhia for >12 months and hot flashes.
If a woman had a hysterectomy [no periods] you measure the FSH levels. 2 consecutive months of >30 = menopause. Estrodiol levels can be measured too
What did the WHI find that ET/EPT put patients at an increased risk for?
What did it decrease?
Increased risk of:
1. breast cancer
4. TE, DVT, PE
1. reduced osteoporosis/hip fractures
2. decreased colon cancer risk
What are the variables that affect the risk/benefit of ET/EPT?
2. TIME SINCE FMP
3. route of delivery [transmural = less thrombogenic compounds made due to decreased first pass in liver]
4. formulation and dose
5. use and type of progestogen
What is the timing or critical window hypothesis?
ET/EPT may prevent coronary artery disease if given early in menopause but can be bad if given in late menopause.
The reverse if thought to be true of breast cancers. ET/EPT is bad if given early, better if given late
What treatment is given for menstrual irregularities associated with menopause?
1. usually nothing as it is considered a normal occurrence
2. Frequent, prolonged, heavy can be treated with low dose OCP which can continue until the period ceases at 52-55
What treatment is given for vasomotor symptoms associated with menopause?
1. ET/EPT improves the freq and duration of hot flashes. They can be pills, patches, transmural, etc. Relief in 4-6 wks
2. SSRI - 50% decline in hot flashes and are used for women with breast cancer where estrogen is contraindicated
3. behavioral therapy- lower ambient temp, dressing in layers, stretching, slow breathing
What is used to treat the vaginal atrophy associated with menopause?
Vaginal estrogens (creams, tablets, ring) improve 80-100% of atrophy.
Progesterone is usually not indicated when low-dose estrogen is administered vaginally
What is the effect of ET/EPT on osteoporosis?
WHI showed a benefit via:
1. 1/3 fewer hip and vertebral fractures
What is the effect of ET/EPT on demetia and cognitive decline.
They should NOT be used for demetia/cogn decline after 65 because they may actually increase the risks.
Timing hypothesis may apply here:
early may prevent dementia, late may worsen prognosis
What is the effect of ET/EPT on colorectal cancer?
37% risk reduction in colon cancer with EPT users
What is the indication for using progestogen therapy?
When you are giving estrogen to a woman who still has a uterus, you must give progesterone to prevent endometrial hyperplasia and cancer from unopposed estrogen.
W/o a uterus, you don't need to give progesterone
What are the 3 most serious adverse effects of ET/EPT therapy?
1. CHD- not recommended for primary or secondary prevention of CHD in women of any age and may increase the risk
2. DVT, PE - ET/EPT increase the risk of VTE and stroke in postmenopausal women [transdermal may decrease the risk by eliminating 1st pass]
3. Breast cancer - estrogen is a promoter that can make E sensitive breast cancers grow faster, but it cannot INITIATE breast cancer.
*Risk of cancer is increased with 5yrs EPT use.
*risk not shown to increase with ET alone
What is the FDA indications for postmenopausal estrogen use?
1. treat moderate/severe vasomotor symptoms
2. treat moderate/severe vulvovaginal atrophy
3. prevent osteoporosis when non-estrogen medications are not appropriate.
Use the smallest dose possible for the shortest amount of time .