Menopause Flashcards
What is menopause?
WHO defines natural menopause as at least 12 consecutive months of amenorrhea not due to physiological/pathological causes.
Natural event reached upon exhaustion of primordial follicles.
The global age at menopause is on average 51 years (range 40-60 years) suggesting a distinct genetic control; strong correlation
exists between mothers and daughters
What is the global age at menopause?
The global age at menopause is on average 51 years (range 40-60 years) suggesting a distinct genetic control; strong correlation exists between mothers and daughters.
What are menopausal health aspects?
bone density(oestrogen has implication on bone density), breast, the cardiovascular system, mood/cognitive function and sexual well being.
Common symptoms of menopause include:
-Hot flushes, night sweats, vaginal dryness and discomfort during sex,
difficulty sleeping, low mood/anxiety, reduced libido
-Physical and emotional changes strongly affect women
- 1:10 women experience suicidal thoughts due to the perimenopause
Changes in the number of germ cells in the human ovary during fetal development and throughout postnatal life.
=> timing of your menopause depends on when you start your periods
rate of decline of Non - Growing Follicle and age of menopause depends on…
The ovarian reserve will determine the rate of decline of NGF & age of the menopause
Model demonstrating the individual variation of the initial size of the non growing follicle
(NGF) pool and subsequent decline in NGFs until ovarian depletion - when NGF count
<1000. At birth the ovary contains about 500,000-1million primordial follicles
Estimated that for 95% of women by 30yrs only 12% of max. pre-birth NGF population is present and by 40yrs only 3% remains.
Schematic representation of the age variations of the various stages of female reproductive aging, depicted in a cumulative fashion.
The ovarian reserve will determine the onset of subfertility to sterility and to complete loss of menstrual cycles (menopause)
Various factors affecting ovarian
reserve
-Genetics
-autoimmunity
-ethnicity
-androgens/PCOS
-Genetic abnormalities, some medications, injury
- in utero environment
- nutrition
What is a serum marker to estimate your ovarian reserve and your potential time of menopasue?
AMH
The levels of AMH in the human circulation vary during the life cycle, with sexually dimorphic pattern.
-high AMH before birth on male fetus in utero (AMH in nanomolar )
- AMH is not present in female fetus in utero
-AMH levels decline in boys and adult men
- In adult male and females in picomolar nanomolar> picomolars (1nM = 100pM)
With age AMH levels decline
AMH is secreted from growing follicles
Declining follicle number with age = declining AMH levels
Below 15 picamolar of AMH baseline = indicates low ovarian reserve = menopause earlier
above 40 picamolar at baseline = high ovarian reserve = related to PCOS = menopause later
so are AMH levels becoming a gold standard biomarker to evaluate an ovarian reserve and predict ovarian response to hormonal stimulation?
- no
-AMH and AFC are used to diagnosed premature ovarian failure/insufficiency
What is the function of AMH?
- inhibits primordial -> primary pre antral transition
- inhibits FSH causing follcilular arrest of secondary, small antral and antral follicle
What happens to inhibin B levels as you approach menopause?
less because inhibin B is produced by the growing follicle to inhibit FSH levels so growing follicle can reach the right size and isn’t overstimulated = approaching menopause follicle number decreases = so less inhibin B
What happens to FSH as you approach menopause?
FSH levels rise during menopause because
1. AMH and Inhibin B levels decrease so less suppresion of FSH, as you approach menopause follicle number decreases so less inhibin B keeping FSH levels low = increase in FSH levels
Hormonal changes during the menopause
- ovarian failure begins around 35 years and ends with menopause around 51 years
-big decline/drop in oestrogen because oestrogen is also coming from granulosa cell of follicle = less follicle number = less oestrogen
-decline in inhibin B = decline in follicles = rise in FSH due to loss of negative feedback inhibin B had - decline in inhibin B and AMH - these factors are secreted by pre-antral, secondary, antral = decline in these cells during menopause
-decline in androgen synthesis from ovary = androgen converted to oestrogen = decline in oestrogen leads to substrate (androgen) also being lost.
Why is there a decline in follicles during menopause in the first place?
- follicles depleted over the years in each menstrual cycle
- we are born with lifetime ovarian reserves and we run out as we get older
What serum conc of hormones are suggestive of menopausal transition?
menopausal transition/perimenopausal = decline in estradiol , testosterone, estrogen and a gradual rise in FSH and LH.
Hormone conc can be measured to diagnose premenopausal state.
What are the symptoms and their onset of menopause
- hot flushes/sweating = linked with drop of oestrogen
- vaginal wall atrophy (smaller) = linked to drop of oestrogen
- urge incontinence = drop of oestrogen
- oestreoprosis = drop oestrogen = a bit later on in menopause
What are limitations of collecting menopausal data?
+ incidence and prevalence of reported symptoms vary from different cohort studies = data is self reported = bias - it is what people feel/no reported clinically = physiological differences in women causes the differences too - subjective = hard to draw general conclusion and generate quantitative data
solution = women are told to record the frequency of symptoms , ie hot flushes frequency rather than how they feel , to make the data more objective and generate quantitative data.
why do we get hot flushes?
- oestrogen drop = oestrogen linked to noradrenergic system in the brain which plays a major role in thermogenesis. Other neuronal systems have also been implicated such as endorphin pathway.
- ‘wet’ flushing occurs through inappropriate vasodilation and activation of sweat glands through both central and peripheral mechanism
Oestroporosis in menopause
- women can lose up to 20% of their bone density om 5 to 7 years after the menopause
- The drop in bone density is caused by falling levels of estrogen which impairs the normal cycle of bone remodeling
- increases the amount of bone reabsorbed (osteoclastic activity) compared to amount deposited (osteoblastic activity) - leading to net loss of bone
- although bone density decreases at menopause, the risk of osteoporosis and bone fractures are relatively low bc other factors are also involved in bone strength
- treatment = calcium and vitamin supplements
Genitourinary syndrome of menopause
GSM - a relatively new term for the condition, previously known as vulvovaginal atrophy , atrophic vaginitis or urogenital atrophy
-post-menopausal hypoestrogenic state of GI tract
- treatment = to reduce symptoms
