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Menopause Flashcards

1
Q

What is menopause?

A

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

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2
Q

What is the global age at menopause?

A

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.

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3
Q

What are menopausal health aspects?

A

bone density(oestrogen has implication on bone density), breast, the cardiovascular system, mood/cognitive function and sexual well being.

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4
Q

Common symptoms of menopause include:

A

-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

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5
Q

Changes in the number of germ cells in the human ovary during fetal development and throughout postnatal life.

A

=> timing of your menopause depends on when you start your periods

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6
Q

rate of decline of Non - Growing Follicle and age of menopause depends on…

A

The ovarian reserve will determine the rate of decline of NGF & age of the menopause

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7
Q

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

A

Estimated that for 95% of women by 30yrs only 12% of max. pre-birth NGF population is present and by 40yrs only 3% remains.

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8
Q

Schematic representation of the age variations of the various stages of female reproductive aging, depicted in a cumulative fashion.

A

The ovarian reserve will determine the onset of subfertility to sterility and to complete loss of menstrual cycles (menopause)

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9
Q

Various factors affecting ovarian
reserve

A

-Genetics
-autoimmunity
-ethnicity
-androgens/PCOS
-Genetic abnormalities, some medications, injury
- in utero environment
- nutrition

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10
Q

What is a serum marker to estimate your ovarian reserve and your potential time of menopasue?

A

AMH

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11
Q

The levels of AMH in the human circulation vary during the life cycle, with sexually dimorphic pattern.

A

-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)

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12
Q

With age AMH levels decline

A

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

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13
Q

so are AMH levels becoming a gold standard biomarker to evaluate an ovarian reserve and predict ovarian response to hormonal stimulation?

A
  • no
    -AMH and AFC are used to diagnosed premature ovarian failure/insufficiency
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14
Q

What is the function of AMH?

A
  • inhibits primordial -> primary pre antral transition
  • inhibits FSH causing follcilular arrest of secondary, small antral and antral follicle
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15
Q

What happens to inhibin B levels as you approach menopause?

A

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

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16
Q

What happens to FSH as you approach menopause?

A

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

17
Q

Hormonal changes during the menopause

A
  • 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.
18
Q

Why is there a decline in follicles during menopause in the first place?

A
  • follicles depleted over the years in each menstrual cycle
  • we are born with lifetime ovarian reserves and we run out as we get older
19
Q

What serum conc of hormones are suggestive of menopausal transition?

A

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.

20
Q

What are the symptoms and their onset of menopause

A
  • 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
21
Q

What are limitations of collecting menopausal data?

A

+ 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.

22
Q

why do we get hot flushes?

A
  • 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
23
Q

Oestroporosis in menopause

A
  • 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
24
Q

Genitourinary syndrome of menopause

A

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

25
Q

Premature ovarian failure (POF) / insufficiency (POI)

A
  • cessation of ovarian function before 40 years
  • affects 1 in 100 women - before 40 Y/O
  • affects 1 in 1000 women - before 30 y/O
26
Q

What are causes of POI?

A
  • genetic
    -congenital enzymatic deficiencies - galactosemia
  • vaccination - Anti - HPV
    -Gonadal dygenesis
  • autoimmune - anti ovarian antibodies
  • oncologic treatment
  • viral infection
27
Q

Investigating POF – hypergonadotrophic - hypogonadism

A

-low estradiol (<20 IU/I)
- elevated FSH - bc lack of follicle = lack of inhibin B = no negative feedback
-low AMH levels
- low inhibin B levels

=> accelerated menopause

28
Q

symptoms and treatment of POF

A
  • similar to normal menopause symptoms ; loss of oestrogen
  • oligomenorrhea, hot flushes, sweating , nervousness, skin changes, decreased bone density, urogenital atrophy

Treatment :
HRT - to increase oestrogen levels and decrease oestrogen related symptoms
combined oral contraceptive pill with high levels of oestrogen

29
Q

Long term consequences and treatment of premature menopause

A
  • adverse effects on health and mortality
  • HRT can lessen some f these risks but not all
    -provide HRT at least until natural age of menopause
  • psychological aspects of early menopause
  • individualising treatment both in terms of HRT and psychological impact.
30
Q

Treatment of menopausal symptoms

A
  1. menopausal hormone therapy (MHT/HRT)
    tablets, patches, gels , vaginal oestrogen
  2. plant based bioidentical hormone
    unregulated and no evidence of effectiveness
  3. CBT and relaxation techniques
  4. non - hormonal prescription medications
    -not as useful as HRT
  5. biphosphonates for density
  6. NKB antagonists for hot flushes : NKB hypothalamic neuropeptide involved in GnRH secretion and thought it stimulate activity of vaomotor centre , resulting in hot flushes
31
Q

HRT treatments needs to be prescribed carefully

A
  • unopposed estrogen cause proliferation of the endometrium - endometrial cancer
  • different preparations of estrogen and progesterone used for HRT and different routes of administration
  • GP needs to adapt and change treatment to tailor it to individuals’ needs
  • its not all about HRT , its about the best option
32
Q

3 large studies 1990s - 2000

A
  1. HERS - heart and estrogen/progestin replacement study (postmenopausal women with CHD)
    - study stopped after 4.1 years due to increased risk
  2. WHI - women health initiative (healthy postmenopausal women)
    - randomised , double blind , placebo controlled
    -evaluated only one hormone combination
    - WHI was stopped at 5.2 years due to increased breast cancer risk
  3. Million women study - started recruiting participants in 1996 to investigate the effect of use of HRT amongst other things
    - study includes 1 in 4 women in UK born between 1935 and 1950
    - participants sent postal resurvey questionnaire every 3-5 years

+ limitation of self report - participant bias , postal survey many people may not fill in the survey - low turnout rate

33
Q

Impact of clinical trials (WHI and the million women) on the use of HRT

A

the press used most alarming statistics and prescribing if HRT dropped dramatically
relative risk was amplified.

34
Q

WHI : risks and benefits of Combined contraception estrogen and progesterone therapy (CCEPT) compared to placebo : Relative vs absolute risk

A

benefits :
-symptoms control , skeletal benefit , decreased CHD

Risks:
venous thrombosis , stroke, breast cancer (E+P), gallstones, dementia (E+P)

35
Q

After press reporting risks and decline in HRT studies were re- evaluated and analysed :

A
  • a subsequent re-examination of data from the WHI and Million Women study showed certain flaws in interpretation and study designs and that risks of the WHI study were not statistically significant apart from venous thrombosis and ischaemic stroke
  • The follow-up showed benefits for use of HRT in younger women (50-59 years ) = decreased coronary disease and all causes of mortality
    so should HRT be part of a prevention strategy at the onset of menopause?
36
Q

menopausal and society

A
  1. aging - seen as loss of status/feeling invisible in women whereas men are seen as wiser
  2. closely associated with psychosocial events in midlife and aging - health issues, children leaving homes, looking after elderly relatives - lots of changes happening all at the same time
  3. campaigning by women resulted in recent publication for all - party parliamentary group on menopause report
37
Q

5 key recommendations from campaigning in parliament by women

A
  1. funding research into benefits of HRT
  2. ensuring doctors are well trained
  3. scrapping prescription charges for HRT in England
  4. national drug formulary for HRT England
  5. summoning all women aged 45 to GP to discuss menopause

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