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NAMS > Physiology/Pathophysiology of the Menopause Transition > Flashcards

Physiology/Pathophysiology of the Menopause Transition Flashcards

1
Q

menopause

A

ovarian follicular exhaustion; changes in bleeding patterns hormone levels, body composition, and psychosocial well-being; climacteric - period of endocrinologic, somatic, and transitory psychological changes (perimenopause)

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2
Q

menopause transition

A

time before FMP, menses cycle becomes variable or menopause-related sxs begin; early (7+day change) or late (60+day wo); stages -2,-1

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3
Q

postmenopause

A

time after menopause; marked by 1 yr after FMP; stage +1a, +1b, +1c, b (late)

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4
Q

mean age of menopause

A

52.54 years; between age 40-58 years

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5
Q

prevalence for menopause

A

life expectancy in women 81.2yrs; by 2020, 64 million women will be +50yo
-women worldwide living longer
>many will spend >40% of life in postmeno
>more than 60% survive at least until 80yo

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6
Q

STRAW +10 stages

A

-5 early reproductive
-4 peak reproductive
-3b late reproductive
-3a late reproductive
-2 early menopause transition (perimeno)
-1 late menopause transition (perimeno)
(0 FMP)
+1a early postmenopause (perimeno)
+1b early postmenopause
+1c early postmenopause
+2 late postmenopause

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7
Q

-5 stage sxs

A

-part of reproductive interval
-early; starts at menarche; cycle starts to regulate

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8
Q

-4 stage sxs

A

-part of reproductive interval
-regular menses
-cycle is regulating; peak years

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9
Q

-3b stage sxs

A

-part of reproductive interval
-regular menses, some changes
-fecundability declines
-menses & FSH normal
-getting into late reproductive yrs; AMH, AFC, Inhibin getting low

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10
Q

-3a stage sxs

A

-part of reproductive interval; some regular menses
-subtle menstrual changes in flow, length, frequency; shorter cycles; variable FSH

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11
Q

-2 stage sxs

A

persistent difference of +7 days in length; variable FSH, low AMH; early meno transition

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12
Q

-1 stage sxs

A

+60 days consecutive days of amenorrhea; late meno transition

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13
Q

+1a stage sxs

A

-the 12mo after FMP, end of perimeno; start VMS
-postmeno

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14
Q

+1b stage sxs

A

second postmeno year; start VMS; stabilizing FSH/estradiol

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15
Q

+1c stage sxs

A

3-6 years postmeno; high FSH, low estradiol

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16
Q

+2 stage sxs

A

5-8 years postmeno through remaining lifespan; more GSM

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17
Q

Endocrine markers used to assess reproductive aging

A

-FSH
-AFC
-AMH
-Inhibin B
-Estradiol

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18
Q

LOOP - Luteal out-of-phase events

A

-can be seen in early/late meno transition
-luteal phase FSH high enough to recruit follicles for subsequent cycle before current cycle is over; causes incr estrogen
-causes very short follicular phase
-can cause perimeno sxs of mastalgia, migraine, menorrhagia, fibroids, endometrial hyperplasia

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19
Q

Clinical implications for high Estradiol

A

-obesity —> more likely anovulatory cycles a/w lower levels in premeno but higher levels in postmeno
-pregnancy —> ovulatory cycles are noted up to FMP; increased risk for twins
-ethnicity —> hormone concentrations differ among ethnic groups; Chinese & Japanese women have lower estradiol levels compared w black, white, Hispanic; FSH concentrations are higher in black women

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20
Q

Estro & Andro alterations

A

-androgens become estrogen via aromatization, in peripheral tissues
-adrenal - androgens (DHEA, DHEA-S, androstenedione)–>estrogen in peripheral tissues ***
-precursor hormones produced by adrenal gland
-DHEA local vag therapy is helpful

21
Q

Adrenal physiology & Meno

A

-DHEAS levels decrease during & after menopause transition:
>SWAN study shows fall in circulating DHEAS levels
>longitudinal analyses of women undergoing meno transition also showed a transient increase in circulating DHEAS levels in the menopause transition
-despite decr in DHEAS in meno, no benefit in DHEA supplementation
-systematic review & meta-analysis of DHEA use in postmeno women w normal adrenal function found no evidence of improvement in sexual sxs, serum lipids, serum glucose, weight, or BMD
-DHEA supplementation of postmeno is not routinely recommended

22
Q

Fertility change / Ovarian reserves

A

-testing as a screening tool is not recommended
-cycle day 3 FSH commonly used test
-AMH capture quantitative but not qualitative data;
-peak at 24.5yo
-can be influenced by exogenous hormones

23
Q

Early Menopause Transition

A

-decreasing ovarian reserve & reduced cohort of follicles; Inhibin B & AMH drop
-loss of Inhibin restraint of FSH leads to:
>monotropic rise in FSH
>faster growth of remaining follicles (short follicular phase)
>incr atresia
>occasional LOOP cycles
-common sxs
>cycle irregularity by >days
>skipped menstrual cycles (bc of ovulatory failure)
>pronounced premenstrual syndrome sxs (bc of longer luteal phase)

24
Q

Late Menopause Transition

A

-number of remaining oocytes drops below critical level, w sporadic follicular development
-ovulation is more sporadic
-rare follicular development results in poor rate of ovulation w low progesterone levels
-eventually follicular development stops, resulting in estradiol deficiency
-common sxs:
>amenorrhea >60 days
>estrogen deficiency sxs such as hot flashes & vaginal dryness

25
Q

POI - Primary Ovarian Insufficiency
a.k.a. premature ovarian failure

A

-cessation of menstrual periods bc of failure of the ovaries before age 40
-hypergonadotrophic hypogonadism in women <40yo; not always complete or permanent
-age-specific incidence of POI: 1% <40yo, 0.1% <30yo, 0.01% <20yo; may rise as childhood ca survival increases
-most common in white 1%, black 1.4%, Hispanic 1.4%, Chinese 0.5%, Japanese 0.1%b
-genetic (X chromosome disorders, gene or reproductive mutations), autoimmune (DM type 1, thyroid, adrenal, etc.), toxic, infectious, metabolic, iatrogenic (chemo, radiation, surgical); most cases are idiopathic

26
Q

Clinical Features & Dx of POI

A

-change in menses function (irregular menses or amenorrhea)
-estrogen deficiency sxs
-sxs masked if woman is on combined OC
-dx: menstrual change such as oligomenorrhea or amenorrhea for >4mo; FSH concentrations in postmeno range >25IU/L on 2 separate occasions w low estradiol

27
Q

Diagnostic work-up POI

A

-H&P, detailed fam hx
-Estradiol, FSH, LH; if elevated FSH, repeat FSH & estradiol at least 4 wks later
-karyotype
-anti-21hydroxylase abs
-fragile x screen
-TSH, free T4, anti-thyroid-peroxidase abs
-glucose, metabolic profile, CBC

28
Q

Management of POI

A

-standard of care is physiologic EPT:
>estrogen 100 mcg transdermal patch, 1.25mg CEE, or 2mg estradiol daily
>if uterus is present, cyclical progestins should be added >12d/mo
>combo hormone contraception or transdermal estradiol-progestin sxs are alternatives
>recommended duration of therapy is at least until natural age of menopause
-if pregnancy is desired -> can still carry a pregnancy but will likely require an egg donor to become pregnant

29
Q

surgical menopause

A

abrupt nonreversible drop in hormones (estro, prog, andro); elective or consequential

can cause bone, cards, cognitive issues, Parkinson’s

30
Q

chemo/rad-induced menopause

A

cause variable gonadotoxic effects

31
Q

consequence of early estrogen loss

A

risk for CVD, psychological consequence - grief, low self-esteem, fertility loss

32
Q

HT for POI and surg meno

A

transdermal patch, conjugated equine estro, or estradiol PO; if uterus is still there, add progestogen (or may cause hyperplasia)

33
Q

Menopause demographics

A

-meno trans natural event
-postmeno defined by FMP & confirmed after 1yr no menses
-represents permanent cessation of menses resulting from loss of ovarian follicular function, usually bc of aging

34
Q

Early menopause

A

FMP before age 45yo

35
Q

Late menopause

A

FMP after age 54yo

36
Q

Natural menopause

A

Permanent cessation of menses bc of loss of follicular activity

37
Q

Induced menopause

A

Surgical or iatrogenic loss of ovarian function

38
Q

Perimenopause

A

Stage in menopause transition characterized by irregular menstrual cycles (early perimenopause) or 2-12 months of amenorrhea (late perimenopause)

39
Q

Postmenopause

A

Defined as 12mo of amenorrhea

40
Q

Premature menopause

A

FMP before age 40

41
Q

Premenopause

A

Reproductive stage between menarche & onset of perimenopause

42
Q

Primary ovarian insufficiency

A

Menopause occurring at age <40yo

43
Q

Menopause S/Sxs

A

-Classic sxs:
>change in menses cycle pattern (during perimenopause)
>VMS (hot flashes, night sweats, etc)
>vulvovaginal sxs, dyspareunia
>sleep disturbances
>psychological sxs (depression, anxiety, moodiness)
-Other sxs sometimes a/w meno:
>cognitive (memory, concentration, intake of new info, etc)
>joint pain
>dry eyes
>change in wt distribution
-there is no one universal menopause syndrome

44
Q

Stages of Reproductive Aging

A

-Aging:
>natural, time-related, genetically determined, & environmentally modified process of deterioration of physiological function
-Reproductive aging:
>loss of locates by ovulation & atresia
>women are born w a finite number of oocytes: @20 wks GA 6-7N, @Birth 1-2M, @Puberty 300-500K, @Menopause 300-400 remaining; lifespan = 400-500 ovulated (most lost through apoptosis)

45
Q

AMH, AFC, FSH, & Estradiol

A

-taken together, predict response to ovarian stimulation in fertility treatment but less predictive of pregnancy

46
Q

AMH

A

-produced by granulosa cells of activated follicles, most reflective of true ovarian reserve
-provides the best single prediction of time of menopause

47
Q

Day 3 FSH

A

-useful for predicting ovarian response (<10 IU/L is normal)
-menopause only if very high
-cycle-to-cycle fluctuates limit usefulness in predicting time to menopause

48
Q

Estradiol

A

-tends to be elevated on days 3 in perimeno; <80pg/ml is normal

49
Q

AFC

A

->12 ultrasound detected follicles 2-10 mm in size predicts ovarian response; normal
-not predictive of time to menopause

NAMS (11 decks)

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