Female Reproductive Phys Flashcards

1
Q

HP Axis

A
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2
Q

Female HPO Axis

A

Pulsatile GnRH

Pulsatile LH & FSH

Follicle recruitment & growth

Leads to estrogen production

Increase levels of estrogen leads to endometrial proliferation

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3
Q

Immature HPO

A

estrogen often unable to provide true feedback

Depends on GnRH

Irregular menstrual cycle lenght

Anovulatory cycle

Breakthrough bleeding

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4
Q

Tanner Stages

A

Tanner stage 1= adrenarche

Stage 2= thelarche, breast bud enlarges

Stage 3= peak growth

Stage 4= menarche

stage 5= cyclicity

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5
Q

Adrenarche

A

zona reticularis of adrenal begins to secreate DHEA & DHEAS

6-8 in girls

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6
Q

Thelarche

A

dev of breast prior to menarche

8-1 yo

If breasts develop before 8 yo or do not develop by age 13 signals abnormality

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7
Q

Menarche

A

1st period

8-13 yo

Functional HPO axis

Cycles irregular 6-12 monhts & may be anovulatory

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8
Q

Mature HPO

A

Granulosa cells secrete estradiol E2, inhibin & activin

Estrogens suppress release of GnRH, FSH & LH

Inhibin suppress release of FSH

Activin stimulates FSH release

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9
Q

2 Cell Theory

A

StAR & conversion of cholesterol by CYP 11A are rate limiting!

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10
Q

Different Follicles- Phys version

A
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11
Q

GnRH influence

A

Primary and secondary are GnRH indep

Teritiary/Graafian are GnRH dep

Only those follicles taht respond to FSH/LH will ovulate

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12
Q

Dominant Follicle Selection- extra

A

99.9% of follicles will die

Wave 1= recruitment, growth & largest follicle undergoes atresia

Wave 2= recruitment, growth, selection

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13
Q

Numbers

A

Woman is born with 1 million follicles

Reduced to 300,000 follicles @ menarche

400-500 dom follicles selected for ovulation

Prenatral follicle atresia- Oocytes die first

Basal atresia- reduced androgen production, reduced IGF-3, distrupted theca (reduced vascularization)

Antral atresia- all follicle sizes, more androgens in than in healthy follicles. Granulosa cells first to die, theca are last.

Luteinisation- smaller cells from theca cells & larger from granulosa. Small produce androgen precursors.

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14
Q

2 Cell Follicular Steroidogensis

A

estradiol- pre ovulatory

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15
Q

Estradiol

A

Unbound- 1-2%

Loosely bound to albumin- 60-70%

Tightly bound to SHBG- 25-30% (unavailable)

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16
Q

SHBG

A

Metabolized in Liver

Conjugated & excreted into bile or back into circulation

Excreted in urine if weaker metabolites

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17
Q

Albumin

A
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18
Q

Estradiol R

A

nuclear:

reg transcription

ER a, ERb

well char & widely distributed

mem bound:

rapid non genomic effects

GPR30

F unclear

**estrogen stimulates up reg of ER a B & GPR30 in most tissues

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19
Q

Pre ovulatory HP axis

A

Rise in estrogen causes HP axis

Increase GnRH

Increase LH/FSH

Sustained high levels of estradiol produced by dom follicle

Activin stim FSH secretion

48-96 hr pre ovulation (+ feedback)

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20
Q

HPO Feedback

A

early to mid

  • dominant follicle starts increasing E2
    • feedback reduces GnRH (low lH & Inhibin inhibits FSH)
  • non dominant follicles can’t respond to low FSH & LH
  • vast majority of non dominant follicles undergo atresia

Late follicular

  • dominant follicle produces large amt of estradiol
    • feedback increase GnRH, FSH & LH
  • leads to ovulation
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21
Q

Ovulation

A

High levels of estradiol prime GnRH feedback

High estradiol increase GnRH 48-96 hr

Increase GnRH & stim LH- LH surge

Peak of LH 10-12 hr prior to ovulation

Rapid rise in basal body temp observed during ovulation

22
Q

Ovulation

A

Rupture of follicle

“put a pin through a grape” - that is how much “ruptures”

23
Q

Corpus Luteum

A

Follicle involutes

Follicle remodeled into CL

High VEGF promot blood bessel growth

CL responds to Lh & secretes progesterone

High rate of blood flow needed b/c progesterone NOT stored!

24
Q

Progesterone

A

CL has lifespan of 12-16 days- if not pregnant

Levels of progesterone very low= infertility

If fertilization & implantation= level of preogesterone remain high & escalate during gestation

Progesterone has been shown to inhibit apoptosis of luteal cells

Progesterone essential for CL

25
Q

Luteal Hormone Syn

A

No FSH required

26
Q

Progesterone Levels

A

Unbound- 1-2%

Albumin bound- 75-80%

Bound to Transcortin CBG- 20%

27
Q

Progesterone R

A

Nuclear:

PR, nPR, PGR

  • reg transcription
  • PR- A & B
  • well characterized

Mem:

  • rapid non genomic effects
  • mPR a, B & g= GPC
  • PGRMC1= inhibits apoptosis, Essential for ovulatory follicle

Progesterone down regulates ERa, B & GPR30 in most tissues.

28
Q

Progesterone Feedback

A
29
Q

HPO Feedback for luteal phase

A

Luteal phase

  • low LH stim progesterone by CL
    • feedback by progesterone reduces GnRH & low levels of FSH & LH
  • follicles cannot respond to low FSH & LH- low FSH inhibit follicle recruitment during luteal phase
  • LH levels continue to fall during luteal phase due to - progesterone feedback

Early- forming CL, rising progesterone

Mid- fully dev CL, high progesterone production, hCG rescue

Late- if no hCG then progesterone declines & CL apoptosis

30
Q

Summary of HPO

A

only + feedback is during late follicular phase b/c its right before ovulation.

31
Q

Hyperprolactinemia

A
32
Q

Menstrual Cycle

A

Estrogen stimulates during early proliferative phase to heal surface.

Progesterone transforms functional layer

33
Q

Menstrual Cycle

A

Late prolif phase- estradiol peak, ovulation @ end

early secretory- CL formed & progesterone rise

mid secretory- progesterone levels high, implantation

late secretory- decidualization progresses

34
Q

Estrogen & Menstrual Cycle

A

early prolif

  • cell division
  • glandular epith cell cover endometrial surface

mid prolif

  • rapid growth & prolif of functional zone. Max elongation of spiral a.
  • high VEGF & R
  • formation of tubular glands
  • stroma cells prolif rapidly

Late prolif

  • max up reg of estrogen & progesterne R
  • maintain high level of mitosis
  • thick functionalis
  • trilaminar endometirum
35
Q

Estrogen Priming

A

Prolif phase- estrogens up reg ERs & PRs

Secretory phase- window of implantaion, full progesterone action, days 17-24

After 10 days of progesterone action, down reg PR in functional zone & decidualize stromal cells.

36
Q

Decidualization

A

Morphological & physiological reprogramming of uterine stroma cells under continued influence of progesterone

  • mid secretory to late- 10 days after progesterone exposure
  • progesterone stim stromal cell secretion- tightly woven matrix
  • endometrial epith- DO NOT DECIDUALIZE
37
Q

Decidualization

A

Receptive endometrium

  • stroma cells- fibroblast like
  • expansive ECM
  • extensive capillary bed

Decidualized endometrium

  • stroma cells contain glycogen droplets
  • dense ECM- due to stroma cell projections
  • cAMP dep

***day 23, stromal cell hypertrophy, increase laminin, fibronectin & collagen.

No pregnancy, after day 23 no implantation- cell projections make it easier to shed

38
Q

Progesterone Changes

A

early secretory

  • increase progesterone induces glandular sacculation
  • luminal & glandular epith secreations increase
  • stromal cells begin to hypertrophy

Mid secretory

  • full progestational effects
  • max hypertrophy of spiral a. Form dense cap network
  • large fule stores
  • window of implantation- functional zone

late secretory

  • stroma cell plump due to glycogen & lipid stores- fuel stores used by blastocyst
  • decidualization- dense ECM
  • pre menstraul period
39
Q

Estrogen Summary

A

prolif- reproductive tissue

follicular maturation

upreg ER & PR

endometrial growth

vaginal epith hypertrophy

breast dev

thinnig of cervical mucus

osteoblast prolif

  • & + feedbcak on hypothal to control FSH & LH & GnRH
40
Q

Progesterone summary

A

differentiation

CL

dwonreg ER & pr

Sacculation of endometrial glands

suppress myometrial contractility

hypertrophy of spiral a.

thickening of cervical mucus

increase basal body temp

  • feedback on GnRH & suppress FSH & alter LH pulse
41
Q

HPO & Menstrual Cycle

A
42
Q

Menstruation

A

Progestrone withdrawal

Decrease @ end late secretory phase

can also be estrogen or testosterone= just has to be acute reduction /removal of hormone from circulation

43
Q

Menstruation

A

Vasoconstrict spiral arterioles leads to tissue breakdown

leads to ischemia, trigerring tissue degrading enzymes MMPs

Tissue & vascular degradation lead to sloughing of functional layer & menstruation

44
Q

Menstrual Blood

A

25- 80 mL

lacks clotting factors

2-7 days

45
Q

Menstrual cycle vs. Menstrual period

A

menstrual cycle

  • menses
  • prolif phase
  • ovulation
  • secretory phase

menstrual period

  • only menses portion

calculate lenght/ ovulation

lenght of period- 14= ovulation!

46
Q

Cuases irregular menstrual cycle

A
  1. hypogonadism- HP dysfunction
  2. inherent variability- missed period/ abnorm menses
  3. pregnancy
  4. pathophys disorders
  5. birth control
  6. depletion of ovarian follicle reserve
47
Q

Definition

A

Primary amenorrhea- absence of menarch by age 16

secondary amenorrhea- cessation of menses after menarche has occurred, at least 2 of the prveious 3 cycles or no menses for 6 months

oligomenorrhea- infrequent at intervals > 35 days

dysmenorrhea- painful periods

polymenorrhea- regular bleeding @ <21 days

menorrhagia- total blood more than 80 mL or longer than 7 days

dysfunctional uterine bleeding- excessive non cyclic endometrial bleeding due to anatomy or systemic disease, anovulatory

48
Q

End of Menstrual Cyclicity

A

woemn over 40= menopause

under 40= premature ovarian failure POF

depletion of ovarian follicues & cessation of ovarian hormone production

49
Q

Menopause

A

Very high LH & FSH levels

50
Q

Menopause

A

Estrone- follicle reserve

E1

estrogen of menopause

binds to Ers

ER lower affinity to E1 than E2

51
Q

Menopause Symptoms

A

irreg menstrual periods

heart pounding/racing

hot flashes

night sweats

vaginal dryness

mood swings

fatigue

headahce

decreased libido

52
Q

Pregnancy & Menopausal transition

A

can still get pregnant because that last follicle can be dominant & get relased

BE PROTECTED

perimenopause