16953841 physio of normal menstrual cycle

8/3/2019 16953841 Physio of Normal Menstrual Cycle

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PHYSIOLOGY OF THE NORMALMENSTRUAL CYCLE

Daisy N. Punzalan, M.D.


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Menstruationendometrial tissueshedding with hemorrhage that isdependent on sex steroid hormone-

directed changes in blood flow in the spiralarteries

Spiral arteriesarise from the arcuatearteries which are branches of the uterinevessels that lie in the myometrium


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HYPOTHALAMIC-PITUITARY-OVARIAN-ENDOMETRIAL AXIS

The success of human reproductiondepends on the highly coordinatedinteractions between the

hypothalamus, anterior pituitarygland, ovaries & uterineendometrium that occur during a

normal menstrual cycle.


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GnRH (gonadotropin-releasinghormone) the hypothalamichormone that controls the

gonadotropic function of the anteriorpituitary

Pituitary Gonadotropins:

1. FSH (follicle-stimulating hormone)

2. LH (luteinizing hormone)


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The Ovarian Cycle

2 PhasesFollicular (Preovulatory) ovarian

phase estradiol 17 is secreted

2 M oocytes birth

400, 000 follicles onset of puberty

400 follicles reproductive life

Oocytes partly control the earlysteps in follicular development


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FSHrequired for further devt of the large antralfollicles. It rises during the late luteal phase of theprevious cycle

(Selection window) >- FSH receptors > aromatize the thecal cell-derived androstenedione into estradiol- the exclusive site of its receptor expression is thegranulosa cells

- a drop on FSH is responsible for the failure ofother follicles to reach preovulatory status theGRAAFIAN FOLLICLE STAGE


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LH stimulates thecal cell production ofandrostenedione and metabolizes toestradiol

The requirement for thecal cells thatrespond to LH and granulosa cells thatrespond to FSH represents the twogonadotropinstwo cell hypothesis forestrogen biosynthesis


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Ovulation

Predicted by the onset of thegonadotropin surge resulting fromincreasing secretion of estrogen by

preovulatory follicles (34-36 hoursprior to ovum release)

LH peak occurs 10-12 hrs. beforeovulation


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The Ovarian Cycle

Luteal (Postovulatory ) OvarianPhase progesterone is secreted

Luteinization corpus luteumdevelops from the remains of the

dominant folicle or graafian follicle


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Just after ovulation, estrogen levelsdecrease followed by a secondaryrise that reaches a peak production of

0.25 mg/ day of 17 beta estradiol inthe midluteal phase

Ovarian production of progesteronepeaks at 25-50 mg/day during themidluteal phase


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If pregnancy occurs, the corpus luteumcontinues production of progesterone inresponse to embryonic hcG. In the

absence of pregnancy, it will regress 9-11days after ovulation.

The regression of the corpus luteum anddrop in circulating steroids during the lateluteal phase leads to MENSTRUATION.


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Hormonal Regulation of the Endometrium

Estrogen the essential hormone signalin which most events in the nornalmenstrual cycle depend.

17 estradiol the most biologicallypotent naturally occuring estrogensecreted by the granulosa cells of thedominant ovarian follicle and luteinized

granulosa cells of the corpus luteum

- involves 2 receptors: ERand ER


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Progesterone decreases the synthesisof estrogen receptor molecules

- increases the rate of

enzymatic inactivation of estradiol 17estradiol dehydrogenase

- increase sulfurylation ofestrogen estrogen sulfotransferase


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The Endometrial Cycle

The endometrium is regeneratedduring each ovarian-endometrialcycle.

The superficial 2/3 of theendometrium is shed andregenerated almost 400x during the

reproductive lifetime of most women.


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2 Phases:

Proliferative (Preovulatory)Endometrial Phase

Early Phaseendometrium is thin,usually less then 2 mm

Late Phase endometrium thickens


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2 Phases:

Secretory (Postovulatory)Endometrial Phase

Early Phase dating of the endometriumis based on the histology of the gladularepithelium

Mid to Late Phase dating of the cyclerelies on the changes seen in theendometrial stroma


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After ovulation, the estrogen primedendometrium responds to rising levelsof progesterone causing accumulation

of glycogen in the basal portion of theglandular epithelium, creatingsubnuclear vacuoles and

pseudostratification > 1st sign ofovulation


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The secretory phase is highlighted by thecontinuing growth and development of the

spiral arteries, lengthen at a rate that isappreciably greater than the rate ofincrease in endometrial thickness leadingto even greater coiling of the already

spiraling vessels. As the regression of theendometrium occur, the coiling becomessufficiently severe that resistance to bloodflow is increased strikingly causing hypoxiaof the endometrium.

The resultant stasis is the primary causeof endometrial ischemia and then tissuedegeneration leading to menstruation.


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Period of Vasoconstriction moststriking and constant event precedingthe onset of menstruation

- serves to limit blood loss duringmenstruation

- e.g. prostaglandins, vasoactivepeptides( endothelins )


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Menstruation

-is the periodic discharge of blood,

mucus, and cellular debris from theuterine mucosa


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Severe coiling

stasis

hypoxia of the endometrium

vasodilatation

intense vasoconstriction

relaxation

hemorrhage


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Role of Prostaglandins &Vasoactive peptides

Prostaglandin

PGF2 vasoconstriction of theendometrial spiral arteries

-causes myometrialcontractions & uterine ischemia

PGE2 & PGI2 - vasodilation


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Vasoactive Peptides

Endothelin-1 a potentvasoconstrictor

Enkephalinase degradesendothelin-1

PTH-rP a vasorelaxant


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Origin of Menstrual Blood

Both arterial and venous origin, butarterial bleeding is greater

Rupture of an arteriole of a coiledartery with consequent formation ofhematoma

Leakage through a spiral artery

Tissue autolysis


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16953841 physio of normal menstrual cycle

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