Physiology of The Menstrual Cycle

PHYSIOLOGY OF PHYSIOLOGY OF THE MENSTRUAL THE MENSTRUAL

CYCLECYCLEDr. SALWA NEYAZIDr. SALWA NEYAZI

CONSULTANT OBSTETRICIAN GYNECOLOGIST CONSULTANT OBSTETRICIAN GYNECOLOGIST PEDIATRIC &ADOLESCENT GYNECOLOGISTPEDIATRIC &ADOLESCENT GYNECOLOGIST

NORMAL MENSTRUAL CYCLENORMAL MENSTRUAL CYCLEWhat is the mean duration of the MC?What is the mean duration of the MC? Mean 28 days (only 15% of ♀)Mean 28 days (only 15% of ♀) Range 21-35Range 21-35

What is the average duration of menses?What is the average duration of menses? 3-8 days3-8 days

What is the normal estimated blood loss?What is the normal estimated blood loss? Approximately 30 mlApproximately 30 ml

When does ovulation occur?When does ovulation occur? Usually day 14Usually day 14 36 hrs after the onset of mid-cycle LH surge36 hrs after the onset of mid-cycle LH surge

NORMAL MENSTRUAL CYCLENORMAL MENSTRUAL CYCLE

What regulate the phases of the MC & ovulation?What regulate the phases of the MC & ovulation? Interaction between hypothalamus, pituitary & Interaction between hypothalamus, pituitary &

ovariesovaries

What is the mean age of menarche & menopause?What is the mean age of menarche & menopause? Menarche 12.7Menarche 12.7 Menopause 51.4 Menopause 51.4

HYPOTHALAMIC- PITUITARY- OVARIAN AXISHYPOTHALAMIC- PITUITARY- OVARIAN AXIS

PHASES OF THE MENSTRUAL CYCLE PHASES OF THE MENSTRUAL CYCLE

Ovulation divides the MC into two phasesOvulation divides the MC into two phases::

1-FOLLICULAR PHASE1-FOLLICULAR PHASE -Begins with menses on day 1 of the menstrual -Begins with menses on day 1 of the menstrual

cyclecycle & ends with ovulation& ends with ovulation

▲ ▲RECRUITMENTRECRUITMENT FSH FSH maturation of a cohort of ovarian maturation of a cohort of ovarian follicles “recruitment”follicles “recruitment” only one reaches maturityonly one reaches maturity

FOLLICULAR PHASEFOLLICULAR PHASE

MATURATION OF THE FOLLICLE (FOLLICULOGENESIS)MATURATION OF THE FOLLICLE (FOLLICULOGENESIS)

♥ ♥ FSH FSH primordial follicle primordial follicle (oocyte arrested in the diplotene stage of the 1(oocyte arrested in the diplotene stage of the 1stst

meiotic division surrounded by a single layer of meiotic division surrounded by a single layer of granulosa cells)granulosa cells)

1ry follicle 1ry follicle (oocyte surrounded by a single layer of granulosa (oocyte surrounded by a single layer of granulosa

cells basement membrane & thica cells)cells basement membrane & thica cells)

2ry follicle or preantral follicle 2ry follicle or preantral follicle (oocyte surrounded by zona pellucida , several (oocyte surrounded by zona pellucida , several

layers of granulosa cells & thica cells) layers of granulosa cells & thica cells)

FOLLICULOGENESIS (2)FOLLICULOGENESIS (2)

tertiary or antral follicletertiary or antral follicle 2ry follicle accumulate fluid in a cavity 2ry follicle accumulate fluid in a cavity

“antrum”“antrum” oocyte is in eccentric positionoocyte is in eccentric position surrounded by granulosa cells “cumulous surrounded by granulosa cells “cumulous

oophorus”oophorus”

FOLLICULOGENESIS (2)FOLLICULOGENESIS (2)

SELECTIONSELECTION ♥ ♥Selection of the dominant follicle occurs day Selection of the dominant follicle occurs day

5-75-7 ♥ ♥It depends on It depends on - the intrinsic capacity of the follicle to- the intrinsic capacity of the follicle to synthesize estrogensynthesize estrogen -high est/and ratio in the follicular fluid-high est/and ratio in the follicular fluid ♥ ♥As the follicle mature As the follicle mature estrogen estrogen FSH FSH “ “-ve feed back on the pituitary”-ve feed back on the pituitary” the follicle the follicle with the highest No. of FSH receptors will with the highest No. of FSH receptors will continue to thrivecontinue to thrive ♥ ♥ The other follicles “that were recruited” willThe other follicles “that were recruited” will become atreticbecome atretic

♥♥FSH ACTIONSFSH ACTIONS -recruitement -recruitement -mitogenic effect -mitogenic effect No. of granulosa cells No. of granulosa cells FSH receptorFSH receptor -stimulates aromatase activity -stimulates aromatase activity conversion of conversion of androgens androgens estrogens “estrone & estradiol” estrogens “estrone & estradiol” - - LH receptors LH receptors ♥ ♥ ESTROGENESTROGEN Acts synergistically with FSH to Acts synergistically with FSH to - induce LH receptors- induce LH receptors - induce FSH receptors in - induce FSH receptors in

granulosagranulosa & thica cells& thica cells♥♥LH LH thica cells thica cells uptake of cholesterol & LDL uptake of cholesterol & LDL androstenedione & testosteroneandrostenedione & testosterone

TWO CELL THEORYTWO CELL THEORY

FOLLICULOGENESIS FOLLICULOGENESIS (3)(3)

OTHER FACTORS THAT PLAY A ROLE IN FOLLICULOGENISISOTHER FACTORS THAT PLAY A ROLE IN FOLLICULOGENISIS-INHIBIN -INHIBIN Local peptide in the follicular fluidLocal peptide in the follicular fluid -ve feed back on pituitary FSH secreation-ve feed back on pituitary FSH secreation Locally enhances LH-induced androstenedione production Locally enhances LH-induced androstenedione production -ACTIVIN-ACTIVIN Found in follicular fluidFound in follicular fluid Stimulates FSH induced estrogen productionStimulates FSH induced estrogen production gonadotropin receptorsgonadotropin receptors androgenandrogen No real stimulation of FSH secretion in vivo (bound to No real stimulation of FSH secretion in vivo (bound to

protein in serum) protein in serum)

PREOVULATORY PERIODPREOVULATORY PERIOD

♥ ♥ NEGATIVE FEEDBACK ON THE PIUITARYNEGATIVE FEEDBACK ON THE PIUITARY -- estradiol & inhibin estradiol & inhibin -ve feed back on pituitary -ve feed back on pituitary

FSHFSH -This mechanism operating since childhood-This mechanism operating since childhood

♥ ♥ POSITIVE FEEDBACK ON THE PITUITARYPOSITIVE FEEDBACK ON THE PITUITARY estradiol estradiol (reaching a threshold concentration(reaching a threshold concentration) )

++ve feed back on the pituitary ve feed back on the pituitary (facilitated by low (facilitated by low levels of progestrone)levels of progestrone) LH surge LH surge secretion of secretion of progestroneprogestrone

Operates after pubertyOperates after puberty +ve feed back on pituitary +ve feed back on pituitary FSH FSH

PREOVULATORY PERIODPREOVULATORY PERIOD

LH SURGELH SURGE Lasts for 48 hrs Lasts for 48 hrs Ovulation occurs after 36 hrsOvulation occurs after 36 hrs Accompanied by rapid fall in estradiol levelAccompanied by rapid fall in estradiol level Triggers the resumption of meiosisTriggers the resumption of meiosis Affects follicular wall Affects follicular wall follicular rupture follicular rupture Granulosa cells Granulosa cells lutenization lutenization progestrone synthesis progestrone synthesis

OVULATIONOVULATION The dominant follicle protrudes from the ovarian The dominant follicle protrudes from the ovarian

cortexcortex Gentle release of the oocyte surrounded by the Gentle release of the oocyte surrounded by the

cumuluscumulus granulosa cellsgranulosa cells

Mechanism of follicular ruptureMechanism of follicular rupture 1-1- Follicular pressure Follicular pressure Changes in composition of the antral fluid Changes in composition of the antral fluid colloid colloid osmotic pressureosmotic pressure2-Enzymatic rupture of the follicular wall2-Enzymatic rupture of the follicular wall LH & FSH LH & FSH granulosa cells granulosa cells production of production of

plasminogen activatorplasminogen activator plasmin plasmin fibrinolytic activity fibrinolytic activity breake down of F. wall breake down of F. wall LH LH prostglandin E prostglandin E plasminogen activator plasminogen activator PG F2PG F2αα lysosomes under follicular wall lysosomes under follicular wall

LUTEAL PHASELUTEAL PHASE LASTS 14 days LASTS 14 days

FORMATION OF THE CORPUS LUTEUMFORMATION OF THE CORPUS LUTEUM

After ovulation the point of rupture in the follicular After ovulation the point of rupture in the follicular wall sealswall seals

Vascular capillaries cross the basement membrane Vascular capillaries cross the basement membrane

& grow into the granulosa cells & grow into the granulosa cells availability of LDL- availability of LDL-cholestrolecholestrole

LH LH LDL binding to receptors LDL binding to receptors 33αα OH steroid dehydrogenase activity OH steroid dehydrogenase activity progestrone progestrone

LUTEAL PHASELUTEAL PHASE Marked Marked in progestrone secretion in progestrone secretion Progestrone actions:Progestrone actions: -suppress follicular maturation on the-suppress follicular maturation on the ipsilateral ovaryipsilateral ovary -thermogenic activity -thermogenic activity basal body temp basal body temp -endometrial maturation-endometrial maturation Progestrone peak 8 days after ovulation (D22 MC)Progestrone peak 8 days after ovulation (D22 MC) Corpus luteum is sustained by LHCorpus luteum is sustained by LH It looses its sensitivity to gonadotropins It looses its sensitivity to gonadotropins luteolysis luteolysis estrogen & progestrone level estrogen & progestrone level desquamation of the desquamation of the

endometrium “menses”endometrium “menses”

LUTEAL PHASELUTEAL PHASE estrogen & progestrone estrogen & progestrone FSH &LH FSH &LH The new cycle stars with the beginning of mensesThe new cycle stars with the beginning of menses If prgnancy occurs If prgnancy occurs hCG secreation hCG secreation maintain maintain

the the corpus luteum corpus luteum

HORMONAL PROFILES DURING THE HORMONAL PROFILES DURING THE MENSTRUAL CYCLEMENSTRUAL CYCLE

ENDOMETRIAL CHANGES DURING THE ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLEMENSTRUAL CYCLE

1-Basal layer of the enometrium1-Basal layer of the enometrium -Adjasent to the mometrium-Adjasent to the mometrium -Unresponsive to hormonal stimulation-Unresponsive to hormonal stimulation -Remains intact throughout the menstrual -Remains intact throughout the menstrual

cyclecycle

2-Functional layer of the endometrium2-Functional layer of the endometrium Composed of two layers:Composed of two layers: -zona compacta -zona compacta superficial superficial

-Spongiosum layer -Spongiosum layer

ENDOMETRIAL CHANGES DURING THE MENSTRUAL ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLECYCLE

1-Follicular /proliferative phase1-Follicular /proliferative phase Estrogen Estrogen mitotic activity in the glands & stroma mitotic activity in the glands & stroma enometrial thickness from 2 to 8 mmenometrial thickness from 2 to 8 mm (from basalis to opposed basalis layer)(from basalis to opposed basalis layer)

2-Luteal /secretory phase2-Luteal /secretory phase Progestrone Progestrone - Mitotic activity is severely restricted- Mitotic activity is severely restricted -Endometrial glands produce then secrete-Endometrial glands produce then secrete glycogen rich vaculesglycogen rich vacules -Stromal edema-Stromal edema -Stromal cells enlargement-Stromal cells enlargement -Spiral arterioles develop, lengthen & coil -Spiral arterioles develop, lengthen & coil

MENSTRUATIONMENSTRUATION

Periodic desquamation of the endometriumPeriodic desquamation of the endometrium The external hallmark of the menstrual cycleThe external hallmark of the menstrual cycle Just before menses the endometrium is infiltrated Just before menses the endometrium is infiltrated

with leucocyteswith leucocytes Prostaglandins are maximal in the endometrium Prostaglandins are maximal in the endometrium

just before menses just before menses Prostaglandins Prostaglandins constriction of the spiral constriction of the spiral

arterioles arterioles ischemia & desquamation ischemia & desquamation Followed byFollowed by arteriolar relaxation, bleeding & arteriolar relaxation, bleeding &

tissue breakdowntissue breakdown

HYPOTHALAMIC ROLE IN THE MENSTRUAL HYPOTHALAMIC ROLE IN THE MENSTRUAL CYCLECYCLE

The hypothalamus secretes GnRH in a pulsatile The hypothalamus secretes GnRH in a pulsatile fashionfashion

GnRH activity is first evident at pubertyGnRH activity is first evident at puberty Follicular phase GnRH pulses occur hourly Follicular phase GnRH pulses occur hourly Luteal phase GnRH pulses occur every 90 minutesLuteal phase GnRH pulses occur every 90 minutes Loss of pulsatility Loss of pulsatility down regulation of pituitary down regulation of pituitary

receptors receptors secretion of gonadotropins secretion of gonadotropins Release of GnRH is modulated by –ve feedback by:Release of GnRH is modulated by –ve feedback by: steroidssteroids gonadotropinsgonadotropins Release of GnRH is modulated by external neural Release of GnRH is modulated by external neural

signalssignals