Property of Department of Obstetrics & Gynecology, Faculty of Medicine, University of Zagazig, Egypt

1. PHYSIOLOGY OFPHYSIOLOGY OF
THE MENSTRUALTHE MENSTRUAL
CYCLECYCLE
Dr. SALWA NEYAZIDr. SALWA NEYAZI
CONSULTANT OBSTETRICIAN GYNECOLOGISTCONSULTANT OBSTETRICIAN GYNECOLOGIST
PEDIATRIC &ADOLESCENT GYNECOLOGISTPEDIATRIC &ADOLESCENT GYNECOLOGIST

2. NORMAL MENSTRUAL CYCLENORMAL MENSTRUAL CYCLE
What 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

3. 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 & ovariesInteraction between hypothalamus, pituitary & ovaries
What is the mean age of menarche & menopause?What is the mean age of menarche & menopause?
Menarche 12.7Menarche 12.7
Menopause 51.4Menopause 51.4

4. HYPOTHALAMIC- PITUITARY- OVARIAN AXISHYPOTHALAMIC- PITUITARY- OVARIAN AXIS

5. PHASES OF THE MENSTRUAL CYCLEPHASES 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 cycle-Begins with menses on day 1 of the menstrual cycle
& ends with ovulation& ends with ovulation
▲▲RECRUITMENTRECRUITMENT
FSHFSH  maturation of a cohort of ovarianmaturation of a cohort of ovarian
follicles “recruitment”follicles “recruitment”
 only one reaches maturityonly one reaches maturity

6. FOLLICULAR PHASEFOLLICULAR PHASE
MATURATION OF THE FOLLICLE (FOLLICULOGENESIS)MATURATION OF THE FOLLICLE (FOLLICULOGENESIS)
♥♥ FSHFSH  primordial follicleprimordial follicle
(oocyte arrested in the diplotene stage of the 1(oocyte arrested in the diplotene stage of the 1stst
meioticmeiotic
division surrounded by a single layer of granulosa cells)division surrounded by a single layer of granulosa cells)
  1ry follicle1ry follicle
(oocyte surrounded by a single layer of granulosa cells(oocyte surrounded by a single layer of granulosa cells
basement membrane & thica cells)basement membrane & thica cells)
  2ry follicle or preantral follicle2ry follicle or preantral follicle
(oocyte surrounded by zona pellucida , several layers of(oocyte surrounded by zona pellucida , several layers of
granulosa cells & thica cells)granulosa cells & thica cells)

7. FOLLICULOGENESIS (2FOLLICULOGENESIS (2((
 tertiary or antral follicletertiary or antral follicle
2ry follicle accumulate fluid in a cavity “antrum”2ry follicle accumulate fluid in a cavity “antrum”
oocyte is in eccentric positionoocyte is in eccentric position
surrounded by granulosa cells “cumulous oophorus”surrounded by granulosa cells “cumulous oophorus”

8. FOLLICULOGENESIS (2FOLLICULOGENESIS (2((
SELECTIONSELECTION
♥♥Selection of the dominant follicle occurs day 5-7Selection of the dominant follicle occurs day 5-7
♥♥It depends onIt 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 matureAs the follicle mature   estrogenestrogen  FSHFSH
““-ve feed back on the pituitary”-ve feed back on the pituitary”  the folliclethe follicle
with the highest No. of FSH receptors willwith 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

9. ♥♥FSH ACTIONSFSH ACTIONS
-recruitement-recruitement
-mitogenic effect-mitogenic effect   No. of granulosa cellsNo. of granulosa cells
 FSH receptorFSH receptor
-stimulates aromatase activity-stimulates aromatase activity  conversion ofconversion of
androgensandrogens  estrogens “estrone & estradiol”estrogens “estrone & estradiol”
--  LH receptorsLH receptors
♥♥ ESTROGENESTROGEN
Acts synergistically with FSH toActs synergistically with FSH to
- induce LH receptors- induce LH receptors
- induce FSH receptors in granulosa- induce FSH receptors in granulosa
& thica cells& thica cells
♥♥LHLH  thica cellsthica cells  uptake of cholesterol & LDLuptake of cholesterol & LDL 
androstenedione & testosteroneandrostenedione & testosterone

10. TWO CELL THEORYTWO CELL THEORY

11. FOLLICULOGENESISFOLLICULOGENESIS (3(3((
OTHER FACTORS THAT PLAY A ROLE INOTHER FACTORS THAT PLAY A ROLE IN
FOLLICULOGENISISFOLLICULOGENISIS
-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 productionLocally 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

12. PREOVULATORY PERIODPREOVULATORY PERIOD
♥♥ NEGATIVE FEEDBACK ON THE PIUITARYNEGATIVE FEEDBACK ON THE PIUITARY
-- estradiol & inhibinestradiol & 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
   estradiolestradiol (reaching a threshold concentration(reaching a threshold concentration))   ++ve feedve feed
back on the pituitaryback on the pituitary (facilitated by low levels of progestrone)(facilitated by low levels of progestrone)  
LH surgeLH surge  secretion of progestronesecretion of progestrone
 Operates after pubertyOperates after puberty
 +ve feed back on pituitary+ve feed back on pituitary   FSHFSH

13. PREOVULATORY PERIODPREOVULATORY PERIOD
LH SURGELH SURGE
 Lasts for 48 hrsLasts 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 wallAffects follicular wall  follicular rupturefollicular rupture
 Granulosa cellsGranulosa cells  lutenizationlutenization  progestrone synthesisprogestrone synthesis

14. OVULATIONOVULATION
 The dominant follicle protrudes from the ovarian cortexThe dominant follicle protrudes from the ovarian cortex
 Gentle release of the oocyte surrounded by the cumulusGentle release of the oocyte surrounded by the cumulus
granulosa cellsgranulosa cells
 Mechanism of follicular ruptureMechanism of follicular rupture
1-1- Follicular pressureFollicular pressure
Changes in composition of the antral fluidChanges in composition of the antral fluid   colloidcolloid
osmotic pressureosmotic pressure
2-Enzymatic rupture of the follicular wall2-Enzymatic rupture of the follicular wall
LH & FSHLH & FSH  granulosa cellsgranulosa cells  production of plasminogenproduction of plasminogen
activatoractivator
  plasminplasmin   fibrinolytic activityfibrinolytic activity  breake down of F. wallbreake down of F. wall
LHLH   prostglandin Eprostglandin E   plasminogen activatorplasminogen activator
  PG F2PG F2αα   lysosomes under follicular walllysosomes under follicular wall

15. LUTEAL PHASELUTEAL PHASE
LASTS 14 daysLASTS 14 days
FORMATION OF THE CORPUS LUTEUMFORMATION OF THE CORPUS LUTEUM
 After ovulation the point of rupture in the follicular wallAfter ovulation the point of rupture in the follicular wall
sealsseals
 Vascular capillaries cross the basement membrane &Vascular capillaries cross the basement membrane &
grow into the granulosa cellsgrow into the granulosa cells  availability of LDL-availability of LDL-
cholestrolecholestrole
LHLH  LDL binding to receptorsLDL binding to receptors
 33αα OH steroid dehydrogenase activityOH steroid dehydrogenase activity
 progestroneprogestrone

16. LUTEAL PHASELUTEAL PHASE
 MarkedMarked  in progestrone secretionin 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 tempbasal 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 gonadotropinsIt looses its sensitivity to gonadotropins  luteolysisluteolysis 
estrogen & progestrone levelestrogen & progestrone level  desquamation of thedesquamation of the
endometrium “menses”endometrium “menses”

17. LUTEAL PHASELUTEAL PHASE
 estrogen & progestroneestrogen & progestrone   FSH &LHFSH &LH
 The new cycle stars with the beginning of mensesThe new cycle stars with the beginning of menses
 If prgnancy occursIf prgnancy occurs  hCG secreationhCG secreation  maintain themaintain the
corpus luteumcorpus luteum

18. HORMONAL PROFILES DURING THEHORMONAL PROFILES DURING THE
MENSTRUAL CYCLEMENSTRUAL CYCLE

19. ENDOMETRIAL CHANGES DURING THEENDOMETRIAL 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 cycle-Remains intact throughout the menstrual cycle
2-Functional layer of the endometrium2-Functional layer of the endometrium
Composed of two layers:Composed of two layers:
-zona compacta-zona compacta  superficialsuperficial
-Spongiosum layer-Spongiosum layer

20. ENDOMETRIAL CHANGES DURING THE MENSTRUALENDOMETRIAL CHANGES DURING THE MENSTRUAL
CYCLECYCLE
1-Follicular /proliferative phase1-Follicular /proliferative phase
EstrogenEstrogen  mitotic activity in the glands & stromamitotic 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
ProgestroneProgestrone - 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

21. 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 withJust before menses the endometrium is infiltrated with
leucocytesleucocytes
 Prostaglandins are maximal in the endometrium justProstaglandins are maximal in the endometrium just
before mensesbefore menses
 ProstaglandinsProstaglandins  constriction of the spiral arteriolesconstriction of the spiral arterioles
ischemia & desquamationischemia & desquamation
Followed byFollowed by arteriolar relaxation, bleeding & tissuearteriolar relaxation, bleeding & tissue
breakdownbreakdown

22. HYPOTHALAMIC ROLE IN THE MENSTRUALHYPOTHALAMIC ROLE IN THE MENSTRUAL
CYCLECYCLE
 The hypothalamus secretes GnRH in a pulsatile fashionThe hypothalamus secretes GnRH in a pulsatile fashion
 GnRH activity is first evident at pubertyGnRH activity is first evident at puberty
 Follicular phase GnRH pulses occur hourlyFollicular phase GnRH pulses occur hourly
 Luteal phase GnRH pulses occur every 90 minutesLuteal phase GnRH pulses occur every 90 minutes
 Loss of pulsatilityLoss of pulsatility down regulation of pituitary receptorsdown regulation of pituitary receptors
  secretion of gonadotropinssecretion 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 neuralRelease of GnRH is modulated by external neural
signalssignals