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Menstrual Cycle
By Dr Nailla Memon
NORMAL MENSTRUAL CYCLE


mean duration of the MC
       Mean 28 days (only 15% of      )
       Range 21-35

average duration of menses
       3-8 days

normal estimated blood loss
       Approximately 30 ml

ovulation occur
       Usually day 14
        36 hrs after the onset of mid-cycle LH surge
NORMAL MENSTRUAL CYCLE


the phases of the MC & ovulation regulates by:
 Interaction between hypothalamus, pituitary & ovaries

mean age of menarche & menopause are:
         Menarche 12.7
         Menopause 51.4
The Cycle
• Strongly linked to the endocrine system
  (hormone based and paracrine based)
• Typically takes 28 days to cycle through 4
  phases
  – Follicular
  – Ovulation
  – Luteal
  – Menstruation
• Hormones raise and fall
Ovulation
Follicular
• Begins when estrogen levels are low
• Anterior pituitary secretes FSH and LH,
  stimulation follicle to develop
• Cells around egg enlarge, releasing
  estrogen
• This causes this uterine lining to thicken
Ovulation
• LH and FSH still being released, for
  another 3-4 days
• Follicle ruptures, releasing ova into the
  Fallopian tubes
Luteal
• Now empty follicle changes to a yellow
  colour, becomes corpus luteum
• Continues to secrete estrogen, but now
  beings to release progesterone
• Progesterone further develops uterine
  lining
• If pregnant, embryo will release hormones
  to preserve corpus luteum
Menstruation
• Menstruation
• If no embryo, the corpus luteum begins to
  disintegrate
• Progesterone levels drop, uterine lining
  detaches, menstruation can begin
• Tissue, blood, unfertilized egg all
  discharged
• Can take from 3-7 days
HYPOTHALAMIC- PITUITARY- OVARIAN AXIS
prof. aj
PHYSIOLOGYOF THE MENSTRUAL
  CYCLE

Ovulation divides the MC into two phases:

1-FOLLICULAR PHASE
     -Begins with menses on day 1 of the menstrual
  cycle
      & ends with ovulation

       RECRUITMENT
        FSH  maturation of a cohort of ovarian
             follicles “recruitment”
         only one reaches maturity
FOLLICULAR PHASE

MATURATION OF THE FOLLICLE (FOLLICULOGENESIS)

 FSH  primordial follicle
  (oocyte arrested in the diplotene stage of the 1st meiotic
 division surrounded by a single layer of granulosa cells)

    Primary follicle
 (oocyte surrounded by a single layer of granulosa cells
  basement membrane & thica cells)

   Secondary follicle or preantral follicle
 (oocyte surrounded by zona pellucida , several layers of
 granulosa cells & theca cells)
FOLLICULOGENESIS (2)

 tertiary or antral follicle
      secondary follicle accumulate fluid in a cavity
 “antrum”
      oocyte is in eccentric position
      surrounded by granulosa cells “cumulous
 oophorus”
FOLLICULOGENESIS (2)

SELECTION
       Selection of the dominant follicle occurs day 5-7
       It depends on
              - the intrinsic capacity of the follicle to
                synthesize estrogen
            -highest/and ratio in the follicular fluid
       As the follicle mature   estrogen  FSH
      “-ve feed back on the pituitary”  the follicle
        with the highest no: of FSH receptors will
        continue to thrive
        The other follicles “that were recruited” will
        become atretic
FSH ACTIONS
    -recruitement
    -mitogenic effect   No. of granulosa cells
                           FSH receptor
    -stimulates aromatase activity  conversion of
      androgens  estrogens “estrone & estradiol”
              -  LH receptors
 ESTROGEN
      Acts synergistically with FSH to
                  - induce LH receptors
                  - induce FSH receptors in granulosa
                     & thica cells
LH  theca cells  uptake of cholesterol & LDL 
         androstenedione & testosterone
TWO CELL THEORY
FOLLICULOGENESIS (3)

OTHER FACTORS THAT PLAY A ROLE IN FOLLICULOGENISIS
-INHIBIN
• Local peptide in the follicular fluid
• -ve feed back on pituitary FSH secreation
• Locally enhances LH-induced androstenedione production
-ACTIVIN
• Found in follicular fluid
• Stimulates FSH induced estrogen production
•  gonadotropin receptors
• androgen
• No real stimulation of FSH secretion in vivo (bound to protein in
   serum)
PREOVULATORY PERIOD

  NEGATIVE FEEDBACK ON THE PIUITARY
 - estradiol & inhibin -ve feed back on pituitary   FSH
 -This mechanism operating since childhood

  POSITIVE FEEDBACK ON THE PITUITARY
•   estradiol (reaching a threshold concentration)   +ve feed back
  on the pituitary (facilitated by low levels of progestrone)   LH
  surge  secretion of progestrone
• Operates after puberty
• +ve feed back on pituitary   FSH
PREOVULATORY PERIOD

LH SURGE

•   Lasts for 48 hrs
•   Ovulation occurs after 36 hrs
•   Accompanied by rapid fall in estradiol level
•   Triggers the resumption of meiosis
•   Affects follicular wall  follicular rupture
•   Granulosa cells  lutenization  progestrone
    synthesis
OVULATION


• The dominant follicle protrudes from the ovarian cortex
• Gentle release of the oocyte surrounded by the cumulus
  granulosa cells

• Mechanism of follicular rupture
 1- Follicular pressure
   Changes in composition of the antral fluid   colloid
   osmotic pressure
2-Enzymatic rupture of the follicular wall
   LH & FSH  granulosa cells  production of plasminogen
   activator
   plasmin   fibrinolytic activity  breake down of F. wall
   LH   prostglandin E   plasminogen activator
        PG F2α   lysosomes under follicular wall
LUTEAL PHASE

LASTS 14 days

FORMATION OF THE CORPUS LUTEUM

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

•    Vascular capillaries cross the basement
     membrane & grow into the granulosa cells 
     availability of LDL-cholestrole
    LH  LDL binding to receptors
       3α OH steroid dehydrogenase activity
       progestrone
LUTEAL PHASE

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

• estrogen & progestrone   FSH &LH
• The new cycle stars with the beginning of menses
• If pregnancy occurs  hCG secreation  maintain the
  corpus luteum
ENDOMETRIAL CHANGES DURING THE
          MENSTRUAL CYCLE

1-Basal layer of the endometrium
          -Adjacent to the myometrium
          -Unresponsive to hormonal stimulation
          -Remains intact throughout the menstrual cycle

2-Functional layer of the endometrium
 Composed of two layers:
                        -zona compacta  superficial
                        -Spongiosum layer
ENDOMETRIAL CHANGES DURING THE MENSTRUAL
                    CYCLE


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

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

• Periodic desquamation of the endometrium
• The external hallmark of the menstrual cycle
• Just before menses the endometrium is infiltrated with
  leucocytes
• Prostaglandins are maximal in the endometrium just
  before menses
• Prostaglandins  constriction of the spiral arterioles
  ischemia & desquamation
  Followed by arteriolar relaxation, bleeding & tissue
  breakdown
HYPOTHALAMIC ROLE IN THE MENSTRUAL
                  CYCLE

• The hypothalamus secretes GnRH in a pulsatile fashion
• GnRH activity is first evident at puberty
• Follicular phase GnRH pulses occur hourly
• Luteal phase GnRH pulses occur every 90 minutes
• Loss of pulsatility down regulation of pituitary receptors  
  secretion of gonadotropins
• Release of GnRH is modulated by –ve feedback by:
               steroids
               gonadotropins
• Release of GnRH is modulated by external neural signals
THANKYOU


  Education’s purpose is to replace
  an empty mind with an open one”
         ~ Malcolm Forbes

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Menstrual cycle

  • 1. Menstrual Cycle By Dr Nailla Memon
  • 2. NORMAL MENSTRUAL CYCLE mean duration of the MC Mean 28 days (only 15% of ) Range 21-35 average duration of menses 3-8 days normal estimated blood loss Approximately 30 ml ovulation occur Usually day 14 36 hrs after the onset of mid-cycle LH surge
  • 3. NORMAL MENSTRUAL CYCLE the phases of the MC & ovulation regulates by: Interaction between hypothalamus, pituitary & ovaries mean age of menarche & menopause are: Menarche 12.7 Menopause 51.4
  • 4. The Cycle • Strongly linked to the endocrine system (hormone based and paracrine based) • Typically takes 28 days to cycle through 4 phases – Follicular – Ovulation – Luteal – Menstruation • Hormones raise and fall
  • 6. Follicular • Begins when estrogen levels are low • Anterior pituitary secretes FSH and LH, stimulation follicle to develop • Cells around egg enlarge, releasing estrogen • This causes this uterine lining to thicken
  • 7. Ovulation • LH and FSH still being released, for another 3-4 days • Follicle ruptures, releasing ova into the Fallopian tubes
  • 8. Luteal • Now empty follicle changes to a yellow colour, becomes corpus luteum • Continues to secrete estrogen, but now beings to release progesterone • Progesterone further develops uterine lining • If pregnant, embryo will release hormones to preserve corpus luteum
  • 9. Menstruation • Menstruation • If no embryo, the corpus luteum begins to disintegrate • Progesterone levels drop, uterine lining detaches, menstruation can begin • Tissue, blood, unfertilized egg all discharged • Can take from 3-7 days
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  • 14. PHYSIOLOGYOF THE MENSTRUAL CYCLE Ovulation divides the MC into two phases: 1-FOLLICULAR PHASE -Begins with menses on day 1 of the menstrual cycle & ends with ovulation RECRUITMENT FSH  maturation of a cohort of ovarian follicles “recruitment”  only one reaches maturity
  • 15. FOLLICULAR PHASE MATURATION OF THE FOLLICLE (FOLLICULOGENESIS) FSH  primordial follicle (oocyte arrested in the diplotene stage of the 1st meiotic division surrounded by a single layer of granulosa cells)   Primary follicle (oocyte surrounded by a single layer of granulosa cells basement membrane & thica cells)   Secondary follicle or preantral follicle (oocyte surrounded by zona pellucida , several layers of granulosa cells & theca cells)
  • 16. FOLLICULOGENESIS (2)  tertiary or antral follicle secondary follicle accumulate fluid in a cavity “antrum” oocyte is in eccentric position surrounded by granulosa cells “cumulous oophorus”
  • 17. FOLLICULOGENESIS (2) SELECTION Selection of the dominant follicle occurs day 5-7 It depends on - the intrinsic capacity of the follicle to synthesize estrogen -highest/and ratio in the follicular fluid As the follicle mature   estrogen  FSH “-ve feed back on the pituitary”  the follicle with the highest no: of FSH receptors will continue to thrive The other follicles “that were recruited” will become atretic
  • 18. FSH ACTIONS -recruitement -mitogenic effect   No. of granulosa cells  FSH receptor -stimulates aromatase activity  conversion of androgens  estrogens “estrone & estradiol” -  LH receptors ESTROGEN Acts synergistically with FSH to - induce LH receptors - induce FSH receptors in granulosa & thica cells LH  theca cells  uptake of cholesterol & LDL  androstenedione & testosterone
  • 20. FOLLICULOGENESIS (3) OTHER FACTORS THAT PLAY A ROLE IN FOLLICULOGENISIS -INHIBIN • Local peptide in the follicular fluid • -ve feed back on pituitary FSH secreation • Locally enhances LH-induced androstenedione production -ACTIVIN • Found in follicular fluid • Stimulates FSH induced estrogen production •  gonadotropin receptors • androgen • No real stimulation of FSH secretion in vivo (bound to protein in serum)
  • 21. PREOVULATORY PERIOD NEGATIVE FEEDBACK ON THE PIUITARY - estradiol & inhibin -ve feed back on pituitary   FSH -This mechanism operating since childhood POSITIVE FEEDBACK ON THE PITUITARY •   estradiol (reaching a threshold concentration)   +ve feed back on the pituitary (facilitated by low levels of progestrone)   LH surge  secretion of progestrone • Operates after puberty • +ve feed back on pituitary   FSH
  • 22. PREOVULATORY PERIOD LH SURGE • Lasts for 48 hrs • Ovulation occurs after 36 hrs • Accompanied by rapid fall in estradiol level • Triggers the resumption of meiosis • Affects follicular wall  follicular rupture • Granulosa cells  lutenization  progestrone synthesis
  • 23. OVULATION • The dominant follicle protrudes from the ovarian cortex • Gentle release of the oocyte surrounded by the cumulus granulosa cells • Mechanism of follicular rupture 1- Follicular pressure Changes in composition of the antral fluid   colloid osmotic pressure 2-Enzymatic rupture of the follicular wall LH & FSH  granulosa cells  production of plasminogen activator   plasmin   fibrinolytic activity  breake down of F. wall LH   prostglandin E   plasminogen activator   PG F2α   lysosomes under follicular wall
  • 24. LUTEAL PHASE LASTS 14 days FORMATION OF THE CORPUS LUTEUM • After ovulation the point of rupture in the follicular wall seals • Vascular capillaries cross the basement membrane & grow into the granulosa cells  availability of LDL-cholestrole LH  LDL binding to receptors  3α OH steroid dehydrogenase activity  progestrone
  • 25. LUTEAL PHASE • Marked  in progestrone secretion • Progestrone actions: -suppress follicular maturation on the ipsilateral ovary -thermogenic activity  basal body temp -endometrial maturation • Progestrone peak 8 days after ovulation (D22 MC) • Corpus luteum is sustained by LH • It looses its sensitivity to gonadotropins  luteolysis  estrogen & progestrone level  desquamation of the endometrium “menses”
  • 26. LUTEAL PHASE • estrogen & progestrone   FSH &LH • The new cycle stars with the beginning of menses • If pregnancy occurs  hCG secreation  maintain the corpus luteum
  • 27. ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE 1-Basal layer of the endometrium -Adjacent to the myometrium -Unresponsive to hormonal stimulation -Remains intact throughout the menstrual cycle 2-Functional layer of the endometrium Composed of two layers: -zona compacta  superficial -Spongiosum layer
  • 28. ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE 1-Follicular /proliferative phase Estrogen  mitotic activity in the glands & stroma   enometrial thickness from 2 to 8 mm (from basalis to opposed basalis layer) 2-Luteal /secretory phase Progestrone - Mitotic activity is severely restricted -Endometrial glands produce then secrete glycogen rich vacoules -Stromal edema -Stromal cells enlargement -Spiral arterioles develop, lengthen & coil
  • 29. MENSTRUATION • Periodic desquamation of the endometrium • The external hallmark of the menstrual cycle • Just before menses the endometrium is infiltrated with leucocytes • Prostaglandins are maximal in the endometrium just before menses • Prostaglandins  constriction of the spiral arterioles ischemia & desquamation Followed by arteriolar relaxation, bleeding & tissue breakdown
  • 30. HYPOTHALAMIC ROLE IN THE MENSTRUAL CYCLE • The hypothalamus secretes GnRH in a pulsatile fashion • GnRH activity is first evident at puberty • Follicular phase GnRH pulses occur hourly • Luteal phase GnRH pulses occur every 90 minutes • Loss of pulsatility down regulation of pituitary receptors   secretion of gonadotropins • Release of GnRH is modulated by –ve feedback by: steroids gonadotropins • Release of GnRH is modulated by external neural signals
  • 31. THANKYOU Education’s purpose is to replace an empty mind with an open one” ~ Malcolm Forbes