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Menstrual
Cycle
By
Dr Nassar Ayoub
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
Menopause
12.7
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
PREOVULATORY PERIOD
NEGATIVE FEEDBACK ON THE PIUITARY
- estradiol -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.
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
1Basal layer of the endometrium
-Adjacent to the myometrium
-Unresponsive to hormonal stimulation
-Remains intact throughout the menstrual cycle
2Functional 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

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Understanding the Menstrual Cycle

  • 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 Menopause 12.7 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
  • 19. PREOVULATORY PERIOD NEGATIVE FEEDBACK ON THE PIUITARY - estradiol -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
  • 20. 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
  • 21. 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
  • 22. 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.
  • 23. 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”
  • 24. LUTEAL PHASE • estrogen & progestrone   FSH &LH • The new cycle stars with the beginning of menses • If pregnancy occurs  hCG secreation  maintain the corpus luteum
  • 25. ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE 1Basal layer of the endometrium -Adjacent to the myometrium -Unresponsive to hormonal stimulation -Remains intact throughout the menstrual cycle 2Functional layer of the endometrium Composed of two layers: -zona compacta  superficial -Spongiosum layer
  • 26. 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
  • 27. 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