Physiology of The Menstrual Cycle

11/18/2018
PHYSIOLOGY OF THE
MENSTRUAL CYCLE
Dr. Azhar Mousa Al-Turiahi
NORMAL MENSTRUAL CYCLE

What is the mean duration of the MC?
Mean 28 days (only 15% of ♀)
Range 21-35
What is the average duration of menses?

3-8 days
What is the normal estimated blood loss?

Approximately 30 ml
When does ovulation occur?

Usually day 14
36 hrs after the onset of mid-cycle LH surge
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NORMAL MENSTRUAL CYCLE
What regulate the phases of the MC & ovulation?

Interaction between hypothalamus, pituitary & ovaries
What is the mean age of menarche & menopause?

Menarche 12.7
Menopause 51.4
Biology and the Menstrual Cycle
 Menstrual cycle is regulated by fluctuating

 levels of sex hormones
 These hormones produce certain changes in
 the ovaries and uterus
 Humans are nearly unique among species in
 having a menstrual cycle
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HYPOTHALAMIC- PITUITARY- OVARIAN AXIS
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4 phases of menstrual cycle

 Menstrual flow
 Proliferative
 Ovulation
 Luteal
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PHASES OF 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)
  1ry follicle
(oocyte surrounded by a single layer of granulosa cells basement
membrane & thica cells)
  2ry follicle or preantral follicle

(oocyte surrounded by zona pellucida , several layers of granulosa
cells & thica cells)
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FOLLICULOGENESIS (2)
 tertiary or antral follicle

2ry follicle accumulate fluid in a cavity “antrum”
oocyte is in eccentric position
surrounded by granulosa cells “cumulous oophorus”
SELECTION
♥Selection of the dominant follicle occurs day 5-7
♥It depends on
- the intrinsic capacity of the follicle to
synthesize estrogen
-high est/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
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♥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  thica cells  uptake of cholesterol & LDL 
androstenedione & testosterone
TWO CELL THEORY
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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
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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
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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”
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LUTEAL PHASE
 estrogen & progestrone   FSH &LH

 The new cycle stars with the beginning of menses
 If prgnancy occurs  hCG secreation  maintain the
corpus luteum
HORMONAL PROFILES DURING THE

MENSTRUAL CYCLE
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ENDOMETRIAL CHANGES DURING THE

MENSTRUAL CYCLE
1-Basal layer of the enometrium
-Adjasent to the mometrium
-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 vacules
-Stromal edema
-Stromal cells enlargement
-Spiral arterioles develop, lengthen & coil
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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
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During which days of the cycle is

FSH at its lowest?
• FSH: follicle stimulating hormones is at its lowest during the last
days of the cycle
When FSH levels are low what is

the size of the follicle
• It is shrinking and
disappearing while a new
set is growing
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Ovulation
• Day 14 of the cycle usually marks an event
called ovulation
• follicle ruptures open and releases the
ripened egg
• Pituitary hormones: LH and FSH are
peaking
• Estrogen is also released from follicle
Hormones and What Happens in

the Ovaries
• Luteal phase - after releasing an egg, the follicle turns into the corpus
luteum
– The corpus luteum manufactures progesterone
• Menstruation - shedding of the inner lining of the uterus
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Length and Timing of the Cycle

Normal menstrual cycle = 20 to 36 to 40 days;
average is about 28 days
– Menstruation begins on day 1 and continues until about
day 4 or 5
– Follicular phase extends from about day 5 to about day
13
– Ovulation occurs on day 14
– Luteal phase extends from day 15 to the end of the
cycle, day 28
Other Cyclic Changes

Two other physiological processes fluctuate
with the menstrual cycle:
– The cervical mucus cycle
– The basal body temperature cycle
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Physiology of The Menstrual Cycle

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11/18/2018

Dr. Azhar Mousa Al-Turiahi

NORMAL MENSTRUAL CYCLE

What is the average duration of menses?

What is the normal estimated blood loss?

When does ovulation occur?

NORMAL MENSTRUAL CYCLE

What regulate the phases of the MC & ovulation?

What is the mean age of menarche & menopause?

Biology and the Menstrual Cycle

 Menstrual cycle is regulated by fluctuating

HYPOTHALAMIC- PITUITARY- OVARIAN AXIS

4 phases of menstrual cycle

PHASES OF THE MENSTRUAL CYCLE

Ovulation divides the MC into two phases:

MATURATION OF THE FOLLICLE (FOLLICULOGENESIS)

♥ FSH  primordial follicle

  2ry follicle or preantral follicle

 tertiary or antral follicle

TWO CELL THEORY

OTHER FACTORS THAT PLAY A ROLE IN FOLLICULOGENISIS

♥ POSITIVE FEEDBACK ON THE PITUITARY

 Lasts for 48 hrs

 Mechanism of follicular rupture

FORMATION OF THE CORPUS LUTEUM

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

 estrogen & progestrone   FSH &LH

HORMONAL PROFILES DURING THE

ENDOMETRIAL CHANGES DURING THE

2-Functional layer of the endometrium

ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE

1-Follicular /proliferative phase

2-Luteal /secretory phase

 Periodic desquamation of the endometrium

HYPOTHALAMIC ROLE IN THE MENSTRUAL

During which days of the cycle is

When FSH levels are low what is

Hormones and What Happens in

Length and Timing of the Cycle

Other Cyclic Changes

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