Physiology of menstruation
Dr: Abir Mohidien Said
2012
The normal menstrual cycle
Menstruation describes the female period, involves
the monthly release of an egg(ovum) in a process
called ovulation, with bleeding due to shedding of
the uterine lining following failure of fertilization of
the oocyte or failure of implantation.
The cycle has an average duration of 28 days, but the
normal range is bet.21-35 days.
The normal menstrual cycle
Menstruation usually starts at an average
age of 13( called menarche) and lasts on
average till age 51 (called menopause).
Normal menstruation is a highly complex
interactions between a number of hormones
produced by 3 organs of the body:
Hypothalamus
Pituitary gland
Ovary
The interactions between these organs are
referred to as the hypothalamic-pituitary-ovarian
axis(HPO axis)
Hypothalamus
The hypothalamus in the forebrain secretes GnRH
which controls of 2 important pituitary hormone
secretion FSH (follicular stimulating hormone)& LH (
luteinising hormone)
GnRH is of great importance in the menstrual cycle, its
release occurs in a pulsatile fashion to stimulate LH &
FSH, anything that interferes with the pulse frequency
of GnRH can stop the menstrual cycle from occurring
If GnRH is given in a constant high dose, it desensitizes
the GnRH receptor & reduces LH & FSH release
Pituitary gland
Anterior pit.gland causes synthesis & release of
gonadotrophic hormones FSH & LH by
stimulation of GnRH.
This process is influence and stimulate the
ovarian sex steroid hormones: oestrogen &
progesterone.
Negative feedback (low level of oestrogen will
↓LH production)
Positive feedback (high level of oestrogen will
↑ LH production)
Pituitary gland
GnRH agonists when administered continuously
they will down regulate the pituitary and ↓ LH
& FSH secretion, this has effects on ovarian
function and oestrogen and progestron levels
also fall and most women become
amenorrhoeic, these drugs are used as
treatment for endometriosis and to shrink
fibroid prior to surgery.
Pituitary gland
As the dominant follicle grows further
oestrogen level ↑ until it is sufficient to exert a
positive feed back effect on the pituitary LH
secretion which is ↑ more rapidly from day 12
onward called the LH surge.
Combined oral contraceptive pill creates
artificially a constant serum oestrogen level in
the negative feedback , inducing low level of
gonadotophin hormone release.
Unlike oestrogen, low level of progesterone
have a positive feedback effect on pituitary LH
& FSH.
Ovary
Females are born with 2-4 mil.primary
follicles. These containing oocytes will activate
and grow in a cyclical fashion, causing
ovulation and menstruation in the onset of
menarche.
No new oocytes are formed during the female
lifetime.
Normal menstruation cycle in the ovary will go
through three phases:
follicular phase
ovulation
luteal phase
Follicular phase
Within the follicles , there are two cell types:
theca and granulosa cells which respond to LH
and FSH stimulation and produce oestrogen,
progestrone , inhibin and activin.
Both FSH & LH are required to generate a
normal cycle with adequate amounts of
oestrogen.
As the follicles grow & oestrogen secretion ↑,
there is negative feedback on the pituitary to ↓
FSH secretion. this select one follicle to
continue in its development towards ovulation
( the dominant follicle)
Follicular phase
While smaller follicles will undergo atresia.
Exogenous gonadotrophins is likely to stimulate
growth of multiple follicles which continue to
develop, risk of multiple gestations about 30%.
Inhibin is secreted by granulosa cells within the
ovaries & it participated in feedback to the
pituitary to down regulate FSH.
Activin is structurally similar to inhibin but has
an opposite action, acts to ↑FSH binding on the
follicles.
Ovulation
The dominant follicle grow to 18-22 mm at
average of 14 days, oestrogen ↑until exert a
positive feedback effort on the hypothalamus
& pituitary to cause the LH surge. This occurs
over 24-36 hours, LH induced dominant follicle
to produce progestrone & causing a small per
ovulatory rise in FSH.
Androgens synthesized in the theca cells ↑at
time of ovulation to stimulat libido & sexual
activity.
Luteal phase
After the release of the oocyte, the remaining
granulosa and theca cells on the ovary form
the corpus luteum ( yellow body), its extensive
vascularization to supply granulosa cells with a
rich blood supply for continued
steroidogenesis.
Highest level of progesterone in luteal phase
to prepares endometrium for pregnancy & has
the effect of suppressing FSH & LH secretion to
a level that will not produce further follicular
growth in the ovary during that cycle.
Luteal phase
In the absence of beta human chorionic
gonadotrophin βHCG which producers from an
implantning embryo, the corpus luteum will
regres & disappear from ovary ( luteolysis).
The withdrawal of progesterone causing
shedding of the endometrium & menstruation.
↓ in levels of progesterone, oestrogen & inhibin
feedingback to pituitary cause ↑gonadotrophic
hormones, particulary FSH & new preantral
follicles begin to be stimulated & begins a
new cycle
Menstruation
In reproductive age its under the influence of
sex hormones. exposur to oestrogen & progest,
will results proliferative & secretory phase.
Menstruation day 1 is the shedding of the dead
endometrium( uppermost layer) and day 5-6 of
cycle regenerates again.
Approximatly 14 days after ovulation ↓in
circulating levels of oestrogen and progestrone
leads to loss of tissue fluid, vasoconstriction of
spiral arterioles and distal ischaemia and this
leads to loss of the upper layer along with
bleeding.
Menstruation
Contraceptive pill or hormone replacement
therapy produces artificially withdrawal
bleeding.
Prostaglandines are produced by the
endometrium and are vasoconstrictors.
Non-steroidal anti-inflammatory agents used
for treatment of heavy and painful periods.
Mefenamic acid is a prostaglandin synthetase
inhibitor used as a treatment for heavy
menstrual bleeding ( reduces blood loss by 2025%)
The proliferative phase
After menstruation enters the proliferative
phase, when glandular and stromal growth
occur, the epithelium changes from single layer
of columnar cells to a pseudostratified
epithelium with frequent mitosis, thickness ↑
rapidly.
The secretory phase
After ovulation and progestrone surge(
generally around day 14), cellular proliferation is
inhibited and endometrial thickness does not
increase any further, the endomerial glands
will become more tortuous, spiral arteries will
grow and fluid is secreted into glandular cells
and uterin lumen.
On the withdrawal of both oestrogen and
progesterone, the decidua will collapse with
vasoconstriction and relaxation of spiral
arteries and shedding of the outer layers of the
endometrium .
Proliferative phase
secretory phase
Measurement of ovarian reserve
Menstruation remaining depends of number
oocytes.
Deficit of gonadotrophin or exposure to toxins
accelerate menopause age.
U/S to measure of ovarian volume, diameter
and antral follicle count to calculate ovarian
reserve.
Biochemical markers: FSH, oestradiol, inhibin
B, anti-Mullerian hormone AMH( is produced in
the granulosa cells and not change in response
to gonadotrophins during the cycle)