THE MENSTRUAL THE MENSTRUAL CYCLE CYCLE

ByByBY: DR. MALAK AL-HAKEEMBY: DR. MALAK AL-HAKEEM

Assistant Professor Assistant Professor and Consultant Of Ob & Gyn.and Consultant Of Ob & Gyn.

Each cycle represents a complex Each cycle represents a complex

interaction between the interaction between the

hypothalamus, pituitary gland, hypothalamus, pituitary gland,

ovaries and endometrium. ovaries and endometrium.

Cyclic changes of gonadotrophins Induce Cyclic changes of gonadotrophins Induce

functional and morphologic changes in the functional and morphologic changes in the

ovary, resulting in follicular maturation, ovary, resulting in follicular maturation,

ovulation and corpus luteum formation ovulation and corpus luteum formation

with production of steroid hormones. with production of steroid hormones.

Similar changes Similar changes at the level of at the level of endometrium endometrium allow for allow for successful successful implantation of implantation of the embryo. the embryo.

PITUITARY GLANDPITUITARY GLAND

Consists of two main partsConsists of two main parts

• adenohypophysis (anterior lobe) and adenohypophysis (anterior lobe) and

• neurohypophysis (post. lobe)neurohypophysis (post. lobe)

The posterior lobe transport oxytocin The posterior lobe transport oxytocin

and vasopressin (antidiuretic hormone)and vasopressin (antidiuretic hormone)

from the hypothalamus to their releasefrom the hypothalamus to their release

into the circulation.into the circulation.

The blood supply to the The blood supply to the pituitary stalk known as the pituitary stalk known as the hypophyseal - pituitary portal hypophyseal - pituitary portal systemsystem represents a major way represents a major way of transport for hypothalamic of transport for hypothalamic secretions to the pituitary.secretions to the pituitary.

The anterior pituitary produces The anterior pituitary produces six protein hormones, six protein hormones, F.S.H, L.H, F.S.H, L.H, T.S.H., G.H, A.C.T.H and Prolactin.T.S.H., G.H, A.C.T.H and Prolactin.

FSH, LH and TSH are glyco-FSH, LH and TSH are glyco-proteins each consists of proteins each consists of αα and ß and ß chain. The chain. The αα chain is identical in chain is identical in all while the ß chain is specific for all while the ß chain is specific for each one.each one.

All hormones produced by the All hormones produced by the anterior pituitary are under anterior pituitary are under stimulatory effect by the stimulatory effect by the hypothalamus except prolactin hypothalamus except prolactin which is under chronic inhibition which is under chronic inhibition by hypothalamic Prolactin by hypothalamic Prolactin inhibitory factor (dopamin).inhibitory factor (dopamin).

HYPOTHALAMUSHYPOTHALAMUS Produces five hormones or Produces five hormones or

factors, factors, GnRH and PIFGnRH and PIF have have direct effect on menstrual direct effect on menstrual cycle.cycle.

GnRH stimulates synthesis and GnRH stimulates synthesis and release of FSH and LH by the release of FSH and LH by the gonadotrophs cells of the gonadotrophs cells of the pituitary gland.pituitary gland.

GnRH is a decapitate secreted by GnRH is a decapitate secreted by the hypothalamus in a the hypothalamus in a pulsatile pulsatile fashionfashion every 90 minutes. every 90 minutes.

Continuous infusion of GnRH Continuous infusion of GnRH results in reversible inhibition of results in reversible inhibition of gonadotrophins secretion (down gonadotrophins secretion (down regulation or desensitization of regulation or desensitization of pituitary gonadotrophs).pituitary gonadotrophs).

Estradiol enhances Estradiol enhances hypothalamic release of hypothalamic release of

GnRH GnRH

while gonadotrophins while gonadotrophins have an inhibitory effect have an inhibitory effect

on GnRH release.on GnRH release.

The hypothalamus also produces The hypothalamus also produces PIF which exerts chronic PIF which exerts chronic inhibition of prolactin release inhibition of prolactin release from lactotrophs.from lactotrophs.

TRH stimulates prolactin release, TRH stimulates prolactin release, this explains the association this explains the association between primary hypothyroidism between primary hypothyroidism and hyper-prolactinaemia.and hyper-prolactinaemia.

OVARIAN CYCLEOVARIAN CYCLE

In the first half of the In the first half of the menstrual cycle, the anterior menstrual cycle, the anterior pituitary secrets FSH and LHpituitary secrets FSH and LH

FSH stimulates the growth FSH stimulates the growth of several primary follicles in of several primary follicles in both ovaries.both ovaries.

Only one Only one follicle reaches follicle reaches maturation to maturation to form the form the graffian follicle graffian follicle which secrets which secrets increasing increasing amount of amount of estrogens estrogens mainly mainly estradiol.estradiol.

The increasing level of The increasing level of

oestrogen first inhibits FSH oestrogen first inhibits FSH

production (negative feed back) production (negative feed back)

then stimulates the production then stimulates the production

of LH surge (positive feed back) of LH surge (positive feed back)

which reaches a peak about 48 which reaches a peak about 48

hours before ovulation.hours before ovulation.

LH surge leads to ovulation LH surge leads to ovulation and formation of corpus and formation of corpus luteum.luteum.

LH maintains the growth of LH maintains the growth of corpus luteum and stimulates corpus luteum and stimulates it to secret oestrogen and it to secret oestrogen and progesterone.progesterone.

The corpus luteum has a limited The corpus luteum has a limited life span (in the absence of life span (in the absence of pregnancy) after which it pregnancy) after which it degenerates. degenerates.

Degeneration of corpus luteum Degeneration of corpus luteum and drop in the level of oestrogen and drop in the level of oestrogen and progesterone cause separation and progesterone cause separation of endometrium and menstruation.of endometrium and menstruation.

The drop in the level of these The drop in the level of these

hormones stimulates hormones stimulates

the hypothalamus and pituitary to the hypothalamus and pituitary to

secret GnRH and secret GnRH and

gonadotrophins to start a new gonadotrophins to start a new

cycle.cycle.

Follicular DevelopmentFollicular Development

FSH receptors are present on FSH receptors are present on the granulose cells. FSH the granulose cells. FSH stimulates the growth and stimulates the growth and maturation of the follicles , it maturation of the follicles , it also stimulates the production also stimulates the production of aromataze enzymes.of aromataze enzymes.

LH receptors are present LH receptors are present

initially on theca cells. LH initially on theca cells. LH

stimulates it to produce stimulates it to produce

androgens which diffuse into androgens which diffuse into

granulose cells to be converted granulose cells to be converted

into estrogen by aromataze into estrogen by aromataze

enzymes.enzymes.

Estrogens (mainly estradiol) Estrogens (mainly estradiol)

increase the no. of FSH increase the no. of FSH

receptors on granulosa cells receptors on granulosa cells

and increase its sensitivity.and increase its sensitivity.

Eestrogen and FSH stimulate Eestrogen and FSH stimulate

granulosa cells to form LH granulosa cells to form LH

receptors.receptors.

The follicle which is chosen to The follicle which is chosen to mature and ovulate has rich mature and ovulate has rich estrogen milieu and high FSH estrogen milieu and high FSH content in it’s follicular fluid.content in it’s follicular fluid.

The follicle which undergoes The follicle which undergoes atresia are androgen atresia are androgen predominant and have low FSH predominant and have low FSH content in it’s follicular fluid.content in it’s follicular fluid.

OvulationOvulation

As a result of LH surge and As a result of LH surge and

36-48 h later ovulation takes 36-48 h later ovulation takes

places and the mature ovum places and the mature ovum

surrounded by corona radiate surrounded by corona radiate

expels from the ovary.expels from the ovary.

Corpus Luteum FormationCorpus Luteum Formation

After ovulation and under the After ovulation and under the effect of LH both granulose effect of LH both granulose cells of the collapsed cells of the collapsed ruptured follicle and the ruptured follicle and the theca cells undergoes theca cells undergoes lutinization to form corpus lutinization to form corpus luteum. luteum.

The corpus luteum secrets large The corpus luteum secrets large amount of progesterone and amount of progesterone and oestrogen hormones.oestrogen hormones.

The normal life span of c. luteum The normal life span of c. luteum is 14 days. After this time it is 14 days. After this time it regresses (unless pregnancy regresses (unless pregnancy occurs), menstruation ensues and occurs), menstruation ensues and the corpus luteum becomes the the corpus luteum becomes the corpus albicans. corpus albicans.

The Endometrium CycleThe Endometrium Cycle

Functionally the endometrium is Functionally the endometrium is divided into two zones:divided into two zones:

1.1. Function outer zone that undergoes Function outer zone that undergoes cyclic changes during menstrual cyclic changes during menstrual cycle and is sloughed off during cycle and is sloughed off during menstruation. It is supplied by spiral menstruation. It is supplied by spiral arteries which are branches from arteries which are branches from basal arteries.basal arteries.

2.2. Basal inner zone which remains Basal inner zone which remains

unchanged during menstrual unchanged during menstrual

cycle, after menstruation it cycle, after menstruation it

provides stem cells for the provides stem cells for the

renewed of the functioning renewed of the functioning

zone.zone.

A. MENSTRUAL PHASEA. MENSTRUAL PHASE

Two to seven days during Two to seven days during

which the superficial layer which the superficial layer

separate leaving the basal separate leaving the basal

layer from which the layer from which the

endometrium regenerates endometrium regenerates

again. again.

B. Proliferative or oestrogenic B. Proliferative or oestrogenic phase. phase.

Starts after the end of menstruation Starts after the end of menstruation

and ends at ovulation and is and ends at ovulation and is

characterized by:characterized by:

• Thickness of endometrium 3-4 mmThickness of endometrium 3-4 mm

• Glands increase in number and Glands increase in number and

length, but remain tubular.length, but remain tubular.

• The stroma cells proliferate and The stroma cells proliferate and

show mitosis.show mitosis.

• Vascularity increase, the spiral Vascularity increase, the spiral

arteries increase in length and arteries increase in length and

traverse the whole endometrium. traverse the whole endometrium.

C.C. Secretary or Progestogenic Secretary or Progestogenic PhasePhase

Fixed duration irrespective of the Fixed duration irrespective of the length of the cycle (14-12)length of the cycle (14-12)

Begins at ovulation and ends by Begins at ovulation and ends by onset of Menstruation. It is onset of Menstruation. It is characterized by:characterized by:

Thickness of endometrium 6-8 Thickness of endometrium 6-8 mm.mm.

Glands continue to Glands continue to grow and become grow and become tortuous, so it appear tortuous, so it appear like corkscrew or like corkscrew or saw-tooth saw-tooth appearance in appearance in longitudinal section. longitudinal section. The lumen is The lumen is distended with distended with secretion (glycogen secretion (glycogen and mucin)and mucin)

The epithelium cells become The epithelium cells become

high colummnar. Secretory high colummnar. Secretory

granules appear first as sub granules appear first as sub

nuclear vacuoles and later as nuclear vacuoles and later as

supranuclear vacuoles.supranuclear vacuoles.

Stroma cells increase in size Stroma cells increase in size become closely packed become closely packed together and polygonal. The together and polygonal. The stroma becomes stroma becomes differentiated into three differentiated into three layers.layers.

1-Superficial compact 1-Superficial compact layer around the neck of layer around the neck of glands.glands.

2.2. Middle spongy layer around the Middle spongy layer around the

distended lumen of the glands.distended lumen of the glands.

3.3. Deep compact layers around Deep compact layers around

the basal part of the glands.the basal part of the glands.

Marked increase in vascularity Marked increase in vascularity

with marked elongation of the with marked elongation of the

spinal arteries.spinal arteries.

Mechanism of MenstruationMechanism of Menstruation Degeneration of C. luteum leads to drop in Degeneration of C. luteum leads to drop in

the level of oestrogen and progesterone.the level of oestrogen and progesterone.

These lead to shrinkage of the These lead to shrinkage of the endometrium causing increase coiling of endometrium causing increase coiling of the spiral arteries (end arteries) with stasis the spiral arteries (end arteries) with stasis and ischemia causing necrosis of the and ischemia causing necrosis of the superficial and middle layers of superficial and middle layers of endometrium which separate leading to endometrium which separate leading to bleeding.bleeding.

The basal layers does no The basal layers does no separate as it is supplied by basal separate as it is supplied by basal arteries which anastemose freely.arteries which anastemose freely.

Normally the endometrium Normally the endometrium contains prostaglandins which contains prostaglandins which show marked increase show marked increase immediately before and during immediately before and during menstruation.menstruation.

There are four prostaglandins There are four prostaglandins

present in the endometrium.present in the endometrium.

• PG F2 and thromboxan both are PG F2 and thromboxan both are

vasoconstrictors and reduce vasoconstrictors and reduce

menstrual loss.menstrual loss.

• PGE2 and prostacyclin both are PGE2 and prostacyclin both are

vasodilator and cause heavy vasodilator and cause heavy

menstrual loss.menstrual loss.

Cyclic changes in cervical mucusCyclic changes in cervical mucus

A. In the A. In the follicular phasefollicular phase under under oestrogen effect the cervical mucus oestrogen effect the cervical mucus become excessive, watery, less become excessive, watery, less viscid, clear and a cellular.viscid, clear and a cellular.

It is stretchable and can reach a It is stretchable and can reach a length of 10-15cm. just before length of 10-15cm. just before ovulation (spinbarkite test) It gives ovulation (spinbarkite test) It gives positive fern testpositive fern test when dried on a when dried on a slide.slide.

B. In the B. In the luteal phaseluteal phase, ,

progesterone makes progesterone makes

cervical mucus scanty, cervical mucus scanty,

viscid, cellular, non viscid, cellular, non

stretchable and gives a stretchable and gives a

negative fern test.negative fern test.

Cyclic Changes in the vaginaCyclic Changes in the vaginaVaginal smear taken from lateral Vaginal smear taken from lateral

vaginal fornix shows different vaginal fornix shows different pictures according to the phase of pictures according to the phase of the cycle.the cycle.

In the follicular phase the smear In the follicular phase the smear consists of many superficial cells with consists of many superficial cells with acidophilic cytoplasm and pyknotic acidophilic cytoplasm and pyknotic nucleus. The back ground is clear nucleus. The back ground is clear with few leucocytes .with few leucocytes .

• In the luteal phase the smear In the luteal phase the smear consists mainly of intermediate consists mainly of intermediate cells with folded edges cells with folded edges (navicular cells). These cells (navicular cells). These cells have basophilic cytoplasm and have basophilic cytoplasm and vesicular nucleus. The back vesicular nucleus. The back ground is unclear with many ground is unclear with many leucocytesleucocytes. .

Normal MenstruationNormal Menstruation

Duration:Duration: 2-7 days 2-7 days

LengthLength of cycle of cycle:: 3-5 weeks with 3-5 weeks with

weeks as an average.weeks as an average.

Amount:Amount: 30-60 mls. loss more 30-60 mls. loss more

than 80 mls is abnormal.than 80 mls is abnormal.

ConsistencyConsistency• Consists of blood rich in leucocytes, Consists of blood rich in leucocytes,

endometrial fragments, cervical endometrial fragments, cervical mucus, desquamated vaginal mucus, desquamated vaginal epithelium cells, bacteria and epithelium cells, bacteria and enzyme.enzyme.

• Normally the menstrual blood does Normally the menstrual blood does not coagulate due to the presence of not coagulate due to the presence of enzyme produced by endometrium enzyme produced by endometrium which digest fibrin.which digest fibrin.