The menstrual cycle
The most manifestation of normal menstrual cycle is the presence of
regular menstrual periods. These occur as the endometrium is shed
following failure of implantation or fertilization of the oocyte.
Menstruation is initiated in response to changes in steroids
produced by the ovaries, which themselves are controlled by the
pituitary and hypothalamus.
Within ovary, the cycle can be divided into three phases :
Follicular phase;
Ovulation;
The luteal phase
Follicular phase :ovary contain thousands of primordial follicles
that are in acontinuous state of development from birth. These
initial stages of follicular development are independent of
hormonal stimulus. Follicular development fails at the preantral
stage, with follicular atresia. Development beyond the preantral
stage is stimulated by the pituitary hormones, LH & FSH, which
can be considered as key regulater of oocyte development.
At the start of menstrual cycle, FSH levels begin to rise as the
pituitary is released from the negative feedback effects of
progesterone, estrogen and inhibin.
Rising FSH levels stimulate follicular growth which contain two
types of cells: Theca & granulose cells.
Within the theca cells, LH stimulates the production of androgens
from cholesterol , within granulose cells ,FSH stimulate conversion
of androgens to estrogens (aromatization) . also FSH is responsible
for proliferation of granulose cells.
Androgen production within the follicle may also regulate
development of the preantral follicle. Low androgens level enhance
aromatization & then increase estrogen production. Incontrast ,
high androgen levels inhibit aromatization & produce follicular
atresia . A delicate balance of FSH& LH is required for early
follicular development . In early menstrual cycle, the LH levels is
low & FSH is high . if the LH levels are high , theca cells produce
large amounts of androgens causing follicular atresia.
The developing follicles grow & only one of these follicles is
destined to grow to pre-ovulatory follicle & be released at
ovulation ( dominant follicle). The dominant follicle secrete
estradiol& inhibin. So FSH level decline in response to negative
feedback effect of estradiol.
The hypothalamus, via the pulsatile secretion of GnRH, stimulate
pituitary LH & FSH secretion. Production of GnRH not only has a
permissive effect on gonadotrophin production , but alterations in
amplitude & frequency of GnRH pulsation throughtout the cycle
are also responsible for some fine tuning of goadotrophin
production.
The response of the pituitary is not constant but is modulated by
ovarian hormones ( estrogen& progesterone). In late follicular
phase , serum levels of estrogen are high so that a positive
feedback effect is triggered thus generating the periovulatory LH
Surge.
In contrast to the effects of estrogen , low levels of progesterone
have a positive feedback effect on pituitary LH& FSH secretion.
Such levels are generated immediately prior to ovulation, and
contribute to the FSH surge .
High levels of progesterone such as those seen in the luteal phase
inhibit pituitary gonadotrophin. In late follicular phase , as the
dominant follicle develops further , follicular estrogen production
increases. The estrogen exerts a positive feedback effect on
pituitary LH secretion. LH levels increase at first slowly ( day 8day12 of the cycle) & then more rapidly after day 12. LH induces
luteinization of granulose cells in the dominant follicle, so
progesterone is produced. Progesterone amplifies the positive
feedback effect of estrogen on pituitary LH secretion, leading to a
surge of LH.
Ovulation occurs 36 hours after onset of the LH surge . the LH
surge is one of the best methods by which the time of ovulation can
be determined.
The periovulatory FSH surge is induced by positive feedback
effects of progesterone. In addition to the rise in LH , FSH&
estrogen that occur around ovulation , a rise in serum androgen
levels also occurs .these androgens are derived from stimulatory
effect of LH on theca cells, particularly those of the non dominant
follicle.
Release of ovum from follicle is coordinated by LH ,FSH &
PROGESTERONE WHICH STIMULATE PROTEOLYTIC
enzyme and prostaglandin.
Luteal phase ; production of progesterone from corpus luteum
within ovary. The corpus luteum is derived from the granulose
cells & from some theca cells which differentiate to become theca
lutein cells.
The production of progesterone from corpus luteum is dependent
on pituitary LH secretion. The corpus luteum remain 14 days and
then regression if no pregnancy occur. As that estrogen,
progesterone &inhibin decline , FSH is released from pituitary
from the negative feedback effects of these hormones.
On the endometrium:
Proliferative phase : within endometrium , the stroma & glands
growth which increase thickness of endometrium from 0.5mm at
menstruation to 3.5-5mm at the end of the proliferative phase.
Secretory phase: is characterized by endometrial glandular
secretory activity, increase glands and spiral arteries tortuosity, in
the late secretory phase, irreversible decidualization of stroma and
leads to endometrial apoptosis and menstruation unless pregnancy
occurs.
Mensturation: is initiated by withdrawal of estrogen &
progesterone. It is initiated by arteriolar vasoconstriction( 75% of
endometrium is shed.
Menstruation ceases as the damaged spiral arteries vasoconstriction
and endometrim regenerates. Fibrinolysis inhibit scar formation (
breakdown the blood clot& then repair of the endometrium and
new blood vessels formation – angiogenesis-