The normal menstrual cycle involves hormonal signaling between the hypothalamus, pituitary gland, and ovaries. During the follicular phase, FSH causes follicles to mature and produce estrogen in the ovaries. Rising estrogen triggers a LH surge, causing ovulation. After ovulation, the corpus luteum forms and produces progesterone, which prepares the endometrium for potential implantation during the luteal phase. If implantation does not occur, falling progesterone triggers menstruation and shedding of the endometrial lining. This begins a new cycle.

1. The Normal Menstrual Cycle
Gaya 

2. Menstrual bleeding occurs due to shedding of
endometrial lining following failure of
fertilization of the oocyte or failure of
implantation.
It depends on ovarian hormonal levels, that are
themselves controlled by the pituitary and
hypothalamus ( hypothalamo-pituitary ovarian
axis )

3. Hypothalamus
Releasing …..
GnRH- stimulate releasing :
Gonadotopic
LH
FSH in anterior pituitary
• If GnRH is given in constant high dose for long
times it desensitizes the GnRH receptor and
reduce LH and FSH release

4. • GnRH agonist ( Buserelin , Goserelin ) mimic GnRH
hormone and downregulate the pituitary and
decrease LH ,FSH secretion
• It effect on ovarian function and oestrogen
and progensteron level falls women become
amenorrhoeic (use in endometriosis / to
shrink fibroids prior to surgery )

5. Pituitary
• Low level of oestrogen have an inhibitory
effect on LH production . (negative feedback)
• High level of oestrogen will increase LH
production . ( positive feedback )
• Positive feedback effect oetrogen involves an
increase in GnRH receptor consentration )
( This mechanism use in combined oral contraceptive pills- creats constant
serum oestrogen level in negative feedback range ,it makes low level of
gonadotropin hormone release )

6. Hypothalamo-pitutiary-ovarian-axis.

7. • Unlike oetrogen low level of progesterone
have positive feedback on pituitary LH and
FSH secretion. (prior to ovulation)
• It decrease GnRH production from the
hypothalamus and decrease sensitivity to
GnRH in the pituitary.
• High level of progesterone ,as seen in luteal
phase, inhibit pituitary LH and FSH
production.

8. Ovary.
• Primordial follicles containing oocytes will
activate and grow in a cyclic fashion ,causing
ovulation and subsequent menstruation.
• Normal menstrual cycle ,ovary will go through
3 phase:
1. Follicular phase
2. Ovulation
3. Luteal phase

9. Follicles has Theca cells and Granulosa cells.

10. Follicular phase.
• Initial stage independent of hormonal
stimulation..
• FSH level rise in 1st d of menstrual cycle
oes.pro and inhibin levels are low.
• This stimulate small antral follicles on the
ovaries to grow.
• LH and FSH stimulate theca cell in follicle and
produce oetrogen –high oestrogen –negative
feedback decreace FSH secretion.

11. • Small follicles will undergo atresia and
dominant follicle will go on producing
oestrogen and inhibin.
Inhibin/ Actine
Inhibin – secreted by granulosa cells within
ovaries and downregulate FSH release and
synthesis androgen .

12. Actine – structurally similar to inhibin bus
opposite action.
Insulin like growth factors ( IGF-1 IGF-11)
In follicular phase IGF-1 produce by theca cells
under control of LH its increase fluid level of
follicle towards ovulation. It contains granulosa
cell also.

14. Ovulation
After 14 days the dominant follicle has grown to approximately
20mm diameter.
FSH induces LH receptors on granulosa cells to
compensate for low FSH and for preparation of
ovulation.
Oestrogen increase due to positive feedback cause
LH surge.(all occur within 24-36 h)
LH induced luteinization of granulosa cells in the
dominant follicle cause progesterone to be
produced.

15. Inhibiting prostaglandin production may result
in failure of ovulation. (hv to advice not to take
aspirin and ibuprofen to women who wishing to
become pregnant.

16. Luteal Phase
After releasing oocyte remaining part of ovary
(theca and granu.) form corpus luteum.
They produce vascular endothelial growth
factor (VEGF)
Granulosa cell activity increase progesterone
production level in their highest.
This is also have effect suppressing FSH and LH
then further follicle growth will nt happen

17. Luteal phase takes 14 days.
Mature corpus luteum is less sensitive to LH
,produce less progesterone.
And it gradually disappear from the ovary.
The withdrawal of progesterone has effect on
uterus of causing shedding of endometrium
(menstruation)

18. Reduction level of progesterone ,oestrogen
,inhibin feeding back to the pituitary cause
increasing of secretion gonadotrophic hormones
(FSH)
New preantral follicles begin to be stimulated
and cycle begins a new.

19. Endometrium
Specific secondary changes taking place in
uterus endometrium. There are 3 phase
1. Menstruation
2. Proliferative phase –follicular phase
3. Secretory phase-luteal phase

20. Menstruation
Day1-Shedding of the ‘dead’ endometrium and
ceases as the endometrium regenerates
(normally 5-6 day)
Apoptosis occurs if there no embryo
implantation.
Uppermost layer of endometrium shedding
during menstruation in approximatly 4 d of
ovulation

21. This result in to tissue breakdown
vasoconstriction of spiral arterioles and
distal ischemia .
Remaining arterioles is seen as menstrual
bleeding.
Enhance fibrinolysis reduces
clotting.

22. The effect of oestrogen and progesterone on
endometrium can be reproduce artificially ,
Ex- taking combine oral contraceptive pills
Or HRT
Asherman’s syndrome –
"Asherman's Syndrome" is a condition characterized by adhesions
and/or fibrosis of the endometrium particularly but can also affect
the myometrium.
Here tissue breakdown and vasoconstriction not occur correctly

23. Paracrine mediators in menstruation
• Prostaglandin F2alpha,Endothelin-1 ,platelet
activating factor (PAF) Vasoconstrictors
• Prostaglandin E2 , Prostacyclin PG1 , NO are
vasodilators
Both are produce by endothelium and they may
be balance and initiating and controlling
mestruation

24. progesterone withdrawal
Increasing endometrial prostaglandin synthesis
and decrease prostaglandin metabolism
COX-2 enzyme and chemokines are involved in
PG synthesis (NSAID) so they use for treatment
of heavy bleeding and painful periods.

25. Mefenamic Acid –
Is a drug which controlling heavy and painful
bleeding .
It is PG synthetase inhibitor and it believed to
act by increasing the ratio of vasoconstrictor
PGF2alpha to PGE2
It reduce menstrual loss by mean value 20-25%
in women with very heavy bleeding .

26. Proliferative phase
Menstruation will normally cease after 3-4 days
and endometrium enter to proliferative phase
where granular and stromal growth occur.
Epithelium lining change from single columnar
cells to a pseudostratified epithelium with
frequent mitoses.
The stroma infiltrate is infiltrate by cells derived
from bone marrow.

27. Endometrial thickness increasing rapidly from
.5mm at menstruation to 3.5-5 mm at the end
of proliferation.

28. Secretory phase
After ovulation generally around 14 days there is
period of endometrial glandular secretory activity .
Following progesterone surge and oestrogen induce
cellular proliferation is inhibited and the
endometrial thickening does not increase further.
Endometrial gland will become more tortuous,
spiral arteries will grow and fluid is secreted in to
glandular cell and uterine lumen .