The normal menstrual cycle

All about normal menstrual pattern and disorders

1. The Normal M enstrual C ycle 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 I t 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: Follicular phase Ovulation Luteal phase

9. Follicles has Theca cells and Granulosa cells.

10. Follicular phase. Initial stage independent of hormonal stimulation.. FSH level rise in 1 st 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.

13. 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.

14. 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.

15. 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

16. 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)

17. 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.

18. Endometrium Specific secondary changes taking place in uterus endometrium. T here are 3 phase Menstruation Proliferative phase –follicular phase Secretory phase-luteal phase

19. 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

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

21. 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

22. 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

23. 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.

24. 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 .

25. 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.

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

27. 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 .