PHYSIOLOGY OF MENSTRUAL CYCLE DR. ZEINAB ABOTALIB Asso.Prof. & Consultant

Each Cycle represents a complex interaction between the hypothalamus, pituitary gland, ovaries and endometrium. Cycle changes of gonadotrophins induce functional and morphologic changes in the ovary, resulting in follicular maturation, ovulation and corpus luteum formation with production of steroid hormones. Similar changes at the level of endometrium allow for successful implantation of the embryo

PITUITARY GLAND Consists of two main parts:  adenohypophysis (anterior lobe)  neurohypophysis (post.lobe) The posterior lobe transport oxytocin and vasopressin (antidiuretic hormone) from the hypothalamus to their release into the circulation. The supply to the pituitary stalk as the hypophyseal – pituitary portal system represent a major way of transport for hypothalamic secretions to the pituitary. The anterior pituitary produces six protein hormones, F.S.H., L.H., T.S.H., G.H., A.C.T.H and prolactin FSH, LH and TSH are glycoprotein consist of alpha and beta chain. The alpha chain is identical in all while the  chain is different. All hormones produced by anterior pituitary are under stimulatory effect by hypothalamus except prolactin which is under chronic inhibition by hypothamus (prolactin inhibition factor, dopamin).

HYPOTHALAMUS Produces five hormones or factors of them GnRH and PIF has direct effect on menstrual cycle GnRH stimulates the synthesis and release of FSH and LH by the gonadotrophs cells of the pituitary GnRH is a decapeptide secreted by hypothalamus in a pulsatile fashion every 90 minutes. Continuous infusion of GnRH results in reversible inhibition of gonadotrophin secretion (down regulation or desensitization of pituitary gonadotrophs).

HYPOTHALAMUS (CON’T). Estradiol enhance hypothalamic release of GnRH while gonadotrophins have an inhibitory effect on GnRH release. Thy hypothalamus also produce PIF (adopamine) which exerts chronic inhibition of prolactin release from lactotrophs. TRH stimulates prolactin release, this explains the association between prim hypothyroidism and hyperprolactinaemia

OVARIAN CYCLE In the first half of the menstural cycle, the anterior pituitary secrets FSH and LH. FSH stimulates the growth of several primary follicles in both ovaries (100-1000). Only one follicles reaches maturation to form the grafian follicle which secrets increasing amount of oestrogens mainly oestradiol The increasing oestrogen first inhibits FSH production (negative feed back mechanism) then stimulates the production of LH surge (positive feed back mechanism) which reaches a peak about 48 hours before ovulation.

OVARIAN CYCLE (con’t.) LH surge lead to ovulation and formation of corpus luteum LH maintain the growth of corpus luteum and stimulates it to secret oestrogen and progesterone. The corpus luteum has limited life span (in the absence of pregnancy) after which it degenerates. Degeneration of corpus luteum and drop in the level of oestrogen and progesterone causing separation of endometrium and menstruation. The drop in the level of these hormones stimulated the hypothalamus and pituitary to secret GnRH gonadotrophins to start new cycle.

FOLLICULAR DEVELOPMENT FSH receptors are present on granulosa cells stimulate its growth and maturation. It also stimulates the production of aromataze enzymes. LH receptors are present initially on theca cells stimulates it to produce androstenedion (androgen) which diffuse into granulose cells to be converted into oestrogen by aromataze enzyme. Oestrogen increase the no. of FSH receptors and its sensitivity

FOLLICULAR DEVELOPMENT (Con’t). Oestrogen and FSH stimulated granulose cell to form LH receptors. The follicle which are chosen to mature and ovulate has rich oestrogen milieu and high FSH content in follicle fluid. The fluid which undergoes atresia are androgen predominant and have low FSH content in follicle fluid.

OVULATION CORPUS LUTEUM FORMATION As a result of LH surge and 36-48 h later ovulation takes places and the mature ovum surrounded by corona radiate expels from the ovary. CORPUS LUTEUM FORMATION After ovulation and under the effect of LH both granulose cells of the collapsed ruptured follicle and the theca cells undergoes lutienization to form corpus luteum. The corpus luteum secrets large amount of progesterone and oestrogen hormones. The normal life span of c. luteum is 14 days

THE ENDOMETRIUM CYCLE Functionally the endometrium is divided into two zones. 1. Function outer zone: Undergoes cyclic during menstrual cycle and is sloughed off during menstruation. It is supplied byrteries which is branches from basal arteries. 2. Basal inner zone: Remain unchanged during menstrual cycle, after menstruation it provides stem cells for the renewed functioning zone.

HISTOLOGICALLY, the endometrium is divided into three stages during the menstrual cycle MENSTRUAL PHASE Two to seven days during which the superficial function layer separate leaving the basal layers from which the endometrium regenerates again.

B. PROLIFERATIVE OR OESTROGENIC PHASE Starts after the end of menstruation and ends at ovulation and is characterized by: 1. Thickness of endometrium 3-4mm 2. Glands are increase in number and length, but remain tubular. 3. The stroma cells proliferate and show mitosis. 4. Vascularity is increased, the spinal arteries increase in length and traverse the whole endometrium.

SECRETARY OR PROGESTOGENIC PHASE - Fixed duration irrespective of the length of the cycle (14-12) - Begins at ovulation and ends by onset of menstruation is characterized by 1. Thickness of endometrium 6-8mm 2. Glands continue to grow and be come tortuous so it appears like corksrew or saw-tooth appearance in longitude section. The lumen is distended with secretion (glycogen and mucin) 3. The epithelium cells become high columnar, secretory granules appear at first as subnuclear vacules and later as supranuclear vacules. 4. Stroma cells increase in size and become closely packed together and polygonal. The stroma becomes differential into three layers.  Superficial compact layer around the neck of glands.  Middle spongy layers around the distended lumen of the glands.  Deep compact layers around the basal part of the glands. 5. Marked increase in vascularity with marked elongation of the spinal arteries.

MECHANISM OF MENSTRUATION Degeneration of C.luteum lead to drop in the level of oestrogen and progesterone. This lead to shrinkage of the endometrium causing increase coiling of the spiral arteries (end arteries) with stasis and ischemia causing necrosis of the superficial and middle layers of endometrium which separate leading to bleeding. The basal layers does no separate as it is supplied by basal arteries which anastomose freely.

MECHANISM OF MENSTRUATION Normally the endometrium contains prostaglandins which show marked increase immediately before and during menstruation. There are four prostaglandins present in endomet. PG F2 and thromboxan both are vasoconstrictors and reduce menstrual loss. PGE2 and prostacylin both are vasodilator and cause heavy menstrual loss.

CYCLIC CHANGES IN CERVICAL MUCUS In the follicular under oestrogen effect the cervical mucus become excessive, watery, clear and a cellur. In the luteal phase, progesterone makes cervical mucus scanty, viscid, cellular, non stretchable and gives a negative fern test.

CYCLIC CHANGES IN THE VAGINA Vaginal smear taken from lateral vaginal fornix show differe according to the phase of the cycle. 1. In follicur (oestrogenic) phase the smear consists of many superficial cells with acidophilic cytoplasm and pyknotic nucleus. The background is clear with few leucocytes. 2. In the luteal (progestogenic) phase the smear consist mainly of intermediate cells with folded edges (navicular cells). These cells have basophilic cytoplasm and vesicular nucleus. The back ground is unclear with many leucocytes.

NORMAL MENSTRUATION Duration 2-7 days Length of cycle 3-5 weeks, 4 weeks average Amount 30-60 mls, loss more than 80 mls is abnormal. Consist of blood rich in leucocytes, endometrial fragments, cervical mucus, desguamented vaginal epithelium cells, bacteria and enzyme. Normally the menstrual blood does not coagulate due to the presence of plasma enzyme produced by endometrium which digest fibrin.

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