The menstrual cycle Dr Ismaiel Abu Mahfouz

Menstruation Definition A woman's monthly bleeding from the reproductive tract induced by hormonal changes of menstrual cycle For menstruation to occur Coordinated HPO axis Responsive endometrium Patent outflow

The menstrual cycle hormones

GnRH A peptide hormone Synthesized and released from GnRH neurons in hypothalamus Responsible for the release of FSH & LH from  anterior pituitary

FSH A glycoprotein polypeptide hormone Granulosa cell proliferation and differentiation Antral follicle development Oestrogen production Inhibin synthesis Induction of LH receptors on dominant follicle

LH A glycoprotein hormone The main promoter of constant androgen production from the theca cell The pre-ovulatory LH surge Triggers ovulation and follicular rupture Induces resumption of oocyte meiotic maturation Causes luteinization of granulosa cells (formation of corpus luteum)

Estradiol Suppresses FSH due to a -ve feedback leading to selection of a dominant follicle Triggers LH surge due to a +ve feedback Increases endometrial thickness Stimulates cervical glands to secrete a particular type of mucus which is essential for sperms to pass through

Progesterone Induces secretory endometrium to enhance embryo implantation Maintains endometrium in 1st week of pregnancy Modifies endometrial glandular structure (more number, more tortuous) Involved in gene expression in endometrium needed for implantation

Inhibin Secreted by granulosa cells in ovary Two hormones : Inhibin A & B Secreted by granulosa cells in ovary Inhibits production of FSH via –ve feedback Involved in control of gamete production, embryonic and fetal development

Hormonal interaction GnRH Sex steroids Gonadotropins - FSH - LH - Esradiol - Progesterone Gonadotropins - FSH - LH

The ovarian cycle The endometrial cycle The menstrual cycle The ovarian cycle The endometrial cycle

The ovarian cycle

The Ovarian Cycle Follicular phase (pre-ovulatory) Recruitment & selection of dominant follicle Increasing levels of estradiol & inhibin B Ovulatory phase LH surge Rupture of pre-ovulatory follicle wall Release of viable ovum Luteal phase (post-ovulatory) Corpus luteum development Increasing levels of progesterone Secretory changes in endometrium Menstrual phase

Follicular Phase A group of the most mature follicles (called “antral follicles”) are recruited Only follicles most sensitive to FSH undergoes a further development Follicle most sensitive to FSH continue to develop and produce a large amount of estradiol and inhibin B Remaining follicles become atretic (99%)

Ovulatory phase An event in the menstrual cycle by which a selected mature follicle breaks and releases a viable oocyte Each month, one egg is released ; occasionally, two or more If pregnancy does not occur, menstruation starts after exactly two weeks

Ovulatory phase Mechanism of follicle rupture Increase of intra-follicular pressure Perifollicular ovarian smooth muscle contractions Vascular alterations in peri-follicular vessels Prostaglandins and proteolytic enzymes Cytokines, O2 free-radicals, nitric oxide and angiotensin II

Ovulatory phase Ovulation Ovulation occurs 34-36 hours after onset of LH surge

Luteal phase Peak level of progesterone occurs 7 days after ovulation This approximates the time of implantation In early pregnancy, hCG maintains luteal function with secretion of progesterone until placental steroidogenesis is established

Menstrual phase Rapid ↓ in steroids → shedding of the unused endometrium Inflammatory mediators (PGs, ILs, and TNF) → vasospasm in spiral arteries → hypoxia and endometrial devitalisation Haemostatic mechanisms will be activated including platelet plugs, coagulation cascade, and fibrinolysis Endometrium shed down to basalis layer

Phases of the endometrium Duration 2-8 days Estrogen Variable Vascular growth Progesterone Fixed 14 days Gland tortuosity & secretion, stromal oedema ,decidual reaction of the endometrium

Endometrial breakdown Basalis layer remains Undergoes repair Endometrium is protected from the lytic enzymes in the menstrual fluid by mucinous layer of carbohydrate products secreted from glands and stromal cells

Menstrual Fluid Autolysed functionalis layer Inflammatory exudate RBC Proteolytic enzymes (mainly plasmin) If rate and flow are high clots are formed

Hypothalamus Ant. Pituitary Inhibin E GnRh -VE FSH LH surge follicle -ve feedback Dominant follicle E Ovulation Estrogen

Cervical changes Follicular phase Luteal phase Internal os: funnel shape Tightly closed Mucus: thin &watery Thick & viscid Stretchability: increased Lost

Normal menstrual cycle Menstrual cycle should be described according to four specific symptomatic components Frequency Duration Volume Regularity

Normal Menstrual Cycle Frequency (Length) Mean is 28 days +/- 7 days Menstrual cycle tends to shorten with age Initially irregular Duration of menstruation Normal range: 4.5 – 8.0 days, Mean: 5 days Prolonged >8 days, shortened < 4.5 days With advancing age: duration decreases Volume of menstrual blood loss (ml) Range: 20 – 50 mls, Mean 40 ml Heavy >80 ml; light < 5 ml