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

o Triggers ovulation and follicular rupture

o Induces resumption of oocyte meiotic

maturation

o 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

• 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

- Esradiol

- Progesterone

Gonadotropins

- FSH

- LH

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

Estrogen

LH surge

GnRh

E

Hypothalamus

FSH

follicle

Ant. Pituitary

Inhibin

Dominant follicle

Ovulation

-VE

+Ve

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