Download Gynaecology – Dr. `Abeer – Lecture 1 – Physiology of Menstruation

Gynaecology – Dr. ‘Abeer – Lecture 1 – Physiology of Menstruation
The normal menstrual cycle
Menstruation describes the female period, involves the
monthly release of an egg(ovum) in a process called
ovulation, with bleeding due to shedding of the uterine
lining following failure of fertilization of the oocyte or failure
of implantation. The cycle has an average duration of 28
days, but the normal range is bet.21-35 days. Menstruation
usually starts at an average age of 13( called menarche) and
lasts on average till age 51 (called menopause).
Normal menstruation is a highly complex interactions
between a number of hormones produced by 3 organs of
the body:
1. Hypothalamus
2. Pituitary gland
3. Ovary
The interactions between these organs are referred to as
the hypothalamic-pituitary-ovarian axis(HPO axis).
Hypothalamus
The hypothalamus in the forebrain secretes GnRH which
controls of 2 important pituitary hormone secretion FSH (follicular stimulating hormone)&
LH ( luteinising hormone)
GnRH is of great importance in the menstrual cycle, its release occurs in a pulsatile fashion
to stimulate LH & FSH, anything that interferes with the pulse frequency of GnRH can stop
the menstrual cycle from occurring. If GnRH is given in a constant high dose, it desensitizes
the GnRH receptor & reduces LH & FSH release
Pituitary gland
Anterior pit.gland causes synthesis & release of gonadotrophic hormones FSH & LH by
stimulation of GnRH. This process is influence and stimulate the ovarian sex steroid
hormones: oestrogen & progesterone.
Negative feedback (low level of oestrogen will ↓LH production)
Positive feedback (high level of oestrogen will ↑ LH production)
GnRH agonists when administered continuously they will down regulate the pituitary and ↓
LH & FSH secretion, this has effects on ovarian function and oestrogen and progestron levels
also fall and most women become amenorrhoeic, these drugs are used as treatment for
endometriosis and to shrink fibroid prior to surgery.
As the dominant follicle grows further oestrogen level ↑ until it is sufficient to exert a
positive feed back effect on the pituitary LH secretion which is ↑ more rapidly from day 12
onward called the LH surge. Combined oral contraceptive pill creates artificially a constant
serum oestrogen level in the negative feedback , inducing low level of gonadotophin
hormone release. Unlike oestrogen, low level of progesterone have a positive feedback
effect on pituitary LH & FSH.
1
Ovary
Females are born with 2-4 mil.primary follicles. These containing oocytes will activate and
grow in a cyclical fashion, causing ovulation and menstruation in the onset of menarche. No
new oocytes are formed during the female lifetime. Normal menstruation cycle in the ovary
will go through three phases:
1. follicular phase
2. ovulation
3. luteal phase
Follicular phase
Within the follicles , there are two cell types: theca and granulosa cells which respond to LH
and FSH stimulation and produce oestrogen, progestrone , inhibin and activin. Both FSH &
LH are required to generate a normal cycle with adequate amounts of oestrogen. As the
follicles grow & oestrogen secretion ↑, there is negative feedback on the pituitary to ↓ FSH
secretion. this select one follicle to continue in its development towards ovulation ( the
dominant follicle). While smaller follicles will undergo atresia.
Exogenous gonadotrophins is likely to stimulate growth of multiple follicles which continue
to develop, risk of multiple gestations about 30%. Inhibin is secreted by granulosa cells
within the ovaries & it participated in feedback to the pituitary to down regulate FSH. Activin
is structurally similar to inhibin but has an opposite action, acts to ↑FSH binding on the
follicles.
Ovulation
The dominant follicle grow to 18-22 mm at average of 14 days, oestrogen ↑until exert a
positive feedback effort on the hypothalamus & pituitary to cause the LH surge. This occurs
over 24-36 hours, LH induced dominant follicle to produce progestrone & causing a small per
ovulatory rise in FSH. Androgens synthesized in the theca cells ↑at time of ovulation to
stimulat libido & sexual activity.
Luteal phase
After the release of the oocyte, the remaining granulosa and theca cells on the ovary form
the corpus luteum ( yellow body), its extensive vascularization to supply granulosa cells with
a rich blood supply for continued steroidogenesis. Highest level of progesterone in luteal
phase to prepares endometrium for pregnancy & has the effect of suppressing FSH & LH
secretion to a level that will not produce further follicular growth in the ovary during that
cycle.
In the absence of beta human chorionic gonadotrophin βHCG which producers from an
implantning embryo, the corpus luteum will regres & disappear from ovary ( luteolysis). The
withdrawal of progesterone causing shedding of the endometrium & menstruation. ↓ in
levels of progesterone, oestrogen & inhibin feedingback to pituitary cause ↑gonadotrophic
hormones, particulary FSH & new preantral follicles begin to be stimulated & begins a new
cycle.
Menstruation
In reproductive age its under the influence of sex hormones. exposur to oestrogen &
progest, will results proliferative & secretory phase. Menstruation day 1 is the shedding of
the dead endometrium( uppermost layer) and day 5-6 of cycle regenerates again.
Approximatly 14 days after ovulation ↓in circulating levels of oestrogen and progestrone
leads to loss of tissue fluid, vasoconstriction of spiral arterioles and distal ischaemia and this
leads to loss of the upper layer along with bleeding.
2
Contraceptive pill or hormone replacement therapy produces artificially withdrawal
bleeding. Prostaglandines are produced by the endometrium and are vasoconstrictors.
Non-steroidal anti-inflammatory agents used for treatment of heavy and painful periods.
Mefenamic acid is a prostaglandin synthetase inhibitor used as a treatment for heavy
menstrual bleeding ( reduces blood loss by 20-25%)
The proliferative phase
After menstruation enters the proliferative phase, when glandular and stromal growth
occur, the epithelium changes from single layer of columnar cells to a pseudostratified
epithelium with frequent mitosis, thickness ↑ rapidly.
The secretory phase
After ovulation and progestrone surge( generally around day 14), cellular proliferation is
inhibited and endometrial thickness does not increase any further, the endomerial glands
will become more tortuous, spiral arteries will grow and fluid is secreted into glandular cells
and uterin lumen.
On the withdrawal of both oestrogen and progesterone, the decidua will collapse with
vasoconstriction and relaxation of spiral arteries and shedding of the outer layers of the
endometrium .
Measurement of ovarian reserve
Menstruation remaining depends of number oocytes. Deficit of gonadotrophin or exposure
to toxins accelerate menopause age. U/S to measure of ovarian volume, diameter and antral
follicle count to calculate ovarian reserve. Biochemical markers: FSH, oestradiol, inhibin B,
anti-Mullerian hormone AMH( is produced in the granulosa cells and not change in response
to gonadotrophins during the cycle).
3