Physiology of Menstruation

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Definition of menstrual cycle

Periodic vaginal bleeding at intervals of


28 +/- 7 days with menstrual flow lasting
4 +/- 2 days and an average blood loss
of 20-60 ml.

Occur with shedding of superficial layer
of endometrium (stratum functionale), in
absence of fertilization of oocyte.
Menstrual cycle
Divided into 2 cycles:

1. Ovarian cycle
2. Endometrial cycle

OVARIAN CYCLE
Phases of ovarian cycle
1. Follicular Phase
2. Ovulation Phase
3. Postovulatory/Luteal Phase
Follicular phase
Day 1-8:
Due to fall of Oestrogen & Progesterone at
menstruation, the FSH & LH level start to
rise.
The initial stage is independent of FSH, early
follicles secrete inhibin B and antimullerian
hormone (AMH) instead until FSH dependent
stage is reached.
FSH level rises stimulates development of
10-20 follicles
But only one or 2 follicles respond to both
FSH & LH

There are 2 layers in developing follicle:
1. Outer theca layer:
Has LH receptors
Synthesize androgens from cholesterol

2. Inner granulosa cells:
Responds to FSH to produce aromatase
enzyme
Aromatase converts androgen produced in
theca cells into oestrogen.

2 cell, 2 gonadotropins theory.




Follicular Phase
Day 9-14:
Rising in Oestradiol level, the negative
feedback on pituitary reduces the
gonadotropin secretions.
THUS prevents production of multiple
follicles and development of one dominant
follicle with highest aromatase activity and
maximum FSH & LH receptors.
The mature follicle is GRAAFIAN FOLLICLE
oocyte is eccentrically placed surrounded
by laters of granulosa cells, and referred as
cumulus oophorus.
Ovulation Phase
Day 14:
As follicular diameter reaches 18-20mm,
rising Oestradiol results in positive
feedback effect and triggers the LH surge.
LH surge stimulates final maturation of
oocyte with completion of meiosis and
extrusion of 1
st
polar body.
LH surge - induce inflammatory reactions
in follicular wall under effect of proteolytic
enzyme, prostaglandins, results in
follicular rupture 36 hours after initiation of
LH surge.
Clinical Application

Antiprostaglandins (Eg. Ibuprofen &
Naproxen) inhibit the inflammatory
response, thus ovulation failure.
Hence, women on these medications
(Eg. endometriosis) and planning for
conception are advised about the
antiovulatory effects and alternative
suggested.
Detection of Ovulation
1. Basal Body Temperature
Oral temp is recorded every morning
before getting out of bed.
Ovulation rise in temperature, which is
maintained until next period starts. In
most, the rise is preceded by slight drop
the day before (about 1celcius)
2. LH Surge
Ovulation preceded by very sharp rise in
blood LH level, and generally occurs
within 24hours of LH surge.
3. Tests on Cervical Mucus
Thinnest when level of oestrogen is
highest, i.e. just around ovulation time
4. Endometrial Biopsy
5. Ultrasonography

Luteal Phase
Day 15-28:
Granulosa cell & theca cells undergo lutenization
and form CORPUS LUTEUM, that produces
progesterone.
Progesterone level peaks one weak after
ovulation (Day 21), and measured as indicator of
ovulation.
IF there is fertilization and implantation corpus
luteum produce hCG.
IF NOT corpus luteum regresses and
withdrawal of progesterone on endometrium
results in menstruation.
Fall of of Progestrerone, Oestrogen, Inhibin A
allow rise of FHS & LH, thus starts of new cycle
with development of Preantral follicles.
ENDOMETRIAL CYCLE
Anatomy of Uterus
Layers of uterine wall:
1) Perimetrium : Fundus (serosa), body
(adventitia)
2) Myometrium : Bundles of smooth
muscle fibers separated by CT
3) Endometrium : Stratum basale
(Retained at menstruation.
Regenerates the endometrium for
the next cycle), Stratum functionale
(Sloughed off at menstruation)
ENDOMETRIUM
A superficial epithelium which lines the
uterine cavity.
2 principle components:
1) Glandular epithelium
2) Supporting stromal cells
During menstrual cycle, the
epithelium differentiates to form three
functional zones; basalis,
spongiosum and stratum
compactum.
DEFINITION:
The shedding and regeneration of
endometrial lining and is controlled by
the ovarian cycle.

PHASES:
1) Menstrual phase
2) Proliferative phase (Ovarian follicular
days 5-14)
3) Secretory phase (Ovarian luteal days
15-28)
MESNTRUAL PHASE
Begins with complete shedding of
spongiosum and stratum compactum
layers (day 1) during menstruation
which lasts for 3 5 days.
Fall in plasma progesterone and
estrogen levels (due to degeneration
of corpus luteum) withdrawal of
hormonal support of the endometrium
causes menstruation.
EVENTS:
1) Profound vasoconstriction of uterine
blood vessels decreased supply of
oxygen and nutrients to
endometrium.
2) Disintegration : Entire lining except
basalis layer (regenerate
endometrium in the next cycle)
3) After initial period of
vasoconstriction, endometrial
arteriole dilates haemorrhage
through vascular capillary walls.
PROLIFERATIVE PHASE
Menstrual flow ceases and
endometrium begins to thicken
(basalis layer).
Period of growth :10 days or so,
between cessation of menstruation
and occurrence of ovulation.
Corresponds to ovarian follicular
phase.
Uterine changes during menstrual
cycle are caused by changes in
plasma concentration of estrogen and
progesterone.
Rising plasma estrogen leads to
reconstruction and growth of
endometrium.
Both glandular and stromal
component achieve peak of
proliferation at 8
th
10
th
days
(corresponds to peak estrogen level)
Endometrium grows : 0.5mm 3.5mm
SECRETORY PHASE
Soon after ovulation the endometrium
begins to secrete various substances.
Phase between ovulation and onset of
next menstruation = secretory phase
The circulating progesterone (which is
secreted by corpus luteum after
ovulation), acts upon the estrogen
primed endometrioum converts it to
actively secreting tissue.

Leads to changes:
1) Glands : Become coiled and filled
with glycogen.
2) Blood vessels : More numerous and
densely coiled.
3) Enzymes : Variously secreted in the
glands and connective tissue.
These changes are essential to
make the endometrium a hospitable
environment for an embryo.
ABNORMAL MENSTRUATION
Amenorrhea
Primary amenorrhea
Absence of menses by 14 years of age
without appropriate development of
secondary sexual characteristics or by
16 years of age regardless of secondary
sexual characters development.

Gonadal dysgenesis
Mullerian abnormalities
Constituitional delay
Kallmans syndrome
Secondary amenorrhea
Cessation of menses for a period of 6
months or a three-cycle interval in
women who have been menstruating
regularly
Physiological
-pregnancy, lactational,
peripubertal, perimenopausal

Pathological
- premature ovarian failure
- stress, exercise
-PCOS
1. Hypergonadotropic(FSH-LH> 20)

2.Hypogonadotropic(FSH-LH<5)

3. Eugonadotropic( FSH-LH : 5-20)
Hypergonadotropic amenorrhea
-Turners syndrome
-Premature ovarian failure
-Gonadal dysgenesis
-Galactosemia
-Enzyme deficiencies-17 hydroxylase
deficiency
Hypogonadotropic amenorrhea
Eating disorders-anorexia,bulimia
Exercise-Female athlete triad
Kallman syndrome-Gnrh deficiency
Medications-birth control pills
Pituitary tumors-adenomas
Stress-increased CRH- decreased
Gnrh
Eugonadotropic amenorrhea
Androgen excess-PCOS
Disorders of outflow tract/uterus
-mullerian anomaly
Asherman syndrome
Androgen insensitivity syndrome
Infections-TB,Schistosomiasis
Menorrhagia
Normal cycle length
Prolonged bleeding or excessive
bleeding

Examples
- Myomas,polyps
- Adenomyosis
- DUB
Polymenorrhea
Shorter cycle length < 21 days
May be associated with menorrhagia

Examples
- Irregular pill intake
-Post abortal/ post child birth
- PID, endometriosis



Oligomenorrhea
Longer cycle length> 35 days
Endometrial ca risk

Examples
- PCOS
- Perimenarche/perimenopausal
Hypomenorrhea
Regular bleeding
Normal cycle length
Scanty bleeding

Examples
- Ocp users
Metrorrhagia
Irregular vaginal bleeding
Loss of cycle rhythm

Examples
- Carcinoma cervix
- Infected submucosal polyps
- Retained products of concetion

Dysfunctional uterine bleeding
No obvious organic pathology found
Diagnosis of exclusion

Examples
- puberty menorrhagia
- Metropathia hemorrhagica
Dysmenorrhea
Painful menstruation

Primary- absence of pelvic pathology

Secondary- presence of pelvic
pathology
Primary dysmenorrhea
- increased endometrial PG secretion
- secretory endometrium
- lytic enzymatic action due to
progesterone withdrawal- increased
phosholipid secretion
-high amplitude uterine contraction
Pain starts few hrs before or with
menses
Lasts 48- 72hrs
Suprapubic cramping, backache
Nausea, vomiting,diarrhea
No clinical findings
Diagnosis of exclusion
Secondary dysmenorrhea
-Associated with pelvic pathology

-1 to 2 weeks before menstrual flow and
persists until a few days after the
cessation of bleeding
Myomas
Adenomyosis
Endometriosis
PID
IUCD users
Genital tract anomalies- obstruction to
menstrual flow
Menopause
Ovaries become less responsive to
FSH and LH
Patterns of GnRH release from the
hypothalamus become altered
Pituitary gland becomes less
responsive to GnRH


Perimenopause
Average age at onset in the late 40s
Irregular menstrual cycles
Somatic and psychological symptoms
emerge
Post-menopause
12 months of amenorrhea
Elevated FSH levels
On average, reached by the early 50s
Factors that may affect timing of
menopause
Smoking
Genetics
Number of pregnancies
Body mass

Symptoms of menopause
Hot flashes
Mood swings
Vaginal dryness
Vaginal atrophy
Fatigue, weight gain, sleep disorders,
headache, cognitive changes..

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