MENSTRUAL CYCLE AND IT’S

HORMONAL CONTROL

Prof Theingi Mya

M.B.,B.S. M. Med Sc (OG)
Dr. Med. Sc (OG)
Obs & Ggy Dept
UMM
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• Introduction
• Menstrual cycle
• Physiology of the menstrual cycle
• Puberty and secondary sexual development
Disorders of sexual development
Disorders of menstrual regularity

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• Normal menstrual cycle is as a result of the
shedding of the endometrial lining following
failure of fertilization of the oocyte or failure of
implantation.

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 Menstrual cycle

• Initiated in response to changed in sterioids

produced by the ovaries which are controlled
by the pituitary and hypothalamus within
the hypothalamo–pituitary–ovarian axis (HPO)
• 400 menstrual cycles during the course of
their lifetimes.

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 Normal menstrual cycle
• 28 days cycle ±7 (21-35) day.
• 4-6 days duration (5 ± 2) day.
• Amount = 30 ml per month (< 80 ml)

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Menorrhagia = heavy or prolonged duration of
cyclical menstrual blood loss
Metrorrhagia = heavy or prolonged acyclical
abnormal menstrual blood loss
Oligomenorrhoea- (infrequent cycle, one cycle
per 2-3 month)/ more than 35 days
cycle
Polymenorrhoea – less than 21 days cycle
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• The cycle depends on changes occurring after
puberty within the ovaries and fluctuation in
ovarian hormone levels, which are themselves
controlled by the pituitary and hypothalamus.

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 negative feedback positive feedback
controls pituitary
LH & FSH
pulsatile fashion secretion

inhibin _ FSH and activin+FSH

periovulatory LH surge

Kiss peptins IGF-I, IGF-II

Eg. combined oral contraceptive pill,

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The ovary
•Starting at menarche, the primordial follicles
containing oocytes, start to activate and grow in a
cyclical fashion, causing ovulation and subsequent
menstruation in the event of non-fertilization.
•In the course of a normal menstrual cycle, the ovary
will go through three phases: follicular, ovulatory
and luteal

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02/04/23 Fig 1 diagram of menstrual cycleProf TGM 11
Follicular phase
•The initial stages of follicular development
are independent of hormone stimulation.

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• FSH levels rise in the first days
• oestrogen, progesterone and inhibin levels are
low.
• This stimulates a cohort of small antral follicles on
the ovaries to grow.
• Within the follicles- two cell types (theca and the
granulosa cells) - respond to LH and FSH
stimulation - involved in the processing of
steroids, including oestrogen and progesterone.

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• As the follicles grow - oestrogen secretion
increases negative feedback on the
pituitary to decrease FSH secretion.
• This assists in the selection of one follicle to
the dominant follicle.

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Ovulation phase
•By the end of the follicular phase, lasts an
average of 14 days
• the dominant follicle - grown to
approximately 20 mm in diameter.
• As the follicle matures, FSH induces LH
receptors on the granulosa cells to
compensate for lower FSH levels and
prepare for the signal for ovulation.

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• Production of oestrogen increases - a positive
feedback effort on the hypothalamus and
pituitary to cause the LH surge.
• This occurs over 24–36 hours, during which
time the LH-induced luteinization of
granulosa cells in the dominant follicle
causes progesterone secretion, adding to the
positive feedback for LH secretion

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• The LH surge is one of the best predictors of
imminent ovulation,
• this the hormone detected in urine by
‘ovulation predictor’ tests.

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• The physical ovulation of the oocyte occurs
after breakdown of the follicular wall takes
place under the influence of LH, FSH and
proteolytic enzymes, such as plasminogen
activators and prostaglandins (PGs).

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Luteal phase
•After the release of the oocyte, the remaining
granulosa and theca cells on the ovary form the
corpus luteum (CL).
•The granulosa cells have a vacuolated
appearance with accumulated yellow pigment,
hence the name CL (‘yellow body’).

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• The CL - extensive vascularization in order to
supply granulosa cells with a rich blood
supply for continued steroidogenesis by local
production of vascular endothelial growth
factor (VEGF).

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• The luteal phase lasts 14 days in most women
• In the absence of beta- human chorionic
gonadotrophin (βhCG) being produced from
an implanting embryo, the CL will regress in
a process known as luteolysis.

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• The mature CL is less sensitive to LH,
produces less progesterone and will gradually
disappear from the ovary.
• The withdrawal of progesterone has the effect
on the uterus of causing shedding of the
endometrium and thus menstruation.

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The endometrium
•The hormone changes effected by the HPO
axis during the menstrual cycle will occur
whether the uterus is present or not.

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The proliferative phase
•The endometrium enters the proliferative
phase after menstruation (glandular and stromal
growth).
•The epithelium lining the endometrial glands
changes from a single layer of columnar cells to a
pseudostratified epithelium with frequent mitoses.
• Endometrial thickness increases rapidly, from
0.5 mm at menstruation to 3.5–5 mm at the end of
the proliferative phase.

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The secretory phase
•After ovulation (generally around day 14),
there is a period of endometrial glandular
secretory activity.
•Following the LH surge, the oestrogen-
induced cellular proliferation is inhibited and
the endometrial thickness does not increase any
further

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• the endometrial glands - more tortuous, spiral
arteries, fluid is secreted into glandular cells and
into the uterine lumen.
• In the initial secretory phase
(Day 15 to 21) the glands begin to coil,
their cells accumulate glycogen
in the basal region
• Later, progesterone induces
the formation the decidua, in stroma.
•
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• Histologically, this is seen as occurring
around blood vessels.
• Stromal cells - increased mitotic activity,
nuclear enlargement and generation of a
basement membrane

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• Apical membrane projections of the
endometrial epithelial cells, known as
pinopodes, appear after day 21–22 and
appear to be a progesterone-dependent stage
in making the endometrium receptive for
embryo implantation

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 Fig 2 Changes in hormone levels, endometrium and follicle development during the menstrual cycle.
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Figure 3. Tissue sections of normal endometrium during proliferative (A) and secretory (B) phases of the menstrual cycle

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Fig 4 Photomicrograph of endometrial pinopods from the implantation window

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Menstruation
•Menstruation (day 1) is the shedding of the
‘dead’ endometrium
•the endometrium regenerates - normally
happens by day 5–6 of the cycle
•. Immediately prior to menstruation, three
distinct layers of endometrium can be seen.

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• The basalis is the lower 25% of the
endometrium, which will remain throughout
menstruation
• The midportion is the stratum spongiosum
with oedematous stroma and exhausted
glands.

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• The superficial portion (upper 25%) is the
stratum compactum with prominent
decidualized stromal cells.
• A fall in circulating levels of oestrogen and
progesterone approximately 14 days after
ovulation leads to loss of tissue fluid,
vasoconstriction of spiral arterioles and
distal ischaemia.

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• This results in tissue breakdown and loss
of the upper layers, along with bleeding
from fragments of the remaining arterioles,
seen as menstrual bleeding.
• Enhanced fibrinolysis reduces clotting.

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• Vaginal bleeding - cease after 5–10 days as
arterioles vasoconstrict
• the endometrium begins to regenerate.

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• The endocrine influences on menstruation -
main
• the paracrine mediators are less effect.
• PG F2α, endothelin-1 and platelet
activating factor (PAF) are vasoconstrictors
that are produced within the endometrium
• balanced by the effect of vasodilator agents
PG E2, prostacyclin (PGI) and nitric oxide,

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• Endometrial repair involves both glandular
and stromal regeneration and angiogenesis
to reconstitute the endometrial vasculature.
• VEGF and fibroblast growth factor (FGF) are
found within the endometrium and both are
powerful angiogenic agents.

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 Estrogen
• Estrogen in blood is mostly bound to albumin.
• Acts through nuclear receptors.
• Has multiple functions:
– stimulates bone and muscle growth
– Maintain female secondary sex characteristics such as
body hair distribution and the location of adipose
tissue deposits
– Affects CNS activity (especially in the hypothalamus,
where it increases the sexual drive)
– Maintains accessory reproductive glands and organs.
– Initiating repair and growth of the uterine
endometrium
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 Progesterone
• Functions of Progesterrone (P):
– It primary functions is to prepare the uterus
for pregnancy by promotion
– the elaboration of the bloaod supply to the
functional zone and stimulating the secretion
of the endometrial glands.

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Changes in cervical mucous:
Failure to demonstrate ferning in prremenstrual
week after a positive finding earlier in the cycle

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 Vaginal smear
• follicular phase: Preponderance of the
superficial cell ( large cornified epithelial
cell with pyknoitic nuclei and pink
cytoplasm
• Luteal phase: The superficial cell with
rolled edges , reapperance of intermediate
cell (basophilic cytoplasm with large pale
vesicular nuclei and presence of
leucocytes).
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