Normal Menstrual Cycle

KIBROM S.(MD)
MARCH,2023
• In the normal menstrual cycle, orderly cyclic
hormone production and parallel proliferation of the
uterine lining prepare for implantation of the
embryo.
• The normal human menstrual cycle can be divided
into two segments:
 the ovarian cycle and the uterine cycle, based on the
organ under examination.
 The ovarian cycle
may be further divided into follicular and luteal
phases,
 uterine cycle
is divided into corresponding proliferative and
secretory phases
• The “typical” menstrual cycle is 28 ± 7 days
with menstrual flow lasting 4 ± 2 days and
blood loss averaging 20 to 60 ml.
• By convention, the 1st day of vaginal
bleeding is considered day 1 of the menstrual
cycle.
• For most women, the luteal
phase of the menstrual cycle is stable, lasting
13 to 14 days.
• Thus, variations in normal cycle length
generally result from variable duration of the
follicular phase.
 Neuroendocrinology

• Hypothalamus
The hypothalamus is a small neural structure situated
at the base of the brain above
the optic chiasm and below the third ventricle .
Major hormones are
 GnRH
 TRH
 CRH
 GHRH
• Pituitary
The pituitary is divided into three regions or
lobes: anterior, intermediate, and
posterior.
 The anterior pituitary (adenohypophysis) is
quite different structurally from
the posterior neural pituitary
(neurohypophysis)
• The anterior pituitary is responsible for the
secretion of the major hormone releasing
factors—FSH, LH, TSH, and ACTH—as well
as GH and prolactin.
• Each hormone is released by a specific
pituitary cell type
• The gonadotropins FSH and LH are produced
by the anterior pituitary gonadotroph
cells and are responsible for ovarian follicular
stimulation.
• Structurally, there is great similarity between
FSH and LH
 Hormonal Variations
• At the beginning of each monthly menstrual cycle,
levels of gonadal steroids are low and have been
decreasing since the end of the luteal phase of the
previous cycle.
• With the demise of the corpus luteum, FSH levels
begin to rise, and a cohort of growing follicles is
recruited.
• These follicles each secrete increasing levels of
estrogen as they grow in the follicular phase. The
increase in estrogen, in turn, is the stimulus for
uterine endometrial proliferation
• Rising estrogen levels (high level) provide negative
feedback on pituitary FSH secretion, which begins to
wane by the midpoint of the follicular phase.
• In addition, the growing follicles produce inhibin-B,
which also suppresses FSH secretion by the pituitary.
• At the end of the follicular phase (just before
ovulation), FSH-induced LH receptors
are present on granulosa cells and, with LH
stimulation, modulate the secretion
of progesterone.
• After a sufficient degree of estrogenic stimulation, the
pituitary LH surge is triggered, which is the
aproximate cause of ovulation that occurs 24 to 36
hours later.
• Ovulation heralds the transition to the luteal–
secretory phase.
• The estrogen level decreases through the early luteal
phase from just before ovulation until the midluteal
phase, when it begins to rise again as a result of
corpus luteum secretion.
• Similarly, inhibin-A is secreted by the corpus luteum.
• Progesterone levels rise precipitously after ovulation
and can be used as a presumptive sign that ovulation
has occurred.
• Progesterone, estrogen, and inhibin-A act centrally to
suppress gonadotropin secretion and new follicular
growth.
• These hormones remain elevated through the lifespan
of the corpus luteum and then wane with its demise,
thereby setting the stage for the next cycle
 Ovarian cycle
• Follicullar phase
• Luteal phase.
 Follicular Development

• Follicular development is a dynamic process

that continues from menarche until
menopause.
• The process is designed to allow the monthly
recruitment of a cohort of follicles and,
ultimately, to release a single mature dominant
follicle during ovulation each month.
Growth of follicles:

Antral Graafia
follicle n
follicle
Primor
dial
follicle

Oocyte
Ovulation
Antrum
Granulosa (fluid
cells filled
Thecal space)
cells
 Two-cell Two-Gonadotrophin Theory

• This theory states that there is a subdivision

and compartmentalization of steroid hormone
synthesis activity in the developing
follicle.
• ovarian steroidgenesis is dependent on the
effects of LH and FSH acting independently
on the theca cells and granulosa cells,
respectively.
• LH stimulates the theca cells to produce
androgens (primarily androstenedione), which
in turn are transferred to the granulosa cells for
FSH-stimulated aromatization into estrogens.
• These locally produced estrogens create a
microenvironment within the follicle that is
favorable for continued growth and nutrition
 Ovulation
• The midcycle LH surge is responsible for a dramatic
increase in local concentrations of prostaglandins and
proteolytic enzymes in the follicular wall.
• These substances progressively weaken the follicular
wall and ultimately allow a perforation to form.
• Ovulation most likely represents a slow extrusion of
the oocyte through this opening in the follicle rather
than a rupture of the follicular structure.
 Luteal Phase
• After ovulation, the remaining follicular shell is
transformed into the primary regulator
of the luteal phase: the corpus luteum.
• Membranous granulosa cells remaining in the
follicle begin to take up lipids and the characteristic
yellow lutein pigment for which the structure
is named.
• These cells are active secretory structures that produce
progesterone, which supports the endometrium of the
luteal phase.
• The hormonal changes of the luteal phase are
characterized by a series of negative feedback
interactions designed to lead to regression of the corpus
luteum if pregnancy does not occur.
• Corpus luteum steroids (estradiol and progesterone) and
inhibin provide negative central feedback and cause a
decrease in FSH and LH secretion.
• Continued secretion of both steroids will decrease the
stimuli for subsequent follicular recruitment. Similarly,
luteal secretion of inhibin also potentiates FSH
withdrawal.
• Continued corpus luteum function depends on
continued LH production. In the absence
of this stimulation, the corpus luteum will invariably
regress after 12 to 16 days and form
the scarlike corpora albicans
• If pregnancy does occur, placental hCG will mimic
LH action and continually stimulate
the corpus luteum to secrete progesterone.
 Uterus
Cyclic Changes of the Endometrium
• Histological cycling of the endometrium
can best be viewed in two parts: the endometrial glands and
the surrounding stroma.
• Decidua functionalis :The superficial two thirds of the
endometrium and the zone that proliferates and
is ultimately shed with each cycle if pregnancy does not
occur.
• The decidua basalis :is the deepest region of
the endometrium. It does not undergo significant monthly
proliferation but, instead, is the source of endometrial
regeneration after each menses.
 Proliferative Phase
• The proliferative phase is characterized by
progressive mitotic growth of the decidua functionalis
in preparation for implantation of the embryo in
response to rising circulating levels of estrogen .
• At the beginning of the proliferative phase, the
endometrium is relatively thin (1–2 mm).
• The predominant change seen during this time is
evolution of the initially straight, narrow, and short
endometrial glands into longer, tortuous structures
• Histologically, these proliferating glands have
multiple mitotic cells, and their organization changes
from a low columnar pattern in the early proliferative
period to a pseudostratified pattern before ovulation.

• Throughout this time, the stroma is a dense compact

layer, and vascular structures are infrequently seen.
 Secretory Phase

• In the typical 28-day cycle, ovulation occurs on

cycle day 14.
• Within 48 to 72 hours following ovulation, the
onset of progesterone secretion produces a shift
in histologic appearance of the endometrium to
the secretory phase, so named for the clear
presence of eosinophilic protein-rich secretory
products in the glandular lumen
• The stroma of the secretory phase remains
unchanged histologically until approximately the
seventh postovulatory day, when there is a
progressive increase in edema.
• Coincident with maximal stromal edema in the
late secretory phase, the spiral arteries become
clearly visible and then progressively lengthen and
coil during the remainder of the secretory phase.
 Menses

• In the absence of implantation, glandular secretion

ceases, and an irregular breakdown
of the decidua functionalis occurs.
• The resultant shedding of this layer of the
endometrium is termed menses.
• The destruction of the corpus luteum and its
production of estrogen and progesterone is the
presumed cause of the shedding.
• With withdrawal of sex steroids, there is a profound
spiral artery vascular spasm that
ultimately leads to endometrial ischemia.
• Simultaneously, there is a breakdown of lysosomes
and a release of proteolytic enzymes, which further
promote local tissue destruction.
• This layer of endometrium is then shed, leaving the
decidua basalis as the source of subsequent
endometrial growth.
• Prostaglandins are produced throughout the
menstrual cycle and are at their highest
concentration during menses .
• Prostaglandin F2α (PGF2α) is a potent
vasoconstrictor, causing further arteriolar
vasospasm and endometrial ischemia.
• PGF2α also produces myometrial contractions
that decrease local uterine wall blood flow and
may serve to physically expel sloughing
endometrial tissue from the uterus.
THANK YOU!
 References
• Berke and Novak gynicology,14th edition
• Williams gynicology,4th edition.