Last edited: 11/16/2021

23. OVULATION & MENSTRUAL CYCLE: OVERVIEW

Ovulation & Menstrual Cycle: Overview Medical Editor: Donna Stewart

OUTLINE
This note will refer to a normal menstrual cycle timeframe
II) HORMONE PRODUCTION of 28 days and will refer to varying physiological events
III) THREE PHASES OF THE OVULATION CYCLE according to this timeframe
IV) THREE PHASES OF THE MENSTRUAL CYCLE Any menstrual cycle which spans between 21 to 39 days is
V) FERTILIZATION AND NON-FERTILIZATION considered a normal timeframe for the cycle
VI) APPENDIX A timeframe either 20 or less days or 40+ days is
VII) REVIEW QUESTIONS considered pathological
VIII) REFERENCES Menstruation will be referred to as a five-day event,
o However, menstruation can vary from female to female,
from being non-existent (amenorrhea) or being longer
I) OVULATION AND THE MENSTRUAL CYCLE and a heavier bleeding event (menorrhagia)

(1) Ovulation
Process where a mature female sex cell (ovum) is
released by a Graafian Follicle to travel to the fallopian
tube in preparation for fertilization
(2) Menstrual Cycle
Periodic event of approximately 28 days
o Begins at puberty and ends at menopause
o Reproductively active females secrete an ovum into
the fallopian tube during ovulation.

II) HORMONE PRODUCTION

Figure 1. Hormone production and distribution in the hypothalamus, anterior pituitary and ovaries.

(A) HYPOTHALAMUS
Has two special nuclei
o Arcuate Nucleus
o Pre-Optic Nucleus
Responsible for the release of gonadotropin-releasing
hormone (GnRH)
o Travels via the blood supply to the anterior pituitary
into the gonadotropic cells

(B) ANTERIOR PITUITARY

Controls the synthesis and release of gonadotrophins
o Follicular Stimulating Hormone (FSH)
o Luteinizing Hormone (LH)
These gonadotrophins work in the ovary

(C) OVARY
Resulting with the release of androgens
o Androgens are converted to estrogen, and the later
release of progesterone

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 III) THREE PHASES OF THE OVULATION CYCLE

Figure 2. Three phases of the ovulation cycle – follicular, ovulatory and luteal phase.
During the formation of the Graafian follicle, follicular fluid
(A) PRE-FOLLICULAR PHASE pockets will expand, coalesce and fill the antrum of the
By birth of a female child, the ovary will contain all the cell with fluid.
oogonium that will be required across their reproductive o Follicular fluid is rich in hyaluronic acid
life Hyaluronic acid stimulates proliferation of the granulation
The oogonium undergo mitosis and produces primordial cells, and the formation of the zona pellucida
follicles which are primary oocytes
(2) Estrogen
(1) Primordial Follicles
Primary oocytes (i) Estrogen Synthesis
Consist of a single layer of simple squamous cells Produced during the follicular phase from day 1 to 14
enveloping its surface surrounding it o FSH stimulates the production of granulosa cells
Frozen in prophase 1 o LH acts upon the thecal cells to convert cholesterol
into androgens (e.g. androstanediol)
o Androgens move into the neighboring granulosa cells
(B) FOLLICULAR PHASE
where FSH, in conjunction with aromatase enzymes,
Follicular phase is day 1 – 14 stimulates its conversion to estrogen
Once a female reaches puberty, local androgens o Estrogen produced enters the blood system
stimulate primordial follicles into developing into a
primary follicle (ii) Mid-Follicular Phase
(1) Follicular Development In mid follicular phase, approximately day 7 to 9
estrogen levels rise causing a negative feedback loop
A certain amount of the primary follicles under the influence o The negative loop inhibits the hypothalamus from
of androgens and will convert to a primary follicle producing GnRH, and the anterior pituitary from
During the maturation of the primary follicles, they will producing FSH and LH, as result estrogen levels
undergo a number of stages: reduce
o Early secondary follicle o The Graafian follicle will continue to produce
o Late secondary follicle estrogen during this phase
o Graafian follicle
This is all triggered by the hypothalamus (iii) Late Follicular Phase
o Secreting GnRH → stimulates the anterior pituitary to At the end of follicular phase, approximately day 13 to
secrete LH and FSH. 15, estrogen levels will continue to rise again.
o FSH stimulates the conversion of a follicle from one o The feedback loop will change from negative to a
phase to another positive feedback loop
o The arcuate and preoptic nuclei within the
(i) What happens to the follicles? hypothalamus will be stimulated to produce massive
More layers of cells are added to the follicle amount of GnRH, and the anterior pituitary will be
Follicular fluid is produced initially filling pockets of fluid stimulated to produce FSH and LH.
during late second phase o At approximately day 14, the Graafian follicle will
produce inhibin B

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  which overrides the anterior pituitary signal and
shuts off the production of FSH
o Therefore, the only hormone being produced at the
end of follicular phase going into ovulatory phase is
LH
 The amount of LH produced is large and is called
the LH surge
Mid-Follicular Phase
↑↑estrogen → negative feedback → inhibits
hypothalamus and anterior pituitary → ↓GnRH →
↓FSH and LH → ↓estrogen levels
Late Follicular Phase
Estrogen continues to rise → negative to positive
feedback → stimulates hypothalamus and anterior
pituitary → ↑GnRH → ↑FSH and LH
Day 14: Graafian follicle produces inhibin B →
overrides anterior pituitary signal → shuts off FSH
production → ↑↑↑↑LH → LH surge
(C) OVULATORY PHASE
Ovulatory phase is day 14-15
Effects of LH surge:
o Causes the blood vessels to be permeable → more
blood enters and becomes follicular fluid
IV) THREE PHASES OF THE MENSTRUAL CYCLE
Figure 3. Three phases of the menstrual cycle – menstrual phase, proliferative phase and secretory phase.
(A) MENSTRUAL PHASE
Menstruation phase is day 1 – 5
Involves sloughing off of the endometrial lining which is
composed of the following:
o Stratum functionalis
o Spiral arteries
o Uterine glands; and
o Any blood collected from the rupture of any spiral
arteries, and residual necrosis of functionalis
Stratum basalis being the basal layer, with the straight
arteries will remain within the uterus.
Straight arteries are from uterine arteries, which come
from internal iliac arteries.
Ovulation & Menstrual Cycle: Overview
 This causes a pressurized environment within
the cell
o Stimulates proteolytic enzymes to cut around the
tissue of the Graafian follicle
 The secondary oocyte pops out of the Graafian
follicle
The fimbriae of the fallopian tubes become stiff and
scrap the surface of the ovary
o Fluid filled currents are produced
o Oocyte is pulled towards the fimbriae
o Fallopian tubes will catch the oocyte
(D) LUTEAL PHASE
Luteal phase is day 15-28
The ruptured Graafian follicle (now called corpus
hemorrhagicum) is stimulated by LH to accumulate
cholesterol, lipids and fat, causing it to turn yellow
The corpus hemorrhagicum turns into the corpus
luteum
o LH stimulates the corpus luteum to produce
progesterone
(B) PROLIFERATIVE PHASE
Proliferative phase is day 6 – 14
Estrogen will regenerate the following:
o Stratum functionalis through regrowth
o Spiral arteries through angiogenesis
o New uterine glands in preparation for secretion
The cervical glands will produce a thin cervical mucus
at the entrance of the cervix, to make it easier for the
entry of sperm for fertilization of the oocyte
The mucus has chemicals that cause capacitation of the
sperm
o Products such as cholesterol and glycoprotein are
cleared from the surface of the sperm head activating
the sperm for capacitation within the ampulla
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 (C) SECRETORY PHASE o Stimulates changes in the cervical mucus from a thin
mucus into a thick cervical plug,
Secretory phase is day 15 – 28
 To prevent entry in the uterus of unwanted
At day 14:
substances or organism, in case fertilization has
o Ovulation occurs
occurred
o LH converts the ruptured Graafian follicle into the
o Stimulates the uterine glands to produce a thick fluid
corpus luteum and it begins producing progesterone.
of glycoproteins, lipids, and proteins,
Progesterone  Serves as the nutritive source for the developing
embryo if it were to be implanted
Effects of progesterone during the secretory phase:
o Stimulates proliferation of the stratum functionalis There is a very small amount of FSH that is produced at
o Stimulates angiogenesis to increase the length of the this stage, whereby small amounts of estrogen can be
spiral arteries. still produced

V) FERTILIZATION AND NON-FERTILIZATION

Figure 4. Fertilization and non-fertilization.

(A) FERTILIZATION Progesterone is important for the strength and health of

Upon implantation of the blastocyst:
o Human chorionic gonadotrophin (hCG) is produced →
stimulates the corpus luteum to make progesterone
o Corpus luteum continues to produce progesterone
until the 12th week of embryology when the placenta
is able to provide progesterone itself
At that stage the corpus luteum will die off
(B) NON-FERTILIZATION
In cases where fertilization does NOT occur:
o Human chorionic gonadotropin (hCG) is not released
o Corpus luteum degenerates into the corpus albicans
and stops producing progesterone
the spiral arteries
o Causes normal vasoconstriction and
vasorelaxation to occur
o Without progesterone, the arteries will spasm, they
will become weakened, and eventually during
vasoconstriction, the capillaries will rupture.
Blood will enter the uterus and accumulate within the
stratum functionalis
The stratum functionalis cells will not receive enough
nutrients and will become ischemic, necrotic, and
eventually die off
o These cells will slough off and menstruation phase
will occur once more

VI) APPENDIX
Table 1. Summary of the follicular, ovulatory and luteal phases.
FOLLICULAR PHASE OVULATORY PHASE LUTEAL PHASE
Day 1-14 Day 14-15 Day 15-28
Conversion of the primary follicle to a Triggered by LH surge Formation of the corpus luteum from
secondary follicle Releases the secondary oocyte to the the Graafian follicle
Produces the following: fallopian tube and transport to the o Produces progesterone
o Multiple layers of granulosa cells area of fertilization
o Zona pellucida
o Corona radiate
o Follicular fluid antrum
o Estrogen

Table 2. Summary of the three phases of the menstrual cycle.

MENSTRUAL PHASE PROLIFERATIVE PHASE
Day 1-5 Day 6-14
Involves sloughing off of the Involves regeneration of the stratum
endometrial lining – stratum functionalis, spiral arteries and
functionalis, spiral arteries and uterine glands through estrogen
uterine glands Production of a thin cervical mucus
that cause capacitation of the sperm
SECRETORY PHASE
Day 15-28
Ovulation occurs and conversion of
Graafian follicle to corpus luteum
Stimulates proliferation of the stratum
functionalis, angiogenesis, and
production of thick cervical plug

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 VII) REVIEW QUESTIONS

1) What produced by the corpus luteum causes the

stratum functionalis to be proliferated during the
secretory phase?
a) GnRH
b) progesterone
c) estrogen
d) luteinizing Hormone
2) Menstruation causes the loss of what?
a) Embryo
b) Graafian follicle
c) Stratum basilis
d) Stratum functionalis
3) What does the thick mucus secreted from the cervix
mucus cells do?
a) Prevents unwanted organisms and organisms from
entering the cervix
b) Causes progesterone to be released from the
corpus luteum
c) Allows sperm to freely enter the cervix
d) Thick mucus is not secreted by cervix mucus cells
4) When does the menstruation phase occur?
a) The last five days of the menstrual cycle
b) The first five days after ovulation
c) The first five days of the menstrual cycle
d) Only after the Graafian follicle ejects the secondary
oocyte
5) In what phase are new uterine glands produced?
a) Menstruation phase
b) Proliferation phase
c) Secretory phase
d) Proliferation and secretory phases

6) What hormones are involved in the production of

estrogen in the follicular phase?
a) GnRH
b) FSH
c) LH
d) FSH and LH
7) What produces Progesterone during the Luteal
phase?
a) Hypothalamus
b) Anterior Pituitary
c) Corpus Luteum
d) Graafian Follicle
8) What timeframe does the luteal phase encompass?
a) Day 15-28
b) Day 14-15
c) Day 7-15
d) Day 1-7
9) What timeframes of the menstrual cycle are
considered pathological?
a) Only 20 days or less
b) Only 40 days or less
c) Less than 20 and more than 40 days
d) Between 20 and 40 days
10) In mid-follicular phase the levels of estrogen in the
blood cause a positive feedback loop on the
hypothalamus and anterior pituitary gland?
a) True
b) False

VIII) REFERENCES

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