THE MESTRUAL CYCLE
During these two
The menstrual cycle refers to the regular
changes in the activity of the ovaries and
the endometrium that make reproduction
possible. The endometrium is the layer of
tissue lining the inside of the uterus. This
lining consists of a functional layer, which
is subject to hormonal changes and is
shed during menstruation, and a thin
basal layer which feeds the overlying
function allayer. The menstrual cycle
actually consists of two interconnected
and synchronized processes. The ovarian
cycle, which centers on the development
of the ovarian follicles and ovulation, and
the uterine or endometrial cycle, which
centers on the way in which the
functional endometrium thickens and
sheds in response to ovarian activity.
Menarche, which refers to the onset of
the first menstrual period, usually occurs
during early adolescence as part of
puberty. Following menarche, the
menstrual cycle recurs on a monthly
basis, pausing only during pregnancy,
until a person reaches menopause, when
her ovarian function declines and she
stops having menstrual periods. The
monthly menstrual cycle can vary in
duration from 20 to 35 days, with an
average of 28 days. Each menstrual cycle
begins on the first day of menstruation,
and this is referred to as day one of the
cycle. Ovulation, or the release of the
oocyte from the ovary, usually occurs 14
days before the first day of menstruation
(i.e., 14 days before the next cycle
begins). So, for an average 28-day
menstrual cycle, this means that there are
usually 14 days leading up to ovulation
(i.e., the preovulatory phase) and 14 days
following ovulation (i.e., the
postovulatory phase).
phases, the ovaries and the endometrium
each undergo their own set of changes,
which are separate but related. As a
result, each phase of the menstrual cycle
has two different names to describe these
two different parallel processes. For the
ovary, the two weeks leading up to
ovulation is called the ovarian follicular
phase, and this corresponds to the
menstrual and proliferative phases of the
endometrium. Similarly, the two weeks
following ovulation is referred to as the
ovarian luteal phase, which also
corresponds to the secretory phase of the
endometrium. So, let’s first focus on the
preovulatory period, starting with the
ovarian follicular phase. This phase starts
on the first day of menstruation and
represents weeks one and two of a four-
week cycle. The whole menstrual cycle is
controlled by the hypothalamus and the
pituitary gland, which are like the
masterminds of reproduction. The
hypothalamus is a part of the brain that
secretes gonadotropin-releasing
hormone, or GnRH, which causes the
nearby anterior pituitary gland to release
follicle stimulating hormone, or FSH, and
luteinizing hormone, or LH. Before
puberty, gonadotropin-releasing hormone
is released at a steady rate, but once
puberty hits, gonadotropin-releasing
hormone is released in pulses, sometimes
more and sometimes less. The frequency
and magnitude of the gonadotropin-
releasing hormone pulses determine how
much follicle stimulating hormone and
luteinizing hormone will be produced by
the pituitary. These pituitary hormones
control the maturation of the ovarian
follicles, each of which is initially made up
of an immature sex cell, or primary
oocyte, surrounded by layers of theca and
granulosa cells, the hormone-secreting
cells of the ovary. Over the course of the
follicular phase, these oocyte-containing
groups of cells, or follicles, grow and
compete for a chance at ovulation. During
the first ten days, theca cells develop
receptors and bind luteinizing hormone,
and in response secrete large amounts of
the hormone androstenedione, an
androgen hormone. Similarly, granulosa
cells develop receptors and bind follicle
stimulating hormone, and in response
produce the enzyme aromatase.
Aromatase converts androstenedione
from the theca cells into 17β-estradiol,
which isa member of the estrogen family.
During days 10 through 14 of these
phases, granulosa cells also begin to
develop luteinizing hormone receptors, in
addition to the follicle stimulating
hormone receptors they already have. As
the follicles grow and estrogen is released
into the bloodstream, increased estrogen
levels act as a negative feedback signal,
telling the pituitary to secrete less follicle
stimulating hormone. As a result of
decreased follicle stimulating hormone
production, some of the developing
follicles in the ovary will stop growing,
regress and die off. The follicle that has
the most follicle stimulating hormone
receptors, however, will continue to
grow, becoming the dominant follicle that
will eventually undergo ovulation. This
dominant follicle continues to secrete
estrogen, and the rising estrogen levels
make the pituitary more responsive to
the pulsatile action of gonadotropin-
releasing hormone from the
hypothalamus. As blood estrogen levels
start to steadily climb higher and higher,
the estrogen from the dominant follicle
now becomes a positive feedback signal –
that is, it makes the pituitary secrete a
whole lot of follicles stimulating hormone
and luteinizing hormone in response to
gonadotropin-releasing hormone. This
surge of follicle stimulating hormone and
luteinizing hormone usually happens a
day or two before ovulation and is
responsible for stimulating the rupture of
the ovarian follicle and the release of the
oocyte. You can think of it this way: for
most of the follicular phase, the pituitary
saves its energy, then when it senses that
the dominant follicle ready for release,
the pituitary uses all its energy to secrete
enough follicle stimulating hormone and
luteinizing hormone to induce ovulation.
While the ovary is busy preparing an egg
for ovulation, the uterus, meanwhile, is
preparing the endometrium for
implantation and maintenance of
pregnancy. This process begins with the
menstrual phase, which is when the old
endometrial lining, or functional layer,
from the previous cycle is shed and
eliminated through the vagina, producing
the bleeding pattern known as the
menstrual period. The menstrual phase
lasts an average of five days and is
followed by the proliferative phase,
during which high estrogen levels
stimulate thickening of the endometrium,
growth of endometrial glands, and
emergence of spiral arteries from the
basal layer to feed the growing functional
endometrium. Rising estrogen levels also
help change the consistency of the
cervical mucus, making it more hospitable
to incoming sperm. The combined effects
of this spike in estrogen on the uterus
and cervix help to optimize the chance of
fertilization, which is highest between day
11 and day 15 of an average 28-day cycle.
Following ovulation, the remnant of the
ovarian follicle becomes the corpus
luteum, which is made up of luteinized
theca and granulosa cells, meaning that
these cells have been exposed to the high
luteinizing hormone levels that occur just
before ovulation. Luteinized theca cells
keep secreting androstenedione, and the
luteinized granulosa cells keep converting
it to 17β-estradiol, as before. However,
luteinized granulosa cells also respond to
the low luteinizing hormone
concentrations that are present after
ovulation by increasing the activity of
cholesterol side-chain cleavage enzyme,
or P450scc for short. This enzyme
converts more cholesterol to
pregnenolone, a progesterone precursor.
So luteinized granulosa cells secrete more
progesterone than estrogen during the
luteal phase. Progesterone acts as a
negative feedback signal on the pituitary,
decreasing release of follicle stimulating
hormone and luteinizing hormone. At the
same time, luteinized granulosa cells
begin secreting inhibin, which similarly
inhibits the pituitary gland from making
follicle stimulating hormone. Both of
these processes result in a decline in
estrogen levels, meaning that
progesterone becomes the dominant
hormone present during this phase of the
cycle. Together with the decreased level
of estrogen, the rising progesterone level
signals that ovulation has occurred and
helps make the endometrium receptive to
the implantation of a fertilized gamete.
Under the influence of progesterone, the
uterus enters into the secretory phase of
the endometrial cycle. During this time
spiral arteries continue to grow, and the
uterine glands begin to secrete more
mucus. After day 15 of the cycle, the
optimal window for fertilization begins to
close. The cervical mucus starts to thicken
and becomes less hospitable to the
sperm. Over time, the corpus luteum
gradually degenerates into the
nonfunctional corpus albicans. The corpus
albicans doesn’t make hormones, so
estrogen and progesterone levels slowly
decrease. When progesterone reaches its
lowest level, the spiral arteries collapse,
and the functional layer of the
endometrium prepares to shed through
menstruation. This shedding marks the
beginning of a new menstrual cycle and
another opportunity for fertilization. All
right, so as a quick recap - the menstrual
cycle begins on the first day of
menstruation. For an average 28-day
menstrual cycle, the changes which occur
in the ovary during the first 14 days are
called the follicular phase. Ovulation
usually occurs at day 14, as a result of the
estrogen-induced surge in luteinizing
hormone. The last 14 days of the cycle
are the luteal phase, during which
progesterone becomes the dominant
hormone. While the length of the
follicular phase can vary, the luteal phase
almost always precedes the onset of
menses by 14 days. The uterus also goes
through its own set of changes. During
the first 14 days of the cycle, the
endometrium goes through the menstrual
phase and the proliferative phase, and
during the last 14 days it goes through
the secretory phase.