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
functional layer. 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). During these two 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, the gonadotropin-releasing hormone is released at a steady rate, but
once puberty hits, the 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 is a member of the estrogen
family. During days 10 through 14 of this phase, 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 follicle 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, which grow a little under the influence of
estrogen, 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 grow the most and become coiled, 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.