MENSTRUAL CYCLE

The Phases
The menstrual cycle (approximately 28 days) can be divided into the following phases or
events. By convention, the first day of bleeding (menses) is called day 1 of the menstrual
cycle.

Follicular phase (first 2 weeks) is also called the proliferative or preovulatory phase. This
phase is dominated by the peripheral effects of estrogen, which include the replacement of
the endometrial cells lost during menses.

Ovulation (approximately day 14) is preceded by the LH surge, whichinduces ovulation.

Luteal phase (approximately 2 weeks) is dominated by the elevated plasma levels of

progesterone, and along with lower levels of secreted estrogen, creates a secretory
quiescent endometrium which prepares the uterus for implantation.

Menstruation Withdrawal of the hormonal support of the endometrium at this time

causes necrosis and menstruation.

FOLLICULAR PHASE (approximately days 1 to 14)

By convention, the first day of bleeding (menses) is called day 1 of the menstrual cycle.
During the follicular phase, FSH secretion is slightly elevated, causing proliferation of
granulosa cells and increased estrogen secretion within a cohort of follicles.
One follicle, possibly the one with the best blood supply, secretes more estradiol than the
others. Because estradiol acts locally within the follicle to increase the granulosa cell's
sensitivity to FSH, this follicle becomes the dominant follicle, i.e., the one destined to grow
and rupture. The remaining follicles, lacking sufficient FSH, synthesize only androgen and
become atretic (die).

The hormonal regulation of the menstrual cycle

Theca Cells: Under LH stimulation, which acts intracellularly via cAMP, cholesterol is
transported into the mitochondria (StAR is activated). The pathway continues through
intermediates to androgens. Little androgen is secreted into the blood; most of the
androgen enters the adjacent granulosa cells.

Granulosa Cells: Possess the follicle's only FSH receptors. When coupled to FSH, these act
via cAMP to increase the activity of aromatase; aromatase converts the androgens to
estrogens (mainly estradiol).

Estrogen: Some of the estrogen produced by the granulosa cells is released into the blood
and inhibits the release of LH and FSH from the anterior pituitary. However, another fraction
of the estrogen acts locally on granulosa cells, increasing their proliferation and sensitivity to
FSH.
This local positive effect of estrogens causes a rising level of circulating estrogens
during the follicular phase, but at the same time FSH is decreasing because of the
inhibitory effect of estrogen on FSH release.
Granulosa cells also release inhibin B.
Inhibin B inhibits the secretion of FSH by the pituitary but their role in the menstral
cycle is poorly understood.
The graphs represent the plasma hormonal levels throughout the cycle. The length of the
menstrual cycle varies, but an average length is 28 days.
Peripheral effects of estrogen produced by the granulosa cells during the follicular phase
include:
Rising levels of estrogens cause the endometrial cells of the uterine mucosal layers
to increase their rate of mitotic division (proliferate) .
Circulating estrogens cause the cervical mucus to b e thin and watery, making the
cervix easy for sperm to traverse.
Circulating estrogens stimulate the female sex accessory organs and secondary sex
characteristics.

OVULATION
Ovulation takes place approximately on day 14. This is an approximation. Since ovulation is
always 14 days before the end of the cycle, you can subtract 14 from the cycle length to find
the day of ovulation. Cycle length - 14 = ovulation day

Near the end of the follicular phase, there is a dramatic rise in circulating estrogen. When
estrogens rise above a certain level, they no longer inhibit the release of LH and FSH.
Instead, they stimulate the release of LH and FSH (negative feedback loop to positive
feedback loop). This causes a surge in the release of LH and FSH. Only the LH surge is
essential for the induction of ovulation and formation of the corpus luteum. The LH surge
and ovulation occur after estrogen peaks.

Follicular rupture occurs 24-36 hours after the onset of the LH surge. During this time
interval, LH removes the restraint upon meiosis, which has been arrested in prophase for
years. The first meiotic division is completed, and the first polar body is extruded.

Positive feedback loops are rare in the body. Only ovulation with estrogen and parturition
with oxytocin represent positive feedback loops.
LUTEAL PHASE (approximately days 14 to 28)

Preovulatory Follicle
In the latter stages of the follicular phase, intracellular changes within the granulosa
and theca cells occur in preparation for their conversion into luteal cells.
Estradiol, in conjunction with FSH, causes the granulosa cells to produce LH
receptors.
The metabolic pathways are then altered to favor the production of progesterone.
 This would include a decrease in the activity of aromatase and a drop in estrogen
production.

LH Surge
Induced by the elevated estrogens, it causes the granulosa cells and theca cells to
be transformed into luteal cells and increases the secretion of progesterone.

Corpus Luteum
The process of luteinization occurs following the exit of the oocyte from the follicle. The
corpus luteum is made up of the remaining granulosa cells, thecal cells, and supportive
tissue. Once formed, the luteal cells are stimulated by LH to secrete considerable
progesterone and some estrogen. Progesterone inhibits LH secretion (negative feedback).

The increased plasma level of progesterone has several actions:

It causes the uterine endometrium to become secretory, providing a source of
nutrients for the blastocyst.
It causes the cervical mucus to become thick, sealing off the uterus from further
entry of sperm or bacteria.
It has thermogenic properties, causing the basal body temperature to increase by
0.5-1 .0 F.
MENSTRUATION
Withdrawal of the hormonal support of the endometrium at this time causes necrosis and
menstruation.

The life of the corpus luteum is finite, hence the luteal phase is only 14 days.
Initially, the corpus luteum is very responsive to LH. Over time however, as the corpus
luteum becomes less functional, it becomes less responsive to LH.
Progesterone exerts negative feedback on LH, which contributes to the demise of the
corpus luteum.
With the demise of the corpus luteum, progesterone and estradiol fall to levels that are
unable to support the endometrial changes, and menses begins.

Menstruation is due to a lack of / fall in sex steroids.