The Menstrual Cycle

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The average menstrual cycle takes about 28 days (25-35 days) to complete and falls into three phases.

The follicular phase is a period of ovarian follicular growth in which the uterine endometrium develops in preparation for the implantation of fertilized ovum. The growing follicles themselves produce high amounts of estrogen, which stimulates the uterine endometrium to proliferate and to synthesize cytosolic receptors for progesterone. Progesterone levels during this phase remain low.

The follicular phase can be divided into two stages. In the preantral stage of follicular growth, luteinizing hormone (LH) stimulates theca interna cells to produce androgens (mainly androstenedione), which diffuse through the basal lamina into the granulosa cell compartment to stimulate proliferation. The follicle grows, accumulates fluid, and forms an antrum. Estradiol levels are not high enough to diffuse into general circulation, so follicle-stimulating hormone (FSH) and LH are not inhibited.

In the antral stage of follicular growth, the combined effects of FSH and estradiol induce LH receptors on the granulosa cells. This enables them to begin producing estradiol from pregnenolone (de novo estradiol synthesis). Spillage of estradiol into the general circulation results from this increased estradiol pool and accelerated follicle growth. Subsequently, a relatively rapid increase in circulating estradiol level is seen during the last 5 or 6 days of the follicular phase.

Initially this rise in estradiol exerts a negative feedback on FSH release. Continued high levels (about a three-fold increase) presented over a 2- to 3-day period exert a positive feedback effect, resulting in a large surge of LH and FSH. The large bolus of LH (preovulatory LH surge) released induces ovulation in about 1 day.

The follicular phase lasts for about 9-15 days, and its duration determines the period of the menstrual cycle itself, since the length of the two subsequent phases remains fairly constant.

The ovulatory phase involves the release of the ovum or egg (ovulation) from the follicles and lasts about 36 hours. Ovulation is probably induced when LH stimulates the production of granulosa plasminogen activator, triggering the formation of plasmin, an enzyme responsible for digesting the basal lamina, and thus the rupture of the follicle.

Women generally experience an increase in the basal body temperature of 0.5 to 1.0 degree F following ovulation. This increase is due to the thermogenic effect of pregnanediol, a metabolite of progesterone.

After ovulation, granulosa cells proliferate in response to the preovulatory LH surge, while theca interna cells and perifollicular blood vessels invade the cavity of the collapsed follicle. Under the influence of LH, the granulosa and evasive theca cells differentiate into luteal cells.

During the luteal phase, the ruptured follicles in the ovary form a corpus luteum. Luteal cells are steroidogenic and produce large amounts of progesterone and moderate amounts of estradiol.

The increase of estrogen and progesterone during the first 4-5 days of the luteal phase promotes endometrium and fallopian tube secretions that allow for proper nourishment and implantation of the fertilized ovum. During this time, circulating levels of estradiol are reduced, a decrease necessary for the proper transport of the ovum through the fallopian tube into the uterus. Exposure to high levels of estrogen during this interval would lead to expulsion of the ovum or to blockage of ovum transport.

The corpus luteum has a life span of about 12 days. If fertilization and implantation do not occur, the corpus luteum degenerates (luteolysis), and its production of progesterone and estradiol rapidly declines, resulting in deterioration of the endometrium and its shedding (menstruation). The first day of menstruation is the first day of the menstrual cycle.

The endometrium is most conducive to implantation during the progesterone peak secretion period, about the 5th day into the luteal phase. If fertilization of the ovum occurs, secretion of chorionic gonadotropin (hCG) by the implanted blastocyst stimulates the corpus luteum to continue producing progesterone, and luteolysis is prevented.⁹

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