The major function of the female genital tract is to produce mature and fertilizable ova. In contrast to other tissues of the body, ovaries and other parts of this system undergo repetitive cyclical changes in response to estrogen and progesterone stimulation. Such changes that occur at approximately monthly intervals are most prominent in the endometrium, and the shedding of uterine lining is called menstruation.

In order to understand menstruation, one must get familiar with menstrual cycle. The first menstrual period of a girl or woman is called menarche, which usually occurs between 12 and 13 years of age across well-nourished populations in developed countries. The menstrual cycle is traditionally divided into three main phases that correlate with the functional activities of the ovary.

Menstruation and other phases of the menstrual cycle

In a majority of women, the menstrual cycle lasts between 25 and 30 days, although some healthy women can have as little as three or four cycles per year. The length of the menstrual cycle can change during a woman's life, while irregular periods become more common as women are approaching menopause (the cessation of menstruation and the menstrual cycle).

The normal cycle starts with the follicular phase. This stage represents a proliferative phase of the menstrual cycle where follicles inside the ovaries develop and mature in preparation for ovulation. Once released from the ovary, the ovum travels to the Fallopian tubes, and the process of liberation of a mature egg from the follicle is named ovulation (the most fertile time during a woman’s menstrual cycle).

The secretory or luteal phase appears after the ovulation when the burst follicle develops into a structure called corpus luteum. This is a small yellow structure in the ovary that secretes both estrogen and progesterone which prepare the endometrium to secrete nutrients that would nourish an implanted egg if case of the fertilization. If there is no implantation, a decrease in the estrogen and progesterone levels occurs.

Such drop triggers the shedding of the endometrium, causing menstruation to begin. This process is what women experience while they are having their menstrual periods and it generally lasts from 3 to 7 days. The menstrual flow actually consists of blood, cervical mucus and tissue. The amount of menstrual fluid lost is usually between 50-100 milliliters of fluid, although it can vary significantly.

An enzyme called plasmin inhibits the blood from clotting, but blood loss (which is sometimes copious) can lead to iron deficiency; hence premenopausal women have higher dietary requirements in order to prevent that from happening. As menstruation is the most prominent phase of the menstrual cycle, cycles are often counted from the first day of menstrual bleeding.

Hormonal markers of the menstrual cycle

There are four dominant hormonal markers that play a role in the menstrual cycle: FSH and LH (of pituitary origin) and estradiol and progesterone (of ovarian origin). In addition to daily hormonal rhythms that form the basis for the menstrual cycle, there are also extremely important ultradian rhythms that are shorter than a day and that shape the hormonal signals.

One of the most striking events of the menstrual cycle is an abrupt rise in concentrations of LH at the end of follicular phase (so called preovulatory LH surge). Mean duration of this surge is 48 hours, while daily variations in LH secretions at other times of the menstrual cycle are modest. It is estimated that ovulation occurs approximately 18 hours after the LH peak, i.e. 36 hours after the start of preovulatory LH surge.

There is also a surge FSH at the end of the follicular phase, albeit more modest when compared to preovulatory LH surge. Significant physiological event is a twofold rise in FSH levels on the day of menstruation (or just preceding this event). Peak FSH values are reached about 24 hours upon the start of menstrual flow.

Estradiol secretion is at low levels during the early follicular phase, but increases one week prior to the gonadotropic surge in the middle of the cycle. Within a few hours after the initiation of such surge, estradiol concentrations fall abruptly and rise again with the appearance of the corpus luteum.

Although progesterone secretion is insignificant throughout the follicular phase, it rises suddenly about 12 hours before the onset of the LH surge, then remains at a plateau for about 12 hours – this event is called the prevoulatory progesteron rise. During the secretory phase, levels of both estradiol and progesterone rise and reach a maximum approximately 7-9 days after the mid-cycle gonadotropin surge.

Regulatory molecules that stimulate or inhibit angiogenesis, cell proliferation and matrix synthesis have been identified in the human endometrium. Among others, they include growth factors and growth factor receptors (such as TGF-β), angiogenesis stimulating factors (erythropoietin), cytokines and various enzymes. These substances operate in a cooperative or competitive fashion with estrogen and progesterone throughout the menstruation and the menstrual cycle.