Menstrual cycle

In the female reproductive system, the menstrual cycle is a recurring cycle of physiologic changes that occurs in reproductive-age females. Overt menstruation (where there is blood flow from the vagina) occurs primarily in humans and close evolutionary relatives such as chimpanzees. The females of other species of placental mammal have estrous cycles, in which the endometrium is completely reabsorbed by the animal (covert menstruation) at the end of its reproductive cycle. This article concentrates on the menstrual cycle as it occurs in human beings.

The menstrual cycle is under the control of the hormone system and is necessary for reproduction. Menstrual cycles are counted from the first day of menstrual flow, because the onset of menstruation corresponds closely with the hormonal cycle. The menstrual cycle may be divided into several phases, and the length of each phase varies from woman to woman and cycle to cycle. Average values are shown below:

Name of phase	Days
menstrual phase	1–4
follicular phase (also known as proliferative phase)	5–13
ovulation (not a phase, but an event dividing phases)	14
luteal phase (also known as secretory phase)	15–26
ischemic phase (some sources group this with secretory phase)	27–28

During the follicular phase the lining of the uterus thickens, stimulated by gradually increasing amounts of estrogen. Follicles in the ovary begin developing under the influence of a complex interplay of hormones, and after several days one or occasionally two follicles become dominant (non-dominant follicles atrophy and die). The dominant follicle releases an ovum or egg in an event called ovulation. (An egg that is fertilized by a spermatozoon will become a zygote, taking one to two weeks to travel down the fallopian tubes to the uterus. If the egg is not fertilized within about a day of ovulation, it will die and be absorbed by the woman's body.) After ovulation the remains of the dominant follicle in the ovary become a corpus luteum; this body has a primary function of producing large amounts of progesterone. Under the influence of progesterone, the endometrium (uterine lining) changes to prepare for potential implantation of an embryo to establish a pregnancy. If implantation does not occur within approximately two weeks, the corpus luteum will die, causing sharp drops in levels of both progesterone and estrogen. These hormone drops cause the uterus to shed its lining in a process termed menstruation.

Terminology

A woman's first menstruation is termed menarche, and is one of the later stages of puberty in girls. The average age of menarche in humans is 12 years, but is normal anywhere between ages 8 and 16. Factors such as heredity, diet and overall health can accelerate or delay menarche. The cessation of menstrual cycles at the end of a woman's reproductive life is termed menopause. The average age of menopause in women is 51 years, with anywhere between 40 and 58 being common. Menopause before age 35 is considered premature. The age of menopause is largely a result of genetics; however, illnesses, certain surgeries, or medical treatments may cause menopause to occur earlier.

The length of a woman's menstrual cycle will typically vary, with some shorter cycles and some longer cycles. A woman who experiences variations of less than eight days between her longest cycles and shortest cycles is considered to have regular menstrual cycles. It is unusual for a woman to experience cycle length variations of less than four days. Length variation between eight and 20 days is considered moderately irregular. Variation of 21 days or more between a woman's shortest and longest cycle lengths is considered very irregular (see cycle abnormalities).

It is important to do a breast exam during the same time of the cycle as opposed to the same time of the month given that most women do not have cycles that correspond exactly with the calendar month and the breast architecture fluctuates considerably given the phase of the menstrual cycle.

Phases of the menstrual cycle

Menstruation

Menstruation is also called menstrual bleeding, menses, a period or catamenia. The flow of menses normally serves as a sign that a woman has not become pregnant. (However, this cannot be taken as certainty, as sometimes there is some flow of blood in early pregnancy.) During the reproductive years, failure to menstruate may provide the first indication to a woman that she may have become pregnant.

Eumenorrhea denotes normal, regular menstruation that lasts for a few days (usually 3 to 5 days, but anywhere from 2 to 7 days is considered normal). The average blood loss during menstruation is 35 millilitres with 10–80 ml considered normal; many women also notice shedding of the endometrium lining that appears as tissue mixed with the blood. An enzyme called plasmin — contained in the endometrium — tends to inhibit the blood from clotting. Because of this blood loss, women have higher dietary requirements for iron than do males to prevent iron deficiency. Many women experience uterine cramps during this time (severe cramps or other symptoms are called dysmenorrhea), as well as other premenstrual syndrome symptoms. A vast industry of sanitary products is marketed to women for use during their menstruation.

Follicular phase

Through the influence of a rise in follicle stimulating hormone (FSH), five to seven tertiary-stage ovarian follicles are recruited for entry into the next menstrual cycle. These follicles, that have been growing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. Under the influence of several hormones, all but one of these follicles will undergo atresia, while one (or occasionally two) dominant follicles will continue to maturity. As they mature, the follicles secrete increasing amounts of estradiol, an estrogen.

The estrogens that follicles secrete initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium. The estrogen also stimulates crypts in the cervix to produce fertile cervical mucus, which may be noticed by women practicing fertility awareness.

Ovulation

When the egg has matured, it secretes enough estradiol to trigger the acute release of luteinizing hormone (LH). In the average cycle this LH surge starts around cycle day 12 and may last 48 hours. The release of LH matures the egg and weakens the wall of the follicle in the ovary. This process leads to ovulation: the release of the now mature ovum, the largest cell of the body (with a diameter of between 0.1 and 0.2 mm). Which of the two ovaries — left or right — ovulates appears essentially random; no known left/right co-ordination exists. The egg is swept into the fallopian tube by the fimbria - a fringe of tissue at the end of each fallopian tube. If fertilization occurs, it will happen in the fallopian tube.

In some women, ovulation features a characteristic pain called mittelschmerz (German term meaning 'middle pain') which may last a few hours. The sudden change in hormones at the time of ovulation also causes light mid-cycle blood flow from the vagina of some women. An unfertilized egg will eventually disintegrate or dissolve.

Luteal phase

The corpus luteum is the solid body formed in the ovaries after the egg has been released into the fallopian tube which continues to grow and divide for a while. After ovulation, the residual follicle transforms into the corpus luteum under the support of the pituitary hormones. This corpus luteum will produce progesterone in addition to estrogens for approximately the next 2 weeks. Progesterone plays a vital role in converting the proliferative endometrium into a secretory lining receptive for implantation and supportive of the early pregnancy. It raises the body temperature by 0.25 °C to 0.5 °C (0.5 °F to 1.0 °F), thus women who record their basal body temperature on a daily basis will notice that they have entered the luteal phase. If fertilization of an egg has occurred, it will travel as an early blastocyst through the fallopian tube to the uterine cavity and implant itself 6 to 12 days after ovulation. Shortly after implantation, the growing embryo will signal its existence to the maternal system. One very early signal consists of human chorionic gonadotropin (hCG), a hormone that pregnancy tests can measure. This signal has an important role in maintaining the corpus luteum and enabling it to continue to produce progesterone. In the absence of a pregnancy and without hCG, the corpus luteum demises and inhibin and progesterone levels fall. This will set the stage for the next cycle. Progesterone withdrawal leads to menstrual shedding ( progesterone withdrawal bleeding), and falling inhibin levels allow FSH levels to rise to raise a new crop of follicles.

The fertile window

The length of the follicular phase — and consequently the length of the menstrual cycle — may vary widely. The luteal phase, however, almost always takes the same number of days for each woman: Some women have a luteal phase of 10 days, others 16 days, while the average is 14 days. Normal sperm life inside a woman ranges from 1-5 days, though a pregnancy resulting from sperm life of 8 days has been documented. The most fertile period (the time with the highest likelihood of pregnancy resulting from sexual intercourse) covers the time from some 5 days before ovulation until 1–2 days after ovulation. In an average 28 day cycle with a 14-day luteal phase, this corresponds to the second and the beginning of the third week of the cycle. Fertility awareness methods of birth control attempt to determine the precise time of ovulation in order to find the relatively fertile and the relatively infertile days in the cycle.

People who have heard about the menstrual cycle and ovulation often mistakenly assume, for contraceptive purposes, that menstrual cycles regularly take 28 days, and that ovulation always occurs 14 days after beginning of the menses. This assumption may lead to unintended pregnancies. Note too that not every event of blood flow counts as a menstruation, and this can mislead people in their calculation of the fertile window.

If a woman wants to conceive, the most fertile time occurs between 19 and 10 days prior to the expected menses. Many women use ovulation detection kits that detect the presence of the LH surge in the urine to indicate the most fertile time. Other ovulation detection systems rely on observation of one or more of the three primary fertility signs ( basal body temperature, cervical fluid, and cervical position).

Among women living closely together, the onsets of menstruation may tend to synchronise somewhat. This McClintock effect was first described in 1971, and possibly explained by the action of pheromones in 1998. However, subsequent research has called this conclusion into question.

Hormonal control

Extreme intricacies regulate the menstrual cycle. For many years, researchers have argued over which regulatory system has ultimate control: the hypothalamus, the pituitary, or the ovary with its growing follicle; but all three systems have to interact. In any scenario, the growing follicle has a critical role: it matures the lining, provides the appropriate feedback to the hypothalamus and pituitary, and modifies the mucus changes at the cervix.

Gonadal

Two sex hormones play a role in the control of the menstrual cycle: estrogen and progesterone:

• Estradiol peaks twice, during follicular growth and during the luteal phase.
• Progesterone remains virtually absent prior to ovulation, but becomes critical in the luteal phase and during pregnancy. Many tests for ovulation check for the presence of progesterone.

After ovulation the corpus luteum — which develops from the burst follicle and remains in the ovary — secretes both estradiol and progesterone. Only if pregnancy occurs do hormones appear in order to suspend the menstrual cycle, while production of estradiol and progesterone continues. Abnormal hormonal regulation leads to disturbance in the menstrual cycle.

Hypothalamus and pituitary

These sex hormones come under the influence of the pituitary gland, and both FSH and LH play necessary roles:

• FSH stimulates immature follicles in the ovaries to grow.
• LH triggers ovulation.

The gonadotropin-releasing hormone of the hypothalamus controls the pituitary, yet both the pituitary and the hypothalamus receive feedback from the follicle.

Cyclic effects upon nervous system

Some women with neurological conditions experience increased activity of their conditions at about the same time every month. 80 percent of women with epilepsy have more seizures than usual in the phase of their cycle when progesterone declines and estrogen increases. This is called "catamenial epilepsy".

Mice have been used as an experimental system to investigate possible mechanisms by which levels of sex steroid hormones might regulate nervous system function. During the part of the mouse estrous cycle when progesterone is highest, the level of nerve-cell GABA receptor subtype delta was high. Since these GABA receptors are inhibitory, nerve cells with more delta receptors are less likely to fire than cells with lower numbers of delta receptors. During the part of the mouse estrous cycle when estrogen levels are higher than progesterone levels, the number of delta receptors decrease, increasing nerve cell activity, in turn increasing anxiety and seizure susceptibility.

Hidden ovulation

Unlike almost all other species, the external physical changes of a human female near ovulation are very subtle. In contrast, other species often signal receptivity through heat, swellings, and/or changes in colour in the genital area. Humans are the only mammal to lack obvious, visible manifestations of ovulation, although some argue that the extended estrus period of the bonobo (reproductive-age females are in heat for 75% of their menstrual cycle) has a similar effect to the lack of a "heat" in human females.

While women can be taught to recognize their own level of fertility ( fertility awareness), whether men can detect fertility in women is highly debated. On one hand, several small studies have found that fertile women (compared to women in infertile portions of the menstrual cycle or on hormonal contraception) appear more attractive. On the other hand, two small studies of monogamous couples found that women initiated sex significantly more frequently when fertile, but male-initiated sex occurred at a constant rate in all phases of the menstrual cycle.

The ovary as an egg-bank

Evidence suggests that eggs are formed from germ cells early in fetal life. The number is reduced to an estimated 400,000 to 450,000 immature ova residing in each ovary at puberty. The menstrual cycle, as a biologic event, allows for ovulation of one egg typically each month. Thus over her reproductive lifetime a woman will ovulate approximately 400 to 450 times. All the other eggs dissolve by a process called atresia. As a woman's total egg supply is formed in fetal life, to be ovulated decades later, it has been suggested that this long lifetime may make the chromatin of eggs more vulnerable to division problems, breakage, and mutation than the chromatin of sperm, which are produced continuously during a man's reproductive life.

Cycle abnormalities

Anovulation

Apparently normal menstrual flow can occur without ovulation preceding it ( anovulatory cycle - "an-" meaning "absence of" +ovulation). In some women, follicular development may start but not be completed; nevertheless, estrogens will form and will stimulate the uterine lining. Anovulatory flow resulting from a very thick endometrium caused by prolonged, continued high estrogen levels is called estrogen breakthrough bleeding. Anovulatory bleeding triggered by a sudden drop in estrogen levels is called estrogen withdrawal bleeding.

Anovulatory bleeding may occur on a regular basis, but more commonly happens with irregular frequency. Anovulatory flow commonly occurs prior to menopause (premenopause) or in women with polycystic ovary syndrome.

Infrequent or irregular ovulation is called oligoovulation.

Flow

Sudden heavy flows or amounts in excess of 80 ml (hypermenorrhea or menorrhagia) are not normal.

Very little flow (less than 10ml) is called hypomenorrhea.

Prolonged flow (metrorrhagia, also meno-metrorrhagia) no longer shows a clear interval pattern. Dysfunctional uterine bleeding refers to hormonally caused flow abnormalities, typically anovulation.

All bleeding abnormalities need medical attention; they may indicate hormone imbalances, uterine fibroids, or other problems. As pregnant patients may bleed, a pregnancy test forms part of the evaluation of abnormal flow.

Cycle length

The medical term for cycles with intervals of 21 days or fewer is polymenorrhea and, on the other hand, the term for cycles with intervals exceeding 35 days is oligomenorrhea (or amenorrhea if intervals exceed 180 days).

Amenorrhea refers to a prolonged absence of menses during the reproductive years of a woman. For example, women with very low body fat, such as athletes, may cease to menstruate. Amenorrhea also occurs during pregnancy.

Early menarche

The condition precocious puberty has caused menstruation to occur in girls as young as eight months old.

Contraception and menstruation

Hormonal options

Estrogens and progesterone-like hormones make up the main active ingredients of hormonal birth control methods such as the pill. Typically they cause regular monthly flow that roughly mimics a menstrual cycle in appearance, but suppresses ovulation. With most pills, a woman takes hormone pills for 21 days, followed by 7 days of non-functional placebo pills or no pills at all, then the cycle starts again. During the 7 placebo days, a withdrawal bleeding occurs; this differs from ordinary menstruation, and skipping the placebos and continuing with the next batch of hormone pills may suppress it. (There are two main versions of the pill: monophasic and triphasic. With triphasic pills, skipping placebos and continuing with the next month's dose can make a woman more likely to experience spotting or breakthrough bleeding.) In 2003, the U.S. Food and Drug Administration (FDA) approved low-dose monophasic birth control pills that induce withdrawal bleeding every 3 months. Yet another version of the pill is the Loestrin Fe, which has only a four-day placebo "week" (the placebos are actually iron supplements intended to replenish iron lost by uterine shedding); the other three placebos are replaced with active hormone pills. This system is intended to help shorten periods. Mircette contains several days of estrogen-only pills in addition to the usual combination estrogen/progestin pills, in the case of women who may have problems with low estrogen during the placebo days with other pills.

Other types of hormonal birth control which affect menstruation include the vaginal Nuvaring and the transdermal patch (like the standard pill pack, active hormones are given for three weeks, followed by a one-week break to allow blood flow) and the injection (which can eliminate all flow as long as the injections are taken every twelve weeks, although spotting is a common side effect).

Effects on menstruation

All such methods are designed to regulate the monthly blood flow. Because of this, they are often chosen by females who wish to regulate the frequency and length of their period, often for basic convenience and especially when such factors are irregular and problematic on their own. Hormonal contraception has also been shown to improve menstrual symptoms such as cramping, heavy flow, and other bothersome physical and emotional issues related to periods.

Control and flexibility

Hormonal methods which are controlled by the user day-to-day, including pills, the ring, and the patch, need not always be used according to the standard cycle/calendar. Their use can be rescheduled and altered in various ways to postpone or skip periods when desired for reasons of convenience (e.g., traveling or scheduled gynecological exams), personal enjoyment (such as expected sexual encounters or events like a wedding or dance), or health (including very painful periods or sensitivity to hormone fluctuations). Similarly, abrupt cessation of use can induce a breakthrough period mid-cycle.

Other contraceptive methods

Most IUDs are not designed to affect menstruation or breakthrough bleeding, but may exacerbate cramps or the heaviness of the flow due to their placement within the uterus. The Mirena IUD releases a small continuous dosage of a progesterone-like hormone, which can sometimes cause menstruation to cease. Tubal sterilization alone will not affect menstruation, though the ablation option often performed at the same time will cause menstruation to cease. Hysterectomy will, of course, completely stop menstruation as it entails the removal of the uterus (and sometimes the ovaries, fallopian tubes, and cervix). Fertility awareness methods do not affect the period in and of themselves, but involve careful observation of various kinds, of which the timing of the period is an essential factor.

Menstruation and the moon

Traditional sources agree that the menstrual cycle is linked to the cycle of the moon. These sources generally indicate that women menstruate at the time of the new moon, and ovulate at the full moon. Although scientific evidence for this has been weak, the problem may be that most women today live in urban environments where the moon is no longer a significant contributor to nocturnal light. The fact that women who work on night shifts, where they are exposed to strong light at night, often experience menstrual irregularities, is just one example of how rhythms of light and darkness do influence hormonal physiology, including the menstrual cycle.

The word "menstruation" is etymologically related to moon. The terms "menstruation" and "menses" come from the Latin mensis (month), which in turn relates to the Greek mene (moon) and to the roots of the English words month and moon — reflecting the fact that the moon also takes close to 28 days to revolve around the Earth (actually 27.32 days). The synodical lunar month, the period between two new moons (or full moons), is 29.53 days long.

A 1975 book by Louise Lacey documented the experience of herself and 27 of her friends, who found that when they removed all artificial night lighting their menstrual cycles began to occur in rhythm with the lunar cycle. She dubbed the technique Lunaception. Later studies in both humans and animals have found that artificial light at night does influence the menstrual cycle in humans and the estrus cycle in mice (cycles are more regular in the absence of artificial light at night), though none have duplicated the synchronization of women's menstrual cycles with the lunar cycle. One author has suggested that sensitivity of women's cycles to nightlighting is caused by nutritional deficiencies of certain vitamins and minerals.

Some have suggested that the fact that other animals' menstrual cycles appear to be greatly different from lunar cycles is evidence that the average length of humans' cycle is most likely a coincidence.

Menstrual cycles in other mammals

Females of most species advertise ovulation to males with visual cues and behavioural cues, pheromones, or both (humans are a species that does not). This period of advertised fertility is known as estrus or heat. However, in animals with menstrual cycles, females can be sexually active at any time in their cycle, even when they are not in heat. Great apes' cycles vary in length from an average of 29 days in orangutans to an average of 37 days in chimpanzees.

By contrast, in species that have estrous cycles rather than menstrual cycles, females are only receptive to copulation while they are in heat (dolphins are an exception). The other significant difference is that in an estrous cycle, if no fertilization takes place, the uterus reabsorbs the endometrium: no menstrual blood flow occurs. Some animals, such as domestic cats and dogs, experience small amounts of bleeding while in heat. This phase of the estrous cycle corresponds most closely to the follicular phase of the menstrual cycle and should not be confused with menstruation.