Menstrual cycle

The menstrual cycle is a series of natural changes in

Each cycle occurs in phases based on events either in the ovary (ovarian cycle) or in the uterus (uterine cycle). The ovarian cycle consists of the follicular phase, ovulation, and the luteal phase; the uterine cycle consists of the menstrual, proliferative and secretory phases. Day one of the menstrual cycle is the first day of the period, which lasts for about five days. Around day fourteen, an egg is usually released from the ovary. Menarche (the onset of the first period) usually occurs around the age of twelve years.

The menstrual cycle can cause some women to experience

Cycles and phases

The menstrual cycle encompasses the ovarian and uterine cycles. The ovarian cycle describes changes that occur in the

Measured from the first day of one menstruation to the first day of the next, the length of a menstrual cycle varies but has a median length of 28 days.^[4] The cycle is often less regular at the beginning and end of a woman's reproductive life.^[4] At puberty, a child's body begins to mature into an adult body capable of sexual reproduction; the first period (called menarche) occurs at around 12 years of age and continues for about 30–45 years.^[5][6] Menstrual cycles end at menopause, which is usually between 45 and 55 years of age.^[7][8]

Ovarian cycle

Between menarche and menopause the ovaries regularly alternate between luteal and follicular phases during the monthly menstrual cycle.^[9] Stimulated by gradually increasing amounts of estrogen in the follicular phase, discharges of blood flow stop and the uterine lining thickens. Follicles in the ovary begin developing under the influence of a complex interplay of hormones, and after several days one, or occasionally two, become dominant, while non-dominant follicles shrink and die. About mid-cycle, some 10–12 hours after the increase in luteinizing hormone, known as the LH surge,^[4] the dominant follicle releases an oocyte, in an event called ovulation.^[10]

After ovulation, the oocyte lives for 24 hours or less without fertilization,^[11] while the remains of the dominant follicle in the ovary become a corpus luteum – a body with the primary function of producing large amounts of the hormone progesterone.^[12][a] Under the influence of progesterone, the uterine lining changes to prepare for potential implantation of an embryo to establish a pregnancy. The thickness of the endometrium continues to increase in response to mounting levels of estrogen, which is released by the antral follicle (a mature ovarian follicle) into the blood circulation. Peak levels of estrogen are reached at around day thirteen of the cycle and coincide with ovulation. If implantation does not occur within about two weeks, the corpus luteum degenerates into the corpus albicans, which does not produce hormones, causing a sharp drop in levels of both progesterone and estrogen. This drop causes the uterus to lose its lining in menstruation; it is around this time that the lowest levels of estrogen are reached.^[14]

In an ovulatory menstrual cycle, the ovarian and uterine cycles are concurrent and coordinated and last between 21 and 35 days, with a population average of 27–29 days.

The ovaries contain a finite number of

The theca cells develop receptors that bind LH, and in response secrete large amounts of androstenedione. At the same time the granulosa cells surrounding the maturing follicle develop receptors that bind FSH, and in response start secreting androstenedione, which is converted to estrogen by the enzyme aromatase. The estrogen inhibits further production of FSH and LH by the pituitary gland. This negative feedback regulates levels of FSH and LH. The dominant follicle continues to secrete estrogen, and the rising estrogen levels make the pituitary more responsive to GnRH from the hypothalamus. As estrogen increases this becomes a positive feedback signal, which makes the pituitary secrete more FSH and LH. This surge of FSH and LH usually occurs one to two days before ovulation and is responsible for stimulating the rupture of the antral follicle and release of the oocyte.^[18][23]

Ovulation

Around day fourteen, the egg is released from the ovary.

Lasting about 14 days,^[4] the luteal phase is the final phase of the ovarian cycle and it corresponds to the secretory phase of the uterine cycle. During the luteal phase, the pituitary hormones FSH and LH cause the remaining parts of the dominant follicle to transform into the corpus luteum, which produces progesterone.^[38][c] The increased progesterone starts to induce the production of estrogen. The hormones produced by the corpus luteum also suppress production of the FSH and LH that the corpus luteum needs to maintain itself. The level of FSH and LH fall quickly, and the corpus luteum atrophies.^[40] Falling levels of progesterone trigger menstruation and the beginning of the next cycle. From the time of ovulation until progesterone withdrawal has caused menstruation to begin, the process typically takes about two weeks. For an individual woman, the follicular phase often varies in length from cycle to cycle; by contrast, the length of her luteal phase will be fairly consistent from cycle to cycle at 10 to 16 days (average 14 days).^[14]

Uterine cycle

The uterine cycle has three phases: menses, proliferative and secretory.^[41]

Menstruation

Menstruation (also called menstrual bleeding, menses or a period) is the first and most evident phase of the uterine cycle and first occurs at puberty. Called menarche, the first period occurs at the age of around twelve or thirteen years.

The proliferative phase is the second phase of the uterine cycle when estrogen causes the lining of the uterus to grow and proliferate.^[40] The latter part of the follicular phase overlaps with the proliferative phase of the uterine cycle.^[31] As they mature, the ovarian follicles secrete increasing amounts of estradiol, an estrogen. The estrogens initiate the formation of a new layer of endometrium in the uterus with the spiral arterioles.^[2]

As estrogen levels increase, cells in the cervix produce a type of

The secretory phase is the final phase of the uterine cycle and it corresponds to the luteal phase of the ovarian cycle. During the secretory phase, the corpus luteum produces progesterone, which plays a vital role in making the endometrium receptive to the implantation of a blastocyst (a fertilized egg, which has begun to grow).^[56] Glycogen, lipids, and proteins are secreted into the uterus^[57] and the cervical mucus thickens.^[58] In early pregnancy, progesterone also increases blood flow and reduces the contractility of the smooth muscle in the uterus^[22] and raises basal body temperature.^[59]

If pregnancy does not occur the ovarian and uterine cycles start over again.^[47]

Anovulatory cycles and short luteal phases

Only two-thirds of overtly normal menstrual cycles are ovulatory, that is, cycles in which ovulation occurs.^[15] The other third lack ovulation or have a short luteal phase (less than ten days^[60]) in which progesterone production is insufficient for normal physiology and fertility.^[61] Cycles in which ovulation does not occur (anovulation) are common in girls who have just begun menstruating and in women around menopause. During the first two years following menarche, ovulation is absent in around half of cycles. Five years after menarche, ovulation occurs in around 75% of cycles and this reaches 80% in the following years.^[62] Anovulatory cycles are often overtly identical to normally ovulatory cycles.^[63] Any alteration to balance of hormones can lead to anovulation. Stress, anxiety and eating disorders can cause a fall in GnRH, and a disruption of the menstrual cycle. Chronic anovulation occurs in 6–15% of women during their reproductive years. Around menopause, hormone feedback dysregulation leads to anovulatory cycles. Although anovulation is not considered a disease, it can be a sign of an underlying condition such as polycystic ovary syndrome.^[64] Anovulatory cycles or short luteal phases are normal when women are under stress or athletes increasing the intensity of training. These changes are reversible as the stressors decrease or, in the case of the athlete, as she adapts to the training.^[60]

Menstrual health

There are common culturally communicated misbeliefs that the menstrual cycle affects women's moods, causes depression or irritability, or that menstruation is a painful, shameful or unclean experience. Often a woman's normal mood variation is falsely attributed to the menstrual cycle. Much of the research is weak, but there appears to be a very small increase in mood fluctuations during the luteal and menstrual phases, and a corresponding decrease during the rest of the cycle.[74] Changing levels of estrogen and progesterone across the menstrual cycle exert systemic effects on aspects of physiology including the brain, metabolism, and musculoskeletal system. The result can be subtle physiological and observable changes to women's athletic performance including strength, aerobic, and anaerobic performance.^[75]

Changes to the brain have also been observed throughout the menstrual cycle^[76] but do not translate into measurable changes in intellectual achievement – including academic performance, problem-solving, memory, and creativity.^[77] Improvements in spatial reasoning ability during the menstruation phase of the cycle are probably caused by decreases in levels of estrogen and progesterone.^[74]

In some women, ovulation features a characteristic pain^[d] called mittelschmerz (a German term meaning middle pain). The cause of the pain is associated with the ruptured follicle, causing a small amount of blood loss.^[20]

Even when normal, the changes in hormone levels during the menstrual cycle can increase the incidence of disorders such as autoimmune diseases,^[81] which might be caused by estrogen enhancement of the immune system.^[4]

Around 40% of women with epilepsy find that their seizures occur more frequently at certain phases of their menstrual cycle. This catamenial epilepsy may be due to a drop in progesterone if it occurs during the luteal phase or around menstruation, or a surge in estrogen if it occurs at ovulation. Women who have regular periods can take medication just before and during menstruation. Options include progesterone supplements, increasing the dose of their regular anticonvulsant drug, or temporarily adding an anticonvulsant such as clobazam or acetazolamide. If this is ineffective, or when a woman's menstrual cycle is irregular, then treatment is to stop the menstrual cycle occurring. This may be achieved using medroxyprogesterone, triptorelin or goserelin, or by sustained use of oral contraceptives.^[82][83]

Hormonal contraception

Hormonal contraceptives prevent pregnancy by inhibiting the secretion of the hormones, FSH, LH and GnRH. Hormonal contraception that contains estrogen, such as

Most

1. Control of sperm-borne pathogens.[93]^[94][95] This hypothesis held that menstruation protected the uterus against pathogens introduced by sperm. Hypothesis 1 does not take into account that copulation can take place weeks before menstruation and that potentially infectious semen is not controlled by menstruation in other species.^[90]
2. Energy conservation.^[94][96] This hypothesis claimed that it took less energy to rebuild a uterine lining than to maintain it if pregnancy did not occur. Hypothesis 2 does not explain other species that also do not maintain a uterine lining but do not menstruate.^[90]
3. A theory based on spontaneous decidualization (a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy, in which the endometrium changes into the decidua). Decidualization leads to the development of the endothelium, which involves cells of the immune system,^[89] the formation of a new blood supply, hormones and tissue differentiation. In non-menstruating mammals, decidualization is driven by the embryo, not the mother.^[94] It evolved in some placental mammals because it confers advantages in that it allows females to prepare for pregnancy without needing a signal from the fetus.^[90] Hypothesis 3 defers to an explanation of the evolutionary origin of spontaneous decidualization and does not explain the evolution of menstruation alone.^[90]
4. Uterine pre-conditioning.^[97] This hypothesis claims that a monthly pre-conditioning of the uterus is needed in species, such as humans, that have deeply invasive (deep-rooted) placentas. In the process leading to the formation of a placenta, maternal tissues are invaded. This hypothesis holds that menstruation was not evolutionary, rather the result of a coincidental pre-conditioning of the uterus to protect uterine tissue from the deeply rooting placenta, in which a thicker endometrium develops.^[97] Hypothesis 4 does not explain menstruation in non-primates.^[90]

Notes

References