Menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eggs and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus to receive an embryo. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a median length of 28 days. Menarche usually occurs around the age of 12 years; menstrual cycles continue for about 30–45 years.
Naturally occurring hormones drive the cycles; the cyclical rise and fall of the follicle stimulating hormone prompts the production and growth of oocytes. The hormone estrogen stimulates the uterus lining to thicken to accommodate an embryo should fertilization occur. The blood supply of the thickened lining provides nutrients to a successfully implanted embryo. If implantation does not occur, the lining breaks down and blood is released. Triggered by falling progesterone levels, menstruation is the cyclical shedding of the lining, and is a sign that pregnancy has not occurred.
Each cycle occurs in phases based on events either in the ovary or in the uterus. 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 5 days. Around day fourteen, an egg is usually released from the ovary.
The menstrual cycle can cause some women to experience premenstrual syndrome with symptoms that may include tender breasts, and tiredness. More severe symptoms that affect daily living are classed as premenstrual dysphoric disorder, and are experienced by 3–8% of women. During the first few days of menstruation some women experience period pain that can spread from the abdomen to the back and upper thighs. The menstrual cycle can be modified by hormonal birth control.
Cycles and phases
The menstrual cycle encompasses the ovarian and uterine cycles. The ovarian cycle describes changes that occur in the follicles of the ovary, whereas the uterine cycle describes changes in the endometrial lining of the uterus. Both cycles can be divided into phases. The ovarian cycle consists of alternating follicular and luteal phases, and the uterine cycle consists of the menstrual phase, the proliferative phase, and the secretory phase. The menstrual cycle is controlled by the hypothalamus in the brain, and the anterior pituitary gland at the base of the brain. The hypothalamus releases gonadotropin-releasing hormone, which causes the nearby anterior pituitary to release follicle-stimulating hormone and luteinizing hormone. Before puberty, GnRH is released in low steady quantities and at a steady rate. After puberty, GnRH is released in large pulses, and the frequency and magnitude of these determine how much FSH and LH are produced by the pituitary.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. The cycle is often less regular at the beginning and end of a woman's reproductive life. At puberty, a child's body begins to mature into an adult body capable of sexual reproduction; the first period occurs at around 12 years of age and continues for about 30–45 years. Menstrual cycles end at menopause, which is usually between 45 and 55 years of age.
Ovarian cycle
Between menarche and menopause the ovaries regularly alternate between luteal and follicular phases during the monthly menstrual cycle. 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, the dominant follicle releases an oocyte, in an event called ovulation.After ovulation, the oocyte lives for 24 hours or less without fertilization, 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. 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 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.
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 average length of the human menstrual cycle is similar to that of the lunar cycle. Some studies have suggested that the menstrual cycle is synchronized with the lunar cycle, though the mainstream view is that they are unrelated.
Follicular phase
The ovaries contain a finite number of egg stem cells, granulosa cells and theca cells, which together form primordial follicles. At around 20 weeks into gestation some 7 million immature eggs have already formed in an ovary. This decreases to around 2 million by the time a girl is born, and 300,000 by the time she has her first period. On average, one egg matures and is released during ovulation each month after menarche. Beginning at puberty, these mature to primary follicles independently of the menstrual cycle. The development of the egg is called oogenesis and only one cell survives the divisions to await fertilization. The other cells are discarded as polar bodies, which cannot be fertilized. The follicular phase is the first part of the ovarian cycle and it ends with the completion of the antral follicles. Meiosis remains incomplete in the egg cells until the antral follicle is formed. During this phase usually only one ovarian follicle fully matures and gets ready to release an egg. The follicular phase shortens significantly with age, lasting around 14 days in women aged 18–24 compared with 10 days in women aged 40–44.Through the influence of a rise in follicle stimulating hormone during the first days of the cycle, a few ovarian follicles are stimulated. These follicles, which have been developing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. All but one of these follicles will stop growing, while one dominant follicle – the one that has the most FSH receptors – will continue to maturity. The remaining follicles die in a process called follicular atresia. Luteinizing hormone stimulates further development of the ovarian follicle. The follicle that reaches maturity is called an antral follicle, and it contains the ovum.
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.
Ovulation
Around day fourteen, the egg is released from the ovary. Called ovulation, this occurs when a mature egg is released from the ovarian follicles into the pelvic cavity and enters the fallopian tube, about 10–12 hours after the peak in LH surge. Typically only one of the 15–20 stimulated follicles reaches full maturity, and just one egg is released. Ovulation only occurs in around 10% of cycles during the first two years following menarche, and by the age of 40–50, the number of ovarian follicles is depleted. LH initiates ovulation at around day 14 and stimulates the formation of the corpus luteum. Following further stimulation by LH, the corpus luteum produces and releases estrogen, progesterone, relaxin, and inhibin.The release of LH matures the egg and weakens the follicle wall in the ovary, causing the fully developed follicle to release its oocyte. If it is fertilized by a sperm, the oocyte promptly matures into an ootid, which blocks the other sperm cells and becomes a mature egg. If it is not fertilized by a sperm, the oocyte degenerates. The mature egg has a diameter of about, and is the largest human cell.
Which of the two ovaries – left or right – ovulates appears random; no left and right coordinating process is known. Occasionally both ovaries release an egg; if both eggs are fertilized, the result is fraternal twins. After release from the ovary into the pelvic cavity, the egg is swept into the fallopian tube by the fimbria – a fringe of tissue at the end of each fallopian tube. After about a day, an unfertilized egg disintegrates or dissolves in the fallopian tube, and a fertilized egg reaches the uterus in three to five days.
Fertilization usually takes place in the ampulla, the widest section of the fallopian tubes. A fertilized egg immediately starts the process of embryonic development. The developing embryo takes about three days to reach the uterus, and another three days to implant into the endometrium. It has reached the blastocyst stage at the time of implantation: this is when pregnancy begins. The loss of the corpus luteum is prevented by fertilization of the egg. The syncytiotrophoblast produces human chorionic gonadotropin, which is very similar to LH and preserves the corpus luteum. During the first few months of pregnancy, the corpus luteum continues to secrete progesterone and estrogens at slightly higher levels than those at ovulation. After this and for the rest of the pregnancy, the placenta secretes high levels of these hormones – along with hCG, which stimulates the corpus luteum to secrete more progesterone and estrogens, blocking the menstrual cycle. These hormones also prepare the mammary glands for milk production.