Menstrual Cycles
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The menstrual cycle is a series of natural changes in
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
production and the structures of the
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
and
ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
of the
female reproductive system The female reproductive system is made up of the internal and external sex organs that function in the reproduction of new offspring. In humans, the female reproductive system is immature at birth and develops to maturity at puberty to be ...
that make
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
possible. The ovarian cycle controls the production and release of
eggs Humans and human ancestors have scavenged and eaten animal eggs for millions of years. Humans in Southeast Asia had domesticated chickens and harvested their eggs for food by 1,500 BCE. The most widely consumed eggs are those of fowl, especial ...
and the cyclic release of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
and
progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive an
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a
median In statistics and probability theory, the median is the value separating the higher half from the lower half of a data sample, a population, or a probability distribution. For a data set, it may be thought of as "the middle" value. The basic fe ...
length of 28 days, and continue for about 30–45 years. Naturally occurring hormones drive the cycles; the cyclical rise and fall of the
follicle stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
prompts the production and growth of
oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...
s (immature egg cells). The hormone estrogen stimulates the uterus lining (
endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...
) to thicken to accommodate an embryo should
fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
occur. The blood supply of the thickened lining provides
nutrient A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
s to a successfully implanted embryo. If implantation does not occur, the lining breaks down and blood is released. Triggered by falling progesterone levels,
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
(a "period", in common parlance) 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 (ovarian cycle) or in the uterus (uterine cycle). The ovarian cycle consists of the
follicular phase The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the estrous cycle (or, in primates for example, the menstrual cycle) during which follicles in the ovary mature from primary follicle to a ful ...
,
ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
, and the
luteal phase The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...
; 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 Menarche ( ; ) is the first menstrual cycle, or first menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fertility. Gir ...
(the onset of the first period) usually occurs around the age of twelve years. 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 Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms that cause significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptom ...
, and are experienced by 3–8% of women. During the first few days of menstruation some women experience
period pain Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in th ...
that can spread from the abdomen to the back and upper thighs. The menstrual cycle can be modified by
hormonal birth control Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origina ...
.


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 The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
, 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 phase The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...
s, and the uterine cycle consists of
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
, the proliferative phase, and the secretory phase. The menstrual cycle is controlled by the
hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
in the brain, and the
anterior pituitary gland A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
at the base of the brain. The hypothalamus releases
gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and release ...
(GnRH), which causes the nearby anterior pituitary to release
follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) and
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH). Before
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
, 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 In statistics and probability theory, the median is the value separating the higher half from the lower half of a data sample, a population, or a probability distribution. For a data set, it may be thought of as "the middle" value. The basic fe ...
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 Sexual reproduction is a type of reproduction that involves a complex life cycle in which a gamete ( haploid reproductive cells, such as a sperm or egg cell) with a single set of chromosomes combines with another gamete to produce a zygote tha ...
; the first period (called
menarche Menarche ( ; ) is the first menstrual cycle, or first menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fertility. Gir ...
) occurs at around 12 years of age and continues for about 30–45 years. Menstrual cycles end at
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
, 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 Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
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 An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...
, in an event called
ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
. After ovulation, the oocyte lives for 24 hours or less without
fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
, 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 Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
. Under the influence of progesterone, the uterine lining changes to prepare for potential implantation of an
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
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 An antral follicle, also known as Graafian follicle and tertiary follicle, is an ovarian follicle during a certain latter stage of folliculogenesis. Definitions differ in where the shift into an antral follicle occurs in the staging of follicul ...
(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 The corpus albicans (Latin for "whitening body"; also known as atretic corpus luteum, corpus candicans, or simply as albicans) is the regressed form of the corpus luteum. As the corpus luteum is being broken down by macrophages, fibroblasts lay d ...
, 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. Although the average length of the human menstrual cycle is similar to that of the
lunar cycle Concerning the lunar month of ~29.53 days as viewed from Earth, the lunar phase or Moon phase is the shape of the Moon's directly sunlit portion, which can be expressed quantitatively using areas or angles, or described qualitatively using the t ...
, there is no causal relation between the two.


Follicular phase

The ovaries contain a finite number of egg stem cells, granulosa cells and
theca cells In biology, a theca (plural thecae) is a sheath or a covering. Botany In botany, the theca is related to plant's flower anatomy. The theca of an angiosperm consists of a pair of microsporangia that are adjacent to each other and share a commo ...
, which together form primordial follicles. At around 20 weeks into
gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...
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 A polar body is a small haploid cell that is formed at the same time as an egg cell during oogenesis, but generally does not have the ability to be fertilized. It is named from its polar position in the egg. When certain diploid cells in animals ...
, 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 An antral follicle, also known as Graafian follicle and tertiary follicle, is an ovarian follicle during a certain latter stage of folliculogenesis. Definitions differ in where the shift into an antral follicle occurs in the staging of follicul ...
.
Meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...
(cell division) 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 Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) 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 :''Although the process is similar in many animals, this article will deal exclusively with human folliculogenesis.'' In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains a ...
, 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 Follicular atresia refers to the process in which a follicle fails to develop, thus preventing it from ovulating and releasing an egg. It is a normal, naturally occurring progression that occurs as mammalian ovaries age. Approximately 1% of mamma ...
.
Luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH) stimulates further development of the ovarian follicle. The follicle that reaches maturity is called an antral follicle, and it contains the
ovum The egg cell, or ovum (plural ova), is the female reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female gamete is ...
(egg cell). 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 Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...
. The estrogen inhibits further production of FSH and LH by the pituitary gland. This
negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...
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 Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
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 Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
, this occurs when a mature egg is released from the ovarian follicles into the
fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
, 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 Relaxin is a protein hormone of about 6000 Da first described in 1926 by Frederick Hisaw. The relaxin family peptide hormones belong to the insulin superfamily and consists of seven peptides of high structural but low sequence similarity; rela ...
(which relaxes the uterus by inhibiting contractions of the
myometrium The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells (also called uterine myocytes) but also of supporting stromal and vascular tissue. Its main function is to induce uterine contractions. Struc ...
), and
inhibin Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...
(which inhibits further secretion of FSH). 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 An immature ovum is a cell that goes through the process of oogenesis to become an ovum. It can be an oogonium, an oocyte, or an ootid. An oocyte, in turn, can be either primary or secondary, depending on how far it has come in its process of me ...
, which blocks the other
sperm cells A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromosomes, ...
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 twin Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
s. After release from the ovary, 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 An ampulla (; ) was, in Ancient Rome, a small round vessel, usually made of glass and with two handles, used for sacred purposes. The word is used of these in archaeology, and of later flasks, often handle-less and much flatter, for holy water or ...
, the widest section of the fallopian tubes. A
fertilized egg A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. In multicellula ...
immediately starts the process of
embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
. 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 The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
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 (the outer layer of the resulting embryo-containing blastocyst that later becomes the outer layer of the placenta) produces
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
(hCG), 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 The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
secretes high levels of these hormones – along with human chorionic gonadotropin (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.


Luteal phase

Lasting about 14 days, 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. 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. 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).


Uterine cycle

The uterine cycle has three phases: menses, proliferative and secretory.


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 average age is generally later in the
developing world A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
and earlier in the
developed world A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
. In
precocious puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of childr ...
, it can occur as early as age eight years, and this can still be normal. Menstruation is initiated each month by falling levels of estrogen and progesterone and the release of
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
s, which constrict the
spiral arteries Spiral arteries are small arteries which temporarily supply blood to the endometrium of the uterus during the luteal phase of the menstrual cycle. In histology, identifying the presence of these arteries is one of the most useful techniques in i ...
. This causes them to
spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...
, contract and break up. The blood supply to the endometrium is cut off and the cells of the top layer of the endometrium (the stratum functionalis) become deprived of oxygen and die. Later the whole layer is lost and only the bottom layer, the stratum basalis, is left in place. An
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
called
plasmin Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...
breaks up the
blood clots A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...
in the menstrual fluid, which eases the flow of blood and broken down lining from the uterus. The flow of blood continues for 2–6 days and around 30–60
milliliters The litre (international spelling) or liter (American English spelling) (SI symbols L and l, other symbol used: ℓ) is a metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic centimetres (cm3) or 0.001 cubic metre (m3) ...
of blood is lost, and is a sign that pregnancy has not occurred. The flow of blood normally serves as a sign that a woman has not become pregnant, but this cannot be taken as certainty, as several factors can cause bleeding during pregnancy. Menstruation occurs on average once a month from menarche to menopause, which corresponds with a woman's fertile years. The average age of menopause in women is 52 years, and it typically occurs between 45 and 55 years of age. Menopause is preceded by a stage of hormonal changes called
perimenopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
. ''Eumenorrhea'' denotes normal, regular menstruation that lasts for around the first 5 days of the cycle. Women who experience
menorrhagia Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding Abnormal uterine bleeding (AUB), also known as (AVB) or as atypical ...
(heavy menstrual bleeding) are more susceptible to
iron deficiency Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key ...
than the average person.


Proliferative phase

The proliferative phase is the second phase of the uterine cycle when estrogen causes the lining of the uterus to grow and proliferate. The latter part of the follicular phase overlaps with the proliferative phase of the uterine cycle. As they mature, the ovarian follicles secrete increasing amounts of
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
, an estrogen. The estrogens initiate the formation of a new layer of endometrium in the uterus with the spiral arterioles. As estrogen levels increase, cells in the cervix produce a type of cervical mucus that has a higher pH and is less
viscous The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the inter ...
than usual, rendering it more friendly to sperm. This increases the chances of fertilization, which occurs around day 11 to day 14. This cervical mucus can be detected as a vaginal discharge that is copious and resembles raw egg whites. For women who are practicing
fertility awareness Fertility awareness (FA) refers to a set of practices used to determine the fertile and infertile phases of a woman's menstrual cycle. Fertility awareness methods may be used to avoid pregnancy, to achieve pregnancy, or as a way to monitor gynec ...
, it is a sign that ovulation may be about to take place, but it does not mean ovulation will definitely occur.


Secretory phase

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 The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
(a fertilized egg, which has begun to grow).
Glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...
,
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s, and
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s are secreted into the uterus and the cervical mucus thickens. In early pregnancy progesterone also increases blood flow and reduces the
contractility Contractility refers to the ability for self-contraction, especially of the muscles or similar active biological tissue *Contractile ring in cytokinesis *Contractile vacuole *Muscle contraction **Myocardial contractility *See contractile cell for ...
of the
smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
in the uterus and raises the woman's basal body temperature. If pregnancy does not occur the ovarian and uterine cycles start over again.


Anovulatory cycles and short luteal phases

Only two-thirds of overtly normal menstrual cycles are ovulatory, that is, cycles in which ovulation occurs. The other third lack ovulation or have a short luteal phase (less than ten days) in which progesterone production is insufficient for normal physiology and fertility. Cycles in which ovulation does not occur (
anovulation Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovula ...
) 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. Anovulatory cycles are often overtly identical to normally ovulatory cycles. 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 Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...
. 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.


Menstrual health

Although a normal and natural process, some women experience premenstrual syndrome with symptoms that may include
acne Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...
, tender breasts, and tiredness. More severe symptoms that affect daily living are classed as
premenstrual dysphoric disorder Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms that cause significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptom ...
and are experienced by 3 to 8% of women.
Dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...
(menstrual cramps or period pain) is felt as painful cramps in the abdomen that can spread to the back and upper thighs during the first few days of menstruation. Debilitating period pain is not normal and can be a sign of something severe such as
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
. These issues can significantly affect a woman's health and quality of life and timely interventions can improve the lives of these women. 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. 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. Changes to the brain have also been observed throughout the menstrual cycle but do not translate into measurable changes in intellectual achievement – including academic performance, problem-solving, memory, and creativity. Improvements in spatial reasoning ability during the menstruation phase of the cycle are probably caused by decreases in levels of estrogen and progesterone. In some women, ovulation features a characteristic pain called ''
mittelschmerz ''Mittelschmerz'' (German: "middle pain") is a colloquial term for "ovulation pain" or "midcycle pain". About 20% of women experience mittelschmerz, some every cycle, some intermittently. Signs and symptoms Mittelschmerz is characterized by lo ...
'' (a German term meaning ''middle pain''). The cause of the pain is associated with the ruptured follicle, causing a small amount of blood loss. Even when normal, the changes in hormone levels during the menstrual cycle can increase the incidence of disorders such as
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s, which might be caused by estrogen enhancement of the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
. Around 40% of women with
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
find that their
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s 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 Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
drug, or temporarily adding an anticonvulsant such as
clobazam Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselec ...
or
acetazolamide Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), urine alkal ...
. 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 Medroxyprogesterone (MP), is a progestin which is not used medically. A derivative, medroxyprogesterone acetate (MPA), is used as a medication in humans, and is far more widely known in comparison. ''Medroxyprogesterone'' is sometimes used as a ...
,
triptorelin Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is a ...
or
goserelin Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast and prostate cancer. It is an injectable gon ...
, or by sustained use of oral contraceptives.


Hormonal contraception

Hormonal contraceptives prevent pregnancy by inhibiting the secretion of the hormones, FSH, LH and GnRH. Hormonal contraception that contains estrogen, such as
combined oral contraceptive pills The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progesti ...
(COCPs), stop the development of the dominant follicle and the mid-cycle LH surge and thus ovulation. Sequential dosing and discontinuation of the COCP can mimic the uterine cycle and produce bleeding that resembles a period. In some cases, this bleeding is lighter. Progestin-only methods of hormonal contraception do not always prevent ovulation but instead work by stopping the cervical mucus from becoming sperm-friendly. Hormonal contraception is available in a variety of forms such as pills, patches, skin implants and hormonal intrauterine devices (IUDs).


Evolution and other species

Most
female mammals Female (symbol: ♀) is the sex of an organism that produces the large non-motile ova (egg cells), the type of gamete (sex cell) that fuses with the male gamete during sexual reproduction. A female has larger gametes than a male. Females ...
have an
estrous cycle The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestrous p ...
, but only ten primate species, four
bat Bats are mammals of the order Chiroptera.''cheir'', "hand" and πτερόν''pteron'', "wing". With their forelimbs adapted as wings, they are the only mammals capable of true and sustained flight. Bats are more agile in flight than most ...
species, the
elephant shrew Elephant shrews, also called jumping shrews or sengis, are small insectivorous mammals native to Africa, belonging to the family Macroscelididae, in the order Macroscelidea. Their traditional common English name "elephant shrew" comes from a perc ...
s and the spiny mouse species Cairo spiny mouse (''Acomys cahirinus'') have a
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 make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
. The cycles are the same as in humans apart from the length, which ranges from 9 to 37 days. The lack of immediate relationship between these groups suggests that four distinct evolutionary events have caused menstruation to arise. In species that have a menstrual cycle, ovulation is not obvious to potential mates and there is no
mating season Seasonal breeders are animal species that successfully mate only during certain times of the year. These times of year allow for the optimization of survival of young due to factors such as ambient temperature, food and water availability, and ch ...
. There are four theories on the evolutionary significance of menstruation: Se
BBC Earth lay summary
20 April 2015.
# Control of sperm-borne pathogens. This hypothesis held that menstruation protected the uterus against
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
s introduced by
sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
. Hypothesis 1 does not take into account that
copulation Sexual intercourse (or coitus or copulation) is a sexual activity typically involving the insertion and thrusting of the penis into the vagina for sexual pleasure or reproduction.Sexual intercourse most commonly means penile–vaginal penetra ...
can take place weeks before menstruation and that potentially infectious
semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Semen i ...
is not controlled by menstruation in other species. # Energy conservation. 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. # A theory based on spontaneous
decidualization Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy. This includes morphological and functional changes (the decidual reaction) to endometrial stromal cells (ESCs), ...
(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 The decidua is the modified mucosal lining of the uterus (that is, modified endometrium) that forms every month, in preparation for pregnancy. It is shed off each month when there is no fertilised egg to support. The decidua is under the influ ...
). Decidualization leads to the development of the
endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...
, which involves cells of the immune system, the formation of a new blood supply, hormones and tissue differentiation. In non-menstruating mammals, decidualization is driven by the embryo, not the mother. 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. Hypothesis 3 defers to an explanation of the evolutionary origin of spontaneous decidualization and does not explain the evolution of menstruation alone. # Uterine pre-conditioning. This hypothesis claims that a monthly pre-conditioning of the uterus is needed in species, such as humans, that have deeply invasive (deep-rooted)
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
s. 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. Hypothesis 4 does not explain menstruation in non-primates.


Notes


References


Book sources

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External links

{{Authority control Menstrual cycle Human female endocrine system Midwifery Periodic phenomena Women's health Human female reproductive system