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 anatomy of the uterus the uterine cycle has three phases: menses, proliferative and secretory. menstruation main article: 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 and earlier in the developed world. in precocious puberty, 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 prostaglandins, which constrict the spiral arteries. this causes them to spasm, 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 called plasmin breaks up the blood clots 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 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. eumenorrhea denotes normal, regular menstruation that lasts for around the first 5 days of the cycle. women who experience menorrhagia (heavy menstrual bleeding) are more susceptible to iron deficiency than the average person. proliferative phase during the menstrual cycle, levels of estradiol (an estrogen) vary by 200 percent. levels of progesterone vary by over 1200 percent. 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, 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 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, 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 (a fertilized egg, which has begun to grow). glycogen, lipids, and proteins are secreted into the uterus and the cervical mucus thickens. in early pregnancy, progesterone also increases blood flow and reduces the contractility of the smooth muscle 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 main article: anovulation 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) 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. 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 a human primary ovarian follicle viewed by microscopy. the round oocyte stained red in the center is surrounded by a layer of granulosa cells, which are enveloped by the basement membrane and theca cells. the magnification is around 1000 times. (h&e stain) although a normal and natural process, some women experience premenstrual syndrome with symptoms that may include acne, tender breasts, and tiredness. more severe symptoms that affect daily living are classed as premenstrual dysphoric disorder and are experienced by 3 to 8% of women. dysmenorrhea (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. 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 (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 diseases, which might be caused by estrogen enhancement of the immune system. 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. hormonal contraception main article: 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 (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 have an estrous cycle, but only ten primate species, four bat species, the elephant shrews and the cairo spiny mouse (acomys cahirinus) have a menstrual cycle. 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. there are four theories on the evolutionary significance of menstruation: control of sperm-borne pathogens. 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. 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 (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, 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) 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. hypothesis 4 does not explain menstruation in non-primates. notes progesterone levels exceed those of estrogen (estradiol) by a hundred-fold. breastfeeding women can experience complete suppression of follicular development, follicular development but no ovulation, or resumption of normal menstrual cycles. in the corpus luteum, cholesterol side-chain cleavage enzyme converts cholesterol to pregnenolone, which is converted to progesterone. uncharacteristic mid-cycle pain may be caused by medical conditions such as ectopic pregnancy or ruptured ovarian cyst or may be confused with appendicitis.