Editing Menstrual cycle (section)

=== Ovarian cycle ===
Between menarche and menopause the ovaries regularly alternate between luteal and follicular phases during the monthly menstrual cycle.{{sfn | Sherwood | 2016 | p=741}} 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,<ref name= Reed2018>{{cite journal |vauthors= Reed BF, Carr BR, Feingold KR, et al |title= The Normal Menstrual Cycle and the Control of Ovulation |journal= Endotext |date= 2018 |pmid= 25905282 |url= https://www.ncbi.nlm.nih.gov/books/NBK279054/?report=classic |type= Review |access-date= 8 January 2021 |archive-date= 28 May 2021 |archive-url=https://web.archive.org/web/20210528022539/https://www.ncbi.nlm.nih.gov/books/NBK279054/?report=classic |url-status= live }}</ref> the dominant follicle releases an [[oocyte]], in an event called [[ovulation]].{{sfn | Sherwood | 2016 | p=747}}

After ovulation, the oocyte lives for 24 hours or less without [[Human fertilization|fertilization]],{{sfn|Tortora|2017|p=957}} 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]].{{sfn|Tortora|2017|p=929}}{{efn|Progesterone levels exceed those of estrogen (estradiol) by a hundred-fold.{{sfn|Prior|2020|p=41}}}} Under the influence of progesterone, the uterine lining changes to prepare for potential [[Implantation (embryology)|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.{{sfn|Tortora|2017|pp=942–946}}

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.{{sfn|Prior|2020|p=45}} Although the average length of the human menstrual cycle is similar to that of the [[lunar cycle]], there is [[Lunar effect|no causal relation]] between the two.{{sfn|Norris|Carr|2013|p= [https://books.google.com/books?id=F_NaW1ZcSSAC&pg=PA361 361]}}

==== Follicular phase ====
{{main|Follicular phase}}
The ovaries contain a finite number of [[Oogonium|egg stem cells]], [[granulosa cells]] and [[Theca of follicle|theca cells]], which together form primordial follicles.{{sfn|Tortora|2017|p=929}} At around 20 weeks into [[gestation]] some 7 million immature eggs have already formed in an ovary. This decreases to around 2&nbsp;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.{{sfn | Ugwumadu | 2014 | p=115}} Beginning at puberty, these mature to primary follicles independently of the menstrual cycle.{{sfn | Watchman | 2020 | p=8}}  The development of the egg is called [[oogenesis]] and only one cell survives the [[Prophase#Meiotic prophase|divisions]] to await fertilization. The other cells are discarded as [[polar body|polar bodies]], which cannot be fertilized.<ref name="pmid21268179">{{cite journal |vauthors=Schmerler S, Wessel GM |title=Polar bodies – more a lack of understanding than a lack of respect |journal=Molecular Reproduction and Development |volume=78 |issue=1 |pages=3–8 |date=January 2011 |pmid=21268179 |pmc=3164815 |doi=10.1002/mrd.21266 |type= Review}}</ref> The follicular phase is the first part of the ovarian cycle and it ends with the completion of the [[antral follicles]].{{sfn | Sherwood | 2016 | p=741}} [[Meiosis]] (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.{{sfn | Tortora | 2017 | p=945}} 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.{{sfn | Tortora | 2017 | pp=942–946}}

Through the influence of a rise in [[follicle stimulating hormone]] (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]], 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]].{{sfn|Johnson|2007|page=86}} [[Luteinizing hormone]] (LH) stimulates further development of the ovarian follicle. The follicle that reaches maturity is called an antral follicle, and it contains the [[ovum]] (egg cell).{{sfn|Tortora|2017|p=942}}

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.{{sfn | Watchman | 2020 | p=8}}{{sfn | Sherwood | 2016 | p=745}}

==== Ovulation ====
{{main|Ovulation}}
[[File:ovulation.jpg|thumb|An ovary about to release an egg]]
Around day fourteen, the egg is released from the ovary.{{sfn | Tortora | 2017 | p=943}}  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.<ref name= Reed2018/> Typically only one of the 15–20 stimulated follicles reaches full maturity, and just one egg is released.{{sfn | Sadler | 2019 | p=48}} 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.{{sfn|Tortora|2017|p=953}} LH initiates ovulation at around day 14 and stimulates the formation of the corpus luteum.{{sfn|Tortora|2017|p=944}} Following further stimulation by LH, the corpus luteum produces and releases estrogen, progesterone, [[relaxin]] (which relaxes the uterus by inhibiting contractions of the [[myometrium]]), and [[inhibin]] (which inhibits further secretion of FSH).{{sfn|Tortora|2017|p=920}}

The release of LH matures the egg and weakens the follicle wall in the ovary, causing the fully developed follicle to release its oocyte.{{sfn | Sherwood | 2016 | p=746}} If it is fertilized by a sperm, the oocyte promptly matures into an [[ootid]], which blocks the other [[spermatozoa|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 {{cvt|0.1|mm}},<ref>{{Cite book| vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |date=2002|chapter=Eggs|title=Molecular Biology of the Cell|edition=4th|isbn=0-8153-3218-1|chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK26842/ |location=New York|publisher=Garland Science |access-date=25 February 2021 |archive-date=16 December 2019 |archive-url= https://web.archive.org/web/20191216042524/https://www.ncbi.nlm.nih.gov/books/NBK26842/ |url-status=live}}</ref> and is the largest human cell.<ref name="pmid30739329">{{cite journal | vauthors = Iussig B, Maggiulli R, Fabozzi G, Bertelle S, Vaiarelli A, Cimadomo D, Ubaldi FM, Rienzi L | title = A brief history of oocyte cryopreservation: Arguments and facts | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 98 | issue = 5 | pages = 550–558 | date = May 2019 | pmid = 30739329 | doi = 10.1111/aogs.13569 | type = Review | doi-access = free }}</ref>

Which of the two ovaries – left or right – ovulates appears random;{{sfn | Parker | 2019 | p=283}} no left and right coordinating process is known.{{sfn|Johnson|2007|pp=192–193}} Occasionally both ovaries release an egg; if both eggs are fertilized, the result is [[fraternal twin]]s.{{sfn|Johnson|2007|p=192}} After release from the ovary into the pelvic cavity, the egg is swept into the fallopian tube by the [[Fimbria (female reproductive system)|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.{{sfn | Sadler | 2019 | p=36}}

Fertilization usually takes place in the [[Ampulla of uterine tube|ampulla]], the widest section of the fallopian tubes. A [[Zygote|fertilized egg]] immediately starts the process of [[Human embryonic development|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.{{sfn | Tortora | 2017 | p=959}} 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]] (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]] secretes high levels of these hormones – along with hCG, which stimulates the corpus luteum to secrete more progesterone and estrogens, blocking the menstrual cycle.{{sfn|Tortora|2017|page=976}} These hormones also prepare the mammary glands for milk{{efn|[[Breastfeeding]] women can experience complete suppression of follicular development, follicular development but no ovulation, or resumption of normal menstrual cycles.<ref name="pmid25869631">{{cite journal |vauthors=Carr SL, Gaffield ME, Dragoman MV, Phillips S |title=Safety of the progesterone-releasing vaginal ring (PVR) among lactating women: A systematic review |journal=Contraception |volume=94 |issue=3 |pages=253–261 |date=September 2016 |pmid=25869631 |doi=10.1016/j.contraception.2015.04.001 |doi-access=free |type= Review}}</ref>}} production.{{sfn|Tortora|2017|page=976}}

==== Luteal phase ====
{{main|Luteal phase}}
Lasting about 14 days,<ref name="Reed2018" /> 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.{{sfn|Johnson|2007|page=91}}{{efn|In the corpus luteum, [[cholesterol side-chain cleavage enzyme]] converts [[cholesterol]] to [[pregnenolone]], which is converted to progesterone.<ref name="pmid22201776">{{cite journal |vauthors=King SR, LaVoie HA |title=Gonadal transactivation of STARD1, CYP11A1 and HSD3B |journal=Frontiers in Bioscience (Landmark Edition) |volume=17 |issue= 3|pages=824–846 |date=January 2012 |pmid=22201776 |doi=10.2741/3959 |doi-access=free }}</ref>}} 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.{{sfn | Ugwumadu | 2014 | p=117}} Falling levels of progesterone trigger menstruation and the beginning of the next cycle. 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).{{sfn | Tortora | 2017 | pp=942–946}}