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Progesterone
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== Role in the Menstrual Cycle == === Cycle Overview === ==== Follicular Phase ==== At the beginning of a woman's cycle, the hypothalamus begins to secrete Gonadotropin Releasing Hormone (GnRH), stimulating the pituitary to create Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), which travel to the ovaries. FSH causes follicles in the ovaries to begin to mature. Several follicles, each of which stores an egg, begin to grow as they mature, and in the process release estrogen. This [[estrogen]] produces a negative feedback during the first 10 days of the cycle that tells to the pituitary to inhibit the release of LH. It is important to note that ''low'' levels of estrogen will inhibit the release of LH from the [[Pituitary gland|pituitary]], while ''high'' levels will stimulate it. ==== Ovulation ==== As estrogen continues to rise due to the maturing follicles, it also causes FSH levels to fall steadily (''low'' estrogen levels trigger the release of FSH). Around day 10 of the cycle, estrogen levels reach a threshold which stops the negative feedback of LH and begins a positive one resulting in the secretion of LH by the pituitary. The resulting spike in LH triggers the most mature follicle to release an egg (or oocyte); this is called ovulation. ==== Luteal Phase ==== After ovulation, the empty follicle will begin to die. This dying follicle is called a corpus luteum. As the corpus luteum degrades, it secretes three hormones: estrogen, inhibin, and progesterone. Inhibin provides a negative feedback to the pituitary to suppress the production of FSH. Progesterone provides a similar feedback to prohibit the release of GnRH, which in turn decreases the levels of LH and FSH. It also stimulates endometrial growth (the interior lining of the uterus). As the corpus luteum degenerates, it will secrete fewer and fewer hormones, and progesterone, estrogen, and inhibin will steadily decrease. In the absence of fertilization, the decreasing levels of progesterone can no longer maintain the lining of the uterine wall, so the wall dies and sheds out of the body, resulting in menstruation. This decrease in progesterone also allows for the secretion of GnRH to begin again, and the cycle repeats. Progesterone only exists in high levels during the second half of the menstrual cycle, the Luteal Phase.<ref>{{Cite book | last = Reed | first=Beverly G. | last2 = Carr | first2 = Bruce R. | date = 2000 | editor-last=Feingold |editor-first = Kenneth R.|editor2-last=Anawalt|editor2-first=Bradley|editor3-last=Boyce |editor3-first=Alison|editor4-last=Chrousos|editor4-first=George|editor5-last=Dungan |editor5-first = Kathleen|editor6-last=Grossman|editor6-first=Ashley|editor7-last=Hershman|editor7-first=Jerome M.|editor8-last=Kaltsas|editor8-first=Gregory|editor9-last=Koch|editor9-first = Christian| title = The Normal Menstrual Cycle and the Control of Ovulation|url=http://www.ncbi.nlm.nih.gov/books/NBK279054/|location=South Dartmouth (MA)|publisher=MDText.com, Inc.|pmid=25905282}}</ref> In the absence of fertilization, the corpus luteum will last for 11 to 17 days; it is during these days a woman can expect progesterone levels to be highest. ===Exogenous Progesterone, Preventing Ovulation, and Contraceptives === Many contraceptives use [[progestin]]s (synthetic progesterone) to prevent ovulation. They can also prevent pregnancy by thickening the cervical mucus, which blocks sperm from entering the uterus, and thinning the lining of the uterine wall, which prevents implantation of a fertilized egg (although endogenous progesterone helps to ''thicken'' this lining, the slightly different structure of some progestins results in the opposite effect). The most common form of birth control, combined oral contraceptive pills, also simply called "The Pill," uses progestins and estrogen to prevent pregnancy. ====How Progestins & Progesterone Prevent Ovulation ==== The chemical process by which progesterone and progestins prevent ovulation centers around their ability in the Follicular Phase to stop the release of Luteinizing Hormone (LH) by the anterior pituitary. Progesterone/progestins naturally create a negative feedback to the Hypothalamus, causing the latter to inhibit the release of Gonadotropin Releasing Hormone (GnRH). Without enough GnRH to stimulate the release of LH from the pituitary, LH levels will not spike as they usually do around day 13-14 in the cycle, and ovulation will not occur. ==== Endogenous Progesterone Levels in Luteal Phase when Ovulation Fails ==== This failure to ovulates means no follicle will release an egg and degrade into a corpus luteum. The corpus luteum (CL), or dying follicle, is the main source of endogenous progesterone in the female cycle, therefore without the CL, endogenous progesterone levels will remain low during the second half of the cycle. Women taking either progestins or exogenous bio-identical progesterone at certain levels should be aware that this process halting the production of endogenous progesterone may be taking place, especially for those trying to conceive and because this hormone plays an important role not only in reproduction, but in the brain as well (see "[[#Progesterone_in_the_Brain|Progesterone in the Brain]]" below). There is currently no research suggesting universally "safe" levels of exogenous bio-identical progesterone doses that will not prevent ovulation from occurring. The hormone feedback loops that are integral to the female cycle are incredibly complex and sensitive, and exogenous progesterone is metabolized at different rates in different females. These factors make ovulation-safe levels very difficult to predict.
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