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Progesterone
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=== Progesterone as a Neurosteroid === Progesterone not only plays a major role in female reproduction, but has many other important roles in both males and females. One such role is as a powerful [[neurosteroid]]. Neurosteroids are steroids synthesized in the brain that regulate the excitability of [[Neuron|neurons]]. It has been shown to be important in [[myelin]] repair in rodents in the sciatic nerve. In this study, the administration of progesterone to the site of brain lesions led to the regeneration of new myelin sheaths.<ref>{{Cite journal | last = Baulieu | first = E. | last2 = Schumacher | first2 = M. | date = Oct 2000| title = Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination|url=https://www.ncbi.nlm.nih.gov/pubmed/11108866|journal=Steroids|volume=65|issue=10-11 | pages = 605–612|issn=0039-128X|pmid=11108866}}</ref> Neurosteroids can have powerful effects on both pain perception and inflammation, and research has suggested that female sex hormones like progesterone play a key role in modulating chronic pain.<ref>{{Cite journal | last = Kuba | first=Tzipora | last2 = Quinones-Jenab | first2 = Vanya | date = 2005-08-15| title = The role of female gonadal hormones in behavioral sex differences in persistent and chronic pain: clinical versus preclinical studies|url=https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16023915|journal=Brain Research Bulletin|volume=66|issue=3|pages=179–188|doi=10.1016/j.brainresbull.2005.05.009|issn=0361-9230|pmid=16023915}}</ref><ref>{{Cite journal | last = Riley | first = Joseph | last2 = Robinson | first2 = Michael | last3 = Wise | first3 = Emily | last4 = Myers | first4 = Cynthia | last5 = Fillingim | first5 = Roger | date = Jan 1998| title = Sex differences in the perception of noxious experimental stimuli: a meta-analysis|url=http://insights.ovid.com/|journal=Pain|language=ENGLISH|volume=74|issue=2-3|pages=181–187|doi=10.1016/S0304-3959(97)00199-1|issn=0304-3959|pmid=9520232}}</ref> Progesterone has been shown in mice to prevent neurodegeneration, increase muscle strength, and enhance respiratory activity. The same study showed that progesterone blocked pro-inflammatory mediators, lessened Iba1+ microglial cells, and decreased symptoms of brain inflammation in mice. It also reduced the production of [[nitric oxide]] and [[TNF-α]].<ref name="Nicola2013" /> Progesterone is neuroprotective, anti-inflammatory, and promyelinating, and could present great benefits for neurological illnesses. However, other studies have shown higher progesterone levels predict worse outcomes for traumatic brain injury in human females.<ref>{{Cite journal | last = Wunderle | first = Kathryn | last2 = Hoeger | first2 = Kathleen M. | last3 = Wasserman | first3 = Erin | last4 = Bazarian | first4 = Jeffrey J.| date = 2014 | title = Menstrual Phase as Predictor of Outcome After Mild Traumatic Brain Injury in Women|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237582/|journal=The Journal of head trauma rehabilitation|volume=29|issue=5| pages = E1–E8|doi=10.1097/HTR.0000000000000006|issn=0885-9701|pmc=5237582|pmid=24220566}}</ref> In the conclusion of a 2018 survey of literature related to neurosteroids, Del Río et. al. wrote the following:<blockquote>"The present review shows that fluctuations in steroid hormones, influenced by factors such as age and health status, have consequences at the level of CNS [central nervous system] and PNS [peripheral nervous system]. Utilizing both classical and non-classical pathways, neurosteroids participate in the physiological regulation of neurogenesis, neuronal survival, synaptic function, and myelin formation, thus influencing neuronal plasticity. Because of these effects, neurosteroids will have different modulatory actions, exerting control over mood, cognition, and behavior. Additionally, they have a neuroprotective role in relation to certain neurocognitive pathologies."<ref>{{Cite journal | last = Del Río | first = Juan Pablo | last2 = Alliende | first2 = María I. | last3 = Molina | first3 = Natalia | last4 = Serrano | first4 = Felipe G. | last5 = Molina | first5 = Santiago | last6 = Vigil | first6 = Pilar | date = 2018-05-23| title = Steroid Hormones and Their Action in Women's Brains: The Importance of Hormonal Balance|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974145/|journal=Frontiers in Public Health|volume=6|doi=10.3389/fpubh.2018.00141|issn=2296-2565|pmc=5974145|pmid=29876339}}</ref></blockquote>
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