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Progesterone
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== Progesterone and Collagen == The existing medical literature presents conflicting data on the relationship between of female sex hormones and connective tissue, joint laxity and tendons. Much more research is needed, but we do know that these hormones are integral to changes in the tissues of the cervix, endometrium, and other parts of the female reproduction system, especially during pregnancy.<ref name="Mahendroo2017">{{Cite journal | last = Mahendroo | first = Mala | last2 = Iozzo | first2 = Renato | last3 = Myers | first3 = Kristin | last4 = Akins | first4 = Meredith | last5 = Yoshida | first5 = Kyoko | last6 = Nallasamy | first6 = Shanmugasundaram | date = 2017-04-01| title = Steroid Hormones Are Key Modulators of Tissue Mechanical Function via Regulation of Collagen and Elastic Fibers|url=https://academic.oup.com/endo/article/158/4/950/2991885|journal=Endocrinology|language=en|volume=158|issue=4 | pages = 950–962|doi=10.1210/en.2016-1930|issn=0013-7227}}</ref><ref name="Eeckhout1992">{{Cite journal | last = Eeckhout | first=Y. | last2 = Courtoy | first2 = P.J. | last3 = Donnez | first3 = J. | last4 = Marbaix | first4 = E. | date = 1992-12-15| title = Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants|url=https://www.pnas.org/content/89/24/11789|journal=Proceedings of the National Academy of Sciences|language=en|volume=89|issue=24|pages=11789–11793|doi=10.1073/pnas.89.24.11789|issn=0027-8424|pmid=1465400}}</ref> One study has shown progesterone had negative effect on ligament strength, measured by the higher likelihood of anterior cruciate ligament injury in female athletes following ovulation.<ref>{{Cite journal | last = Wojtys | first = Edward M. | last2 = Huston | first2 = Laura J. | last3 = Lindenfeld | first3 = Thomas N. | last4 = Hewett | first4 = Timothy E. | last5 = Greenfield | first5 = Mary Lou V.H. | date = 1998-09-01| title = Association Between the Menstrual Cycle and Anterior Cruciate Ligament Injuries in Female Athletes|url=https://doi.org/10.1177/03635465980260050301|journal=The American Journal of Sports Medicine|language=en|volume=26|issue=5 | pages = 614–619|doi=10.1177/03635465980260050301|issn=0363-5465}}</ref> Other studies support this finding.<ref>{{Cite journal | last = Deie | first = Masataka | last2 = Sakamaki | first2 = Yukie | last3 = Sumen | first3 = Yoshio | last4 = Urabe | first4 = Yukio | last5 = Ikuta | first5 = Yoshikazu | date = 2002-06-01| title = Anterior knee laxity in young women varies with their menstrual cycle|url=https://doi.org/10.1007/s00264-001-0326-0|journal=International Orthopaedics|language=en|volume=26|issue=3|pages=154–156|doi=10.1007/s00264-001-0326-0|issn=1432-5195|pmc = 3620888|pmid=12073107}}</ref> However, Miller et. al. have shown that "there is no effect of menstrual cycle phase, at rest or in response to an acute bout of exercise, on myofibrillar protein synthesis and muscle collagen synthesis in women."<ref>{{Cite journal | last = Miller | first=Benjamin F. | last2 = Hansen | first2 = Mette | last3 = Olesen | first3 = Jens L. | last4 = Flyvbjerg | first4 = Allan | last5 = Schwarz | first5 = Peter | last6 = Babraj | first6 = John A. | last7 = Smith | first7 = Kenneth | last8 = Rennie | first8 = Michael J. | last9 = Kjaer | first9 = Michael | date = 2006-01-01| title = No effect of menstrual cycle on myofibrillar and connective tissue protein synthesis in contracting skeletal muscle|url=https://www.physiology.org/doi/full/10.1152/ajpendo.00300.2005|journal=American Journal of Physiology-Endocrinology and Metabolism|volume=290|issue=1| pages = E163–E168|doi=10.1152/ajpendo.00300.2005|issn=0193-1849}}</ref> There is evidence that combined oral contraceptives (containing both estradiol and progestins) have an "inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I [insulin-like growth factor]."<ref>{{Cite journal | last = Hansen | first = M. | last2 = Miller | first2 = B.F. | last3 = Holm | first3 = L. | last4 = Doessing | first4 = S. | last5 = Petersen | first5 = S.G. |last6 = Skovgaard | first6 = D. | last7 = Frystyk | first7 = J. | last8 = Flyvbjerg | first8 = A. | last9 = Koskinen | first9 = S. | date = 2009-04-01| title = Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women|url=https://www.physiology.org/doi/full/10.1152/japplphysiol.90933.2008|journal=Journal of Applied Physiology|volume=106|issue=4|pages=1435–1443|doi=10.1152/japplphysiol.90933.2008|issn=8750-7587}}</ref> Estrogen and/or testosterone are believed to have a protective effect on collagen strength as skin ages.<ref>{{Cite journal | last = Cooper | first= D. | last2 = Magos | first2 = A. | last3 = Darby | first3 = A.J. | last4 = Studd | first4 = J.W. | last5 = Moniz | first5 = C.F. |last6 = Brincat | first6 = M. | date = 1983-11-05| title = Sex hormones and skin collagen content in postmenopausal women.|url=https://www.bmj.com/content/287/6402/1337|journal=Br Med J (Clin Res Ed)|language=en|volume=287|issue=6402|pages=1337–1338|doi=10.1136/bmj.287.6402.1337|issn=0007-1447|pmid=6416400}}</ref> The results of one analysis of 386 women with [[Hypermobile EDS|Hypermobility Type Ehlers Danlos Syndrome]] (hEDS), a connective tissue disorder, suggested that hEDS symptoms, including fatigue, improve with the administration of progestins. About one-third of the women reported a worsening of symptoms around menstruation (when both estrogen and progesterone are low).<ref name="PMC5020453">{{Cite journal | last = Hugon-Rodin | first = Justine | last2 = Lebègue | first2 = Géraldine | last3 = Becourt | first3 = Stéphanie | last4 = Hamonet | first4 = Claude | last5 = Gompel | first5 = Anne | date = 2016-09-13| title = Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study|url=https://doi.org/10.1186/s13023-016-0511-2|journal=Orphanet Journal of Rare Diseases|volume=11|issue=1|pages=124|doi=10.1186/s13023-016-0511-2|issn=1750-1172|pmc = PMC5020453|pmid=27619482}}</ref> The following two tables are from the aforementioned study: ==== Gynecological symptoms and prevalence of endometriosis==== {| class="wikitable" !Symptoms !''n'' (%) |- |Menorrhagia |292 (76) |- |Metrorrhagia |83 (22) |- |Dysmenorrhea |278 (72) |- |Deep dyspareuniea |118 (38) |- |Intromission dyspareuniea |148 (43) |- |Endometriosis |20 (6)<ref name="PMC5020453" /> |} ==== The influence of Hormones on hEDS Symptoms (hEDS Symptoms: Chronic Pain, Fatigue) ==== {| class="wikitable" !hEDS patients not influenced by menstruation ''n'' = 197 (%) !hEDS patients influenced by menstruation ''n'' = 133 (%) !''p'' |- |Influenced by puberty |85/197 (43.2) |79/133 (58.7) |- | colspan="3" |'''Impact of CHC*''' |- |Worsened on CHC |5/90 (5.6) |15/58 (25.9) |- |Improved on CHC |12/90 (13.3) |9/58 (15.5) |- |Unchanged on CHC |73/90 (81.1) |34/58 (58.6) |- |Improved by menopause |6/33 (18.2) |3/17 (17.7)<ref name="PMC5020453" /> |} <nowiki>*</nowiki>Combined hormonal contraceptives (estrogen and progestins)
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