Noretisteron: Perbedaan antara revisi

Efek samping noretisteron termasuk ketidakteraturan menstruasi, [[sakit kepala]], mual, [[nyeri payudara]], perubahan [[suasana hati]], jerawat, dan [[hirsutisme]].<ref name="Aygestin-Label">https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/018405s023lbl.pdf {{Webarchive|url=https://web.archive.org/web/20170210100747/http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/018405s023lbl.pdf |date=10 February 2017 }} {{Bare URL PDF|date=March 2022}}</ref><ref name="pmid14450719" /> Noretisteron adalah progestin, atau [[progestogen]] sintetik, dan karenanya merupakan agonis reseptor progesteron, yakni [[target biologis]] progestogen seperti [[progesteron]].<ref name="pmid16112947" /><ref name="pmid8520623" /> Ia memiliki aktivitas [[androgen]]ik dan estrogenik yang lemah, sebagian besar pada dosis tinggi, dan tidak ada aktivitas [[hormon]]al penting lainnya.<ref name="pmid16112947" /><ref name="HumansOrganization2007" />

Noretisteron disintesis pertama kali oleh ahli kimia Luis Miramontes, Carl Djerassi, dan George Rosenkranz di Syntex di [[Kota Meksiko|Mexico City]] pada tahun 1951.<ref name="DjerassiMiramontes1954">{{cite journal | vauthors = Djerassi C, Miramontes L, Rosenkranz G, Sondheimer F, Longo LD | title = Steroids LIV. Synthesis of 19-nor-17alpha-ethynyltestosterone and 19-nor-17alpha-methyltestosterone. 1954 | journal = American Journal of Obstetrics and Gynecology | volume = 194 | issue = 1 | pages = 289; discussion 290 | date = January 2006 | pmid = 16389045 | doi = 10.1021/ja01645a010 }}</ref> Obat ini berasal dari etisteron, dan ditemukan memiliki potensi 20 kali lipat lebih besar sebagai progestogen jika dibandingkan.{{Citation needed|date=December 2019|reason=removed citation to predatory publisher content}} Noretisteron adalah [[progestogen]] oral pertama yang sangat aktif yang disintesis, dan didahului (sebagai progestogen) oleh progesteron (1934), etisteron (1938), 19-norprogesteron (1944), dan 17α-metilprogesteron (1949) serta oleh nandrolon (1950), sedangkan noretinodrel (1952) dan noretandrolon (1953) mengikuti sintesis noretisteron.<ref name="Shoupe2007">{{cite book| vauthors = Shoupe D |title=The Handbook of Contraception: A Guide for Practical Management|url=https://books.google.com/books?id=sczb0Tk_2IwC&pg=PA15|date=7 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-150-5|pages=15–}}</ref><ref name="Marks2010">{{cite book| vauthors = Marks L |title=Sexual Chemistry: A History of the Contraceptive Pill|url=https://books.google.com/books?id=_i-s4biQs7MC&pg=PA74|year=2010|publisher=Yale University Press|isbn=978-0-300-16791-7|pages=74, 76}}</ref> Obat ini diperkenalkan sebagai Norlutin di [[Amerika Serikat]] pada tahun 1957.<ref name="Publishing2013">{{cite book| author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2935-IA46|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=2935–}}</ref> Noretisteron kemudian digabungkan dengan mestranol dan dipasarkan sebagai ''Ortho-Novum'' di Amerika Serikat pada tahun 1963. Obat ini adalah progestin kedua, setelah noretinodrel pada tahun 1960, yang digunakan dalam kontrasepsi oral.<ref name="Marks2010" /> Pada tahun 1964, sediaan kontrasepsi tambahan yang mengandung noretisteron yang dikombinasikan dengan mestranol atau [[etinilestradiol]], seperti Norlestrin dan Norinyl, dipasarkan di Amerika Serikat.<ref name="Marks2010" />

Noretisteron dosis tinggi (10 mg/hari) telah dikaitkan dengan penyakit veno-oklusif hati, dan karena efek buruk ini, noretisteron tidak boleh diberikan kepada pasien yang menjalani transplantasi [[sumsum tulang]] alogenik, karena hal ini dikaitkan dengan kelangsungan hidup satu tahun pasca transplantasi yang jauh lebih rendah.<ref name="Aronson2009">{{cite book| vauthors = Aronson JK |title=Meyler's Side Effects of Endocrine and Metabolic Drugs|url=https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA217|date=21 February 2009|publisher=Elsevier|isbn=978-0-08-093292-7|pages=217, 253, 275}}</ref>{{rp|217}}<ref name="pmid9845522">{{cite journal | vauthors = Hägglund H, Remberger M, Klaesson S, Lönnqvist B, Ljungman P, Ringdén O | title = Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation | journal = Blood | volume = 92 | issue = 12 | pages = 4568–72 | date = December 1998 | pmid = 9845522 | doi = 10.1182/blood.V92.12.4568 }}</ref>

Karena aktivitas progestogeniknya, norethisteronenoretisteron menekan sumbu hipotalamus-hipofisis-gonad (sumbu HPG) dan karenanya memiliki efek antigonadotropik.<ref name="pmid16112947" /><ref name="Kuhl2011" /> Aktivitas estrogenik norethisteronenoretisteron pada dosis tinggi juga diharapkan berkontribusi terhadap efek antigonadotropiknya.<ref name="pmid12466187">{{cite journal | vauthors = Anderson RA, Baird DT | title = Male contraception | journal = Endocrine Reviews | volume = 23 | issue = 6 | pages = 735–62 | date = December 2002 | pmid = 12466187 | doi = 10.1210/er.2002-0002 | url = http://www.hormonebalance.org/images/documents/Anderson%2002%20Male%20Contraception%20ER.pdf | doi-access = free | access-date = 11 December 2019 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828191401/https://www.hormonebalance.org/images/documents/Anderson%2002%20Male%20Contraception%20ER.pdf | url-status = live }}</ref> Karena efek antigonadotropiknya, norethisteronenoretisteron menekan produksi hormon seks [[gonad]], menghambat ovulasi pada wanita, dan menekan [[spermatogenesis]] pada pria.<ref name="pmid16112947" /><ref name="Kuhl2011" /><ref name="KamischkeNieschlag2004">{{cite journal | vauthors = Kamischke A, Nieschlag E | title = Progress towards hormonal male contraception | journal = Trends in Pharmacological Sciences | volume = 25 | issue = 1 | pages = 49–57 | date = January 2004 | pmid = 14723979 | doi = 10.1016/j.tips.2003.11.009}}</ref>

Dosis norethisteronenoretisteron oral dan NETA oral yang menghambat ovulasi adalah sekitar 0,5 mg/hari pada wanita.<ref name="pmid16112947" /><ref name="Rudel1968">{{cite journal | vauthors = Rudel HW | title = Pharmacology of oral contraceptives | journal = Clinical Obstetrics and Gynecology | volume = 11 | issue = 3 | pages = 632–44 | date = September 1968 | pmid = 4878826 | doi = 10.1097/00003081-196811030-00002 }}</ref><ref name="pmid14667980">{{cite journal | vauthors = Stanczyk FZ | title = All progestins are not created equal | journal = Steroids | volume = 68 | issue = 10–13 | pages = 879–90 | date = November 2003 | pmid = 14667980 | doi = 10.1016/j.steroids.2003.08.003 | s2cid = 44601264 }}</ref> Namun, ada beberapa data yang bertentangan, yang menunjukkan bahwa dosis yang lebih tinggi mungkin diperlukan untuk menghambat ovulasi sepenuhnya.<ref name="pmid22078182">{{cite journal | vauthors = Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B | title = Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide | journal = Contraception | volume = 84 | issue = 6 | pages = 549–57 | date = December 2011 | pmid = 22078182 | doi = 10.1016/j.contraception.2011.04.009}}</ref> Suntikan NETE 200 mg intramuskular telah terbukti mencegah ovulasi dan menekan kadar [[estradiol]], progesteron, [[hormon luteinizingpelutein]] (LH), dan [[hormon perangsang folikel]] (FSH) pada wanita.<ref name="Shoupe1993">{{cite book| vauthors = Shoupe D | title=Contraception| chapter=Injectable Contraceptives and Contraceptive Vaginal Rings| series=Clinical Perspectives in Obstetrics and Gynecology|year=1993|pages=144–157| publisher=Springer|issn=0178-0328|doi=10.1007/978-1-4612-2730-4_13|isbn=978-1-4612-7645-6}}</ref><ref name="pmid1122756">{{cite journal | vauthors = Weiner E, Johansson ED | title = Plasma levels of norethindrone after i.m. injection of 200 mg norethindrone enanthate | journal = Contraception | volume = 11 | issue = 4 | pages = 419–25 | date = April 1975 | pmid = 1122756 | doi = 10.1016/0010-7824(75)90004-9 }}</ref><ref name="pmid606499">{{cite journal | vauthors = Fotherby K, Howard G, Shrimanker K, Elder M, Bye PG | title = Effect of norethisterone oenanthate on serum gonadotrophin levels | journal = Contraception | volume = 16 | issue = 6 | pages = 591–604 | date = December 1977 | pmid = 606499 | doi = 10.1016/0010-7824(77)90060-9 }}</ref><ref name="pmid572279">{{cite journal | vauthors = Goebelsmann U, Stanczyk FZ, Brenner PF, Goebelsmann AE, Gentzschein EK, Mishell DR | title = Serum norethindrone (NET) concentrations following intramuscular NET enanthate injection. Effect upon serum LH, FSH, estradiol and progesterone | journal = Contraception | volume = 19 | issue = 3 | pages = 283–313 | date = March 1979 | pmid = 572279 | doi = 10.1016/0010-7824(79)90022-2 }}</ref>

Studi awal tentang norethisteronenoretisteron oral pada pria yang menggunakan dosis 20 hingga 50 mg/hari mengamati penekanan [[ekskresi]] 17-ketosteroid, peningkatan ekskresi estrogen (karena konversi menjadi etinilestradiol),; penekanan spermatogenesis, [[libido]], dan fungsi [[ereksi,]]; dan kejadian [[ginekomastia]].<ref name="pmid793446" /><ref name="pmid13583821">{{cite journal | vauthors = Heller CG, Laidlaw WM, Harvey HT, Nelson WO | title = Effects of progestational compounds on the reproductive processes of the human male | journal = Annals of the New York Academy of Sciences | volume = 71 | issue = 5 | pages = 649–65 | date = July 1958 | pmid = 13583821 | doi = 10.1111/j.1749-6632.1958.tb54641.x | s2cid = 32637425 }}</ref><ref name="pmid14400846">{{cite journal | vauthors = Heller CG, Moore DJ, Paulsen CA, Nelson WO, Laidlaw WM | title = Effects of progesterone and synthetic progestins on the reproductive physiology of normal men | journal = Federation Proceedings | volume = 18 | pages = 1057–65 | date = December 1959 | pmid = 14400846 | url = https://www.popline.org/node/472874 | access-date = 11 December 2019 | archive-date = 18 December 2018 | archive-url = https://web.archive.org/web/20181218193350/https://www.popline.org/node/472874 | url-status = dead }}</ref><ref name="pmid13942007">{{cite journal | vauthors = Paulsen CA, Leach RB, Lanman J, Goldston N, Maddock WO, Heller CG | title = Inherent estrogenicity of norethindrone and norethynodrel: comparison with other synthetic progestins and progesterone | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 22 | issue = 10 | pages = 1033–9 | date = October 1962 | pmid = 13942007 | doi = 10.1210/jcem-22-10-1033 }}</ref><ref name="pmid14261416">{{cite journal | vauthors = Paulsen CA | title = Progestin Metabolism: Special Reference to Estrogenic Pathways | journal = Metabolism | volume = 14 | issue = 3 | pages = SUPPL:313–9 | date = March 1965 | pmid = 14261416 | doi = 10.1016/0026-0495(65)90018-1 }}</ref> Dosis norethisteronenoretisteron oral 25 mg/hari selama 3 minggu pada pria telah dilaporkan menekan kadar testosteron sekitar 70%, hingga 100 hingga 200 ng/dL, dalam waktu 4 atau 5 hari, serta menekan jumlah sperma dan mengurangi jumlah sperma. tidak berpengaruh pada libido atau fungsi ereksi dalam jangka waktu singkat ini.<ref name="MougdalSuresh1995">{{cite journal | vauthors = Moudgal NR, Suresh R | title = Some thoughts on development of chemically based male contraceptives | journal = Current Science (Bangalore) | year = 1995 | volume = 68 | issue = 4 | pages = 470–474 | issn = 0011-3891 | url = https://www.currentscience.ac.in/Downloads/article_id_068_04_0470_0474_0.pdf | access-date = 11 December 2019 | archive-date = 11 December 2019 | archive-url = https://web.archive.org/web/20191211133812/https://www.currentscience.ac.in/Downloads/article_id_068_04_0470_0474_0.pdf | url-status = dead }}</ref><ref name="JohonssonNygren1973">{{cite journal| vauthors = Johonsson ED, Nygren KG |title=Depression of plasma testosterone levels in men with norethindrone|journal=Contraception|volume=8|issue=3|year=1973|pages=219–226|issn=0010-7824|doi=10.1016/0010-7824(73)90032-2}}</ref> Pada pria muda yang sehat, NETA saja dengan dosis 5 hingga 10 mg/hari secara oral selama 2 minggu menekan kadar testosteron dari ~527 ng/dL hingga ~231 ng/dL (–56%).<ref name="pmid28189123">{{cite journal | vauthors = Zitzmann M, Rohayem J, Raidt J, Kliesch S, Kumar N, Sitruk-Ware R, Nieschlag E | title = Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial | journal = Andrology | volume = 5 | issue = 3 | pages = 516–526 | date = May 2017 | pmid = 28189123 | doi = 10.1111/andr.12328 | s2cid = 41502711 | doi-access = free }}</ref>

Suntikan NETE intramuskular 200 mg tunggal atau dalam kombinasi dengan 2 mg [[estradiol valerat]] telah terbukti menghasilkan penurunan kadar [[gonadotropin]] dan testosteron yang cepat, kuat, dan berkelanjutan hingga satu bulan pada pria.<ref name="KamischkeNieschlag2004" /><ref name="Amory2003">{{cite book| vauthors = Amory JK |title=Androgens in Health and Disease | url = https://archive.org/details/androgensinhealt0000unse |chapter=Androgens and Male Contraception |series=Contemporary Endocrinology |year=2003|pages=405–417[https://archive.org/details/androgensinhealt0000unse/page/405 405]–417|publisher=Humana Press |doi=10.1007/978-1-59259-388-0_21|isbn=978-1-61737-314-5}}</ref><ref name="pmid10971453">{{cite journal | vauthors = Kamischke A, Diebäcker J, Nieschlag E | title = Potential of norethisterone enanthate for male contraception: pharmacokinetics and suppression of pituitary and gonadal function | journal = Clinical Endocrinology | volume = 53 | issue = 3 | pages = 351–358 | date = September 2000 | pmid = 10971453 | doi = 10.1046/j.1365-2265.2000.01097.x | s2cid = 70515136 }}</ref> Suntikan NETE 200 mg intramuskular setiap 3 minggu sekali juga terbukti menekan spermatogenesis pada pria.<ref name="pmid793446">{{cite journal | vauthors = Neumann F, Diallo FA, Hasan SH, Schenck B, Traore I | title = The influence of pharmaceutical compounds on male fertility | journal = Andrologia | volume = 8 | issue = 3 | pages = 203–235 | date = 1976 | pmid = 793446 | doi = 10.1111/j.1439-0272.1976.tb02137.x | s2cid = 24859886 | doi-access = free }}</ref><ref name="PetryMauss1970">{{cite book| vauthors = Petry R, Mauss J, Senge T, Rausch-Stroomann JG |title=Über den Einfluß von Cyproteronacetat, Norethisteronönanthat und Gestonoroncapronat auf die Hypophysen-Gonadenachse beim Mann|chapter=Influence of Cyproterone-acetate, Norethisterone-enanthate and Gestonorone-capronate on the Hypophyseal-Gonadal-Axis in the Male |trans-title=Influence of Cyproterone-acetate, Norethisterone-enanthate and Gestonorone-capronate on the Hypophyseal-Gonadal-Axis in the Male|year=1970|pages=428–430|doi=10.1007/978-3-642-80591-2_118|journal=Endokrinologie der Entwicklung und Reifung|series=Symposion der Deutschen Gesellschaft für Endokrinologie in Ulm vom 26.—28. Februar 1970 |publisher=Springer |isbn=9783642805912 }}</ref> Demikian pula, suntikan intramuskular tunggal 50 mg NETE yang dikombinasikan dengan 5 mg estradiol valerat terbukti sangat menekan kadar testosteron pada pria.<ref name="ValleAlvarez2011">{{cite thesis | type = MSc | vauthors = Alvarez BD | title = Efecto de una Dosis de 50 mg de Enantato de Noretisterona y 5 mg de Valerato de Estradiol en los Niveles de Testosterona Total en Hombres Mexicanos Sanos | trans-title = Effect of a Dose of 50 mg of Norethisterone Enanthate and 5 mg of Estradiol Valerate on Total Testosterone Levels in Healthy Mexican Men | date = 11 May 2011 | publisher = National Polytechnic Institute of Mexico | url = http://repositoriodigital.ipn.mx/handle/123456789/12490 | access-date = 12 September 2022 | archive-date = 16 September 2022 | archive-url = https://web.archive.org/web/20220916063742/https://repositoriodigital.ipn.mx/handle/123456789/12490 | url-status = live }}</ref> Kadar testosteron menurun dari ~503 ng/dL pada awal menjadi ~30 ng/dL pada titik terendah (–94%) yang terjadi pada hari ke 7 pasca injeksi.<ref name="ValleAlvarez2011" />

[[File:Norethisterone synthesis.svg|450px|right|thumb|Sintesis noretisteron #1.<ref name="DjerassiMiramontes1954" /><ref name="Colton">Frank B. Colton, {{US patent|2,655,518}} (1952 to [[G.D. Searle, LLC|Searle]] & Co).</ref>]]

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