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====Aktivitas androgenik====
Norethisterone memiliki sekitar 15% afinitas metribolon [[steroid anabolik]]-androgenik (AAS) metribolon (R-1881) untuk AR, dan karenanya, bersifat androgenik lemah.<ref name="pmid16112947" /> Berbeda dengan norethisteronenoretisteron, 5α-DHNET, metabolit utama norethisteronenoretisteron, menunjukkan afinitas yang lebih tinggi terhadap AR, dengan sekitar 27% afinitas terhadap metribolon.<ref name="pmid16112947" /> Namun, meskipun 5α-DHNET memiliki afinitas yang lebih tinggi terhadap AR dibandingkan norethisteronenoretisteron, ia telah berkurang secara signifikan dan bahkan hampir menghilangkan potensi androgenik dibandingkan dengan norethisteronenoretisteron dalam [[bioasaibioassay]] [[hewan pengerat]].<ref name="pmid19028512">{{cite journal | vauthors = Fragkaki AG, Angelis YS, Koupparis M, Tsantili-Kakoulidou A, Kokotos G, Georgakopoulos C | title = Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure | journal = Steroids | volume = 74 | issue = 2 | pages = 172–97 | date = February 2009 | pmid = 19028512 | doi = 10.1016/j.steroids.2008.10.016 | quote = Many synthetic steroids with high myotrophic activity exhibit myotrophic–androgenic dissociation, since, due to changes introduced in the structure of ring A, they will probably not be substrates for the 5α-reductases [85]. 5α-Reduction does not always amplify the androgenic potency in spite of high RBA of androgens to the AR. This is the case for norethisterone (Fig. 1, 34), a synthetic 19-nor-17α-ethynyl testosterone derivative, which also undergoes enzyme-mediated 5α-reduction and exerts potent androgenic effects in target organs. 5α-Reduced norethisterone displays a higher AR binding but shows a significantly lower androgenic potency than unchanged norethisterone [102,103]. | s2cid = 41356223 }}</ref><ref name="pmid9182866">{{cite journal | vauthors = Lemus AE, Enríquez J, García GA, Grillasca I, Pérez-Palacios G | title = 5alpha-reduction of norethisterone enhances its binding affinity for androgen receptors but diminishes its androgenic potency | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 60 | issue = 1–2 | pages = 121–9 | date = January 1997 | pmid = 9182866 | doi = 10.1016/s0960-0760(96)00172-0 | s2cid = 33771349 }}</ref> Temuan serupa diamati untuk ethisteroneetisteron (17α-ethynyltestosteroneetiniltestosteron) dan metabolitnya yang tereduksi 5α, sedangkan reduksi 5α meningkatkan afinitas AR dan potensi androgenik [[testosteron]] dan nandrolonenandrolon (19-nortestosteron) dalam bioasaibioassay hewan pengerat.<ref name="pmid9182866" /> Dengan demikian, nampaknya gugus etinil norethisteronenoretisteron pada posisi C17α bertanggung jawab atas hilangnya androgenisitasnya pada reduksi 5α.<ref name="pmid9182866" />
NorethisteroneNoretisteron (0,5 hingga 3 mg/hari) terbukti menurunkan kadar SHBG dalam sirkulasi secara ketergantungan dosis, yang merupakan sifat umum androgen dan disebabkan oleh penekanan produksi SHBG hati yang dimediasi oleh AR. Obat ini juga mempunyai aktivitas estrogenik, dan estrogen diketahui meningkatkan produksi SHBG di hati dan kadar sirkulasi, sehingga aktivitas androgenik norethisteronenoretisteron mengalahkan aktivitas estrogeniknya dalam hal ini.<ref name="pmid9494772">{{cite journal | vauthors = Kuhnz W, Heuner A, Hümpel M, Seifert W, Michaelis K | title = In vivo conversion of norethisterone and norethisterone acetate to ethinyl etradiol in postmenopausal women | journal = Contraception | volume = 56 | issue = 6 | pages = 379–85 | date = December 1997 | pmid = 9494772 | doi = 10.1016/s0010-7824(97)00174-1 }}</ref>
NorethisteroneNoretisteron terikat sebagian besar (36%) pada SHBG yang beredar.<ref name="pmid16112947" /> Meskipun memiliki afinitas yang lebih rendah terhadap SHBG dibandingkan androgen dan estrogen endogen,<ref name="FilshieGuillebaud2013">{{cite book| vauthors = Filshie M, Guillebaud J |title=Contraception: Science and Practice|url=https://books.google.com/books?id=Ug3-BAAAQBAJ&pg=PA26|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-6366-6|pages=26–|quote=Norethisterone binds to SHBG with less affinity than endogenous androgens and oestrogens [...]}}</ref> Norethisteronenoretisteron dapat menggantikan testosteron dari SHBG dan dengan demikian meningkatkan kadar testosteron bebas, dan tindakan ini mungkin berkontribusi terhadap efek androgeniknya yang lemah.<ref name="Azziz2007">{{cite book| vauthors = Azziz R |title=Androgen Excess Disorders in Women|url=https://books.google.com/books?id=Ch-BsGAOtucC&pg=PA124|date=8 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-179-6|pages=124–}}</ref>
====Aktivitas estrogenik====
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