{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T20:37:28Z","timestamp":1754599048424},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T00:00:00Z","timestamp":1357516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the effects of tibolone or oestradiol (<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content><jats:sub>2<\/jats:sub>)\/norethisterone acetate (<jats:styled-content style=\"fixed-case\">NETA<\/jats:styled-content>) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Single\u2010centre double\u2010blind placebo\u2010controlled randomized clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects\/Methods<\/jats:title><jats:p>We randomized 105 healthy postmenopausal women to tibolone 2\u00b75\u00a0mg daily, continuous combined oral <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content><jats:sub>2<\/jats:sub> 2\u00a0mg\/<jats:styled-content style=\"fixed-case\">NETA<\/jats:styled-content> 1\u00a0mg daily or placebo over a 2\u2010year study. We performed intravenous glucose tolerance tests (<jats:styled-content style=\"fixed-case\">IVGTT<\/jats:styled-content>) with measurements of plasma glucose, insulin and <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010peptide concentrations and the <jats:styled-content style=\"fixed-case\">IVGTT<\/jats:styled-content> glucose elimination rate, <jats:italic>k<\/jats:italic>. Mathematical modelling was performed to determine measures of insulin sensitivity, <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>, pancreatic insulin secretion and hepatic and plasma insulin elimination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tibolone decreased <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> to 53\u201363% and <jats:italic>k<\/jats:italic> to 72\u201379% of baseline values but increased <jats:styled-content style=\"fixed-case\">IVGTT<\/jats:styled-content> phase 2 <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010peptide concentrations 1\u00b76\u20131\u00b78\u2010fold and pancreatic insulin secretion 2\u00b72\u20132\u00b74\u2010fold, so overall <jats:styled-content style=\"fixed-case\">IVGTT<\/jats:styled-content> glucose concentrations were unaffected. Similar, but for <jats:italic>k<\/jats:italic>, significantly smaller changes in insulin and <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010peptide secretion were seen with <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content><jats:sub>2<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">NETA<\/jats:styled-content>, also with no effect on overall <jats:styled-content style=\"fixed-case\">IVGTT<\/jats:styled-content> glucose concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2265.2012.04491.x","type":"journal-article","created":{"date-parts":[[2012,7,10]],"date-time":"2012-07-10T07:20:26Z","timestamp":1341904826000},"page":"297-302","source":"Crossref","is-referenced-by-count":7,"title":["Effects of tibolone or continuous combined oestradiol\/norethisterone acetate on glucose and insulin metabolism"],"prefix":"10.1111","volume":"78","author":[{"given":"Nik","family":"Manassiev","sequence":"first","affiliation":[{"name":"Goodrest Croft Surgery Yardley Wood"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian F.","family":"Godsland","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Medicine Department of Medicine Faculty of Medicine St Mary's Hospital Imperial College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Proudler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Good Hope Hospital Heart of England Foundation NHS trust Sutton Coldfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm I.","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Main Outpatients Portland Hospital UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"National Heart &amp; Lung Institute Imperial College London Royal Brompton Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(01)00044-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2004.02.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0029-7844(95)00468-8"},{"key":"e_1_2_8_5_1","first-page":"259","article-title":"Effects of tibolone on serum concentrations of lipoprotein (a) in postmenopausal women","volume":"128","author":"Rymer J.","year":"1993","journal-title":"Acta Endocrinologica"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5122(90)90058-E"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1210\/jcem.82.6.3995","article-title":"Tibolone: influence on markers of cardiovascular disease","volume":"82","author":"Bjarnason N.H.","year":"1997","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_8_8_1","first-page":"1595","article-title":"Role of insulin resistance in human disease","volume":"37","author":"Reaven G.M.","year":"1988","journal-title":"Banting Lecture 1988. 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