{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:31:45Z","timestamp":1761647505516},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,6,14]],"date-time":"2007-06-14T00:00:00Z","timestamp":1181779200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Idoxifene is a selective estrogen receptor modulator similar to tamoxifen but is no longer in pharmaceutical development due to adverse genitourinary effects in the clinic. Histologic observations of the reproductive system and mammary glands are presented from female dogs treated with idoxifene for up to 12 months. <jats:bold>METHODS:<\/jats:bold> Studies were conducted as part of regulatory requirements to support clinical development. Idoxifene was given orally by capsule, once daily, for 1, 6, or 12 months to female Beagle dogs (n = 3 or 4\/group) aged 11\u201314 months (start of dosing) at dosages 0, 0.03, 0.3, 1.5, or 3\u2009mg\/kg\/day. Evaluations included the following: clinical observations, hematology, hemostasis, chemistry, toxicokinetics, and histology. <jats:bold>RESULTS:<\/jats:bold> Dose\u2010 and time\u2010dependent findings were present in dogs given \u22650.03\u2009mg\/kg\/day and included abnormal vaginal discharge, minor increases of platelet and neutrophil counts, and microscopic observations in the ovary (atrophy and mesothelial [ovarian surface epithelium] hyperplasia), endometrium (edema, inflammation, glandular atrophy, squamous metaplasia, increased collagen), myometrium (edema, increased collagen), vagina (squamous hyperplasia, keratinization), and mammary gland (atrophy). <jats:bold>CONCLUSION:<\/jats:bold> Dogs given idoxifene exhibited estrogenic effects in ovary, uterus(), and vagina but antiestrogenic effects in endometrial and mammary glands consistent with several observations in clinical trials in post\u2010menopausal women treated with triphenylethylenes. <jats:italic>Birth Defects Res (Part B)<\/jats:italic>, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20119","type":"journal-article","created":{"date-parts":[[2007,6,14]],"date-time":"2007-06-14T16:46:47Z","timestamp":1181839607000},"page":"225-232","source":"Crossref","is-referenced-by-count":10,"title":["Histologic changes in ovary, uterus, vagina, and mammary gland of mature beagle dogs treated with the SERM idoxifene"],"prefix":"10.1002","volume":"80","author":[{"given":"Sabine","family":"Rehm","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk A.","family":"Solleveld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samm T.","family":"Portelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"Wier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,6,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/13697130500117946"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.3.6.681"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050927"},{"key":"e_1_2_5_5_1","first-page":"5851","article-title":"Pyrrolidino\u20104\u2010iodotamoxifen and 4\u2010iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer","volume":"51","author":"Chander SK","year":"1991","journal-title":"Can Res"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/019262301301418883"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004040050276"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00236416"},{"key":"e_1_2_5_9_1","first-page":"355","volume-title":"Pharmacological and biochemical properties of drug substances","author":"Furr BJ","year":"1979"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(90)90087-I"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb04028.x"},{"key":"e_1_2_5_12_1","first-page":"63","volume-title":"Pharmacology of estrogens. International encyclopedia of pharmacology and therapeutics, Section 106","author":"Heywood R","year":"1981"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00132a006"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2000.01001.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(01)02221-4"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612023393404"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/030098587601300209"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.12.6343"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(02)00711-8"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016340500345691"},{"key":"e_1_2_5_21_1"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(69)90010-6"},{"key":"e_1_2_5_23_1","unstructured":"Summary Basis of Approval Evista application number 020815.1998. \u201cCenter for Drug Evaluation and Research.\u201d Rockville MD 205p."},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90250-3"},{"key":"e_1_2_5_25_1","first-page":"125","volume-title":"Safety testing of new drugs. Laboratory predictions and clinical performance","author":"Tucker MJ","year":"1984"},{"key":"e_1_2_5_26_1","first-page":"258","article-title":"Effects of tamoxifen on the human female genital tract: review of the literature","volume":"24","author":"Varras M","year":"2003","journal-title":"Eur J Gynaecol Oncol"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339802600603"}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrb.20119","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrb.20119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T05:43:00Z","timestamp":1695620580000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrb.20119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["10.1002\/bdrb.20119"],"URL":"https:\/\/doi.org\/10.1002\/bdrb.20119","archive":["Portico"],"relation":{},"ISSN":["1542-9733","1542-9741"],"issn-type":[{"value":"1542-9733","type":"print"},{"value":"1542-9741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6]]}}}