{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T14:05:43Z","timestamp":1770991543242,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,7,20]],"date-time":"2004-07-20T00:00:00Z","timestamp":1090281600000},"content-version":"vor","delay-in-days":49,"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":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Lasofoxifene is a nonsteroidal selective estrogen receptor modulator (SERM). With high affinity to the \u03b1 and \u03b2 human estrogen receptors and greater potency than other SERMs, lasofoxifene is potentially a superior treatment for postmenopausal osteoporosis. In light of the known effects of estrogen\u2010modulating compounds on female reproductive indices, two studies were conducted to evaluate the effects of lasofoxifene on female rat cyclicity, reproduction, and parturition. <jats:bold>METHODS:<\/jats:bold> One study evaluated effects of lasofoxifene on estrous cyclicity, and the second study assessed effects on implantation and parturition. In the cyclicity study, lasofoxifene was administered to female rats at doses of 0.1, 0.3, and 1.0\u2009mg\/kg\/day for 14 consecutive days. After treatment, there was a 3\u2010week reversibility phase followed by a mating phase. In the implantation study, lasofoxifene was administered to pregnant female rats at doses of 0.01, 0.03, and 0.1\u2009mg\/kg\/day for 7 consecutive days (gestation day [GD] 0\u20136). Some animals were euthanized on GD 21, and the remainder of the group was allowed to deliver the F<jats:sub>1<\/jats:sub> generation. Several developmental indices were evaluated in the F<jats:sub>1<\/jats:sub> pups through post\u2010natal day (PND) 21. <jats:bold>RESULTS:<\/jats:bold> In the cyclicity study, all lasofoxifene\u2010treated females were anestrous by Study Day 7 (1.0\u2009mg\/kg) or 9 (0.3 and 0.1\u2009mg\/kg). The reversibility phase resulted in restoration of normal estrous cycles by the end of 1 (0.1\u2009mg\/kg) or 2 weeks (0.3 and 1.0\u2009mg\/kg). During the mating phase, no adverse effects occurred in pregnancy success or reproductive parameters. In the implantation study, all doses of lasofoxifene increased pre\u2010 and post\u2010implantation losses, increased gestation length, and reduced litter size. None of the developmental parameters measured on the F<jats:sub>1<\/jats:sub> generation was adversely affected. <jats:bold>CONCLUSION:<\/jats:bold> Lasofoxifene reversibly altered the estrous cycle and inhibited implantation, consistent with what would be expected from a member of the SERM class. <jats:italic>Birth Defects Res B<\/jats:italic> 71:150\u2013160, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20009","type":"journal-article","created":{"date-parts":[[2004,7,20]],"date-time":"2004-07-20T15:08:43Z","timestamp":1090336123000},"page":"150-160","source":"Crossref","is-referenced-by-count":6,"title":["Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in female 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