Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy.
Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. The purpose of this article is to review the effects of lasofoxifene, a new-generation SERM that has completed the Phase III development program for the prevention and treatment of osteoporosis and vaginal atrophy in postmenopausal women. This compound selectively binds to both ERs with high affinity. Lasofoxifene also has a remarkably improved oral bioavailability with respect to other SERMs such as raloxifene and tamoxifen, owing to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term clinical studies, this compound showed a favorable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. More recently, Phase III clinical trials have confirmed the efficacy and safety of this new SERM in the prevention of bone loss and vertebral and nonvertebral fractures. Moreover, in postmenopausal women with osteoporosis, lasofoxifene treatment also reduced ER positive breast cancer risk and the occurrence of vaginal atrophy. With its increased potency and efficacy on the prevention of nonvertebral fractures and its positive effects on the vagina, this new SERM may represent an alternative therapy for osteoporosis in postmenopausal women.
Gennari
Luigi
L
University of Siena, Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, Viale Bracci 1, 53100 Siena, Italy. gennari@unisi.it
D001284:Atrophy / Q000188:drug therapy; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011759:Pyrrolidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014621:Vagina / Q000187:drug effects* / Q000473:pathology; D014623:Vaginal Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
D011759:Pyrrolidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene