Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study.
OBJECTIVE
Selective estrogen receptor modulators are novel compounds that bind to the estrogen receptor and have mixed agonistic and antagonistic activities. Recently, an increase in urinary incontinence has been reported with hormone replacement therapy use. A decrease in surgical procedures for pelvic floor relaxation has been recently reported with raloxifene, a selective estrogen receptor modulator that is not uterotropic. Levormeloxifene is a selective estrogen receptor modulator that was developed for the purpose of the treatment and prevention of postmenopausal osteoporosis.


METHODS
This was a multicentered prospective study of healthy women aged >or=65 years with osteoporosis who were randomized to blindly receive placebo or levormeloxifene 0.5 mg or 1.25 mg daily as part of a planned 3-year osteoporosis treatment study. Multiple medical and gynecologic evaluations were performed. Adverse events were reported to investigators and coded with the use of World Health Organization terminology. This study was halted after 10 months because of the large number of gynecologic and other adverse events.


RESULTS
Among 2924 women who were studied, those women who were treated with levormeloxifene had a marked increase compared with placebo in leukorrhea (30% vs 3%), increased endometrial thickness on ultrasound scan (19% vs 1%), enlarged uterus (17% vs 3%), uterovaginal prolapse (7% vs 2%), urinary incontinence (17% vs 4%), increased micturition frequency (9% vs 4%), lower abdominal pain (17% vs 6%), hot flushes (10% vs 3%), and leg cramps (6% vs 0.8%). All of these differences were highly statistically significant with a probability value of.0001 for each.


CONCLUSIONS
Levormeloxifene results in multiple adverse gynecologic and other events in postmenopausal women with osteoporosis.
Goldstein
Steven R
SR
Department of Obstetrics and Gynecology, New York University School of Medicine, NY, USA. steven.goldstein@med.nyu.edu
Nanavati
Nayan
N
D015746:Abdominal Pain / Q000139:chemically induced; D000368:Aged; D003248:Constipation / Q000139:chemically induced; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D011446:Prospective Studies; D011759:Pyrrolidines / Q000009:adverse effects*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D014549:Urinary Incontinence / Q000139:chemically induced; D014621:Vagina / Q000187:drug effects
D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; C108255:levormeloxifene