Tissue-selective estrogen complex inhibits bone loss without breast, uterine effects
Last Updated: 2007-06-05 12:28:19 -0400 (Reuters Health)
By Martha Kerr
NEW YORK (Reuters Health) - A tissue-specific estrogen complex (TSEC) relieves postmenopausal symptoms and has positive effects on bone, without stimulating breast and uterine tissue.
Results of a number of studies of a new TSEC, consisting of the novel selective estrogen receptor modulator (SERM) bazedoxifene plus conjugated estrogen, were presented at the Endocrine Society's 89th annual meeting in Toronto, Canada (ENDO 07).
Dr. James Pickar of Wyeth Research in Collegeville, Pennsylvania, reported findings of a double-blind, placebo-controlled study of various formulations of the TSEC in 3,397 postmenopausal women randomized to one of six treatment arms for 2 years. The women were generally healthy, between the ages of 40 and 75 years and had an intact uterus.
The six treatment arms were bazedoxifene 10 mg, 20 mg or 40 mg each combined with either 0.625 mg or 0.45 mg conjugated estrogen. Controls were women on placebo or raloxifene.
Endometrial biopsies were performed at one and two years. Cumulative amenorrhea, defined as no bleeding or spotting over time and breast pain were recorded by patients in daily diaries.
Dr. Pickar reported that in combination with conjugated estrogen, "increasing doses of bazedoxifene resulted in decreasing incidences of endometrial hyperplasia."
The incidence of cumulative amenorrhea was the same in all arms of the study, as was the incidence of breast tenderness.
"Bazedoxifene plus conjugated estrogen represents a new paradigm for menopausal therapies because of its favorable endometrial and tolerability profile," Dr. Pickar stated.
In another report, Dr. Robert Lindsay of Helen Hayes Hospital in West Haverstraw, New York, presented findings of the TSEC on bone mineral density in a substudy of the same population of women. It consisted of 1,451 women more than five years post-menopause and 861 women who had undergone menopause during the five years prior to study.
In both groups of women, "TSECs containing 20 mg bazedoxifene were associated with greater increases in lumbar spine bone mineral density than raloxifene at two years, and all TSECs were associated with greater changes in serum bone markers at two years compared with placebo," Dr. Lindsay told meeting attendees.
In a third study of the TSEC, using animal models, Dr. Barry S. Komm of Duke University Medical Center in Durham, North Carolina, and colleagues assessed the effects of bazedoxifene, raloxifene and lasofoxifene and two estrogens, 17-beta-estradiol and conjugated estrogens, given in various combinations.
The investigators found that uterine effects were least with bazedoxifene, followed by raloxifene and lasofoxifene, while "the skeletal responses to conjugated estrogen were not substantially affected by the SERMs." Furthermore, "the pairing of bazedoxifene with conjugated estrogen did not abrogate activity in a rat hot flash model."
They conclude: "Thus, it appears that the appropriate SERM/estrogen pairing results in a favorable uterine response without compromising the beneficial effects of estrogens in bone and the CNS."
