Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis.
OBJECTIVE
The aim of this study was to examine the endometrial, ovarian, and breast safety of bazedoxifene, a novel selective estrogen-receptor modulator, in postmenopausal women at risk for osteoporosis.


METHODS
Healthy postmenopausal women (N = 1,583; mean age, 57.6 y) with lumbar spine or femoral neck bone mineral density T scores between -1 and -2.5 and/or other clinical risk factors for osteoporosis were enrolled in a 24-month, phase 3, randomized, double-blind, placebo- and active-controlled trial. They received daily treatment with bazedoxifene 10, 20, or 40 mg; placebo; or raloxifene 60 mg. Reproductive safety assessments included periodic transvaginal ultrasound measurements of endometrial thickness, ovarian volume, and presence of ovarian cysts; periodic endometrial biopsies; and adverse event reporting.


RESULTS
Bazedoxifene was not associated with a significant change from baseline in mean endometrial thickness at month 24. The percentage of participants with a change from baseline in endometrial thickness or endometrial thickness greater than 5 mm at month 24 was similar among groups. There was no consensus diagnosis of endometrial hyperplasia or malignancy in the bazedoxifene or raloxifene groups; the rates of other histologic findings, including endometrial polyps, were low (<5%) and similar among groups. No significant between-group differences were found in the change from baseline in ovarian volume, number or size of ovarian cysts, or incidence of ovarian cancer. Reports of breast pain (<4%) and breast cancer (<1%) were low and evenly distributed among groups.


CONCLUSIONS
A favorable endometrial, ovarian, and breast safety profile was found after 2 years of treatment with bazedoxifene in healthy, recently postmenopausal women at risk for osteoporosis.
Pinkerton
JoAnn V
JV
University of Virginia, Charlottesville, VA 22908, USA. jvp9u@virginia.edu
Archer
David F
DF
Utian
Wulf H
WH
Menegoci
José C
JC
Levine
Amy B
AB
Chines
Arkadi A
AA
Constantine
Ginger D
GD
D015519:Bone Density; D001940:Breast / Q000187:drug effects*; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D004311:Double-Blind Method; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010048:Ovarian Cysts / Q000139:chemically induced / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects*; D010919:Placebos; D017698:Postmenopause; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D014463:Ultrasonography
D007211:Indoles; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene