Bazedoxifene, a selective estrogen receptor modulator: effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women.
OBJECTIVE
The aim of this study was to evaluate the endometrial, ovarian, and breast safety of bazedoxifene used as a treatment for postmenopausal osteoporosis.


METHODS
Healthy women (aged 55-85 y) with osteoporosis were enrolled in a randomized, double-blind, placebo-controlled phase 3 trial. Participants were randomized to treatment with bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo daily for 3 years. Endometrial and ovarian safety was assessed by periodic transvaginal ultrasonography and endometrial biopsy through 24 months. Gynecologic and breast-related adverse events were recorded throughout the study.


RESULTS
Among 753 participants with available transvaginal ultrasonography data, there were no significant between-group differences in overall endometrial thickness or in the percentage of participants with endometrial thickness greater than 5 mm at 12 or 24 months. Changes in the mean endometrial thickness (+/-SE) from baseline were -0.07 +/- 0.11 mm (bazedoxifene 20 mg), 0.10 +/- 0.11 mm (bazedoxifene 40 mg), 0.16 +/- 0.12 mm (raloxifene 60 mg), and -0.08 +/- 0.11 mm (placebo) at 24 months. There was one report of endometrial hyperplasia in each group, and there were zero, two, two, and three reports of endometrial carcinoma with bazedoxifene 20 and 40 mg, raloxifene 60 mg, and placebo, respectively. There were no clinically important changes from baseline in the number or size of ovarian cysts among groups. There was a significantly lower incidence of fibrocystic breast disease (P <or= 0.05) with bazedoxifene compared with raloxifene 60 mg.


CONCLUSIONS
Bazedoxifene was associated with a favorable endometrial, ovarian, and breast safety profile in postmenopausal women with osteoporosis.
Archer
David F
DF
CONRAD Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA. archerdf@evms.edu
Pinkerton
JoAnn V
JV
Utian
Wulf H
WH
Menegoci
José C
JC
de Villiers
Tobie J
TJ
Yuen
Chui Kin
CK
Levine
Amy B
AB
Chines
Arkadi A
AA
Constantine
Ginger D
GD
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001940:Breast / Q000187:drug effects*; D047688:Breast Cyst / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology; D004311:Double-Blind Method; D004714:Endometrial Hyperplasia / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000453:epidemiology; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005348:Fibrocystic Breast Disease / Q000453:epidemiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects*; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects; D014463:Ultrasonography
D007211:Indoles; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene