Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial.
OBJECTIVE
This phase 3 study evaluated the endometrial safety of bazedoxifene (BZA)/conjugated estrogens (CE) and bone mineral density (BMD) effects vs BZA alone, hormone therapy, and placebo (PBO).


METHODS
The Selective estrogens, Menopause, And Response to Therapy (SMART)-5 trial was a multicenter, randomized, double-blind, PBO- and active-controlled study in postmenopausal women with an intact uterus (N = 1843; aged 40-65 years) seeking treatment for menopausal symptoms. Subjects received daily oral BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, CE 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or PBO. Primary endpoints were incidence of endometrial hyperplasia and percent change in lumbar spine BMD at 12 months. Secondary endpoints included additional osteoporosis parameters and assessments of tolerability and safety.


RESULTS
At 12 months, endometrial hyperplasia incidence was low (<1%) and similar among groups. The BZA/CE group showed significantly greater increases in lumbar spine and total hip BMD vs decreases with PBO (P < .001); the CE/MPA group had increased lumbar spine BMD compared with that in the BZA/CE group. The BZA 20 mg/CE 0.45 and 0.625 mg groups had cumulative amenorrhea rates similar to those with PBO and BZA and significantly higher than those with CE 0.45 mg/MPA 1.5 mg (P < .001). The incidence of breast tenderness with BZA/CE was similar to that with PBO and BZA and significantly lower than with that with CE/MPA (P < .01). Although adverse event (AE) rates were similar among the groups, the incidence of serious AEs overall and AE-related discontinuation rates were higher with CE/MPA than with BZA/CE, BZA, or PBO.


CONCLUSIONS
BZA/CE showed low rates of endometrial hyperplasia and improved lumbar spine and total hip BMD and was generally safe and well tolerated.
Department of Obstetrics and Gynecology, Division of Midlife Health (J.V.P.) and Department of Radiology (J.A.H.), University of Virginia Health System, Charlottesville, Virginia 22908; Department of Medicine (R.L.), Helen Hayes Hospital, West Haverstraw, New York 10993; Women's Health (K.P., A.A.C., S.M.), Pfizer Inc, Collegeville, Pennsylvania 19426; and Department of Obstetrics and Gynecology (D.F.A.), Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia 23510.
Joann V
JV
Pinkerton
Jennifer A
JA
Harvey
Robert
R
Lindsay
Kaijie
K
Pan
Arkadi A
AA
Chines
Sebastian
S
Mirkin
David F
DF
Archer
D000328:Adult; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia / Q000139:chemically induced*; D004717:Endometrium / Q000187:drug effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D008159:Lumbar Vertebrae / Q000187:drug effects*; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; D017258:Medroxyprogesterone Acetate; C447119:bazedoxifene