Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile.
OBJECTIVE
To evaluate the effects of a tissue-selective estrogen complex (TSEC) composed of bazedoxifene/conjugated estrogens (BZA/CE) on menopausal symptoms, metabolic parameters, and overall safety.


METHODS
Multicenter, double-blind, placebo- and active-controlled phase 3 trial (Selective estrogens, Menopause, And Response to Therapy [SMART]-1).


METHODS
Outpatient clinical.


METHODS
Healthy, postmenopausal women (n = 3,397) age 40 to 75 with an intact uterus.


METHODS
Single tablets of BZA (10, 20, or 40 mg), each with CE (0.625 or 0.45 mg); raloxifene 60 mg; or placebo taken daily for 2 years.


METHODS
Hot flushes, breast pain, vaginal atrophy, metabolic parameters, and adverse events.


RESULTS
BZA (20 mg)/CE (0.625 or 0.45 mg) significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy compared with placebo. At week 12, the daily number of hot flushes decreased by 51.7% to 85.7% with all BZA/CE doses vs. 17.1% for placebo. BZA/CE improved lipid parameters and homocysteine levels, did not significantly change carbohydrate metabolism, and had only minor effects on some coagulation parameters. The incidences of breast pain and adverse events were similar between BZA/CE and placebo.


CONCLUSIONS
The TSEC composed of BZA (20 mg)/CE (0.625 or 0.45 mg) is an effective and safe treatment for menopausal symptoms.
Lobo
Rogerio A
RA
Columbia University Medical Center, New York, New York. Electronic address: ral35@columbia.edu.
Pinkerton
JoAnn V
JV
University of Virginia Health System, Charlottesville, Virginia.
Gass
Margery L S
MLS
University of Cincinnati College of Medicine, Cincinnati, Ohio.
Dorin
Maxine H
MH
University of New Mexico Medical School, Albuquerque, New Mexico.
Ronkin
Sheila
S
Wyeth Research, Collegeville, Pennsylvania.
Pickar
James H
JH
Wyeth Research, Collegeville, Pennsylvania.
Constantine
Ginger
G
Wyeth Research, Collegeville, Pennsylvania.
D000328:Adult; D000368:Aged; D001284:Atrophy / Q000188:drug therapy / Q000473:pathology; D050260:Carbohydrate Metabolism / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006710:Homocysteine / Q000378:metabolism; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008593:Menopause / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010045:Outpatients; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014621:Vagina / Q000187:drug effects / Q000473:pathology*
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; D006710:Homocysteine; C447119:bazedoxifene