Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conjugated estrogens as a menopausal therapy.
OBJECTIVE
To evaluate the endometrial safety of a tissue selective estrogen complex (TSEC; pairing of a selective estrogen receptor modulator [SERM] with estrogens) composed of bazedoxifene/conjugated estrogens (BZA/CE) in postmenopausal women.


METHODS
Randomized, double-blind, multicenter, placebo- and active-controlled, phase 3 study (Selective estrogen Menopause And Response to Therapy [SMART]-1).


METHODS
Outpatient clinical.


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


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


METHODS
Incidence of endometrial hyperplasia at 12 months in the efficacy evaluable population.


RESULTS
Treatment with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was associated with low rates (<1%) of endometrial hyperplasia that were not significantly different from those reported with placebo over 24 months. Endometrial thickness with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was not significantly different from that with placebo.


CONCLUSIONS
When combined with CE (0.625 mg or 0.45 mg), BZA (20 mg) was the lowest effective dose that prevented endometrial hyperplasia over 2 years of study, creating the possibility for a new, progestin-free menopausal therapy.
Pickar
James H
JH
Wyeth Research, Collegeville, Pennsylvania. Electronic address: pickarj@wyeth.com.
Yeh
I-Tien
IT
University of Texas Health Science Center, San Antonio, Texas.
Bachmann
Gloria
G
Robert Wood Johnson University Hospital, New Brunswick, New Jersey.
Speroff
Leon
L
Oregon Health and Science University, Portland, Oregon.
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia / Q000517:prevention & control; D016889:Endometrial Neoplasms / Q000517:prevention & control; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004967:Estrogens / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; 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; D008875:Middle Aged; D010045:Outpatients; D017698:Postmenopause / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene