Direct and indirect effects of conjugated estrogens/bazedoxifene treatment on quality of life in postmenopausal women.
OBJECTIVE
Determine the direct and indirect effects of conjugated estrogens/bazedoxifene (CE/BZA) treatment on menopause-specific quality of life in a post-hoc analysis of 2 phase 3 Selective estrogens, Menopause, And Response to Therapy (SMART-1, SMART-2) trials.


METHODS
Data from participants in SMART-1 and SMART-2 who received CE 0.45mg/BZA 20mg, CE 0.625mg/BZA 20mg, or placebo were analyzed, including week 12 data from 1274 healthy postmenopausal women in SMART-1 and pooled week 1-4 and 9-12 data from 332 women with moderate to severe vasomotor symptoms (≥7 HFs/d or ≥50/wk) in SMART-2.


METHODS
A statistical mediation model included treatment as a binary predictor variable (pooled active treatment vs placebo), Menopause-Specific Quality of Life (MENQOL) questionnaire domains (vasomotor, sexual, psychosocial, and physical function) as the outcomes variables, and frequency/severity of hot flushes (HFs) as treatment effect mediators on MENQOL.


RESULTS
Vasomotor function was affected directly (SMART-1: 35.8%, P<0.05; SMART-2: 48.7%, P<0.05)] by CE/BZA and indirectly through improvements in HF severity (57.0%, P<0.05; 42.1%, P<0.05), and to a lesser extent, through reduction in HF frequency (7.2%, P<0.05; 9.2%, P<0.05). The effects of CE/BZA on the sexual, psychosocial, and physical function domains were fully mediated via improvements in HF severity. Final models for both studies were similar, indicating that direct and indirect effects of CE/BZA on menopause-specific quality of life are consistent and stable in different samples of women.


CONCLUSIONS
CE/BZA affected the MENQOL vasomotor domain both directly and indirectly, whereas effects on other domains were fully mediated via HF severity reductions.
Pfizer Ltd, Walton Oaks, Dorking Road, Walton on the Hill, Tadworth, Surrey KT20 7NS, United Kingdom. Electronic address: Lucy.Abraham@pfizer.com.
Lucy
L
Abraham
Pfizer Inc, Eastern Point Road, Groton, CT 06340, United States. Electronic address: Andrew.G.Bushmakin@pfizer.com.
Andrew G
AG
Bushmakin
Pfizer, Global Innovative Pharma, 23-25 avenue du Dr. Lannelongue, F-75668 Paris Cedex 14, France. Electronic address: Erika.Dragon@Pfizer.com.
Erika
E
Dragon
Pfizer Inc, 500 Arcola Road, Rm E4217, Collegeville, PA 19426, United States. Electronic address: barry.komm@pfizer.com.
Barry S
BS
Komm
University of Virginia Health System, Box 801104, Charlottesville, VA 22903, United States. Electronic address: jvp9u@virginia.edu.
JoAnn V
JV
Pinkerton
D004311:Double-Blind Method; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008593:Menopause / Q000187:drug effects; D008875:Middle Aged; D008960:Models, Psychological; D017698:Postmenopause / Q000187:drug effects*; D011788:Quality of Life; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D012725:Sexual Behavior / Q000187:drug effects
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene
Bazedoxifene; Conjugated estrogens; Hot flashes; Mediation modeling; Menopause; Quality of life; Tissue selective estrogen complex