Estrogen alone and joint symptoms in the women's health initiative randomized trial

Rowan T. Chlebowski, Dominic J. Cirillo, Charles B. Eaton, Marcia L. Stefanick, Mary Pettinger, Laura D Carbone, Karen C. Johnson, Michael S. Simon, Nancy F. Woods, Jean Wactawski-Wende

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. Methods: A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. Results: At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. Conclusions: The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.

Original languageEnglish (US)
Pages (from-to)600-608
Number of pages9
JournalMenopause
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2013

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Women's Health
Arthralgia
Estrogens
Joints
Random Allocation
Placebos
Logistic Models
Conjugated (USP) Estrogens
Menopause
Hysterectomy
Observational Studies
Randomized Controlled Trials
Pain

Keywords

  • Estrogen
  • Joint pain
  • Joint swelling
  • Postmenopausal women
  • Randomized clinical trial
  • Women's Health Initiative

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Chlebowski, R. T., Cirillo, D. J., Eaton, C. B., Stefanick, M. L., Pettinger, M., Carbone, L. D., ... Wactawski-Wende, J. (2013). Estrogen alone and joint symptoms in the women's health initiative randomized trial. Menopause, 20(6), 600-608. https://doi.org/10.1097/gme.0b013e31828392c4

Estrogen alone and joint symptoms in the women's health initiative randomized trial. / Chlebowski, Rowan T.; Cirillo, Dominic J.; Eaton, Charles B.; Stefanick, Marcia L.; Pettinger, Mary; Carbone, Laura D; Johnson, Karen C.; Simon, Michael S.; Woods, Nancy F.; Wactawski-Wende, Jean.

In: Menopause, Vol. 20, No. 6, 01.06.2013, p. 600-608.

Research output: Contribution to journalArticle

Chlebowski, RT, Cirillo, DJ, Eaton, CB, Stefanick, ML, Pettinger, M, Carbone, LD, Johnson, KC, Simon, MS, Woods, NF & Wactawski-Wende, J 2013, 'Estrogen alone and joint symptoms in the women's health initiative randomized trial', Menopause, vol. 20, no. 6, pp. 600-608. https://doi.org/10.1097/gme.0b013e31828392c4
Chlebowski RT, Cirillo DJ, Eaton CB, Stefanick ML, Pettinger M, Carbone LD et al. Estrogen alone and joint symptoms in the women's health initiative randomized trial. Menopause. 2013 Jun 1;20(6):600-608. https://doi.org/10.1097/gme.0b013e31828392c4
Chlebowski, Rowan T. ; Cirillo, Dominic J. ; Eaton, Charles B. ; Stefanick, Marcia L. ; Pettinger, Mary ; Carbone, Laura D ; Johnson, Karen C. ; Simon, Michael S. ; Woods, Nancy F. ; Wactawski-Wende, Jean. / Estrogen alone and joint symptoms in the women's health initiative randomized trial. In: Menopause. 2013 ; Vol. 20, No. 6. pp. 600-608.
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abstract = "Objective: Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. Methods: A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9{\%} random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. Results: At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77{\%} with joint pain and 40{\%} with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3{\%} vs 79.2{\%}, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1{\%} vs 39.7{\%}, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. Conclusions: The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.",
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AU - Pettinger, Mary

AU - Carbone, Laura D

AU - Johnson, Karen C.

AU - Simon, Michael S.

AU - Woods, Nancy F.

AU - Wactawski-Wende, Jean

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