Menopausal symptoms and treatment-related effects of estrogen and progestin in the women's health initiative

Vanessa M. Barnabei, Barbara B. Cochrane, Aaron K. Aragaki, Ingrid Nygaard, R. Stan Williams, Peter G. McGovern, Ronald L. Young, Ellen C. Wells, Mary Jo O'Sullivan, Bertha Chen, Robert Schenken, Susan R. Johnson

Research output: Contribution to journalArticle

207 Citations (Scopus)

Abstract

OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean ± standard deviation 63.3 ± 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04-3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24 -1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27-1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.

Original languageEnglish
Pages (from-to)1063-1073
Number of pages11
JournalObstetrics and Gynecology
Volume105
Issue number5 I
DOIs
StatePublished - May 1 2005
Externally publishedYes

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Women's Health
Progestins
Estrogens
Gynecologic Surgical Procedures
Placebos
Curettage
Uterine Hemorrhage
Therapeutics
Hemorrhage
Hysterectomy
Dilatation
Breast
Conjugated (USP) Estrogens
Pain
Medroxyprogesterone Acetate
Metrorrhagia
Sweat
Arthralgia
Tablets
Uterus

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Barnabei, V. M., Cochrane, B. B., Aragaki, A. K., Nygaard, I., Williams, R. S., McGovern, P. G., ... Johnson, S. R. (2005). Menopausal symptoms and treatment-related effects of estrogen and progestin in the women's health initiative. Obstetrics and Gynecology, 105(5 I), 1063-1073. https://doi.org/10.1097/01.AOG.0000158120.47542.18

Menopausal symptoms and treatment-related effects of estrogen and progestin in the women's health initiative. / Barnabei, Vanessa M.; Cochrane, Barbara B.; Aragaki, Aaron K.; Nygaard, Ingrid; Williams, R. Stan; McGovern, Peter G.; Young, Ronald L.; Wells, Ellen C.; O'Sullivan, Mary Jo; Chen, Bertha; Schenken, Robert; Johnson, Susan R.

In: Obstetrics and Gynecology, Vol. 105, No. 5 I, 01.05.2005, p. 1063-1073.

Research output: Contribution to journalArticle

Barnabei, VM, Cochrane, BB, Aragaki, AK, Nygaard, I, Williams, RS, McGovern, PG, Young, RL, Wells, EC, O'Sullivan, MJ, Chen, B, Schenken, R & Johnson, SR 2005, 'Menopausal symptoms and treatment-related effects of estrogen and progestin in the women's health initiative', Obstetrics and Gynecology, vol. 105, no. 5 I, pp. 1063-1073. https://doi.org/10.1097/01.AOG.0000158120.47542.18
Barnabei, Vanessa M. ; Cochrane, Barbara B. ; Aragaki, Aaron K. ; Nygaard, Ingrid ; Williams, R. Stan ; McGovern, Peter G. ; Young, Ronald L. ; Wells, Ellen C. ; O'Sullivan, Mary Jo ; Chen, Bertha ; Schenken, Robert ; Johnson, Susan R. / Menopausal symptoms and treatment-related effects of estrogen and progestin in the women's health initiative. In: Obstetrics and Gynecology. 2005 ; Vol. 105, No. 5 I. pp. 1063-1073.
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abstract = "OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean ± standard deviation 63.3 ± 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7{\%} versus 57.7{\%}, respectively; odds ratio 4.40; 95{\%} confidence interval 3.40-5.71), night sweats (77.6{\%} versus 57.4{\%}; 2.58; 2.04-3.26), vaginal or genital dryness (74.1{\%} versus 54.6{\%}; 2.40; 1.90-3.02), joint pain or stiffness (47.1{\%} versus 38.4{\%}; 1.43; 1.24 -1.64), and general aches or pains (49.3{\%} versus 43.7{\%}; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3{\%} versus 2.4{\%}, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1{\%} versus 1.0{\%}; 4.47; 3.44-5.81), vaginal or genital irritation (4.2{\%} versus 2.8{\%}; 1.52; 1.27-1.81), and headaches (5.8{\%} versus 4.7{\%}; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51{\%} of women on E+P and 5{\%} of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1{\%} versus 2.5{\%} for hysterectomy, hazard ratio = 1.23, P = .026; 5.4{\%} versus 2.4{\%} for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.",
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TY - JOUR

T1 - Menopausal symptoms and treatment-related effects of estrogen and progestin in the women's health initiative

AU - Barnabei, Vanessa M.

AU - Cochrane, Barbara B.

AU - Aragaki, Aaron K.

AU - Nygaard, Ingrid

AU - Williams, R. Stan

AU - McGovern, Peter G.

AU - Young, Ronald L.

AU - Wells, Ellen C.

AU - O'Sullivan, Mary Jo

AU - Chen, Bertha

AU - Schenken, Robert

AU - Johnson, Susan R.

PY - 2005/5/1

Y1 - 2005/5/1

N2 - OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean ± standard deviation 63.3 ± 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04-3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24 -1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27-1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.

AB - OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean ± standard deviation 63.3 ± 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04-3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24 -1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27-1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.

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