The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus

A randomized trial

Jill P. Buyon, Michelle Petri, Mimi Y. Kim, Kenneth C. Kalunian, Jennifer Grossman, Bevra H. Hahn, Joan T. Merrill, Lisa Sammaritano, Michael Lockshin, Graciela S. Alarcón, Susan Manzi, H. Michael Belmont, Anca D. Askanase, Lisa Sigler, Mary Anne Dooley, Joan Von Feldt, W. Joseph McCune, Alan Friedman, Jane Wachs, Mary Cronin & 3 others Michelene Hearth-Holmes, Mark Tan, Frederick Licciardi

Research output: Contribution to journalArticle

Abstract

Background: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE). Objective: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE. Design: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002. Setting: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states. Patients: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE, Interventions: 12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group. Measurements: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite, Results: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis. Limitations: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis. Conclusions: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.

Original languageEnglish (US)
JournalAnnals of Internal Medicine
Volume142
Issue number12 I
StatePublished - Jun 21 2005
Externally publishedYes

Fingerprint

Hormone Replacement Therapy
Systemic Lupus Erythematosus
Progesterone
Estrogens
Placebos
Venous Thrombosis
Thrombosis
Medroxyprogesterone
Conjugated (USP) Estrogens
Lupus Coagulation Inhibitor
Anticardiolipin Antibodies
Rheumatology
Therapeutics
Stroke
Hormones
Transplants
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus : A randomized trial. / Buyon, Jill P.; Petri, Michelle; Kim, Mimi Y.; Kalunian, Kenneth C.; Grossman, Jennifer; Hahn, Bevra H.; Merrill, Joan T.; Sammaritano, Lisa; Lockshin, Michael; Alarcón, Graciela S.; Manzi, Susan; Belmont, H. Michael; Askanase, Anca D.; Sigler, Lisa; Dooley, Mary Anne; Von Feldt, Joan; McCune, W. Joseph; Friedman, Alan; Wachs, Jane; Cronin, Mary; Hearth-Holmes, Michelene; Tan, Mark; Licciardi, Frederick.

In: Annals of Internal Medicine, Vol. 142, No. 12 I, 21.06.2005.

Research output: Contribution to journalArticle

Buyon, JP, Petri, M, Kim, MY, Kalunian, KC, Grossman, J, Hahn, BH, Merrill, JT, Sammaritano, L, Lockshin, M, Alarcón, GS, Manzi, S, Belmont, HM, Askanase, AD, Sigler, L, Dooley, MA, Von Feldt, J, McCune, WJ, Friedman, A, Wachs, J, Cronin, M, Hearth-Holmes, M, Tan, M & Licciardi, F 2005, 'The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: A randomized trial', Annals of Internal Medicine, vol. 142, no. 12 I.
Buyon, Jill P. ; Petri, Michelle ; Kim, Mimi Y. ; Kalunian, Kenneth C. ; Grossman, Jennifer ; Hahn, Bevra H. ; Merrill, Joan T. ; Sammaritano, Lisa ; Lockshin, Michael ; Alarcón, Graciela S. ; Manzi, Susan ; Belmont, H. Michael ; Askanase, Anca D. ; Sigler, Lisa ; Dooley, Mary Anne ; Von Feldt, Joan ; McCune, W. Joseph ; Friedman, Alan ; Wachs, Jane ; Cronin, Mary ; Hearth-Holmes, Michelene ; Tan, Mark ; Licciardi, Frederick. / The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus : A randomized trial. In: Annals of Internal Medicine. 2005 ; Vol. 142, No. 12 I.
@article{fe2cbc430ca24acba2c3e18e699ca987,
title = "The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: A randomized trial",
abstract = "Background: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE). Objective: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE. Design: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002. Setting: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states. Patients: 351 menopausal patients (mean age, 50 years) with inactive (81.5{\%}) or stable-active (18.5{\%}) SLE, Interventions: 12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82{\%} for the HRT group and 87{\%} for the placebo group. Measurements: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite, Results: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95{\%} CI for the treatment difference was 0.078, within the prespecified margin of 9{\%} for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis. Limitations: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis. Conclusions: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.",
author = "Buyon, {Jill P.} and Michelle Petri and Kim, {Mimi Y.} and Kalunian, {Kenneth C.} and Jennifer Grossman and Hahn, {Bevra H.} and Merrill, {Joan T.} and Lisa Sammaritano and Michael Lockshin and Alarc{\'o}n, {Graciela S.} and Susan Manzi and Belmont, {H. Michael} and Askanase, {Anca D.} and Lisa Sigler and Dooley, {Mary Anne} and {Von Feldt}, Joan and McCune, {W. Joseph} and Alan Friedman and Jane Wachs and Mary Cronin and Michelene Hearth-Holmes and Mark Tan and Frederick Licciardi",
year = "2005",
month = "6",
day = "21",
language = "English (US)",
volume = "142",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "12 I",

}

TY - JOUR

T1 - The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus

T2 - A randomized trial

AU - Buyon, Jill P.

AU - Petri, Michelle

AU - Kim, Mimi Y.

AU - Kalunian, Kenneth C.

AU - Grossman, Jennifer

AU - Hahn, Bevra H.

AU - Merrill, Joan T.

AU - Sammaritano, Lisa

AU - Lockshin, Michael

AU - Alarcón, Graciela S.

AU - Manzi, Susan

AU - Belmont, H. Michael

AU - Askanase, Anca D.

AU - Sigler, Lisa

AU - Dooley, Mary Anne

AU - Von Feldt, Joan

AU - McCune, W. Joseph

AU - Friedman, Alan

AU - Wachs, Jane

AU - Cronin, Mary

AU - Hearth-Holmes, Michelene

AU - Tan, Mark

AU - Licciardi, Frederick

PY - 2005/6/21

Y1 - 2005/6/21

N2 - Background: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE). Objective: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE. Design: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002. Setting: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states. Patients: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE, Interventions: 12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group. Measurements: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite, Results: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis. Limitations: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis. Conclusions: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.

AB - Background: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE). Objective: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE. Design: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002. Setting: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states. Patients: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE, Interventions: 12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group. Measurements: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite, Results: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis. Limitations: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis. Conclusions: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.

UR - http://www.scopus.com/inward/record.url?scp=20544443248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20544443248&partnerID=8YFLogxK

M3 - Article

VL - 142

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 12 I

ER -