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Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?

This recently published study from Finland generated headlines when its authors concluded that stopping HT elevates the risk of mortality from cardiovascular disease (CVD), including cardiac and cerebrovascular events. Using nationwide data, investigators compared the CVD mortality rate among women who discontinued HT during the years 1994 through 2009 (n = 332,202) with expected (not actual) CVD mortality rates in the background population.
Within the first year after HT discontinuation, elevations in death rates from cardiac events and stroke were noted (standardized mortality ratio, 1.26 and 1.63, respectively), while in the subsequent year, reductions in such mortality were observed (P<.05 for all comparisons).
The absolute increased risk of death from cardiac events reported within the first year after discontinuation of HT was 4 deaths per 10,000 woman-years of exposure. The absolute risk of death from stroke was 5 additional events per 10,000 woman-years. This level of risk is considered to be rare.

How these data compare to those of other studiesIn contrast with these Finnish data, findings from the Women’s Health Initiative—the largest randomized trial of menopausal HT—do not indicate an increase in mortality or an increase in coronary heart or stroke events among women stopping HT.1,2
It seems likely that limitations associated with the Finnish observational data account for this discordance. For example, Mikkola and colleagues did not know why women discontinued HT, raising the possibility that women with symptoms suggestive of CVD or development of new risk factors preferentially stopped HT, potentially introducing important bias into the Finnish analysis.

What this evidence means for practiceWomen and their clinicians should make decisions regarding whether to continue, reduce the dose, or discontinue HT through shared decision making, focusing on individual patient quality of life parameters as well as changing risk concerns related to such entities as cancer, CVD, and osteoporosis.3 Dramatic as they are, findings from this Finnish report should not impact how we counsel women regarding use or discontinuation of HT.
—Andrew M. Kaunitz, MD; JoAnn E. Manson, MD, DrPH; and Cynthia A. Stuenkel, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

References
  1. Heiss G, Wallace R, Anderson GL, et al; WHI investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299(9):1036–1045.
  2. LaCroix AZ, Chlebowski RT, Manson JE, et al; WHI investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. JAMA. 2011;305(13):1305–1314.
  3. Kaunitz AM. Extended duration use of menopausal hormone therapy. Menopause. 2014;21(6):679–68.
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Andrew M. Kaunitz, MD
University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz directs Menopause and Gynecologic Ultrasound Services, UF Women’s Health Specialists–Emerson. He serves on the OBG Management Board of Editors.

JoAnn E. Manson, MD, DrPH
Chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston and Professor of Medicine at Harvard Medical School. Dr. Manson is a Past President of the North American Menopause
Society (NAMS) and one of the principal investigators of the Women’s Health Initiative.

Cynthia A. Stuenkel, MD
Clinical Professor of Medicine, University of California, San Diego, School of Medicine, and Past President of NAMS.

Dr. Kaunitz reports that he is a consultant (contraception) to Actavis, Bayer, and Pfizer. The University of Florida receives clinical trial support from Bayer and TherapeuticsMD. Drs. Manson and Stuenkel report no financial relationships relevant to this article.

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Andrew M. Kaunitz MD,JoAnn E. Manson MD,Cynthia A. Stuenkel MD,discontinuation of menopausal hormone therapy,cardiovascular risk,hormone therapy,HT,cardiovascular disease,CVD,stroke,Women’s Health Initiative,WHI,osteoporosis,quality of life
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Andrew M. Kaunitz, MD
University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz directs Menopause and Gynecologic Ultrasound Services, UF Women’s Health Specialists–Emerson. He serves on the OBG Management Board of Editors.

JoAnn E. Manson, MD, DrPH
Chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston and Professor of Medicine at Harvard Medical School. Dr. Manson is a Past President of the North American Menopause
Society (NAMS) and one of the principal investigators of the Women’s Health Initiative.

Cynthia A. Stuenkel, MD
Clinical Professor of Medicine, University of California, San Diego, School of Medicine, and Past President of NAMS.

Dr. Kaunitz reports that he is a consultant (contraception) to Actavis, Bayer, and Pfizer. The University of Florida receives clinical trial support from Bayer and TherapeuticsMD. Drs. Manson and Stuenkel report no financial relationships relevant to this article.

Author and Disclosure Information

Andrew M. Kaunitz, MD
University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz directs Menopause and Gynecologic Ultrasound Services, UF Women’s Health Specialists–Emerson. He serves on the OBG Management Board of Editors.

JoAnn E. Manson, MD, DrPH
Chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston and Professor of Medicine at Harvard Medical School. Dr. Manson is a Past President of the North American Menopause
Society (NAMS) and one of the principal investigators of the Women’s Health Initiative.

Cynthia A. Stuenkel, MD
Clinical Professor of Medicine, University of California, San Diego, School of Medicine, and Past President of NAMS.

Dr. Kaunitz reports that he is a consultant (contraception) to Actavis, Bayer, and Pfizer. The University of Florida receives clinical trial support from Bayer and TherapeuticsMD. Drs. Manson and Stuenkel report no financial relationships relevant to this article.

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This recently published study from Finland generated headlines when its authors concluded that stopping HT elevates the risk of mortality from cardiovascular disease (CVD), including cardiac and cerebrovascular events. Using nationwide data, investigators compared the CVD mortality rate among women who discontinued HT during the years 1994 through 2009 (n = 332,202) with expected (not actual) CVD mortality rates in the background population.
Within the first year after HT discontinuation, elevations in death rates from cardiac events and stroke were noted (standardized mortality ratio, 1.26 and 1.63, respectively), while in the subsequent year, reductions in such mortality were observed (P<.05 for all comparisons).
The absolute increased risk of death from cardiac events reported within the first year after discontinuation of HT was 4 deaths per 10,000 woman-years of exposure. The absolute risk of death from stroke was 5 additional events per 10,000 woman-years. This level of risk is considered to be rare.

How these data compare to those of other studiesIn contrast with these Finnish data, findings from the Women’s Health Initiative—the largest randomized trial of menopausal HT—do not indicate an increase in mortality or an increase in coronary heart or stroke events among women stopping HT.1,2
It seems likely that limitations associated with the Finnish observational data account for this discordance. For example, Mikkola and colleagues did not know why women discontinued HT, raising the possibility that women with symptoms suggestive of CVD or development of new risk factors preferentially stopped HT, potentially introducing important bias into the Finnish analysis.

What this evidence means for practiceWomen and their clinicians should make decisions regarding whether to continue, reduce the dose, or discontinue HT through shared decision making, focusing on individual patient quality of life parameters as well as changing risk concerns related to such entities as cancer, CVD, and osteoporosis.3 Dramatic as they are, findings from this Finnish report should not impact how we counsel women regarding use or discontinuation of HT.
—Andrew M. Kaunitz, MD; JoAnn E. Manson, MD, DrPH; and Cynthia A. Stuenkel, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

This recently published study from Finland generated headlines when its authors concluded that stopping HT elevates the risk of mortality from cardiovascular disease (CVD), including cardiac and cerebrovascular events. Using nationwide data, investigators compared the CVD mortality rate among women who discontinued HT during the years 1994 through 2009 (n = 332,202) with expected (not actual) CVD mortality rates in the background population.
Within the first year after HT discontinuation, elevations in death rates from cardiac events and stroke were noted (standardized mortality ratio, 1.26 and 1.63, respectively), while in the subsequent year, reductions in such mortality were observed (P<.05 for all comparisons).
The absolute increased risk of death from cardiac events reported within the first year after discontinuation of HT was 4 deaths per 10,000 woman-years of exposure. The absolute risk of death from stroke was 5 additional events per 10,000 woman-years. This level of risk is considered to be rare.

How these data compare to those of other studiesIn contrast with these Finnish data, findings from the Women’s Health Initiative—the largest randomized trial of menopausal HT—do not indicate an increase in mortality or an increase in coronary heart or stroke events among women stopping HT.1,2
It seems likely that limitations associated with the Finnish observational data account for this discordance. For example, Mikkola and colleagues did not know why women discontinued HT, raising the possibility that women with symptoms suggestive of CVD or development of new risk factors preferentially stopped HT, potentially introducing important bias into the Finnish analysis.

What this evidence means for practiceWomen and their clinicians should make decisions regarding whether to continue, reduce the dose, or discontinue HT through shared decision making, focusing on individual patient quality of life parameters as well as changing risk concerns related to such entities as cancer, CVD, and osteoporosis.3 Dramatic as they are, findings from this Finnish report should not impact how we counsel women regarding use or discontinuation of HT.
—Andrew M. Kaunitz, MD; JoAnn E. Manson, MD, DrPH; and Cynthia A. Stuenkel, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

References
  1. Heiss G, Wallace R, Anderson GL, et al; WHI investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299(9):1036–1045.
  2. LaCroix AZ, Chlebowski RT, Manson JE, et al; WHI investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. JAMA. 2011;305(13):1305–1314.
  3. Kaunitz AM. Extended duration use of menopausal hormone therapy. Menopause. 2014;21(6):679–68.
References
  1. Heiss G, Wallace R, Anderson GL, et al; WHI investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299(9):1036–1045.
  2. LaCroix AZ, Chlebowski RT, Manson JE, et al; WHI investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. JAMA. 2011;305(13):1305–1314.
  3. Kaunitz AM. Extended duration use of menopausal hormone therapy. Menopause. 2014;21(6):679–68.
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Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
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Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
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Andrew M. Kaunitz MD,JoAnn E. Manson MD,Cynthia A. Stuenkel MD,discontinuation of menopausal hormone therapy,cardiovascular risk,hormone therapy,HT,cardiovascular disease,CVD,stroke,Women’s Health Initiative,WHI,osteoporosis,quality of life
Legacy Keywords
Andrew M. Kaunitz MD,JoAnn E. Manson MD,Cynthia A. Stuenkel MD,discontinuation of menopausal hormone therapy,cardiovascular risk,hormone therapy,HT,cardiovascular disease,CVD,stroke,Women’s Health Initiative,WHI,osteoporosis,quality of life
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