• About Us
    • Contact Us
    • Login
    • ObGFirst
  • Alerts
  • OB
  • 2T US Atlas
  • The Genome
  • GYN
    • GYN
    • Sexual Health
  • Primary Care
  • Your Practice
  • GrandRounds
  • My Bookshelf
  • COVID-19
About Us Contact Us Login ObGFirst
  • Alerts
  • OB
  • 2T US Atlas
  • The Genome
  • GYN
    • GYN
    • Sexual Health
  • Primary Care
  • Your Practice
  • GrandRounds
  • My Bookshelf
  • COVID-19
Grand Rounds

The WHI Randomized Trials: Is Menopausal Hormone Therapy Associated with Long-Term Mortality?

image_pdfFavoriteLoadingFavorite

PURPOSE:

  • The original WHI trials were designed to assess risk vs benefits of menopausal hormone therapy
  • Double-blinded, placebo-controlled, randomized clinical trials, conducted among US postmenopausal women aged 50 to 79 years at enrollment using the following 2 drug regimens
    • Conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for women with an intact uterus
    • CEE alone for women with hysterectomy
  • The CEE plus MPA trial was stopped early (after 5.6 years) due to an increased risk of breast cancer and overall risks exceeding benefits
  • CEE-alone trial was stopped after 7.2 years due to an increased risk of stroke
  • Postintervention follow up has been ongoing
  • Manson et al. (JAMA, 2017) report the extended follow up on all-cause and cause-specific mortality with attention to age

METHODS:

  • Postintervention follow up study of the two WHI studies (1993-1998)
  • Total 27,347 postmenopausal women ages 50 to 79 years were recruited at 40 US clinical centers
    • 16,608 women with a uterus received daily oral CEE (0.625 mg) plus MPA (2.5 mg) or placebo
    • 10,739 women with hysterectomy received daily oral CEE (0.625 mg) alone or placebo
  • Primary outcome: All-cause mortality
    • Cause-specific mortality (cardiovascular disease cancer and other major causes)
  • 18 year follow up in 2 trials separately and combined (pooled)

RESULTS:

  • All-cause mortality
    • Pooled cohort: 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03])
    • CEE plus MPA: HR 1.02 (95% CI, 0.96-1.08)
    • CEE alone: HR 0.94 (95% CI, 0.88-1.01)
  • Cardiovascular mortality
    • Pooled cohort: HR 1.00 (95% CI, 0.92-1.08)
  • Total cancer mortality
    • Pooled cohort: HR 1.03 (95% CI, 0.95-1.12)
  • Other causes
    • Pooled cohort: HR 0.95 (95% CI, 0.88-1.02)
    • results did not differ significantly between trials
  • Comparing younger women (50-59 years) to older women (70-79 years) in the pooled cohort for all-cause mortality
    • During intervention phase: all-cause mortality reduced compared to older women
      • ratios of HRs 0.61 (95% CI, 0.43-0.87)
    • During cumulative 18-year follow-up: no difference seen in all-cause mortality compared to older women
      • ratios of HRs 0.87 (95% CI, 0.76-1.00)
    • No significant difference between trials

CONCLUSION:

  • There was no long-term association between hormone replacement and all-cause or cause-specific mortality during a follow up period of 18 years in women who used combination estrogen plus progestin for 5.6 or estrogen-alone group for 7.2 years
  • Limitations include specific hormone replacement formulations and therefore results may not be generalizable
  • Cause-specific mortality results should be considered exploratory because multiple smaller subgroups were analyzed
  • The accompanying editorial states that this present study supports the recently released 2017 NAMS guidance and women should be reassured and hormone therapy appears “safe and efficacious”.

Learn More – Primary Sources:

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials

Menopausal Hormone Therapy: Understanding Long-term Risks and Benefits (JAMA Editorial)

image_pdfFavoriteLoadingFavorite

< Previous
All Grand Rounds Posts
Next >

Related ObG Topics:

North American Menopause Society: Hormone Therapy Statement
Early-Onset Menopause – Increased Risk of Cardiovascular Disease?
Treating Postmenopausal Vaginal Atrophy When Estrogen is Not an Option
Practical info on evidence based medicine for your women's healthcare practice
Does Estrogen Therapy Have Cardiovascular Benefit in Early Postmenopause?
Does Hormone Therapy Protect Against Alzheimer’s?

Sections

  • Alerts
  • OB
  • GYN
    • GYN
    • Sexual Health
  • 2T US Atlas
  • The Genome
  • Primary Care
  • Your Practice
  • Grand Rounds
  • My Bookshelf
  • COVID-19

Are you an
ObG Insider?

Get specially curated clinical summaries delivered to your inbox every week for free

  • Site Map/
  • © ObG Project/
  • Terms and Conditions/
  • Privacy/
  • Contact Us/
© ObG Project
SSL Certificate


  • Already an ObGFirst Member?
    Welcome back

    Log In

    Want to sign up?
    Get guideline notifications
    CME Included

    Sign Up

Sign In

Lost your password?

Sign Up for ObGFirst and Stay Ahead

  • - Professional guideline notifications
  • - Daily summary of a clinically relevant
    research paper
  • - Includes 1 hour of CME every month

ObGFirst Free Trial

Already a Member of ObGFirst®?

Please log in to ObGFirst to access the 2T US Atlas

Password Trouble?

Not an ObGFirst® Member Yet?

  • - Access 2T US Atlas
  • - Guideline notifications
  • - Daily research paper summaries
  • - And lots more!
ObGFirst Free Trial

Media - Internet

Computer System Requirements

OBG Project CME requires a modern web browser (Internet Explorer 10+, Mozilla Firefox, Apple Safari, Google Chrome, Microsoft Edge). Certain educational activities may require additional software to view multimedia, presentation, or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Apple QuickTime, Adobe Acrobat, Microsoft PowerPoint, Windows Media Player, or Real Networks Real One Player.

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

Jointly provided by

NOT ENOUGH CME HOURS

It appears you don't have enough CME Hours to take this Post-Test. Feel free to buy additional CME hours or upgrade your current CME subscription plan

Subscribe

JOIN OBGFIRST AND GET CME/CE CREDITS

One of the benefits of an ObGFirst subscription is the ability to earn CME/CE credits from the ObG entries you read. Tap the button to learn more about ObGFirst

Learn More
Leaving ObG Website

You are now leaving the ObG website and on your way to PRIORITY at UCSF, an independent website. Therefore, we are not responsible for the content or availability of this site