Final Research Plan

Hormone Therapy in Postmenopausal Women: Primary Prevention of Chronic Conditions

October 22, 2015

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from June 25 until July 22, 2015 at 5:00 p.m., ET.

Abbreviation: KQ = key question.

*Definitions of perimenopausal and postmenopausal women are based on STRAW+10 criteria (from Harlow SD, Gass M, Hall JE, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012;19(4):387-95.).

Text Description.

This figure is an analytic framework depicting the key questions (KQs) to be addressed in the systematic review. This figure illustrates the pathway for the population of interest, namely generally healthy perimenopausal and postmenopausal women eligible for hormone therapy. There are two overarching questions for the review that span the entire analytic framework. The first (KQ 1) examines the improved health outcomes that may result from hormone therapy when used for the primary prevention of chronic conditions and the second (KQ 3) evaluates whether those benefits differ by subgroup or by timing of intervention. Alternatively, KQ 2 examines the adverse effects associated with hormone therapy and KQ 3 evaluates whether those harms differ by subgroup or by timing of intervention.

  1. What are the benefits of menopausal hormone therapy when used for the primary prevention of chronic conditions?
  2. What are the harms of menopausal hormone therapy when used for the primary prevention of chronic conditions?
  3. Do the benefits and harms of menopausal hormone therapy differ by subgroup (race/ethnicity; women with premature menopause; women with surgical menopause; age during hormone therapy use; duration of use; type, dose, and mode of delivery of hormone therapy; and comorbid condition) or by timing of intervention (initiation of hormone therapy during perimenopause vs. postmenopause)?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the average treatment duration of hormone therapy in women who initiate its use for the treatment of menopausal symptoms?
  2. Does the use of hormone therapy vary by subgroup?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Included Excluded
Population Generally healthy perimenopausal and postmenopausal women who are eligible for menopausal hormone therapy; women with and without menopausal symptoms will be included if the focus of the analysis is on the prevention of chronic conditions Animals; men; premenopausal women; postmenopausal women with contraindications for hormone therapy use, such as history of breast cancer, coronary heart disease, previous venous thromboembolic event or stroke, active liver disease, or women who are at high risk for these complications; populations that are not applicable to U.S. primary care
Interventions Systemic therapy with estrogen-only formulations or estrogen combined with progestin for the prevention of chronic conditions: U.S. Food and Drug Administration–approved medications that are available for use in the United State Localized (nonsystemic) treatments, such as rings or gels, contraceptives, and other hormones or treatments of menopausal symptoms (such as over-the-counter preparations that are not approved by the U.S. Food and Drug Administration)
Control interventions Placebo, no treatment Active comparator
Outcomes KQs 1–3:
  • Overall mortality
  • Disease-specific mortality (if related to chronic conditions of interest)
  • Coronary heart disease
  • Stroke
  • Thromboembolism
  • Cancer (breast, colorectal, endometrial, ovarian, and nonsmall cell lung)
  • Cholecystitis
  • Fractures
  • Cognition
  • Quality of life (if related to chronic conditions of interest)
  • Functional capacity
  • Urinary incontinence
  • Diabetes
Any outcomes that are not health outcomes of chronic conditions associated with hormone therapy (e.g., intermediate outcomes, such as bone density and cholesterol level)
Duration of intervention ≥1 year of treatment <1 year of treatment
Publication language English Non-English language
Study design All outcomes:
  • Randomized, controlled trials
  • Controlled clinical trials
  • Systematic reviews

Large cohort studies (>10,000 women) for outcomes with no evidence from trials or systematic reviews

All other study designs
Publication type Published or unpublished original research Nonsystematic review article, letter, or editorial; results reported elsewhere; no original data
Geography U.S. adult population or comparable populations (i.e., those categorized as “Very High” on the Human Development Index, as defined by the United Nations Development Programme) Settings not comparable or applicable to U.S. adult population
Date of search January 2011 onward Before January 2011
Setting Primary care or primary care–like settings Inpatient facilities, nursing homes, and specialist settings (such as endocrinology)
A draft version of the research plan was posted for public comment on the USPSTF Web site from June 25 to July 22, 2015. The USPSTF received several comments requesting that it include women who are receiving hormone therapy for the treatment of menopausal symptoms in the populations studied. While treatment of menopausal symptoms is beyond the scope of this review, the USPSTF clarified that studies of women who are receiving hormone therapy for the treatment of menopausal symptoms will be included if the primary prevention of a chronic condition is also assessed. The USPSTF also revised a key question to clarify that subgroup analyses based on timing of initiation of treatment and race/ethnicity will be performed.