Draft Research Plan
Menopausal Hormone Therapy in Postmenopausal Women: Primary Prevention of Chronic Conditions
February 18, 2021
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a Definitions of perimenopausal and postmenopausal women are based on STRAW+ 10 criteria.
Abbreviations: KQ=key question; STRAW+=Stages of Reproductive Aging Workshop + 10.
- What are the benefits of menopausal hormone therapy (HT) when used for the primary prevention of chronic conditions?
- What are the harms of menopausal HT when used for the primary prevention of chronic conditions?
- Do the benefits and harms of menopausal HT differ by subgroup (e.g., by race/ethnicity; women with premature menopause; women with surgical menopause; age during HT use; duration of use; type, dose, and mode of delivery of HT; and comorbid condition) or by timing of intervention (initiation of HT during perimenopause vs. postmenopause)?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- What is the average treatment duration in women who start HT for menopausal symptoms?
- Does the use of HT vary by subgroup?
The Proposed 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 apply to all of the key questions.
|Interventions||Systemic therapy with estrogen-only formulations or combinations with progestin for prevention of chronic conditions. Medications are FDA approved and available for use in the United States. See Table 2.||Localized (nonsystemic) treatments such as rings or gels, contraceptives, other hormones, or treatments of menopausal symptoms such as over-the-counter preparations or compounded bioidentical therapies that are not FDA approved.|
|Control interventions||Placebo, no treatment||Active comparator|
||Any outcomes that are not health outcomes of chronic conditions associated with HT; such as bone density and cholesterol level|
|Duration of intervention||1 year of treatment||Less than 1 year of treatment|
|Publication language||English||Non-English language|
|Study design||All outcomes:
For outcomes or subgroups with no evidence from trials or systematic reviews
|All other study designs|
|Publication type||Published or unpublished original research||Nonsystematic review article, letter, editorial, results reported elsewhere, no original data|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)||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, hormone specialist offices|
Abbreviations: FDA=Food and Drug Administration; HT=hormone therapy; RCT=randomized, controlled trial; U.S.=United States.
|Category of Hormone Therapy
and Generic Name
|Brand Name||Product Type||Dosage†|
|Estradiol‡||Alora||Patch||0.025–0.1 mg worn for 24 hours twice weekly|
|Synthetic conjugated estrogens||Cenestin||Pill||0.3–1.25 mg/day|
|Estradiol‡||Climara||Patch||0.025–0.1 mg worn for 24 hours once weekly|
|Estradiol valerate||Delestrogen||Injection||10/20/40 mg/mL/month|
|Estradiol‡||Estraderm||Patch||0.05–0.1 mg continuously or cyclically§|
|Estradiol‡||Menostar||Patch||0.014 mg worn for 24 hours once weekly|
|Estradiol‡||Minivelle||Patch||0.025–0.1 mg worn for 24 hours twice weekly|
|Micronized progesterone||Prometrium||Pill||0.625 mg/day|
|Medroxyprogesterone acetate||Provera||Pill||100–200 mg/day|
|Estradiol‡||Vivelle-Dot||Patch||0.025–0.1 mg worn for 24 hours twice weekly|
|Estradiol acetate‡||Femtrace||Pill||0.45–1.8 mg/day|
|Esterifield estrogen‡||Menest||Pill||0.3–1.25 mg/day cyclically§|
|Conjugated estrogens¶||Premarin||Pill, injection||0.3 mg/day cyclically,§ single 25-mg injection|
|Synthetic conjugated estrogens#||Enjuvia||Pill||0.3 mg/day|
|Combination Estrogen Plus Progestin Formulations|
|Estradiol‡ + drospirenone**||Angeliq||Pill||Drospirenone 0.25–0.5 mg/day with estradiol 0.5–1.0 mg/day|
|Estradiol‡ + norethindrone acetate#||Activella||Pill||Estradiol 0.5–1.0 mg/day with norethindrone 0.1 mg/day|
|Estradiol‡ + norgestimate**||Prefest||Pill||Repeat estradiol 1 mg/day for 3 days followed by estradiol 1 mg/day with norgestimate 0.09 mg/day for 3 days|
|Estradiol‡ + levonorgestrel**||Climara Pro||Patch||Estradiol 0.045 mg with levonorgestrel 0.015 mg worn for 24 hours once weekly|
|Estradiol‡ + norethindrone acetate**||Combipatch||Patch||Estradiol 0.05 mg with norethindrone 0.14–0.25 mg worn for 24 hours once weekly|
|Conjugated estrogene + medroxyprogesterone acetate**||Prempro||Pill||Conjugated estrogen 0.625 mg/day with medroxyprogesterone acetate 5 mg/day|
|Ethinyl estradiol‡ + norethindrone acetate#||Femhrt||Pill||Ethinyl estradiol 0.0025 mg/day with norethindrone acetate 0.500 mg/day|
* Source: U.S. Food and Drug Administration. Menopause: Medicines to Help You. https://www.fda.gov/consumers/free-publications-women/menopause-medicines-help-you. Accessed January 28, 2021.
† Dosages are based on the package inserts for the brand name formulations.
? Estradiol can be from natural sources or prepared synthetically.
§ Cyclically means “within a cycle” (e.g., repeat 3 weeks of treatment and 1 week off).
? Natural estrogenic substance prepared from purified crystalline estrone.
¶ Conjugated estrogens, such as conjugated equine estrogens, are derived wholly or partially from the urine of pregnant mares or synthetic estrone and equilin.
# Synthetic conjugated estrogens are prepared using plant sources, such as yams and soy, and use only synthetic resources.
** Synthetic progestin.