Hormone Therapy For Menopause

Publication Date: July 1, 2017
Last Updated: March 14, 2022

Recommendations

General

Hormone therapy is the most effective treatment for vasomotor symptoms (VMS) and genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. (Level I)
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Benefits are most likely to outweigh risks for symptomatic women who initiate hormone therapy (HT) when aged younger than 60 years or who are within 10 years of menopause onset. (Level I)
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Hormone therapy should be individualized, taking into account the indication(s) or evidence-based treatment goals, consideration of the woman’s age and/or time since menopause in relation to initiation or continuation, the woman’s personal health risks and preferences, and the balance of potential benefits and risks of HT versus nonhormone therapies or options. (Level III)
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The risks of HT in the Women’s Health Initiative (WHI) and other studies differ overall for estrogen therapy (ET) and estrogen-progestogen therapy (EPT), with a more favorable safety profile for ET. (Level II)
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Practitioners should use an appropriate HT type, dose, formulation, route of administration, and duration of use to meet treatment objectives, with periodic reassessment of changes in a woman’s health, and anticipated benefits, risks, and treatment goals over time. (Level III)
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Assessment of risk for estrogen-sensitive cancers, bone loss, heart disease, stroke, and VTE is appropriate when counseling menopausal women. (Level III)
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Decision making about HT should be incorporated into a broader discussion of lifestyle modification to manage symptoms and risks for chronic diseases of aging. (Level III)
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FDA-approved indications

Vasomotor symptoms

Hormone therapy is recommended as first-line therapy for bothersome VMS in women without contraindications. (Level I)
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Prevention of bone loss

Hormone therapy may be considered as a primary therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk of osteoporosis or fractures, primarily for women aged younger than 60 years or who are within 10 years of menopause onset. Bone-specific medications are also options; each has potential benefits and risks. (Level I)
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Hypoestrogenism

For women with hypoestrogenism caused by hypogonadism, POI, or premature surgical menopause without contraindications, HT is recommended until at least the median age of menopause (52 y). (Level II)
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The genitourinary syndrome of menopause/Vulvovaginal atrophy

When isolated genitourinary symptoms caused by menopause are present, low-dose vaginal ET is recommended over systemic ET as first-line medical therapy. (Level I)
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Hormone therapy: type, dose, regimen, and duration of use

Type, dose, and regimen

The type of HT, specific options, dose, and regimen should be individualized, using shared decision making and determined on the basis of known AE profiles and safety information, along with an individual woman’s health risks and personal preferences. (Level III)
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Compounded bioidentical HT should be avoided, given concerns about safety, including the possibility of overdosing or underdosing, lack of efficacy and safety studies, and lack of a label providing risks. (Level I) If compounded bioidentical HT is prescribed, concerns about safety should be discussed, and the indication for prescribing compounded rather than governmentapproved bioidentical HT should be documented (allergy, medical need for lower-than-available dose, different preparation). (Level III)
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Endometrial protection
  • For women with a uterus using systemic estrogen, endometrial protection requires an adequate dose and duration of a progestogen or use of the combination CEE with bazedoxifene.
(Level I)
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  • Progestogen therapy is not recommended with low-dose vaginal ET, but appropriate evaluation of the endometrium should be performed if vaginal bleeding occurs, given the limits of safety data.
(Level I)
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Lowering doses and/or changing to transdermal HT may be appropriate as women age or in those with metabolic syndromes such as hypertriglyceridemia with risk of pancreatitis or fatty liver. (Level III)
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Duration of use

Decisions about duration of HT require individualization, including consideration of personal preferences, balancing potential ongoing benefits and risks, and decisions to continue HT for preventive and/or QOL purposes. (Level III)
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In women with POI or early natural or induced menopause or who have had surgical menopause before age 45, and particularly before age 40, and who are otherwise appropriate candidates for HT, early initiation of HT and continued use at least until the median age of menopause (52 y) is recommended. This is based on observational evidence of potential prevention of risks related to early estrogen loss on CHD, osteoporosis, affective disorders, sexual dysfunction, GSM, and lowered cognitive function. (Level II)
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Discussions of duration of therapy should account for the woman’s health risks and the more favorable safety profile of CEE alone compared with the CEE + MPA seen in the WHI overall cohort.
  • Decision making about HT duration should take into account the woman’s risk (personal or familial) of breast cancer, CHD, VTE, and stroke.
(Level III)
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  • There is more flexibility for duration of ET use because reduced incidence of breast cancer was found with CEE in the WHI and seen with estradiol in the less-powered, openlabel Danish Osteoporosis Prevention Study. This reduced effect has not been shown in all other observational studies, and some show increased risk with long duration of use.
(Level II)
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  • For EPT, discussions of duration should include information about the potential of increased (rare) risk of breast cancer (absolute risk < 1 additional case/1,000 person-years of use) that began after 3 years of standard-dose CEE Ăľ MPA in the WHI. This increased risk was not seen in the subanalysis of the cohort without prior use of HT but was seen in past users. An increased risk of breast cancer over time has not been observed uniformly in other (less-powered) RCTs of HT using various EPT regimens.
(Level II)
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  • Discussion of benefits and risks of HT should include heart disease and all-cause mortality, particularly the reduced risk if started in women aged younger than 60 years or within 10 years of menopause onset and greater risks if initiated further from menopause onset or in women aged 60 years and older.
(Level I)
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  • Prevention of bone loss and fracture may be an indication for extended duration in select women after appropriate counseling about benefits and risks,
(Level III)
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  • recognizing that rapid bone loss is seen on discontinuation, but no rebound increase in fracture.
(Level I)
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  • Benefits and risks after withdrawing HT require consideration when deciding duration of therapy.
(Level II)
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Special populations

Early menopause

For women with POI or premature surgical menopause without contraindications, HT is recommended until at least the median age of menopause (52 y), because observational studies suggest that benefits outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood. (Level II)
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Family history of breast cancer: Observational evidence suggests that use of HT does not further alter the risk for breast cancer in women with a family history of breast cancer, although family history is one risk, among many, that should be assessed when counseling women regarding HT. (Level II)
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Women who are BRCA-positive without breast cancer

Women who are BRCA-positive without breast cancer are at higher genetic risk of breast cancer, primarily ER-negative. For those who have undergone surgical menopause (bilateral oophorectomy), benefits of estrogen to decrease health risks caused by premature loss of estrogen need to be considered. (Level II)
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On the basis of limited observational studies, consider offering systemic HT until the median age of menopause (52 y). Discussions about longer use should be individualized. (Level II)
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Breast and endometrial cancer survivors—systemic or vaginal hormone therapy

Bothersome VMS—consideration of systemic HT

Survivors of endometrial and breast cancer with bothersome VMS should be encouraged to consider nonhormone therapies that have been studied in RCTs in this population and found to be effective. (Level III)
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For survivors of endometrial cancer with prior early endometrial cancer treated with hysterectomy and with bothersome VMS not well controlled with nonhormone therapies, decisions about use of systemic HT should be made in conjunction with an oncologist. (Level III)
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For survivors of breast cancer, particularly estrogen-sensitive cancers, for which systemic HT is generally not offered, decisions about systemic HT should be made for compelling reasons after nonhormone or complementary options have been unsuccessful and after detailed counseling, with shared decision making and in conjunction with an oncologist. (Level III)
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Bothersome GSM symptoms—consideration of lowdose vaginal ET

Low-dose vaginal ET used for the GSM has minimal systemic absorption (blood levels in the postmenopause range) and, on the basis of limited observational data, appears to hold minimal to no demonstrated risk for recurrence of endometrial or breast cancer. (Level II)
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For women with early endometrial cancer who have completed successful treatment, including hysterectomy, consideration may be given for low-dose vaginal ET for relief of GSM if nonhormone options are not successful, based on limited short-term safety trials. (Level II)
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For women who are survivors of breast cancer, decisions about low-dose vaginal ET should involve the woman’s oncologist, particularly for women using AIs who have lowered overall estradiol levels. (Level III)
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Recommendation Grading

Overview

Title

Hormone Therapy For Menopause

Authoring Organization

Publication Month/Year

July 1, 2017

Last Updated Month/Year

January 17, 2024

Supplemental Implementation Tools

Document Type

Consensus

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Diagnosis, Management, Treatment

Diseases/Conditions (MeSH)

D008593 - Menopause, D017698 - Postmenopause

Keywords

breast cancer, estrogen, cardiovascular disease, menopause, hormone therapy, cognition, vaginal atrophy, vasomotor symptoms, Breast Cancer