Hormone Therapy in Postmenopausal Women : Preventive Medications --Postmenopausal women


General

Grade: D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.

Specific Recommendations

The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal women.

Frequency of Service

No information available.

Risk Factor Information

This recommendation statement applies to an average-risk population. Risk factors for a specific chronic condition or individual characteristics that affect the likelihood of experiencing a specific therapy-associated adverse event may cause a woman’s net balance of benefits and harms to differ from that of the average population.


Clinical

Patient Population Under Consideration

This recommendation statement applies to asymptomatic, postmenopausal women who are considering hormone therapy for the primary prevention of chronic medical conditions. It does not apply to women who are considering hormone therapy for the management of menopausal symptoms, such as hot flashes or vaginal dryness. It also does not apply to women who have had premature menopause (primary ovarian insufficiency) or surgical menopause.

Assessment of Risk

This recommendation statement applies to an average-risk population. Risk factors for a specific chronic condition or individual characteristics that affect the likelihood of experiencing a specific therapy-associated adverse event may cause a woman’s net balance of benefits and harms to differ from that of the average population.

Treatment and Intervention

Menopausal hormone therapy refers to the use of combined estrogen and progestin in women with an intact uterus, or estrogen alone in women who have had a hysterectomy, taken at or after the time of menopause. For this recommendation, the USPSTF considered evidence on the benefits and harms of systemic (ie, oral or transdermal) menopausal hormone therapy but not local formulations (eg, creams or rings) of hormone therapy, because these are not generally used for the primary prevention of chronic conditions.

Indications for hormone therapy approved by the US Food and Drug Administration (FDA) in menopausal women are limited to the treatment of menopausal symptoms and the prevention of postmenopausal osteoporosis. An FDA-issued black box warning indicates that estrogen therapy, with or without progestin, should be prescribed at the lowest effective dose and for the shortest duration consistent with the patient’s treatment goals and risks.2

Several different formulations of menopausal hormone therapy are approved by the FDA for use in the United States; the specific formulation used in the WHI trial, the largest trial reviewed by the USPSTF, was 0.625 mg/d of oral conjugated equine estrogens, with or without 2.5 mg/d of medroxyprogesterone acetate. Currently, evidence to determine whether different types, doses, or modes of delivery of hormone therapy affect its benefit-to-harm profile for the prevention of chronic conditions is limited.1

The use of menopausal hormone therapy is associated with both benefits and harms. Combined estrogen and progestin use is associated with a decreased risk of fractures, diabetes, and colorectal cancer; however, it is also associated with an increased risk of invasive breast cancer, coronary heart disease, thromboembolic events, stroke, dementia, gallbladder disease, and self-reported urinary incontinence. Estrogen use alone is associated with a decreased risk of fractures, invasive breast cancer, and diabetes; however, it is also associated with an increased risk of thromboembolic events, stroke, dementia, gallbladder disease, and self-reported urinary incontinence. The reason for the discordant effect of estrogen alone compared with combined estrogen and progestin on the risk of invasive breast cancer is unclear. Table 1 and Table 2 show the estimated absolute event rate differences associated with the use of combined estrogen and progestin and estrogen alone, compared with placebo, for these health outcomes.1

Other Approaches to Prevention

Several interventions and preventive medications to reduce the risk of chronic conditions in women have been studied. For example, the use of medications such as tamoxifen and raloxifene in women at increased risk of breast cancer who do not have contraindications and are at low risk of adverse medication effects is a potential strategy to reduce risk of breast cancer.3 The USPSTF recommends behavioral counseling interventions to promote a healthful diet and physical activity for the prevention of cardiovascular disease in adults who are overweight or obese and have additional cardiovascular disease risk factors.4 The USPSTF also recommends daily use of low-dose aspirin to decrease the risk of colorectal cancer and cardiovascular disease in appropriate candidates.5


Rationale

Importance

Menopause is defined as the permanent cessation of a woman’s menstrual cycle. It is typically defined in retrospect, 12 months after a woman’s final menstrual period. Menopause occurs at a median age of 51.3 years, and the average US woman who reaches menopause is expected to live another 30 years. The prevalence and incidence of most chronic conditions, such as coronary heart disease, dementia, stroke, fractures, and breast cancer, increase with age; however, the excess risk for these conditions that can be attributed to menopause alone is uncertain. Since the publication of findings from the Women’s Health Initiative (WHI) that hormone therapy use was associated with serious adverse health effects in postmenopausal women, use of menopausal hormone therapy has declined, from 44% of US women using or having used hormone therapy in 1988–1994 to 4.7% of women in 2010.1

Benefits of Preventive Medication

Combined Estrogen and Progestin

Many health outcomes potentially associated with the use of hormone therapy in postmenopausal women have been examined. The USPSTF found convincing evidence that use of combined estrogen and progestin has a moderate benefit in reducing the risk of fractures in postmenopausal women and adequate evidence that it has a small benefit in reducing the risk of diabetes.

Estrogen Alone

The use of estrogen without progestin has generally been restricted to women who have had a hysterectomy, because unopposed estrogen use increases the risk of endometrial cancer in women with an intact uterus. The USPSTF found convincing evidence that use of estrogen alone has a moderate benefit in reducing the incidence of fractures in postmenopausal women. The USPSTF found adequate evidence that the use of estrogen alone has a moderate benefit in reducing the risk of developing or dying of invasive breast cancer and a small benefit in reducing the risk of diabetes. The USPSTF found convincing evidence that estrogen use does not have a beneficial effect on risk of coronary heart disease.

Harms of Preventive Medication

Combined Estrogen and Progestin

The USPSTF found convincing evidence that use of combined estrogen and progestin is associated with moderate harms, including increased risk of invasive breast cancer and venous thromboembolism, and a small to moderate harm of increased risk of coronary heart disease. The USPSTF also found adequate evidence of other moderate harms, such as increased risk of stroke, dementia, gallbladder disease, and urinary incontinence.

Estrogen Alone

The USPSTF found adequate evidence that use of estrogen alone is associated with moderate harms, including increased risk of stroke, dementia, gallbladder disease, urinary incontinence, and venous thromboembolism.

USPSTF Assessment

The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin has no net benefit for the primary prevention of chronic conditions in most postmenopausal women with an intact uterus.

The USPSTF concludes with moderate certainty that the use of estrogen alone has no net benefit for the primary prevention of chronic conditions in most postmenopausal women who have had a hysterectomy.


Others

Other Considerations Research Needs and Gaps Evidence is limited whether the benefits and harms of menopausal hormone therapy vary by age, race/ethnicity, or timing of initiation after menopause. In the WHI trial, the test for trend by age group showed a statistically significant trend toward lower all-cause mortality among younger women (aged 50 to 59 years at time of randomization) assigned to estrogen alone but not women assigned to combined estrogen and progestin. There is no evidence that women of different races/ethnicities experience a different balance of benefits and harms with menopausal hormone therapy; however, the majority (approximately 80%) of women in the largest trial (WHI) where white, so these analyses may be underpowered to detect such differences. Data regarding whether the timing of initiation of hormone therapy after menopause affects the balance of benefits and harms are conflicting. A meta-analysis of individual-patient data may be helpful to determine whether the balance of benefits and harms of hormone therapy is different in any of these subgroups.   Update of Previous USPSTF Recommendations As in its 2012 recommendation on the use of menopausal hormone therapy for the primary prevention of chronic conditions, the USPSTF continues to recommend against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal women and against the use of estrogen alone in postmenopausal women who have had a hysterectomy.   Recommendations of Others The American Heart Association33 and the American College of Obstetricians and Gynecologists34 recommend against the use of hormone therapy for the primary or secondary prevention of coronary heart disease, and most clinical guidelines, including those of the Canadian Task Force on Preventive Health Care35 and the American Academy of Family Physicians,36 recommend against the use of hormone therapy for prevention of any chronic conditions. The American Association of Clinical Endocrinologists3738 recommends that cardiovascular risk, age, and time from menopause be considered when using hormone therapy in symptomatic postmenopausal women and notes that hormone therapy is approved by the FDA for use in women at increased risk of osteoporosis and fractures. The American College of Obstetricians and Gynecologists mentions that the effect of hormone therapy on risk of cardiovascular disease may differ based on early vs late initiation of hormone therapy with respect to onset of menopause. The North American Menopause Society39 focuses primarily on considerations for women with symptoms; it notes that hormone therapy has been shown to prevent fractures and that treatment should be individualized to balance the potential health benefits and risks for each woman. The Endocrine Society40 also focuses primarily on the use of hormone therapy for the treatment of symptoms of menopause.


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