What are the risks and benefits of hormone therapy for perimenopause symptoms?

From the Guidelines

Hormone therapy for perimenopause symptoms should be used at the lowest effective dose for the shortest time needed, typically less than 5 years, and before age 60, to maximize benefits while minimizing risks. The primary benefits of hormone therapy include effective relief from hot flashes, night sweats, vaginal dryness, mood swings, and sleep disturbances. Common hormone therapy options include estrogen-only therapy (typically estradiol in patch form at 0.025-0.05mg, or oral at 0.5-1mg daily) for women without a uterus, or combined estrogen-progestin therapy (such as estradiol with micronized progesterone 100-200mg daily for 12-14 days per month or continuously) for women with a uterus to prevent endometrial cancer.

• The risks associated with hormone therapy include slightly increased chances of blood clots, stroke, and breast cancer, with the latter risk particularly associated with combined therapy used for more than 5 years 1.
• Heart disease risk may increase if therapy starts more than 10 years after menopause 1.
• Women with a history of breast cancer, blood clots, stroke, liver disease, or unexplained vaginal bleeding should avoid hormone therapy and consider non-hormonal alternatives like SSRIs, gabapentin, or lifestyle modifications 1.
• The USPSTF recommends that hormone therapy be used for the treatment of menopausal symptoms and the prevention of osteoporosis, but not for the primary prevention of chronic conditions such as heart disease or breast cancer 1.
• The quality of evidence on the benefits and harms of hormone therapy varies for different hormone regimens, and most of the evidence comes from observational studies that did not differentiate among the effects of specific hormone preparations 1.
• The FDA has approved indications for hormone therapy in postmenopausal women for the treatment of menopausal symptoms and the prevention of osteoporosis, with a black box warning indicating that estrogen with or without progestin should be prescribed at the lowest effective dose and for the shortest duration of use consistent with treatment goals and risks for the individual woman 1.

From the FDA Drug Label

ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2. 5 mg) relative to placebo. The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

The risks of hormone therapy during perimenopause include:

• Endometrial cancer: increased risk with estrogen use
• Cardiovascular events: increased risk of myocardial infarction, stroke, and deep vein thrombosis
• Breast cancer: increased risk with estrogen plus progestin therapy, and a smaller increased risk with estrogen-alone therapy
• Ovarian cancer: increased risk with hormonal therapy
• Abnormal mammograms: increased risk with estrogen-alone and estrogen plus progestin therapy

The benefits of hormone therapy during perimenopause are not explicitly stated in the provided drug labels, but it is generally known that hormone therapy can help alleviate symptoms of perimenopause, such as hot flashes and vaginal dryness. However, due to the potential risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman 2, 2, 2.

From the Research

Benefits of Hormone Therapy

• Hormone therapy ameliorates the quality of life by resolving atrophic symptoms and vasomotor problems, protecting from osteoporosis, maintaining skin and connective tissue turgor, as well as improving libido, mood, and depression during the menopausal transition 3.
• Hormone therapy prevents and treats osteoporosis, and is effective for relieving vasomotor symptoms such as hot flashes and vaginal atrophy 4, 5.
• Estrogen-based hormonal therapies are the most effective treatments for many menopausal symptoms, and have a generally favorable benefit:risk ratio for women below age 60 and within 10 years of the onset of menopause 6.

Risks of Hormone Therapy

• Hormone therapy increases the risk of coronary heart disease, particularly in older women and those a number of years beyond menopause 4.
• An increased risk of breast cancer with extended use is another reason short-term treatment is advised 4, 7.
• Hormone therapy may increase the incidence of some chronic diseases, such as venous thromboembolism and endometrial cancer 7.
• Contraindications to hormone therapy use include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active liver disease 4.

Individualized Treatment

• The type, doses, and duration of hormone therapy should be individualized, based on a woman's medical history, needs, and preferences 3, 5.
• The lowest effective estrogen dose should be provided for the shortest duration necessary, as risks increase with increasing age, time since menopause, and duration of use 4, 5.
• Initiating hormone therapy close to menopause at the lowest effective dose is more likely to have maximal benefits and the lowest risks 7.