What are the benefits, risks, and complications of Hormone Replacement Therapy (HRT) for a woman considering treatment?

From the Guidelines

Hormone Replacement Therapy (HRT) should be considered for women experiencing severe menopausal symptoms, with the goal of using the lowest effective dose for the shortest possible time, as the benefits of symptom relief and prevention of bone loss must be weighed against the potential risks of blood clots, stroke, and breast cancer, as noted in studies such as 1 and 1. When discussing HRT with a woman, it's essential to explain the benefits, risks, and complications associated with this therapy. Benefits include relief from hot flashes, night sweats, vaginal dryness, mood changes, and sleep disturbances. HRT can also help prevent bone loss and reduce fracture risk, with studies such as 1 demonstrating a 27% reduction in nonvertebral fractures. Common estrogen options include:

• Oral tablets (like Premarin 0.3-1.25mg daily or Estrace 0.5-2mg daily)
• Patches (like Climara or Vivelle-Dot 0.025-0.1mg/day)
• Gels
• Vaginal preparations for localized symptoms Women with an intact uterus need progesterone (like Provera 2.5-10mg daily or Prometrium 100-200mg daily) to prevent endometrial cancer. Risks and complications include:
• Slightly increased chances of blood clots, stroke, and breast cancer, particularly with combined estrogen-progesterone therapy used long-term, as noted in 1 and 1
• Breast tenderness, bloating, headaches, and breakthrough bleeding
• HRT is contraindicated in women with a history of breast cancer, certain types of uterine cancer, blood clots, stroke, liver disease, or unexplained vaginal bleeding Treatment should be individualized based on symptoms, medical history, and personal preferences, with regular follow-up to assess effectiveness and adjust dosing as needed, as recommended by 1 and 1.

From the FDA Drug Label

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 WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer [relative risk (RR) 0. 80] Estrogens with or without progestins should not be used for the prevention of cardiovascular disease The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases Retinal vascular thrombosis has been reported in patients receiving estrogens

The benefits of Hormone Replacement Therapy (HRT) include relief from menopausal symptoms. However, the risks and complications of HRT include:

• Increased risk of invasive breast cancer
• Increased risk of cardiovascular disease, including myocardial infarction, stroke, and deep vein thrombosis
• Increased risk of gallbladder disease
• Increased risk of hypercalcemia in patients with breast cancer and bone metastases
• Increased risk of retinal vascular thrombosis
• Increased risk of abnormal mammograms
• Increased risk of dementia in postmenopausal women 65 years of age or older
• Increased risk of ovarian cancer All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors and prior mammogram results 2, 2, 3.

From the Research

Benefits of Hormone Replacement Therapy (HRT)

• HRT is an effective treatment for menopausal symptoms, including vasomotor symptoms and genitourinary syndrome of menopause 4
• HRT has positive effects on bone health 4
• Age-stratified analyses indicate more favorable effects on coronary heart disease and all-cause mortality in younger women (close proximity to menopause) than in women more than a decade past menopause 4
• HRT can relieve symptoms and improve quality of life 5
• New data indicates there are medical benefits to HRT beyond quality of life measures 5
• HRT significantly reduces all-cause mortality and cardiovascular disease (CVD) when initiated in women at younger than 60 years and/or at or near menopause 6
• HRT is a sex-specific and time-dependent primary CVD prevention therapy that concomitantly reduces all-cause mortality, as well as other aging-related diseases with an excellent risk profile 6

Risks and Complications of HRT

• The risk:benefit ratio and safety profile of HRT differed markedly by clinical characteristics of the participants, especially age, time since menopause, and comorbidity status 4
• The perceived risks of HRT have decreased use over the past two decades, but previously stated risks of HRT overestimated the concern with menopausal therapy 5
• The magnitude and type of HRT-associated risks, including breast cancer, stroke, and venous thromboembolism, are rare (<10 events/10,000 women) and comparable with other medications 6
• The use of estrogen and progestogen combo-therapy is associated with increased risk of breast cancer, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin 7

Patient-Specific Considerations

• Recently menopausal women with moderate or severe symptoms are appropriate candidates for HRT, in the absence of contraindications or other major comorbidities 4
• The timing of HRT initiation, type and route of administration, and patient-specific considerations should be weighed when prescribing HRT 4, 8
• Health care providers and patients can use cumulated HRT data in making clinical decisions concerning chronic disease prevention including CVD and mortality reduction 6
• The implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths, and risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen 7