What is the role of Hormone Replacement Therapy (HRT) for postmenopausal women?

From the Guidelines

Hormone replacement therapy (HRT) should not be used routinely for the primary prevention of chronic conditions in postmenopausal women due to its associated risks and benefits. The U.S. Preventive Services Task Force (USPSTF) recommends against the routine use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women, citing a grade D recommendation 1. This decision is based on the finding of fair to good evidence that the combination of estrogen and progestin has both benefits, such as increased bone mineral density and reduced risk for fracture and colorectal cancer, and harms, including increased risk for breast cancer, venous thromboembolism, coronary heart disease, stroke, and cholecystitis 1.

Some of the key benefits of HRT include:

• Increased bone mineral density (good evidence) 1
• Reduced risk for fracture (fair to good evidence) 1
• Reduced risk for colorectal cancer (fair evidence) 1

However, these benefits are outweighed by the potential harms, which include:

• Increased risk for breast cancer (good evidence) 1
• Venous thromboembolism (good evidence) 1
• Coronary heart disease (CHD) (fair to good evidence) 1
• Stroke (fair evidence) 1
• Cholecystitis (fair evidence) 1

Given the potential risks and benefits associated with HRT, it is essential to carefully evaluate each patient's individual risk factors and medical history before considering HRT. This evaluation should include a comprehensive health assessment, including breast examination, mammogram, and cardiovascular risk evaluation. HRT should only be considered for women with severe menopausal symptoms that significantly impact their quality of life, and it should be used at the lowest effective dose and for the shortest duration needed to control symptoms.

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 be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Hormone Replacement Therapy (HRT) for postmenopausal women should be prescribed with caution, considering the potential risks and benefits.

• The risks of HRT include increased chances of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis.
• The benefits of HRT may include prevention of vertebral bone mass loss and reduction of menopausal symptoms.
• Estrogen-alone therapy may have a lower risk of breast cancer compared to estrogen plus progestin therapy.
• The duration and dose of HRT should be individualized to minimize risks and maximize benefits.
• Regular monitoring of women taking HRT is essential to detect any potential adverse effects early 2, 2, 2.

From the Research

Hormone Replacement Therapy (HRT) for Postmenopausal Women

• HRT is an effective treatment for menopausal symptoms, including vasomotor symptoms and genitourinary syndrome of menopause 3.
• Randomized trials have demonstrated positive effects of HRT on bone health, and age-stratified analyses indicate more favorable effects on coronary heart disease and all-cause mortality in younger women than in women more than a decade past menopause 3.
• The Women's Health Initiative (WHI) hormone therapy trials clarified the benefits and risks of HRT, including how the results differed by age 3.

Selective Estrogen Receptor Modulators (SERMs) as an Alternative to HRT

• SERMs, such as raloxifene and tamoxifen, produce beneficial estrogen-like effects on bone and lipid metabolism, while antagonizing estrogen in reproductive tissue 4, 5.
• Raloxifene stimulates neither the endometrium nor the mammary gland and probably even lowers the risk of breast cancer, making it a potentially ideal profile for postmenopausal hormone replacement treatment 4.
• SERMs can be used in women free of climacteric symptoms for the prevention and treatment of postmenopausal osteoporosis with no increased risk of phlebitis 4.

Current Recommendations for HRT Use in Menopausal Women

• The benefits of HRT in improving the symptoms of menopause are well-established, and HRT can also play a role in managing long-term sequelae such as osteoporosis and cardiovascular disease 6.
• However, the use of HRT has been limited by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years 7, 6.
• Current recommendations emphasize the importance of individualized treatment approaches, taking into account the clinical characteristics of the patient, including age, time since menopause, and comorbidity status 3, 6.