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

From the Guidelines

Hormone Replacement Therapy (HRT) should not be used routinely for the primary prevention of chronic diseases in women, but may be considered for the management of menopausal symptoms after a thorough discussion of individual risks and benefits. When considering HRT for women, it is essential to weigh the potential benefits against the risks, as the quality of evidence on the benefits and harms of HRT varies for different hormone regimens 1. The potential risks of HRT include an increased risk of venous thromboembolism, coronary heart disease, and stroke, particularly within the first 1 to 2 years of therapy, as well as an increased risk of breast cancer with longer-term use 1. Some key points to consider when discussing HRT with patients include:

• The use of the lowest effective dose for the shortest possible time to minimize risks
• The importance of individualized decision-making, taking into account a woman's medical history, risk factors, and preferences
• The availability of alternative strategies for preventing osteoporosis and fractures, such as lifestyle modifications and other medications
• The need for regular monitoring and follow-up to assess the effectiveness of HRT and minimize potential harms. In terms of specific regimens, the evidence is most robust for daily conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), but other hormone preparations may also be considered, and the decision should be made on a case-by-case basis 1. Ultimately, the decision to initiate or continue HRT should be made after a thorough discussion between a woman and her clinician, taking into account the latest evidence and individual circumstances.

From the FDA Drug Label

The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the WHI substudy of daily CE (0. 625 mg)-alone. In 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]. Consistent with the Women’s Health Initiative (WHI clinical trials), observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy and a smaller, but still increased risk, for estrogen-alone therapy after several years of use

The use of estrogen-alone therapy, such as estradiol, may not be associated with an increased risk of invasive breast cancer. However, estrogen plus progestin therapy may be associated with an increased risk of breast cancer.

• Key points:
  • Estrogen-alone therapy: no increased risk of invasive breast cancer
  • Estrogen plus progestin therapy: increased risk of breast cancer
  • Risk may be dependent on duration of use and may last up to >10 years after discontinuation of therapy 2

From the Research

Benefits of HRT for Women

• HRT can improve symptoms of menopause, such as hot flushes, and has a potential role in managing long-term sequelae, including bone and cardiovascular health 3.
• Transdermal administration of estradiol may provide a safer alternative to orally administered conjugated equine estrogens (CEE), with a lower risk of stroke and breast cancer 4, 5.
• Estradiol and progesterone may have a better safety profile compared to CEE and progestins, with potential benefits for cardiovascular outcomes, breast cancer, and bone health 6.

Types of HRT

• Bioidentical menopausal hormone therapy, using registered hormones such as estradiol and progesterone, may be a safer and more effective option than conventional hormone therapy 4.
• Transdermal administration of estradiol and progesterone may be preferred over oral administration, due to a lower risk of venous thromboembolism and ischemic stroke events 4, 5.
• Estriol, a weaker estrogen, may be an alternative to estradiol, with potential benefits for menopausal symptoms and a lower risk of breast cancer 5.

Risks and Controversies

• The use of HRT for primary prevention of chronic conditions is not recommended, due to the potential risks of adverse clinical outcomes, including coronary heart disease, thromboembolic events, and breast cancer 7.
• The Women's Health Initiative (WHI) and other studies have reported an increased risk of adverse outcomes with HRT use, although subgroup analyses have suggested that lower-dose preparations and bioidentical hormones may be safer 7.
• The U.S. Preventive Services Task Force (USPSTF) and other professional groups have issued recommendations against the use of HRT for primary prevention of chronic conditions 7.