Is hormone replacement therapy (HRT) indicated in a woman with a history of myocardial infarction (MI)?

From the Guidelines

Hormone replacement therapy (HRT) is generally not recommended for women with a history of myocardial infarction (MI) due to the increased risk of thrombotic events and potential worsening of cardiovascular outcomes. The risks of HRT in this population typically outweigh the benefits, as estrogen-containing therapies can increase the risk of cardiovascular events, particularly in the first year of treatment 1. If menopausal symptoms are severe and significantly affecting quality of life, non-hormonal options should be tried first, such as selective serotonin reuptake inhibitors (SSRIs) like paroxetine 7.5-25mg daily or venlafaxine 37.5-150mg daily for hot flashes, or vaginal moisturizers and lubricants for vaginal symptoms.

According to the most recent guidelines, a history of myocardial infarction is considered a contraindication to menopausal hormone therapy use 1. If HRT must be considered due to severe symptoms unresponsive to alternatives, it should be used at the lowest effective dose for the shortest possible time, preferably using transdermal estrogen (such as estradiol patch 0.025-0.05mg) which carries a lower thrombotic risk than oral formulations, along with appropriate cardiovascular risk management including antiplatelet therapy, statins, and blood pressure control.

The decision should involve careful individualized risk assessment and shared decision-making, with close monitoring for cardiovascular complications. Key considerations include:

• Assessing for contraindications to menopausal hormone therapy use, such as history of breast cancer, liver disease, and thrombophilic disorders 1
• Selecting menopausal hormone therapy preparations with shared decision-making, considering factors such as age, time since menopause onset, and cardiovascular risk profile
• Monitoring for abnormal vaginal bleeding and endometrial hyperplasia during menopausal hormone therapy use
• Considering alternative nonhormonal therapy options if contraindications are present

Overall, the recommendation against routine HRT in women with prior MI stems from clinical trials showing increased cardiovascular events, particularly in the first year of treatment, though more recent data suggests the timing of HRT initiation relative to menopause and MI may influence risk 1.

From the FDA Drug Label

The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2. 5 mg], relative to placebo. In the WHI estrogen plus progestin substudy, a statistically non-significant increased risk of coronary heart disease (CHD) events (defined as nonfatal myocardial infarction [MI], silent MI, or CHD death) reported in women receiving daily CE (0. 625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). In postmenopausal women with documented heart disease (n = 2,763, average age 66. 7 years), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study [HERS]), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit.

Hormone Replacement Therapy (HRT) is not indicated in a woman with a history of myocardial infarction (MI) due to the increased risk of cardiovascular events, including myocardial infarction, associated with estrogen plus progestin therapy 2, 2.

• The risks of cardiovascular disorders, including myocardial infarction, should be carefully considered before initiating HRT in women with a history of MI.
• Alternative treatments should be considered to manage menopausal symptoms in women with a history of MI.

From the Research

Hormone Replacement Therapy in Women with Myocardial Infarction

• The use of hormone replacement therapy (HRT) in women with a history of myocardial infarction (MI) is a complex issue, with various studies providing conflicting evidence 3, 4, 5, 6, 7.
• A study published in the BMJ found that women who discontinued HRT after MI did not have a significantly different risk of reinfarction, cardiovascular mortality, or all-cause mortality compared to those who continued HRT 3.
• Another study published in Current Opinion in Cardiology suggested that HRT should not be prescribed for cardiovascular risk prevention, but may be appropriate for symptom-related indications in women who are less than 10 years post-menopause 4.
• In contrast, a study published in the Journal of the American College of Cardiology found that initiation of HRT after MI was associated with an increased risk of cardiac events, particularly unstable angina 5.
• An audit of current practice published in the British Journal of Obstetrics and Gynaecology found that only a small percentage of women with MI were prescribed HRT, despite evidence suggesting its potential benefits 6.
• A nationwide study published in the British Journal of Clinical Pharmacology found that the majority of women who used HRT at the time of MI continued to use it after discharge, with a remarkably low increase in discontinuation after 2002 7.

Key Findings

• Discontinuation of HRT after MI may not be associated with a significantly different risk of adverse cardiovascular events 3.
• HRT may be appropriate for symptom-related indications in women who are less than 10 years post-menopause, but should not be prescribed solely for cardiovascular risk prevention 4.
• Initiation of HRT after MI may be associated with an increased risk of cardiac events 5.
• The use of HRT in women with MI is not widespread, despite potential benefits 6.
• The majority of women who use HRT at the time of MI continue to use it after discharge 7.