What are the considerations for Hormone Replacement Therapy (HRT) in patients with Coronary Artery Disease (CAD)?

From the Guidelines

Hormone replacement therapy (HRT) should generally be avoided in women with established coronary artery disease (CAD), as it may increase the risk of cardiovascular events, particularly in the first year of treatment and with oral formulations. For women with CAD who experience severe menopausal symptoms, the lowest effective dose of HRT for the shortest duration possible may be considered after careful discussion of risks. Transdermal estrogen preparations (like patches) at doses of 0.025-0.05 mg/day with micronized progesterone (100-200 mg/day for women with an intact uterus) are preferred if HRT must be used, as they carry lower thrombotic risk than oral formulations 1. Non-hormonal alternatives should be tried first, including SSRIs like paroxetine (7.5 mg daily) or escitalopram (10-20 mg daily), gabapentin (300 mg daily, titrated as needed), or clonidine (0.1 mg daily). This cautious approach is based on evidence from the Women's Health Initiative and HERS trials, which demonstrated increased risk of heart attacks, strokes, and blood clots with HRT use in older women and those with existing CAD 1. Key considerations for HRT in patients with CAD include:

• Avoiding HRT in women with established CAD, unless severe menopausal symptoms are present
• Using the lowest effective dose of HRT for the shortest duration possible
• Preferring transdermal estrogen preparations over oral formulations
• Trying non-hormonal alternatives first
• Carefully discussing the risks and benefits of HRT with patients. The most recent and highest quality study, 1, supports this cautious approach, highlighting the potential risks of HRT in women with established CAD.

From the Research

Considerations for Hormone Replacement Therapy (HRT) in Patients with Coronary Artery Disease (CAD)

• The use of HRT in patients with CAD is controversial, as observational studies have reported a beneficial effect on metabolic and vascular factors, but randomized clinical trials have questioned its efficacy in primary and secondary CAD prevention 2, 3, 4.
• Selective estrogen receptor modulators (SERMs) have been suggested as an alternative to HRT, as they may offer a favorable effect on the cardiovascular system without the adverse effects on the breast and endometrium 2, 3, 5, 4.
• Raloxifene, a second-generation SERM, has been shown to have a beneficial effect on the lipid-lipoprotein profile, decrease serum homocysteine levels and C-reactive proteins, and increase the nitric oxide-endothelin-1 ratio, contributing to proper endothelial function and vasodilation 2, 3, 5, 4.
• The effect of raloxifene on CAD is still uncertain, but the Multiple Outcomes of Raloxifene Evaluation (MORE) trial suggests that it may offer some protection to women with CAD or those at high risk 3, 5, 4.
• Other SERMs, such as tamoxifen, have also been studied, but the data on their effects on CAD are limited 3, 4.
• Medical management of stable CAD requires a comprehensive approach, including lipid-lowering, antihypertensive, and antiplatelet agents, as well as treatment of anginal symptoms 6.

Key Factors to Consider

• The balance between the beneficial and adverse effects of HRT and SERMs on the cardiovascular system 2, 3, 5, 4.
• The individual patient's risk profile and medical history 3, 4.
• The need for further research to fully understand the effects of HRT and SERMs on CAD 2, 3, 5, 4.
• The importance of a comprehensive medical management approach for patients with stable CAD 6.