Hormone Replacement Therapy (HRT) is a standard treatment for menopausal symptoms, but concerns about the risk of blood clots have made many women hesitant to pursue this option. However, recent studies have highlighted that the method of estrogen delivery can significantly impact the associated risks. Notably, transdermal estrogen therapy has been shown to have a lower risk of causing blood clots compared to oral estrogen therapy.
Understanding Estrogen Therapy
Estrogen therapy is used to alleviate symptoms of menopause, such as hot flashes, night sweats, and vaginal dryness. It can also help prevent bone loss (osteoporosis) that can occur after menopause. Estrogen can be administered orally, transdermally (through the skin), or vaginally. Each method of administration has different implications for health risks and benefits.
Blood Clots and Oral Estrogen
Oral estrogen therapy has been associated with an increased risk of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). This increased risk is thought to arise because oral estrogen passes through the liver first, where it can increase the production of clotting factors. A significant body of research has documented this risk:
The Women's Health Initiative (WHI) Study: This landmark study found that women taking oral conjugated equine estrogens had a higher incidence of VTE than those taking a placebo.
The ESTHER Study: This French study showed that oral estrogen increases the risk of VTE by about four times compared to non-users.
Transdermal Estrogen and Blood Clots
Transdermal estrogen, delivered via patches, gels, or sprays, bypasses the liver and enters the bloodstream directly through the skin. This route of administration is associated with a lower risk of blood clots:
Observational Studies: Several observational studies have indicated that transdermal estrogen does not significantly increase the risk of VTE. For instance, the ESTHER study found no increased risk of blood clots in women using transdermal estrogen compared to non-users.
Meta-Analyses: A meta-analysis of various studies comparing oral and transdermal estrogen concluded that transdermal administration is associated with a lower risk of VTE. This analysis highlighted the difference in risk profiles between the two methods.
Mechanistic Insights: Research suggests that because transdermal estrogen bypasses the liver, it does not increase the levels of clotting factors in the same way oral estrogen does.
Clinical Implications
The evidence suggesting that transdermal estrogen does not increase the risk of blood clots has significant clinical implications. It offers a safer alternative for women who require HRT but are concerned about VTE risk. Healthcare providers can consider this route of administration for patients with a higher baseline risk of blood clots, such as those with a history of thromboembolic events or genetic predispositions.
Conclusion
Transdermal estrogen therapy represents a promising alternative for women needing HRT, with a significantly lower risk of blood clots compared to oral estrogen therapy. As always, patients should consult with their healthcare providers to discuss the most appropriate treatment options based on their individual health profiles and risk factors.
References
Women's Health Initiative (WHI) Study. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA, 288(3), 321-333.
Canonico, M., et al. (2007). Hormone therapy and venous thromboembolism among postmenopausal women. Circulation, 115(7), 840-845.
Vinogradova, Y., Coupland, C., & Hippisley-Cox, J. (2019). Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ, 364, k4810.
Scarabin, P. Y., Oger, E., & Plu-Bureau, G. (2003). Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet, 362(9382), 428-432.
By Dr Purity Carr
GP & Menopause Doctor
Harvey, WAs 6220
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