Hormone Replacement Therapy and Thromboembolic Risk: Review of Current Evidence

Hormone Replacement Therapy (HRT) is widely used for relief of menopausal symptoms and improvement of quality of life. However, its impact on thromboembolic risk has been a constant concern. In this article, we review the latest evidence on the relationship between HRT and venous thromboembolism (VTE), considering different routes of administration and types of hormones.

HRT and Venous Thromboembolism Risk

Studies indicate that oral HRT is associated with a significant increase in VTE risk, especially in the first months of use. The literature points to a relative risk (RR) of 2 to 4 for users of combined oral HRT compared to non-users.

On the other hand, transdermal HRT presents a lower risk. Meta-analyses demonstrate that there is no statistically significant increase in risk with this route of administration (OR 0.97). Additionally, transdermal formulations containing only estrogen present an even lower relative risk (OR 0.95).

Influence of Progestogens on VTE Risk

The type of progestogen used in HRT also impacts thrombotic risk:

• Micronized progesterone and dydrogesterone: associated with lower risks
• Medroxyprogesterone acetate: may increase VTE risk

The combination of transdermal estrogen with micronized progesterone is considered a safer option for women with predisposition to thrombotic events.

HRT in Women with Thrombophilia

The presence of hereditary thrombophilias, such as:

• Factor V Leiden mutation
• Prothrombin mutation

Requires careful evaluation before HRT indication.

Studies suggest that oral HRT may exacerbate thrombotic risk in individuals with these conditions, especially when there are additional factors, such as obesity or immobility.

Clinical Considerations and Conclusion

Although many healthy women can safely use HRT, those with history of VTE or thrombophilia require a personalized approach. Transdermal HRT, associated with lower-risk progestogens, is generally preferable in these high-risk populations.

Clinical Recommendations

1. Detailed evaluation of thrombosis history before HRT prescription
2. Collaboration with specialists in hematology in more complex cases
3. Continuous monitoring of women on HRT with risk factors
4. Individualization of therapy based on patient's risk profile

Physicians should perform detailed evaluations of thrombosis history before prescribing HRT. In more complex cases, collaboration with hematology specialists may be essential for safe and effective management of hormone therapy.

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Authored by Dr. Francisco Tostes, Scientific Director of SottoPelle Brasil.