Hormone replacement therapy in women with history of thrombosis or a thrombophilia

Abstract

Findings from the Women’s Health Initiative (WHI) randomised placebo-controlled trial (RCT) were published at the beginning of this century. They suggested that hormone replacement therapy (HRT) use increased the risk of cardiovascular disease and venous thromboembolism including pulmonary embolism and deep vein thrombosis The findings led to a decline in HRT prescriptions and negative publicity about the use of HRT for women with significant menopausal symptoms. Subsequent studies have shown that the risk of thrombosis with HRT relates to whether oestrogen is combined with a progestogen and the route of administration of oestrogen. In healthy women with no background medical problems, transdermal hormone replacement is not associated with an increased risk of thrombosis. However, much less is known about the safety of various HRT preparations in women with a high background risk of thrombosis. These cases can often be challenging for clinicians with uncertainties around testing for thrombophilia, use of anticoagulation and striking a balance between the risks and benefits of prescribing HRT. This article will review the mechanism of thrombosis with differing types of HRT and present the evidence from the relevant trials. The article will also present the evidence that specifically relates to women with a personal history of thrombosis or thrombophilia (heritable and acquired) to enable clinicians to better individualise the risk assessment for each woman requesting HRT and understand the role of thrombophilia screening or concomitant anticoagulation in such situations.

Russian Eligibility Criteria Prescribing Menopausal Hormonal Hormones Therapy for Patients With Cardiovascular and Metabolic Diseases. Consensus Document of the Russian Cardiological Society, Russian Society of Obstetricians and Gynecologists, Russian Association of Endocrinologists, Eurasian Association of Therapists, Association of Phlebologists of Russia

“…По данным наблюдательных исследований, на фоне применения трансдермального эстрадиола в низких (<50 мкг/сут) и более высоких дозах в монорежиме, а также его сочетания с гестагеном в циклическом или непрерывном режимах риск ВТЭО не увеличивался [34][35][36][37]. При этом, с одной стороны, есть свидетельства, что трансдермальный путь поступления эстрогенов ассоциируется с более низким риском ВТЭО, чем его пероральный прием, с другой -есть указание на отсутствие различий [34][35] [38][39][40].…”

Treatments and Management of Menopausal Symptoms: Current Status and Future Challenges

“…There are no long-term safety data on progestins. Before prescribing HRT, and periodically as therapy continues, physicians should discuss the risks and benefits with women [160,161].…”

Exploring the potential for a set of UK hormone replacement therapy eligibility guidelines: A suggested proposal on the topic of venous thromboembolism

“…12,20 In contrast, for women that use oral HRT, including estrogen alone or combined preparations, risk of VTE is increased 2-4-fold and is greatest in the first year after initiation. 1,23 Exceptions are for tibolone and preparations containing dydrogesterone or micronised progesterone which are discussed separately.…”

“…The most common thrombophilias are heterozygous Factor V Leiden (FVL) and the prothrombin 20210A gene mutation. 23 Studies undertaken to date have mostly included women with these mutations. Data for more rare thrombophilias (including homozygous types, antiphospholipid (APL) syndrome, protein C deficiency, protein S deficiency and antithrombin deficiency) is limited and no trial data are available.…”

“…89,90 As mentioned earlier, for women using oral HRT, including estrogen alone or combined preparations, risk of VTE is increased 2–4-fold, and is greatest in the first year after initiation. 1,23 (Table 10)…”