Transdermal HRT: Best Bet for Lower VTE Risk

Among different types of hormone replacement therapy (HRT), a transdermal formulation appeared safest in terms of venous thromboembolism (VTE) risk, according to researchers in England.

In a retrospective analysis of about 80,000 women who experienced VTE and some 390,000 non-VTE control women, 7.2% of VTE patients were exposed to HRT within 90 days of the index date compared with 5.5% controls, according to Yana Vinogradova, PhD, of the University of Nottingham, and colleagues.

But there was no added risk for VTE associated with HRT patches, gel, or subcutaneous formulas (adjusted odds ratio 0.93, 95% CI 0.87-1.01), they wrote in BMJ.

Only oral therapy was tied to a significantly increased risk for VTE among women, ages 40 to 79, while 85% of women who experienced this were on an oral formulation versus 78% of those who didn’t have VTE (adjusted OR 1.58, 95% CI 1.52-1.64). This increased risk remained significant for both oral-only preparations of therapy (aOR 1.40, 95% CI 1.32-1.48), as well as combination formulas (aOR 1.73, 95% CI 1.65-1.81).

However, when compared with conjugated equine estrogen and combined formulas, women on estradiol had reduced risk for VTE (aOR 0.85, 95% CI 0.76-0.95; aOR 0.83, 95% CI 0.76-0.91, respectively).

As for conjugated equine estrogen, when this formula included medroxyprogesterone acetate, women had more than doubled odds for VTE compared with women who weren’t on any HRT (aOR 2.10, 95% CI 1.92-2.31).

Also, estradiol with dydrogesterone showed a slightly elevated risk for VTE, but still had the lowest association out of any oral formula (aOR 1.18, 95% CI 0.98-1.42).

Vinogradova noted that the findings were “broadly in line with most previous research.” In the current study, 80% of the women on HRT therapy were prescribed oral preparations rather than transdermal formulas.

A joint 2017 position statement by the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) recommended the use of transdermal formulas over oral estrogen, as the former may be less likely to increase thrombotic risk, and may also pose less of a risk for stroke and coronary artery disease.

“Although HRT medications are generally relatively safe, the background risk of VTE increases with age and with presence of other risk factors,” Vinogradova explained to MedPage Today. “Patches and gels should perhaps be considered as a first choice because of no evidence of increased risk from using them. If for some reason this treatment route is not acceptable, then there is a wide choice of tablets, and preference should be given to those based on synthetic estradiol rather than conjugated equine estrogen.”

In the study, more than half of the women who had VTE were ages ≥65, and were more likely to have comorbidities (cancer, heart disease) versus controls (56% vs 36%). Women with VTE also were more likely than controls to have recent medical events (27% vs 12%), such as respiratory or urinary infection, hip fracture or operation, or hospital admission.

Study limitations included the authors’ inability to assess differences in risks for women who had recently started, or restarted HRT, because most of the women had been using HRT for more than 84 days. Also, exposure information was based on HRT prescriptions and not confirmed use.