British women recently exposed to oral hormone therapy were 58% more likely to receive a primary diagnosis of venous thromboembolism than women not exposed to HT, with risk increasing for certain combined preparations, according to findings published in The BMJ.
“Our study has shown that, for oral treatments, different tablets are associated with different risks of developing blood clots, depending on the active components,” Yana Vinogradova, PhD, a research fellow in medical statistics at the University of Nottingham, U.K., said in a press release. “It has also confirmed that risks of thrombosis for patients using HRT treatments other than tablets (patches or gels) is very low. This lower risk has been known for more than 10 years and — although patches or gels may not be acceptable in some circumstances — it was surprising to find that only 20% of HRT prescriptions to date have been for nonoral treatments. Our findings are particularly important information for women, who require HRT treatment and are already at increased risk of developing blood clots.”
Vinogradova and colleagues conducted nested case-control studies using data from two U.K. primary care research databases, identifying two cohorts of women aged 40 to 79 years with an incident VTE between January 1998 and February 2017 (n = 80,396). Researchers matched the women with up to five control participants by birth year and general practice in each database (n = 391,494). Overall exposure to HT was defined as any exposure to oral or transdermal preparations containing estradiol, recent exposure was defined as within 90 days before the index date (date of incident VTE) and past exposure was defined as 91 to 365 days before index date. Oral preparations included estrogen-only preparations (conjugated equine estrogen and estradiol) and combined preparations (estrogen with medroxyprogesterone acetate, dydrogesterone or norethisterone). Transdermal HT preparation included estrogen-only and combined estradiol and was analyzed separately. Researchers used conditional logistic regression analysis to estimate ORs to assess associations between HT exposure and VTE risk.
Within the cohort, 5,795 patients in the case group (7.2%) and 21,670 participants in the control group (5.5%) were exposed to HT within 90 days of their index date. Among those, 82% of patients in the case group and 72% of participants in the control group used oral HT preparations.
Researchers found that overall, recent exposure to HT was associated with a 43% increased risk for VTE (adjusted OR = 1.43; 95% CI, 1.38-1.48) vs. no HT exposure in the past year. This risk rose to 58% when assessing oral preparations only (aOR = 1.58; 95% CI, 1.52-1.64), whereas transdermal HT was not associated with VTE risk. Compared with transdermal HT, oral HT was associated with a 70% increased risk for VTE (OR = 1.7; 95% CI, 1.56-1.85).
Different types of estrogen preparations were associated with varying VTE risk, according to researchers. Compared with conjugated equine estrogen, estradiol was associated with a 15% lower VTE risk (OR = 0.85; 95% CI, 0.76-0.95). For combined oral HT, conjugated equine estrogen with medroxyprogesterone was associated with the highest VTE risk, with an OR of 2.1 (95% CI, 1.91-2.31), whereas estradiol with dydrogesterone was associated with the lowest VTE risk, with an OR of 1.18 (95% CI, 0.98-1.42).
“No association with transdermal use and VTE risk was expected because of the metabolic process, which has been confirmed in previous studies,” the researchers wrote. “Our study, however, has shown that the vast majority of women choosing HRT continue to be prescribed oral preparations. Particularly for patients with already increased VTE risk from comorbidities or obesity, our study has underlined that women reaching menopause and doctors should both give greater consideration to transdermal HRT in line with the [National Institute for Health and Care Excellence] guideline.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.