Does the type of menopausal HT used increase the risk of venous thromboembolism?
Yes, according to a case-control study that analyzed data from 2 large UK databases in which 80,396 women aged 40 to 79 with a primary diagnosis of venous thromboembolism (VTE) between 1998 and 2017 were matched to 391,494 controls. Use of oral conjugated equine estrogen (CEE) or estradiol was associated with an elevated risk of VTE (odds ratio [OR], 1.49 and 1.27, respectively), while transdermal preparations were safest (OR, 0.96) when risk of VTE was assessed.
Study strengths and weaknesses
This study used data from the 2 largest primary care databases in the United Kingdom. Analyses were adjusted for numerous confounding factors, including acute and chronic conditions, lifestyle factors, and social deprivation. Additional sensitivity analyses were conducted and yielded results similar to those of the main analysis.
Several limitations could have resulted in some residual confounding bias. For example, drug exposure information was based on HT prescriptions and not actual use; data on some factors were not available, such as indications for HT, age at menopause, and education level; and for a small proportion of women, some data (smoking status, alcohol consumption, BMI) were missing and had to be imputed for analysis.
Although randomized trials have not compared VTE risk with oral versus transdermal estrogen, prior observational studies have consistently suggested that transdermal estrogen does not elevate VTE risk; this is consistent with the results from this large UK study. In my practice, congruent with the authors’ suggestions, I recommend transdermal rather than oral estrogen for patients (notably, those who are obese) who at baseline have risk factors for VTE. For menopausal women for whom use of oral estrogen is indicated, I recommend estradiol rather than CEE, since estradiol is less expensive and, based on this study’s results, may be safer than CEE.
,ANDREW M. KAUNITZ, MD
