Oral preparations of hormone replacement therapy (HRT) for the treatment of menopausal symptoms are associated with a greater risk for venous thromboembolism (VTE) compared with transdermal HRT, according to study results published in BMJ.
VTE has been associated with the use of estrogen-only oral HRT, but research examining VTE risk and other HRT preparations is lacking. To compare types of HRT and associated VTE risks, researchers conducted a nested case-control study using data from 2 United Kingdom primary care research databases to identify 5795 women with VTE and 21,670 matched control participants who were exposed to HRT containing estradiol within 90 days of index date. Cases of VTE were identified using practice, hospital, and mortality records.
In women prescribed HRT, 4915 women with VTE (85%) and 16,938 control participants (78%) received oral preparations, with 102 women with VTE (1.8%) and 312 control participants (1.4%) also receiving transdermal HRT. Transdermal HRT preparations were used alone in 880 women with VTE (14%) and 4731 control participants (19%). Most transdermal preparations were in patches (87%), with only a small proportion being subcutaneous or gel preparations.
Overall, use of oral therapy was associated with a significantly increased risk for VTE (odds ratio [OR], 1.58; 95% CI, 1.52-1.64) compared with no exposure, whereas transdermal HRT was not associated with increased VTE risk (OR, 0.93; 95% CI, 0.87-1.01).
For estrogen-only HRT, estradiol had a lower comparative risk vs conjugated equine estrogen (OR, 0.85; 95% CI, 0.76-0.95); combined estradiol preparations also had a lower risk compared with conjugated equine estrogen (OR, 0.83; 95% CI, 0.76-0.91).
For combined HRT, compared with no exposure, conjugated equine estrogen with medroxyprogesterone acetate carried the highest risk for VTE (OR, 2.10; 95% CI, 1.92-2.31), and estradiol with dydrogesterone carried the lowest risk (OR, 1.18; 95% CI, 0.98-1.42). Results for all HRT preparations were consistent in a subgroup analysis in which participants were categorized by body mass index.
The researchers noted that the data on HRT therapy exposure were based on prescription data and not actual use. In addition, data did not include precise indications for HRT or age at onset of menopause.
“Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations,” wrote the researchers. “When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT.”
Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.