How Safe Is Vaginal Estrogen in Women With a History of DVT?

My patient is a 52-year-old woman who is premenopausal but who experiences dyspareunia as a result of vaginal dryness. She has tried over-the-counter lubricants, but they have not relieved her symptoms. She takes warfarin, 5 mg qod/7 mg qod, to prevent recurrent deep venous thrombosis (DVT). Her first DVT was in 1978 and was associated with the use of an oral contraceptive. Is low-dose vaginal estrogen cream a safe option for this patient?

——Jenny Cokerham, FNP-C
San Antonio, Tex

Hormones increase the risk of thrombosis in all users; however, there is also a hierarchy of risk that is dependent on dose and route of administration. Thus, oral formulations of hormones have clear risk documentation, whereas the risk associated with transdermal or vaginal formulations is less clear—if it exists at all. And, in the case of vaginal formulations, the absorption and drug levels are maximal in the first 2 weeks of use, then taper as mucosa is built up by the therapy. Finally, there are differences in the doses of hormones delivered by different preparations.

Your patient has a solid indication for anticoagulation: clinical hypercoagulability as evidenced by recurrent DVTs. Because she seems to have done well long term on stable warfarin anticoagulation, I believe that after discussion with her and the obtaining of informed consent, she can be offered a lowdose vaginal estrogen cream. She needs to be aware that this therapy may increase her risk of recurrent DVT, but that available data suggest that if this risk indeed exists, it is quite small. Moreover, the fact that she is receiving effective thrombosis prophylaxis further reduces this risk.

——Ronald N. Rubin, MD
Professor of Medicine
Temple University School of Medicine
Chief, Clinical Hematology
Temple University Hospital
Philadelphia