Postmenopausal Estrogen Therapy: Advantages of Transdermal Delivery

Practice Watch |
May 2, 2013

Postmenopausal Estrogen Therapy: Advantages of Transdermal Delivery

  1. Robert W. Rebar, MD

ACOG suggests clinicians should consider transdermal forms of estrogen for their possible thrombosis-sparing effects.

  1. Robert W. Rebar, MD

Administration of either combined estrogen-progestin or estrogen-only therapy to postmenopausal women is associated with as much as fivefold excess risk for venous thromboembolism (VTE). Moreover, this risk increases with age and certain common preexisting conditions (e.g., obesity, immobility, fracture, underlying cardiovascular disease). Now, the American College of Obstetricians and Gynecologists has released a Committee Opinion on route of estrogen administration and VTE risk.

Most studies of postmenopausal estrogen therapy and risk for VTE have involved oral hormone administration. First-pass metabolism of oral estrogen in the liver is thought to cause prothrombotic and proinflammatory effects through the hepatic induction of substances such as coagulation factors and C-reactive protein. By contrast, transdermally administered estrogens show little or no effect on prothrombotic factors and a reduction in proinflammatory markers. In addition, the estradiol-acetate–containing vaginal ring does not seem to raise risk for VTE. The Committee Opinion includes cautions about the use of transbuccal lozenges and troches, noting that, although these compounded preparations are intended to eliminate first-pass effects and are widely used in the U.S., few safety data are available. Taken together, these observations led the Committee on Gynecologic Practice to recommend that clinicians — together with informed patients — carefully assess the risks and benefits of various estrogen preparations to determine the best form of therapy. In healthy women with negative risk histories, the “probability of [VTE] is generally low.”


When these observations are considered along with pharmacologic findings that transdermally administered estrogen more closely approximates physiologic levels of circulating estrogen, the transdermal route seems safer than oral preparations in most postmenopausal women who would benefit from estrogen therapy. However, taking individual patient preferences and risk factors into account is more important than insisting on transdermal estrogen for everyone.


Reader Comments (3)


Synthetic progesTIN (as opposed to bio-identical progesterone) has been shown to be carcinogenic in many well-designed European research studies as well as a few American studies. The time has come for your publication and other media sources to start making this distinction so that women and their Gynecologists can understand risk distinctions. A simple google search can inform of this distinction. Using the word progestin to cover all forms of synthetic and bio-identical progesterone does great harm to women as well as being a term that is misguided and misleading. Formulations of HRT that use Estrogen and bio-identical progesterone are almost as heart-protective as Estrogen alone.(PEPI Trial, 1995) Progestins negate this heart protective effect of Estrogen. Since that landmark study, we have learned of other deleterious effects of progestins and for the life of me I cannot understand any physician prescribing it knowing what the researchers know.

Carol Roberts, MD Physician, Unspecified, Naples, Florida

I have administered - and taken - bioidentical hormones for thousands of women (and a few men) and normally prefer the sublingual route. In twenty plus years I have had zero instances of thrombosis. Anecdotal, to be sure. Won't someone start studying the natural human hormones? Check the research coming out of France and Germany on these, it is eye-opening.

Zeev Blumenfeld

I totally aggree. For women with an intact uterus the safest E+P combination is probably TDE+ IU Levonorgestrel secreting IUD [ Mirena], as published: "Blumenfeld Z et al, High C-reactive protein levels are associated with oral hormonal menopausal therapy but not with intrauterine levonorgestrel and transdermal estradiol. Scand J Clin Lab Invest. 2007;67(3):257-63."

Competing interests: None declared

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