Questions and Answers About Menopause Therapy with Dr. Robert L. Reid

By Robert L. Reid, MD, FRCSC

Professor of Obstetrics and Gynecology
Chair, Division of Reproductive Endocrinology and Infertility
Queen’s University,
Kingston, Ontario


What potential benefits does transdermal estrogen offer over oral estrogen?

Transdermal delivery of hormones is not merely the delivery of the same drug by a different route –rather it is a delivery method with significant pharmacokinetic differences that can modify or influence the action of the medication. Advantages of transdermal hormone therapy include avoidance of “first pass” effects (liver metabolism and gastrointestinal breakdown of oral medication) while achieving sustained release of drugs with short half lives (where oral dosing would create peaks and troughs in the circulating concentration). Daily administration of a transdermal gel offers simplicity and the cosmetic advantage of a simple skin application whereas intermittent patch application once or twice weekly may be more convenient for some women.

There is no evidence that one route of delivery is more efficacious than the other for control of menopausal symptoms or osteoporosis protection but emerging evidence suggests that transdermal therapy may be preferred in specific clinical circumstances. Liver metabolism of estrogen is accelerated in cigarette smokers (hence they are at increased risk for osteoporosis and tooth loss) and avoidance of the “first pass” effect in these women may improve efficacy of therapy.

There are theoretical reasons to consider transdermal delivery in women requiring systemic estrogen therapy with complaints of low libido. Both routes of estrogen delivery can reduce postmenopausal androgen production from the ovary however oral therapy results in a greater increase in Sex Hormone Binding Globulin (SHBG) which binds avidly to androgens in circulation thus reducing the amount of free testosterone – thought to be important for some aspects of female sexuality.

Does the route of administration of estrogen therapy influence thromboembolic risk?

Venous thromboembolism (VTE) is a risk for women receiving menopausal hormone therapy (MHT), especially in the first year of treatment. Since the risk of VTE is small in healthy, active, recently menopausal women, following these patients’ preferences for route of delivery is appropriate as a means of enhancing compliance. However, initiation of MHT in women older than 60 years, or in women with obesity, reduced mobility or a personal or family history of VTE, should generally employ a transdermal delivery system. Transdermal delivery of estrogen has been shown to have less impact on pro-coagulant factors produced in the liver, and observational data have shown that MHT-associated VTE risk may be reduced or eliminated with this approach.


1. Potts RO, Lobo RA. Transdermal drug delivery: clinical considerations for the obstetrician-gynecologist. Obstet Gynecol 2005; 105(5):953-61.

2. Olie V, Canonico M, Scarabin PY. Risk of venous thrombosis with oral versus transdermal estrogen therapy among postmenopausal women. Curr Opin Hematol 2010; 17(5):457-63.

Development of this article was sponsored by Merck Canada Inc. The author had complete editorial independence in the development of this article and is responsible for its accuracy. The sponsor exerted no influence in the selection of content or material published.