Weighing the risks of transdermal ERT

By Ivy M. Alexander, MS, C-ANP

Adult Nurse Practitioner, Assistant Professor

Yale University School of Nursing

Adult and Family Nurse Practitioner Specialty

New Haven, CT

(Editor’s note: This is the conclusion of a two-part series on transdermal estrogen replacement therapy. The first installment, which reviewed potential benefits, appeared in the December 1999 Contraceptive Technology Update, p. 145.)

As more women experience and live beyond menopause, interest in risks and benefits associated with estrogen replacement therapy (ERT) has increased. Estrogen can be administered via oral, parenteral, intravaginal, and transdermal routes. Oral administration is the most common, followed by the transdermal route.1 The purpose of this column is to examine the disadvantages of transdermal estrogen delivery systems. They include:

Breast cancer risk. Although generally safe, several potential risks or disadvantages accompany ERT and transdermal delivery systems. One issue that concerns many women is the risk of breast cancer. Although still controversial, it appears that if any association exists between ERT and breast cancer, the association is very small.1,2

Endometrial hyperplasia. Hyperplasia of the endometrial lining is a risk for women with an intact uterus receiving unopposed ERT. The risk is minimized by administering cyclical or continuous progesterone. Continuous administration is preferred by many women because menstrual flow usually ceases after the first few months of therapy.1,3 Combination therapy is available in patch form or can be achieved by daily oral progesterone administration.4 Progesterone patches are being studied but are not yet commercially available.3

Dose-related side effects. Systemic dose-related side effects are comparable with oral and transdermal delivery systems. Some women who experience nausea or headache while taking oral preparations may have fewer side effects with transdermal delivery.1

Weight gain. Reports on weight gain are controversial. Although some weight increase during initial therapy has been noted, most research studies have not identified an increase in weight attributable to HRT with long-term therapy.5 However, changes in fat mass and distribution have been identified. Those changes may differ according to route of administration. One study reported increased fat mass and decreased lean body mass with oral administration as compared with transdermal therapy.6

Deep-vein thrombosis. The risk of thromboembolism while on oral ERT is generally highest in the first year of therapy. Because few data are available on risk among women receiving transdermal estrogen, the interaction between embolic risk and transdermal administration is uncertain. How ever, the absolute risk for venous thromboembol ism with oral estrogen administration is low.2

Rash at administration site. The most common problem associated with transdermal ERT is developing a skin rash at the site of administration. That can be reduced by rotating patch locations and not using the same site in succession. Additionally, removing the patch for swimming or bathing can be helpful because moisture under the patch appears to increase irritation.1

Overall, benefits associated with ERT tend to outweigh risks. Careful screening to identify women at heightened risk for negative outcomes is appropriate. Clear discussion on advantages and disadvantages can help a woman decide. ERT is clearly associated with reduced menopausal symptoms and improved overall quality of life.1,2,5 Once a woman experiences relief of vasomotor symptoms, she may be more inclined to consider long-term ERT and reap additional systemic benefits.


1. Connell EB. Transdermal estrogen therapy. Postgrad Med 1997;101-130.

2. Wenger NK. HRT and coronary heart disease: Answers to your top 12 questions. Women’s Health in Primary Care 1999; 2:305-321.

3. Rozenberg S, Ylikorkala O, Arrenbrecht S. Comparison of continuous and sequential transdermal progestogen with sequential oral progestogen in postmenopausal women using continuous transdermal estrogen: Vasomotor symptoms, bleeding patterns, and serum lipids. Int J Fertil Womens Med 1997; 42(Suppl 2):376-387.

4. Prescriber’s Letter. June 1999. Internet document: Estrogen Patches.

5. Lubbert H, Nauert C. Continuous versus cyclic transdermal estrogen replacement therapy in postmenopausal women: Influence on climacteric symptoms, body weight, and bleeding pattern. Maturitas 1997; 28:117-125.

6. O’Sullivan AJ, Crampton LJ, Freund J, et al. The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women. J Clin Invest 1998; 102:1,035-1,040.