Pharmacology Update

Estradiol Topical Emulsion (Estrasorb)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

A topical estradiol emulsion has been approved for treating symptoms of menopause. Currently available estrogen products include pills, patches, and vaginal rings. The new estrogen emulsion provides another option for estrogen therapy. Novavax Inc markets this topical formulation as Estrasorb.

Indications

Estradiol emulsion is indicated for the treatment of moderate-to-severe vasomotor symptoms associated with menopause.1

Dosage

The content of a pouch is applied to the clean, dry skin of each leg each morning. The emulsion should be applied to the thigh and calf. Each 1.74 g pouch contains 4.35 mg of estradiol hemihydrate. Two pouches are designed to deliver 0.05 mg of estradiol daily.1 Estrasorb is supplied in boxes of 56 pouches.

Potential Advantages

Estradiol emulsion offers a new option for estrogen therapy that some women may find more acceptable. The emulsion appears to be well tolerated.

Potential Disadvantages

Estradiol emulsion does not relieve local vaginal symptoms or vulvar atrophy. There is potential for estradiol transfer to males who have physical contact with female application sites. A 25% increase in serum estradiol concentration was observed in adult males upon contact at 2 and 8 hours after application for a 2-day period.1

The application of sunscreen 10 minutes before estrogen emulsion increases the exposure of estradiol by about 35% and by 15% if applied 25 minutes after estradiol emulsion.1

Comments

Estradiol emulsion is formulated with soybean oil, water, polysorbate 80, and ethanol. Its efficacy was demonstrated in a 12-week, randomized, placebo-controlled trial involving 200 postmenopausal women.

There was a 66% reduction in the number of hot flushes at 4 weeks and 85% reduction at 12 weeks compared to 45% and 53% for those treated with placebo. Severity scores of hot flushes at 12 weeks were reduced by 61% with the estradiol emulsion compared to 23% for placebo.1 The emulsion is generally well tolerated. Pruritus was reported in 4% of patients and appeared to be the only formulation-specific side effects. There are currently no published trials comparing the estradiol emulsion with other formulations of estradiol. The cost of the emulsion was not available at the time of this review.

Clinical Implications

Findings from the Women’s Health Initiative indicated that oral estrogen increases the risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep-vein thrombosis.2 The FDA recommends that estrogen be considered for treating moderate-to-severe vasomotor symptoms and moderate-to-severe symptoms of vulvar and vaginal atrophy. The use should be at the lowest dose and for the shortest duration possible.3 Estradiol emulsion is not indicated for genitourinary symptoms. It thus becomes an alternative to oral tablets or the transdermal patch. Tablets are subject to first-pass metabolism, and the patch has been associated with local reactions. Oral estrogen, but not transdermal estrogen, has been associated with increased levels of C-reactive protein, an independent predictor of cardiovascular events.4-6 The clinical relevance of this difference is, however, not clear as increased C-reactive protein may be related to metabolic hepatic activation or expression rather than a systemic pro-inflammatory effect, as no increase in other markers of inflammation was detected.4-7  

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.

References

1. Estrasorb Product Information. Novavax Inc. October 2003.

2. WHI Investigators. JAMA. 2002;288:321-333.

3. FDA Press Release. January 8, 2003.

4. Lacut K, et al. Thromb Haemost. 2003;90(1):124-131.

5. Frohlich M, et al. Ann Med. 2003;35(5):353-361.

6. Vongpatanasin W, et al. J Am Coll Cardiol. 2003; 41(8):1358-1363.

7. Silvestri A, et al. Circulation. 2003;107(25):3165-3169.