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FDA Black-Box Warning [required for all estrogen-containing products] Endometrial Cancer Cardiovascular and Other Risks |
FDA Black-Box Warning [required for all estrogen-containing products] Endometrial Cancer Cardiovascular and Other Risks The Women’s Health Initiative (WHI) estrogen alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8 years and 7.1 years, respectively, of treatment with daily oral conjugated estrogens (CE 0.625 mg), relative to placebo. The estrogen plus progestin WHI substudy reported increased risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and DVT in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE 0.625 mg combined with medroxyprogesterone acetate (MPA 2.5 mg), relative to placebo. The Women’s Health Initiative Memory Study (WHIMS), a substudy of the WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE 0.625 mg alone and during four years of treatment with daily CE 0.625 mg combined with MPA 2.5 mg, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. |
The Food and Drug Administration (FDA) issued a public warning on July 29, 2010, about the dangers that the topical estrogen product estradiol transdermal spray (EVAMIST) poses to children and pets. Estradiol spray is approved for the treatment of moderate to severe hot flashes due to menopause.
From July 2007 — when estradiol spray was first approved — through June 2010, the FDA received eight post-approval adverse event reports regarding children three to five years of age who had been unintentionally exposed to the spray. Adverse events reported in these children included premature puberty, nipple swelling and breast development in girls, and breast enlargement in boys.
Two reports also were received by the FDA’s Center for Veterinary Medicine about secondary exposure to estradiol spray in dogs. Pets exposed to estradiol spray may exhibit signs such as mammary and/or nipple enlargement and vulvar swelling.
Estradiol spray is usually used by applying one, two or three sprays each morning to the inner surface of the forearm, starting near the elbow. If women often lift small children or pets, the spray may rub off on them.
The effectiveness of estrogens for hot flashes
Estrogen treatment is effective for reducing the number of hot flashes experienced by postmenopausal women. In a clinical trial that supported the approval of estradiol spray, a group of women had an average of about 11 hot flashes per day at the beginning of the study. This was reduced to an average of eight per day after the women began using three estradiol sprays daily. The women in the placebo group experienced about 12 hot flash episodes per day.
FDA-approved patient information for estrogens
The FDA requires that the professional product labels for all estrogen-containing products display a black-box warning about the increased risks of endometrial cancer, heart attack, stroke and blood clots associated with the use of estrogen. It also warns women over age 65 that they risk developing dementia with estrogen use.
These warnings apply to so-called bioidentical estrogens hawked by compounding pharmacies and alternative medicine physicians as well.
In addition, regulations require that all estrogen-containing drugs be dispensed with information — written specifically for patients by the FDA — outlining the risks and benefits of estrogen. This information can be obtained for free from the U.S. National Library of Medicine’s DailyMed website: dailymed.nlm.nih.gov.
What You Can Do
When estrogens, including estradiol spray, are prescribed to postmenopausal women, generally a progestin also should be started to reduce the risk of endometrial cancer.
Estradiol spray should not be used in women with any of the following conditions:
- Undiagnosed abnormal genital bleeding
- Known or suspected breast cancer
- Known or suspected estrogen-dependent neoplasia (tumor growth)
- Active deep vein thrombosis, pulmonary embolism or history of these conditions
- Active or recent (within the past year) arterial thromboembolic disease (e.g., stroke and heart attack)
- Known liver dysfunction or disease
- Known or suspected pregnancy
You should not allow children to come in contact with the area of the arm where estradiol is sprayed. If contact does occur, wash the child’s skin with soap and water as soon as possible.
Pets should not be allowed to lick or touch the arm where estradiol is sprayed. Small pets may be especially sensitive to the estrogen in this product.
If direct contact between children or pets and the estradiol spray cannot be avoided, wear a garment that covers the area where the drug was applied.
Consumers may report serious adverse events with estradiol spray or other estrogen-containing products to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.
Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Regular Mail: Use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) FDA-0178
Phone: (800) FDA-1088
