Estrace Vaginal Cream Side Effects

Generic name: estradiol topical

Note: This document contains side effect information about estradiol topical. Some of the dosage forms listed on this page may not apply to the brand name Estrace Vaginal Cream.

Some side effects of Estrace Vaginal Cream may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to estradiol topical: vaginal cream, vaginal ring, vaginal tablet

Get emergency medical help if you have any of these signs of an allergic reaction while taking estradiol topical (the active ingredient contained in Estrace Vaginal Cream) hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Remove the vaginal ring and seek emergency medical attention if you have: fever with nausea, vomiting, diarrhea, muscle pain, dizziness, fainting, and/or sunburn-like skin rash. These may be signs of a life-threatening disease called toxic shock syndrome.

Stop using this medication and call your doctor at once if you have a serious side effect such as:

• chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

• sudden numbness or weakness, sudden severe headache, sudden vision changes, problems with speech or balance;

• sudden cough, wheezing, rapid breathing, coughing up blood;

• pain, swelling, warmth, or redness in one or both legs;

• swelling or tenderness in your stomach;

• jaundice (yellowing of the skin or eyes);

• unusual vaginal bleeding;

• a lump in your breast;

• numbness or tingly feeling around your mouth, fast or slow heart rate, muscle tightness or contraction, overactive reflexes; or

• dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).

Less serious side effects of estradiol topical may include:

• breast swelling and tenderness, nipple discharge;

• vaginal itching or discharge;

• mild nausea, stomach cramps, diarrhea, bloating;

• swelling of your ankles or feet;

• migraine headaches or dizziness;

• cold symptoms such as stuffy nose, sneezing, sore throat;

• acne or skin color changes, increased facial hair, thinning scalp hair;

• depressed mood; or

• changes in your menstrual periods, break-through bleeding.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to estradiol topical: transdermal film extended release, vaginal cream, vaginal ring, vaginal tablet

Gastrointestinal

Gastrointestinal effects of estrogen use are common and most often include nausea and vomiting. Some studies have demonstrated a 2 to 4 fold increase in gallbladder disease in postmenopausal women taking estrogen therapy.

Cases of oral pigmentation and ischemic colitis have been reported rarely.

Oncologic

A number of studies have suggested that the risk of endometrial carcinoma is removed (or delayed) by the administration of progestins in combination with estrogen therapy.

The increased risk of breast cancer due to use of estrogens is controversial. Several studies have suggested that long-term estrogen therapy may be associated with a slightly increased risk of breast cancer. Meta analysis of 51 studies (epidemiological data) supports a modest risk increase associated with long-term hormone replacement therapy (HRT).

One study of Swedish women has reported that a 10% increase in the relative risk of breast cancer may occur and that the risk is related to increasing duration of estrogen therapy. In that study, women with more than nine years of estrogen use had a 70% greater relative risk of breast cancer than controls. That study, however, examined use of a variety of estrogen preparations of which estradiol was the most frequently prescribed. In addition, women who took progestins did not demonstrate a decreased risk of breast cancer and may even have been at higher risk.

The Toronto Breast Cancer Study has reported that women who receive unopposed conjugated estrogens for less than 15 years are not at increased risk of breast cancer. In that study, an increase in the risk of breast cancer for women who used conjugated estrogens for more than 15 years was not ruled out.

The Case-Control Surveillance Study has reported that there is "no evidence that the use of unopposed conjugated estrogens increases the risk of breast cancer, even after long duration of use or long latent intervals, but the possibility of a modest increase (less than a doubling) could not be excluded."

Follow-up to the Nurses' Health Study of 1992 concluded, however, that there is an increased risk of breast cancer in women taking estrogen replacement therapy and that the risk is not reduced by concurrent use of progestins. (In that study, greater risk was associated with advanced age and prolonged duration of hormonal therapy.)

A study of middle-aged women in the Puget Sound area concluded that "on the whole, the use of estrogen with progestin HRT [hormone replacement therapy] does not appear to be associated with an increased risk of breast cancer in middle-aged women."

A prospective cohort study (11 years) of 37,105 women by Gapstur et al evaluated the histology of the breast cancer in women who ever used HRT. No association was found between duration of ever HRT use and the incidence of ductal carcinoma in situ or invasive ductal/lobular carcinoma. The duration of ever HRT use was associated with risk of invasive carcinoma with a favorable prognosis (relative risk (RR) = 1.81, 95% confidence interval (CI), 1.07 to 3.07 for HRT use <= 5yrs and RR = 2.65, CI, 1.32 to 5.23 for HRT use > 5yrs, p = 0.005). The relative risk of invasive carcinoma with a favorable prognosis for current users (adjusted for age and other risk factors) was 4.42, CI, 2.00 to 9.76 for <= 5yrs and 2.63, CI, 1.18 to 5.89 for > 5yrs). Risk of invasive ductal or lobular carcinoma for current users <= 5yrs was RR = 1.38, CI, 1.03 to 1.85.

Use of unopposed estrogen therapy has been associated with an increased risk of endometrial carcinoma in patients with an intact uterus and less persuasively, with an increased risk of breast cancer.

Cardiovascular

Studies suggest that unopposed estrogen therapy may decrease the risk of coronary heart disease by as much as 35%. Combination therapy with a progestin may also decrease coronary risk. However, the extent of risk reduction with combination therapy has not yet been determined. Data are available that suggest combination therapy do not reduce the overall rate of coronary heart disease in postmenopausal women with established coronary disease.

The reported effects of estrogens on cardiovascular activity are variable. Alterations in lipid profiles in treated women are thought to be responsible for reducing cardiovascular risks. Data suggest estrogen use may increase blood pressure, particularly in patients receiving high doses, decrease blood pressure, or result in no change. In addition, noncontraceptive use of estrogens in young women (particularly smokers) may substantially increase the risk of nonfatal myocardial infarction. Other studies have concluded that no increased risk of myocardial infarction exists.

Metabolic

Metabolic effects include generally favorable alterations in plasma lipid profiles. Specifically, increased HDL and decreased cholesterol and LDL levels occur. Estrogen therapy may lead to increased serum triglyceride levels resulting in pancreatitis in patients with familial lipoprotein metabolic defects.

Metabolic adverse effects such as hypercalcemia have occurred in patients with breast cancer and bone metastases administered estrogens.

Endocrine

Estrogen use may result in increased levels of thyroxin-binding globulin, leading to an increase in total thyroid serum levels and a decrease in resin uptake of T3. Free thyroid hormone levels remain unchanged. Other endocrine effects include decreased fasting plasma glucose.

General

Estrogens may cause some degree of fluid retention and mastodynia. Alterations in libido have occurred.

Hepatic

Cases of focal nodular hyperplasia, liver cell adenomas, hepatic hemangiomas and well-differentiated hepatocellular carcinomas have been reported rarely in association with estrogen therapy. Aggravation of porphyria has been reported.

Many of the reports of hepatic tumors have occurred in women taking long-term oral contraceptives. However, some tumors have been reported in women taking isolated estrogen therapy.

Hematologic

Hypercoagulability has been reported in women taking estrogens, although the clinical significance of such hypercoagulability in postmenopausal women taking estrogens has not been determined.

Hypersensitivity

Hypersensitivity reactions including anaphylaxis have been reported in association with estrogen use and the dyes contained in some conjugated estrogen formulations.

Ocular

Ocular side effects of estrogen therapy include alterations in corneal curvature and contact lens discomfort.

Other

Estrogen therapy may increase the risk of "fibrocystic breast disease" by as much as two-fold.

Psychiatric

Psychiatric effects of estrogen use include case reports of rapid mood cycling in patients with severe depression.

Nervous system

Nervous system side effects include dizziness, mental depression, and new onset or exacerbation of migraine headaches. A case of chorea has been reported in association with estrogen therapy.

Genitourinary

Estrogens may also cause abnormal uterine bleeding (which must be carefully distinguished from bleeding related to endometrial carcinoma). In addition, estrogens may increase the size of preexisting uterine leiomyomata.

Dermatologic

Dermatologic effects of estrogen use include chloasma or melasma, which may not resolve following discontinuation of estrogen therapy. Scalp hair loss, hirsutism, erythema nodosum, and hemorrhagic eruptions have occurred.

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