Estring® (estradiol vaginal system) | Home Page

Important Safety Information

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia.

The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women during 7.1 years of treatment with daily oral conjugated estrogens (CE) 0.625 mg alone, relative to placebo. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women 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 WHI Memory Study (WHIMS) reported an increased risk of developing probable dementia in postmenopausal women aged 65 years and older, in both the estrogen-alone and estrogen plus progestin arms. It is unknown whether these findings apply to younger postmenopausal women.

The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE or CE and MPA, and other dosage forms of estrogens or combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.

Estring should not be used in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or a history of breast cancer; known or suspected estrogen-dependent neoplasia; active DVT, pulmonary embolism, or a history of these conditions; active arterial thromboembolic disease (eg, stroke, myocardial infarction), or a history of these conditions; anaphylactic reaction, angioedema, or hypersensitivity to Estring; liver impairment or disease; thrombophilic disorders; and pregnancy.

Observational studies have reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. One large meta-analysis of prospective cohort studies reported increased risks that were dependent upon duration of use and could last up to >10 years after discontinuation of estrogen plus progestin therapy and estrogen‑alone therapy. Extension of the WHI trials also demonstrated increased breast cancer risk associated with estrogen plus progestin therapy.

The WHI estrogen plus progestin substudy reported a statistically nonsignificant increased risk of ovarian cancer. A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown.

Estrogens increase the risk of gallbladder disease. Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia, or cholestatic jaundice occurs. Monitor thyroid function in women on thyroid replacement therapy because estrogens may be associated with increased thyroid binding globulin (TBG) levels.

The most frequently reported adverse events (≥5%) associated with Estring were headache, leukorrhea, back pain, genital moniliasis, upper respiratory tract infection, vaginitis, and vaginal discomfort/pain.

Indication

Estring is indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.

Please see full Prescribing Information, including BOXED WARNING and Patient Information.