See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.

The following additional adverse reactions have been reported with estrogen and/or progestin therapy.

Genitourinary system

Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting, dysmenorrhea
Increase in size of uterine leiomyomata
Vaginitis, including vaginal candidiasis
Change in amount of cervical secretion
Changes in cervical ectropion
Ovarian cancer; endometrial hyperplasia; endometrial cancer

Breasts

Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer

Cardiovascular

Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure

Gastrointestinal

Nausea, vomiting
Abdominal cramps, bloating
Cholestatic jaundice
Increased incidence of gallbladder disease
Pancreatitis
Enlargement of hepatic hemangiomas

Skin

Chloasma or melasma that may persist when drug is discontinued
Erythema multiforme
Erythema nodosum
Hemorrhagic eruption
Loss of scalp hair
Hirsutism
Pruritus, rash

Eyes

Retinal vascular thrombosis
Steepening of corneal curvature
Intolerance to contact lenses

Central Nervous System

Headache, migraine, dizziness
Mental depression
Chorea
Nervousness, mood disturbances, irritability
Exacerbation of epilepsy
Dementia

Miscellaneous

Increase or decrease in weight
Reduced carbohydrate tolerance
Aggravation of porphyria
Edema
Arthralgias; leg cramps
Changes in libido
Urticaria
Angioedema
Anaphylactoid/anaphylactic reactions
Hypocalcemia
Exacerbation of asthma
Increased triglycerides

Read the Estrace (estradiol) Side Effects Center for a complete guide to possible side effects »

Drug/Laboratory Test Interactions

1. Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.
2. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by ^{radioimmunoassay) or T}3 ^{levels by radioimmunoassay. T}3 resin uptake is decreased, ^{reflecting the elevated TBG. Free T}4 ^{and free T}3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.
3. Other binding proteins may be elevated in serum, i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased circulating corticosteroids and sex steroids, respectively. Free or biologically active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
4. ^{Increased plasma HDL and HDL}2 subfraction concentrations, reduced LDL cholesterol concentration, increased triglycerides levels.
5. Impaired glucose tolerance.
6. Reduced response to metyrapone test.

Last reviewed on RxList: 10/3/2008
This monograph has been modified to include the generic and brand name in many instances.