Estring Side Effects

Generic Name: estradiol topical

Please note - some side effects for Estring may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Estring - for the Consumer

Estring Ring

All medicines may cause side effects, but many people have no, or minor side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Estring Ring:

Breast pain or tenderness; hair loss; headache; mild nausea or vomiting; spotting or breakthrough bleeding; stomach cramps or bloating.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); back pain; breast discharge or a lump in the breast; breast lumps; breast pain; calf or leg pain or swelling; changes in vaginal bleeding (eg, spotting, breakthrough bleeding, prolonged bleeding); changes in vision or speech (eg, change in contact lens fit, loss of vision); chest pain; coughing up blood; dark urine; depression; diarrhea; dizziness; fainting; fever; memory problems; mental or mood changes; muscle pain; one-sided weakness; painful or difficult urination; persistent or severe breast pain or tenderness; persistent or severe headache, nausea, or vomiting; severe or persistent stomach pain; severe stomach pain or swelling; slurred speech; sudden shortness of breath; sunburn-like skin rash; swelling of feet, hands, or legs;unusual vaginal discharge, itching, or odor; vision changes; vomiting; weakness or numbness of an arm or leg; yellowing of the skin or eyes.

Estring Side Effects - for the Professional

Estring

See BOXED WARNINGS, WARNINGS and PRECAUTIONS

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In the two pivotal controlled studies, discontinuation of treatment due to an adverse event was required by 5.4 percent of patients receiving Estring and 3.9 percent of patients receiving conjugated estrogens vaginal cream. The most common reasons for withdrawal from Estring treatment due to an adverse event were vaginal discomfort and gastrointestinal symptoms.

The adverse events reported with a frequency of 3 percent or greater in the two pivotal controlled studies by patients receiving Estring or conjugated estrogens vaginal cream are listed in Table 4.

Other adverse events (listed alphabetically) occurring at a frequency of 1 to 3 percent in the two pivotal controlled studies by patients receiving Estring include: anxiety, bronchitis, chest pain, cystitis, dermatitis, diarrhea, dyspepsia, dysuria, flatulence, gastritis, genital eruption, urogenital pruritus, hemorrhoids, leg edema, migraine, otitis media, skin hypertrophy, syncope, toothache, tooth disorder, urinary incontinence.

Post-Marketing Experience

1. A few cases of toxic shock syndrome (TSS) have been reported in women using vaginal rings. TSS is a rare, but serious disease that may cause death. Warning signs of TSS include fever, nausea, vomiting, diarrhea, muscle pain, dizziness, faintness, or a sunburn-rash on face and body.
2. A few cases of ring adherence to the vaginal wall, making ring removal difficult, have been reported. Vaginal wall ulceration or erosion should be carefully evaluated. If an ulceration or erosion has occurred, consideration should be given to leaving the ring out and not replacing it until healing is complete in order to prevent the ring from adhering to the healing tissue.
3. A few cases of bowel obstruction and vaginal ring use have been reported. Persistent abdominal complaints consistent with obstruction should be carefully evaluated.

The following additional adverse events were reported at least once by patients receiving Estring in the worldwide clinical program, which includes controlled and uncontrolled studies. A causal relationship with Estring has not been established.

Body as a Whole: allergic reaction

CNS/Peripheral Nervous System: dizziness

Gastrointestinal: enlarged abdomen, vomiting

Metabolic/Nutritional Disorders: weight decrease or increase

Musculoskeletal: arthropathy (including arthrosis)

Psychiatric: depression, decreased libido, nervousness

Reproductive: breast engorgement, breast enlargement, intermenstrual bleeding, genital edema, vulval disorder

Skin/Appendages: pruritus, pruritus ani

Urinary: micturition frequency, urethral disorder

Vascular: thrombophlebitis

Vision: abnormal vision

The following additional adverse reactions have been reported with estrogens:

Genitourinary system: abnormal uterine bleeding/spotting; dysmenorrheal/pelvic pain; 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, rash

Eyes: retinal vascular thrombosis; intolerance to contact lenses

Central Nervous System: headache; migraine; dizziness; mental depression; exacerbation of chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia

Miscellaneous: increase or decrease in weight; glucose intolerance; aggravation of porphyria; edema; arthralgias; leg cramps; changes in libido; angioedema; anaphylactoid/anaphylactic reactions; hypocalcemia (preexisting condition); exacerbation of asthma; increased triglycerides

Side Effects by Body System

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.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.