(estradiol)
In ESTRING-treated menopausal women with a uterus with persistent or recurring abnormal genital bleeding of unknown etiology, perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to assess for endometrial cancer.
There is an increased risk of endometrial cancer with the use of systemic estrogens alone in women with a uterus. The reported endometrial cancer risk among unopposed systemic estrogen users is about 2 to 12 times greater than in non-users and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with the use of systemically administered estrogens for less than one year. The greatest risk appears to be associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more. This risk has been shown to persist for at least 8 to 15 years after systemic estrogen therapy is discontinued. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose.
Adding a progestogen to estrogen-alone therapy has been shown to reduce the risk of endometrial hyperplasia (possible precursor to endometrial cancer). There is, however, a different risk profile associated with the use of progestogens plus estrogens compared to estrogen-alone regimens.
If ESTRING is administered with a progestogen, there are possible risks associated with the concomitant use of estrogen with progestogen that differ from those of estrogen-alone regimens. Refer to the prescribing information for progestogens indicated for the prevention of endometrial hyperplasia in nonhysterectomized women receiving estrogens for a discussion of the risks of estrogen and progestogen concomitant therapy.
Systemic absorption occurs with the use of ESTRING, although the exposure is generally lower than that of systemic estrogens indicated for vasomotor symptoms. As such, the relevance or extent of the following risks of systemic estrogens to ESTRING is not known. The following adverse reactions have been reported with systemic estrogen therapy:
Cardiovascular diseases: The Women’s Health Initiative (WHI) estrogen-alone trial reported increased risks of pulmonary embolism (PE), deep vein thrombosis (DVT), and stroke, in postmenopausal women (50 to 79 years of age, average age 63.4 years) during 7.2 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] relative to placebo. (See CLINICAL STUDIES.)
Breast cancer: In the WHI estrogen-alone trial, after an average follow-up of 7.1 years, daily oral CE-alone was not associated with an increased risk of invasive breast cancer. (See CLINICAL STUDIES.) However, a large meta-analysis including 24 prospective studies of postmenopausal women comparing current use of estrogen-only products with use duration of 5 to 14 years (average of 9 years) versus never use reported a relative risk for breast cancer of 1.33 (95% CI, 1.28 to 1.38).
Ovarian cancer: A large meta-analysis including 17 prospective studies of postmenopausal women compared current use of estrogen-only products versus never user and reported a relative risk for ovarian cancer of 1.37 (95% CI 1.26, 1.50). The duration of hormone therapy use that was associated with an increased risk of ovarian cancer is unknown.4
Others: gallbladder disease requiring surgery, severe hypercalcemia in women with breast cancer and metastases, retinal vascular thrombosis, substantial increases in blood pressure from idiosyncratic reactions, exacerbation of hypertriglyceridemia leading to pancreatitis, cholestatic jaundice, exacerbation of hypothyroidism, fluid retention, hypocalcemia, exacerbation of conditions including hereditary angioedema, asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas.
Some women have experienced moving or gliding of ESTRING within the vagina. Instances of ESTRING being expelled from the vagina in connection with moving the bowels, strain, or constipation have been reported. If this occurs, ESTRING can be rinsed in lukewarm water and reinserted into the vagina by the patient.
ESTRING may not be suitable for women with narrow, short, or stenosed vaginas. Narrow vagina, vaginal stenosis, prolapse, and vaginal infections are conditions that make the vagina more susceptible to ESTRING-caused irritation or ulceration. Women with signs or symptoms of vaginal irritation should alert their physician.
Vaginal infection is generally more common in postmenopausal women due to the lack of the normal flora of fertile women, especially lactobacillus, and the subsequent higher pH. Vaginal infections should be treated with appropriate antimicrobial therapy before initiation of ESTRING. If a vaginal infection develops during use of ESTRING, then ESTRING should be removed and reinserted only after the infection has been appropriately treated.
Physicians are advised to discuss the PATIENT INFORMATION leaflet with women for whom they prescribe ESTRING.
Serum FSH and estradiol levels have not been shown to be useful in the management of moderate to severe symptoms of vulvar and vaginal atrophy.
Long-term, continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testes and liver.
ESTRING should not be used during pregnancy.
There appears to be little or no increased risk of birth defects in children born to women who have used estrogens as an oral contraceptive inadvertently during early pregnancy.
ESTRING should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the breast milk of mothers receiving estrogens. Caution should be exercised when ESTRING is administered to a nursing woman.
ESTRING is not indicated in children. Clinical studies have not been conducted in the pediatric population.
There have not been sufficient numbers of geriatric patients involved in studies utilizing ESTRING to determine whether those over 65 years of age differ from younger subjects in their response to ESTRING.
In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age. (See CLINICAL STUDIES.)
In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women who received oral CE-alone compared to those who received placebo. (See CLINICAL STUDIES.)
Since trial was conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women. (See CLINICAL STUDIES.)
ESTRING
(estradiol vaginal system)
Read this Patient Information before you start using ESTRING and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment.
What is ESTRING?
ESTRING (estradiol vaginal system) is an off-white, soft, flexible ring with a center that contains 2 mg of estradiol (an estrogen hormone). ESTRING releases estradiol into the vagina in a consistent, stable manner for 90 days. The soft, flexible ring is placed in the upper third of the vagina (by the physician or the patient). ESTRING should be removed after 90 days of continuous use. If continuation of therapy is indicated, the flexible ring should be replaced.
What is ESTRING used for?
ESTRING is used after menopause to treat moderate to severe menopausal changes in and around the vagina.
You and your healthcare provider should talk regularly about whether you still need treatment with ESTRING to control these problems.
Who should not use ESTRING?
Do not start using ESTRING if you:
What should I tell my healthcare provider before I use ESTRING?
Before you use ESTRING, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how ESTRING works. ESTRING may also affect how your other medicines work.
What are the possible side effects of ESTRING?
If you experience any of the following side-effects, immediately remove ESTRING if possible and contact your healthcare provider. If you experience difficulty or pain when trying to remove the ring please do not continue and contact your healthcare provider:
The most frequently reported side effect with ESTRING use is increased vaginal secretions. Many of these vaginal secretions are like those that occur normally prior to menopause and indicate that ESTRING is working. Vaginal secretions that are associated with a bad odor, vaginal itching, or other signs of vaginal infection are NOT normal and may indicate a risk or a cause for concern. Other side effects may include vaginal discomfort, abdominal pain, or genital itching.
What are the possible side effects of estrogens?
Side effects are grouped by how serious they are and how often they happen when you are treated.
Serious, but less common side effects include:
Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:
Less serious, but common side effects include:
These are not all the possible side effects of ESTRING. For more information, ask your healthcare provider or pharmacist for advice about side effects. Tell your healthcare provider if you have any side effect that bothers you or does not go away.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to Pfizer at 1-800-438-1985.
What can I do to lower my chances of getting a serious side effect with ESTRING?
General information about safe and effective use of ESTRING
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use ESTRING for conditions for which it was not prescribed. Do not give ESTRING to other people, even if they have the same symptoms you have. It may harm them.
Keep ESTRING out of the reach of children.
This leaflet provides a summary of the most important information about ESTRING. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about ESTRING that is written for health professionals. You can get more information by calling the toll free number 1-888-691-6813.
What are the ingredients in ESTRING?
ESTRING (estradiol vaginal system) is a slightly opaque ring with a whitish core containing a drug reservoir of 2 mg estradiol (an estrogen hormone). Estradiol, silicone polymers, barium sulfate and silicone fluid (as dispersing agent) are combined to form the ring.
Storage: Store at controlled room temperature 15° to 25 °C (59 °F to 77 °F).
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