Dosage & Administration
One ESTRING (estradiol vaginal system) is to be inserted as deeply as possible into the upper one-third of the vaginal vault. The ring is to remain in place continuously for three months, after which it is to be removed and, if appropriate, replaced by a new ring. The need to continue treatment should be assessed at 3 or 6 month intervals.
Should the ring be removed or fall out at any time during the 90-day treatment period, the ring should be rinsed in lukewarm water and re-inserted by the patient, or, if necessary, by a physician or nurse.
Retention of the ring for greater than 90 days does not represent overdosage but will result in progressively greater underdosage with the attendant risk of loss of efficacy and increasing risk of vaginal infections and/or erosions.
Estring Prescribing Information
• Using estrogen-alone may increase your chance of getting cancer of the uterus (womb).• Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function).• Using estrogen-alone may increase your chances of getting strokes or blood clots.• Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older.• Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia.• Using estrogens with progestins may increase your chance of getting heart attacks, strokes, breast cancer, or blood clots.• Using estrogens with progestins may increase your chance of getting dementia, based on a study of women 65 years of age or older.• You and your healthcare provider should talk regularly about whether you still need treatment with ESTRING.
ESTRING is indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.
One ESTRING (estradiol vaginal system) is to be inserted as deeply as possible into the upper one-third of the vaginal vault. The ring is to remain in place continuously for three months, after which it is to be removed and, if appropriate, replaced by a new ring. The need to continue treatment should be assessed at 3 or 6 month intervals.
Should the ring be removed or fall out at any time during the 90-day treatment period, the ring should be rinsed in lukewarm water and re-inserted by the patient, or, if necessary, by a physician or nurse.
Retention of the ring for greater than 90 days does not represent overdosage but will result in progressively greater underdosage with the attendant risk of loss of efficacy and increasing risk of vaginal infections and/or erosions.
ESTRING is contraindicated in women with any of the following conditions:
1. Undiagnosed abnormal genital bleeding.2. Known, suspected, or history of breast cancer.3. Known or suspected estrogen-dependent neoplasia.4. Active DVT, PE, or a history of these conditions.5. Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions.6. Known anaphylactic reaction or angioedema or hypersensitivity to ESTRING.7. Known liver impairment or disease.8. Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.9. Known or suspected pregnancy.
See
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 and random endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal genital bleeding. (See
Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia. (See
The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo. (See
The WHI Memory Study (WHIMS)estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See
In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens.
Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. (See
The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo. (See
The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See
The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer. (See
In the absence of comparable data, these risks should be assumed to be similar for other doses of CE plus MPA, and other combinations and dosage forms of estrogens and progestins.
Estrogens with or without progestins should be prescribed at the lowest doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
ESTRING is a vaginal administered product with low systemic absorption following continuous use for 3 months (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Absorption). However, the warnings, precautions, and adverse reactions associated with oral estrogen and/or progestin therapy should be considered in the absence of comparable data with other dosage forms of estrogens and/or progestins.
An increased risk of stroke and DVT has been reported with estrogen-alone therapy. An increased risk of stroke, DVT, PE, and MI has been reported with estrogen plus progestin therapy. Should any of these occur or be suspected, estrogens with or without progestin therapy should be discontinued immediately.
Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.
In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year one and persisted. (See
Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).
In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years). The increase in risk was demonstrated after the first year and persisted. (See
In the WHI estrogen-alone substudy, no overall effect on CHD events (defined as nonfatal MI, silent MI and CHD death) was reported in women receiving estrogen-alone compared to placebo. (See
Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women with less than 10 years since menopause (8 versus 16 per 10,000 women-years).
In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of CHD events reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5. (See
In postmenopausal women with documented heart disease (n = 2,763, average 66.7 years of age), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study [HERS]), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established CHD. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred and twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the combined continuous CE plus MPA treatment group and the placebo group in HERS, HERS II, and overall.
In the WHI estrogen-alone substudy, the risk of VTE (DVT and PE) was increased for women receiving daily CE (0.625 mg)-alone compared to women receiving placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the first 2 years. (See
In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was observed during the first year and persisted. (See
If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The reported endometrial cancer risk among unopposed 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 use of estrogens for less than 1 year. The greatest risk appears 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 estrogen therapy is discontinued.
Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. 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 vaginal bleeding. 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 progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.
The WHI substudy of daily CE (0.625 mg)-alone provided information about breast cancer in estrogen‑alone users. In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer (relative risk [RR] 0.80). (See
After a mean follow-up of 5.6 years, the estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA. In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women. The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for CE plus MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for CE plus MPA compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years, for CE plus MPA compared with placebo. In the same substudy, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the placebo group. Metastatic disease was rare with no apparent difference between the two groups. Other prognostic factors such as histologic subtype, grade and hormone receptor status did not differ between the groups. (See
Consistent with the WHI clinical trials, observational studies have also 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. Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy. However, these studies have not generally found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration.
The use of estrogen alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation.
All women should receive yearly breast exams by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.
The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95 percent CI, 0.77–3.24). The absolute risk for CE plus MPA was 4 versus 3 cases per 10,000 women-years.
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 primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies. The relative risks associated with current use of hormonal therapy was 1.41 (95% confidence interval [CI] 1.32 to 1.50); there was no difference in the risk estimates by duration of the exposure (less than 5 years [median of 3 years] vs. greater than 5 years [median of 10 years] of use before the cancer diagnosis). The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27–1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown.
In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo. After an average follow-up of 5.2 years, 28 women in the CE-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83–2.66). The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years. (See
In the WHIMS estrogen plus progestin ancillary study, a population of 4,532 postmenopausal women 65 to 79 years of age was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo.
After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE/MPA versus placebo was 2.05 (95 percent CI, 1.21–3.48). The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years. (See
When data from the two populations in the WHIMS estrogen-alone and estrogen plus progestin ancillary studies were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19–2.60). Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women. (See
A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level.
Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be discontinued.
Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.
Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer.
There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen alone regimens. These include a possible increased risk of breast cancer.
In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogen therapy on blood pressure was not seen.
In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of treatment if pancreatitis occurs.
Estrogens may be poorly metabolized in patients with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised and in the case of recurrence, medication should be discontinued.
Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4and T3serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.
Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.
Estrogens may cause some degree of fluid retention. Women with conditions that might be influenced by this factor, such as a cardiac or renal impairment, warrant careful observation when estrogen-alone is prescribed.
A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For women known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.
Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.
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
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.
1.000000000000000e+00 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.2.000000000000000e+00 Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels, as measured by protein-bound iodine (PBI), T4levels (by column or by radioimmunoassay) or T3levels by radioimmunoassay. T3resin uptake is decreased, reflecting the elevated TBG. Free T4and free T3concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone.3.000000000000000e+00 Other binding proteins may be elevated in serum, (i.e., corticosteroid binding globulin [CBG], sex hormone-binding globulin [SHBG]), leading to increased circulating corticosteroid and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).4.000000000000000e+00 Increased plasma high-density (HDL) and HDL2cholesterol subfraction concentrations, reduced low-density (LDL) cholesterol concentration, increased triglycerides levels.5.000000000000000e+00 Impaired glucose tolerance.
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. (See
There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins 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.
In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age. (See
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 receiving estrogen-alone or estrogen plus progestin when compared to placebo. (See
Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women.
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 ESTRING 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.
ADVERSE EVENT | ESTRING (n = 257) % | Conjugated Estrogens Vaginal Cream (n = 129) % |
|---|---|---|
Musculoskeletal | ||
Back Pain | 6 | 8 |
Arthritis | 4 | 2 |
Arthralgia | 3 | 5 |
Skeletal Pain | 2 | 4 |
CNS/Peripheral Nervous System | ||
Headache | 13 | 16 |
Psychiatric | ||
Insomnia | 4 | 0 |
Gastrointestinal | ||
Abdominal Pain | 4 | 2 |
Nausea | 3 | 2 |
Respiratory | ||
Upper Respiratory Tract Infection | 5 | 6 |
Sinusitis | 4 | 3 |
Pharyngitis | 1 | 3 |
Urinary | ||
Urinary Tract Infection | 2 | 7 |
Female Reproductive | ||
Leukorrhea | 7 | 3 |
Vaginitis | 5 | 2 |
Vaginal Discomfort/Pain | 5 | 5 |
Vaginal Hemorrhage | 4 | 5 |
Asymptomatic Genital Bacterial Growth | 4 | 6 |
Breast Pain | 1 | 7 |
Resistance Mechanisms | ||
Genital Moniliasis | 6 | 7 |
Body as a Whole | ||
Flu-Like Symptoms | 3 | 2 |
Hot Flushes | 2 | 3 |
Allergy | 1 | 4 |
Miscellaneous | ||
Family Stress | 2 | 3 |
ESTRING® (estradiol vaginal system) is a slightly opaque ring with a whitish core containing a drug reservoir of 2 mg estradiol. Estradiol, silicone polymers, barium sulfate and silicone fluid (as dispersing agent) are combined to form the ring. When placed in the vagina, ESTRING releases estradiol, approximately 7.5 mcg per day, in a consistent stable manner over 90 days. ESTRING has the following dimensions: outer diameter 55 mm; cross-sectional diameter 9 mm; core diameter 2 mm. One ESTRING should be inserted into the upper third of the vaginal vault, to be worn continuously for three months.
Estradiol is chemically described as estra-1, 3, 5(10)-triene-3, 17β-diol. The molecular formula of estradiol is C18H24O2 and the structural formula is:
The molecular weight of estradiol is 272.39.