Estradiol Side Effects: Common, Serious & FDA Warnings

Common Side Effects of Estradiol

The most-reported reactions in the FDA Adverse Event Reporting System (FAERS) for estradiol. Percentages reflect the share of reports mentioning each reaction; a single report may include multiple reactions. Reports indicate co-occurrence, not causation.

Serious Outcomes and FDA Warnings

FAERS reports flagged with a serious outcome (death, hospitalization, life-threatening, disability, or congenital anomaly), plus reactions surfaced in the FDA-approved label's Warnings section. Reports indicate co-occurrence, not causation.

From the FDA-approved label, Section 5.1: Thromboembolic Disorders and Other Vascular Conditions Stop

Iclevia if an arterial or venous thrombotic/thromboembolic event occurs. Stop Iclevia if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately. Discontinue Iclevia during prolonged immobilization. If feasible, stop Iclevia at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism.

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Start Iclevia no earlier than 4 weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week. Before starting Iclevia evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Iclevia is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases [see Contraindications (4) ] . Arterial Events COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity. Iclevia is contraindicated in women over 35 years of age who smoke [ see Contraindications (4) ]. Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Venous Events Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of COCs [see Contraindications (4) ] . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years. The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued. Figure 1 shows the risk of developing a VTE for females who are not pregnant and do not use oral contraceptives, for females who use oral contraceptives, for pregnant females and for females in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 females who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these females will develop a VTE. Use of levonorgestrel and ethinyl estradiol tablets provides women with more hormonal exposure on a yearly basis than conventional monthly COCs containing the same strength synthetic estrogens and progestins (an additional 9 weeks of exposure per year). In the clinical trial, one case of pulmonary embolism was reported. Postmarketing adverse reactions of VTE have been reported in women who used levonorgestrel and ethinyl estradiol tablets. Figure 1

From the FDA-approved label, Section 5.4: Hypertension

Iclevia is contraindicated in females with uncontrolled hypertension or hypertension with vascular disease [see Contraindications (4) ]. For all women, including those with well-controlled hypertension, monitor blood pressure at routine visits and stop Iclevia if blood pressure rises significantly. An increase in blood pressure has been reported in females taking COCs, and this increase is more likely in older women and with extended duration of use. The effect of COCs on blood pressure may vary according to the progestin in the COC.

Estradiol Recalls

FDA enforcement actions matched to estradiol via openFDA's structured generic_name field and the NDC bridge. Ongoing recalls are listed below (verify on FDA →); closed recalls are grouped in the disclosure that follows.

Estradiol Shortages

FDA-listed shortages of estradiol products. Strength and dosage-form level detail.

Is Estradiol Safe?

Estradiol is FDA-approved. The label's Warnings and Precautions section covers thromboembolic disorders and other vascular conditions stop (Section 5.1), liver disease elevated liver enzymes (Section 5.2), risk of liver enzyme elevations with concomitant hepatitis c treatment (Section 5.3), hypertension (Section 5.4), age-related (Section 5.5), gallbladder disease (Section 5.6), adverse carbohydrate and lipid metabolic effects hyperglycemia (Section 5.7), headache (Section 5.8), bleeding irregularities and amenorrhea (Section 5.9), depression (Section 5.10), malignant neoplasms breast cancer (Section 5.11), effect on binding (Section 5.12), hereditary (Section 5.13), chloasma (Section 5.14).

As with any prescription, the assessment of safety is individual; consult a clinician about your own risk profile.

FDA-Approved Indications

Estradiol is FDA-approved for use in the condition categories below. The FDA-approved label’s Indications and Usage section is shown verbatim.

• Hormones & reproductive

Iclevia TM (levonorgestrel and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy. Iclevia is a combination of levonorgestrel, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )

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Data Sources & Methodology

How each section of this page is sourced, and how often the data is refreshed.

What we do not do. We do not invent, paraphrase, or extrapolate drug claims. Every figure on this page comes from a query against an openFDA endpoint. If the data is unavailable, the section gracefully omits rather than filling the space with editorial guesswork.