Estradiol Side Effects

Estradiol is a type of estrogen, which is the female sex hormone secreted by the ovaries and required for many bodily processes.

Estradiol is used as a treatment for symptoms caused by the menopause such as vaginal dryness, burning, irritation and hot flushes. It is also used to prevent osteoporosis developing in women who have gone through the menopause and as a therapy for conditions such as ovarian failure that lead to a lack of natural estrogen in the body.

Image Credit: Tero Vesalainen / Shutterstock
Image Credit: Tero Vesalainen / Shutterstock

The use of estradiol in medications such as the contraceptive pill or hormone replacement therapy is associated with several adverse effects and some of these are described below:

  • Abnormal vaginal bleeding
  • Painful periods or dysmenorrhea
  • Fibroid enlargement
  • Vaginal infections such as candidiasis
  • Changes in the amount of vaginal secretion
  • Cervical ectropion or cervical erosion/abrasion
  • Galactorrhea or the spontaneous flow of milk from the nipple when a woman is not nursing
  • Nipple discharge

In cases of prolonged use, the risk of the following side effects is also raised:

  • Ovarian cancer, endometrial cancer, breast cancer
  • Endometrial hyperplasia or thickening of the womb lining
  • Chest pain
  • Deep vein thrombosis
  • Pulmonary embolism
  • Thrombophlebitis
  • Heart attack or myocardial infarction
  • Stroke
  • High blood pressure or hypertension

Skin-related effects

Skin-related side effects include skin pigmentation, chloasma and melasma. Other skin effects include loss of scalp hair, erythema multiforme, erythema nodosum, hirsuitism (growth of body hair), itching and rash.

Gastrointestinal effects

When taken orally, gastrointestinal side effects may develop including nausea, vomiting, bloating, diarrhea, water retention, jaundice, gall stones, gastritis, dyspepsia, pancreatitis, liver enlargement and liver tumors. Weight gain may also be noted in some women.

Neurological effects

Estradiol medication can cause depression, mood swings, irritability, anger, dizziness and headaches. Epileptic patients may also experience worsening seizures.

Oncologic effects

Some studies have reported that estrogen therapy is associated with an increased risk of endometrial cancer and breast cancer. Some research has shown that the risk of endometrial cancer is removed when progestins are administered in combination with estrogen therapy.

Cardiovascular effects

Studies have demonstrated variable effects of estrogen therapy on cardiovascular factors. Some have shown that the treatment can cause altered lipid levels that reduce cardiovascular risk, while others have suggested the therapy can increase the risk of high blood pressure, especially when it is administered in high doses. Furthermore, the use of estrogens as noncontraceptives has been shown to increase the risk of nonfatal myocardial infarction in young females, particularly if they smoke, while other studies have suggested no such increase in risk exists.

Metabolic effects

Overall, research has generally demonstrated that favorable alterations in plasma lipids occur with the use of estrogen therapy. The treatment has been reported to cause a rise in the level of high-density lipoproteins (HDLs) and a decrease in the level of low-density lipoproteins (LDLs) and cholesterol. On the other hand, the therapy has been shown to cause hypercalcemia in patients with breast cancer and bone metastases, as well as pancreatitis in those with inherited lipoprotein disorders.

Hepatic effects

Reported adverse effects on the liver have included the development of liver cell adenomas, hepatocellular carcinoma, focal nodular hyperplasia and hepatic hemangiomas. Many of the studies that suggested an increased risk of hepatic tumors were based on populations of women who took oral contraceptives over long periods.

Endocrine effects

Adverse endocrine effects that have been reported include an increase in thyroxin-binding globulin that, in turn, leads to an increase in the serum total thyroid level and a decrease in T3 uptake. A decrease in fasting plasma glucose has also been observed.

Ocular effects

Some studies have shown that estrogen therapy can lead to ocular side effects such as lens discomfort, altered corneal curvature and retinal vascular thrombosis.

Effects in pregnant women

Women who are pregnant should avoid the use of estradiol because it has been shown to cause birth defects.

Allergic reaction

Although a severe allergic reaction to estradiol is rare, immediate medical attention should be sought if symptoms such as a rash, dizziness, swelling, itching or breathing difficulty develop.

Further Reading

Last Updated: Mar 11, 2021

Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.


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  1. sam nellco sam nellco United States says:

    I just started taking Estradiol vaginal inserts and am experiencing a lot of irritability and almost anger at some points— does that subside after awhile? If not I may stop

  2. Israely Vitória Israely Vitória Brazil says:

    Pode para de tom vacina estradiol valerato? Não causa nenhum problema?

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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