What are the Side Effects of Estradiol?

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Every woman goes through menopause at some point in their lives, and unfortunately, the symptoms that accompany this biological change can be pretty uncomfortable. In the United States, women commonly undergo menopause at an average age of 51. Menopause is accompanied by low levels of hormones, including follicle-stimulating hormone and estrogen, which can cause physical symptoms like vaginal dryness, disrupted sleep, hot flashes, and lower energy that can be extremely disruptive. One popular solution is hormone replacement therapy using naturally occurring estrogens like estradiol, which can offer relief from symptoms for women experiencing menopause. Premenopausal women and women of all ages may also benefit from estradiol to help with ovarian failure, adrenal gland dysfunction, sexual function, and other endocrinology-related issues. 

What is Estradiol?

Estradiol is a form of estrogen and a naturally occurring female sex hormone that is produced by the body. Estradiol, sometimes referred to as oestradiol (E2), is the strongest of the three estrogens that humans produce, and both men and women possess certain levels of estradiol, although women have higher levels of the hormone. Estradiol is responsible for carrying out numerous functions in the body, including the maturation and maintenance of the female reproductive system. As estradiol levels rise during the menstrual cycle, these higher levels cause the ovaries to mature and release an egg. Estradiol levels also cause the uterine lining to thicken, allowing a fertilized egg to implant in the uterus, which can result in pregnancy. Estradiol levels decrease as women age and pass their reproductive years, particularly during menopause, which can cause unpleasant menopausal symptoms. Estradiol is a naturally produced hormone, but scientists are able to recreate it for therapeutic use as a medication to aid in relieving symptoms of menopause along with other indications that call for estrogen therapy, as usually indicated by a blood test. The generic name for the oral form of the hormone is estradiol oral, but the hormone is also marketed under a wide variety of brand names, including Vivelle, Elestrin, Climara, Menostar, Estrace, Estradot, and many more. Estradiol is available in the form of an oral tablet, vaginal cream, topical gel or patch, or as an injection to women who need to increase their levels of the hormone. 

What is Estradiol Used to Treat?

Hormone replacement therapy with hormones like estradiol can treat a number of symptoms that result from hormonal imbalances. Estradiol is typically prescribed to help menopausal women manage their symptoms, which may include painful intercourse, sleep disorders, hot flashes, decreased sexual desire, mood changes, vaginal dryness, and anxiety. These symptoms occur as a result of the drop in estradiol levels, resulting in discomfort for many women. In addition to relieving these symptoms, use of estradiol can help mitigate the increased risk of osteoporosis, which grows during menopause. Other conditions resulting from hormonal imbalance that can be managed or resolved with estradiol include delayed puberty, other ovarian issues, primary ovarian insufficiency, certain types of acne, and certain cases of prostate cancer. 

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How Much Does Estradiol Cost?

Estradiol comes in many different forms, and the cost varies significantly depending on which form of the hormone is prescribed (oral tablet, vaginal cream, topical gel or patch, or as an injection). Additionally, the cost of the hormone varies depending on whether a generic or brand name prescription is issued. Estradiol cream costs approximately 57 dollars for a one month supply. A 30-day supply of generic estradiol tablets costs approximately 13 dollars, while the same quantity of Vagifem, a brand name form of the medication, costs approximately 670 dollars and is only available in limited strengths. Many, but not all, forms of commercial insurance offer coverage for generic estradiol, but patients can also receive substantial savings on estradiol through the use of a pharmacy discount card, which offers discounts on all FDA-approved medications, whether brand name or generic, regardless of their insured status.  

As noted above, the generic version of estradiol is far less expensive than the brand name medication in most cases. Patients who are concerned about the quality and safety of generic drugs can be assured  that generic medications are extremely safe and just as effective as the brand name versions of the medications. Generic medications are subjected to the same stringent quality and safety testing by the U.S. Food and Drug Administration (FDA) as brand name medications, so they are guaranteed to be both safe and effective. The primary difference between generic and brand name medications is in inactive ingredients that do not affect how the medication works but may affect the color, size, shape, or taste of the medication. 

What Dose of Estradiol Should I Take?

Each patient will take a different dosage of estradiol depending on their age, the form of estradiol that is prescribed, and the condition or symptoms being treated. When taken for postmenopausal symptoms, oral tablets of estradiol are generally taken in a dose of 1 to 2 mg once per day, and the dose is taken cyclically (3 weeks on, 1 week off). Estradiol is also commonly prescribed as a topical gel for the treatment of postmenopausal symptoms. When used in this manner,  most patients will apply 1 pump of gel applied as a thin layer once per day. Other patients use vaginal inserts, which are given in a dose of 10 mcg that is inserted vaginally daily for 2 weeks, followed by 1 insert twice per week. There are other forms of estradiol available that may be best for your specific condition. Talk to your healthcare provider in order to determine the proper dose, as well as to discuss possible drug interactions or interaction with herbal products. 

What Are the Side Effects of Estradiol?

Estradiol has some side effects that are common and generally do not require medical attention, while others can be serious and should receive medical attention immediately. Common side effects of estradiol that generally do not require medical attention include:

  • Mood changes
  • Cold symptoms including stuffy nose, sore throat, and sinus pain
  • Headache
  • Nausea
  • Diarrhea
  • Changes in menstrual periods
  • Vomiting
  • Stomach cramps
  • Breast pain
  • Sleep problems
  • Weight gain
  • Back pain
  • Vaginal itching or discharge
  • Breakthrough bleeding
  • Thinning scalp hair

Other side effects are serious and require immediate medical attention. These include:

  • Signs of a stroke, including
    • Slurred speech
    • Sudden severe headache
    • Sudden numbness or weakness, particularly when it occurs on one side of the body
    • Problems with balance or vision
  • Heart attack symptoms, including:
    • Sweating
    • Nausea
    • Pain or pressure in the chest
    • Pain that spreads to the jaw or shoulder
  • Signs of a blood clot, including:
    • Pain or warmth in one or both legs
    • Stabbing chest pain
    • Sudden vision loss
    • Feeling short of breath
    • Coughing up blood
  • Unusual behavior
  • Pelvic pain
  • Swelling or tenderness in the abdomen
  • Memory problems
  • High levels of calcium in the blood, as indicated by:
    • Muscle weakness
    • Lack of energy
    • Vomiting
    • Nausea
    • Constipation
    • Increased thirst or urination
    • Bone pain
  • Jaundice (yellowing of the eyes or skin)
  • Unusual vaginal bleeding
  • A lump in the breast
  • Confusion
  • Increased risk of uterine fibroids

What Are the Benefits of Estradiol?

There are four main health benefits associated with estradiol and other types of estrogen hormone replacement therapy. Estradiol helps relieve uncomfortable symptoms associated with menopause, including chills, excessive sweating, hot flashes, vaginal dryness, and difficulty sleeping, which occur as a result of the natural decline in estrogen production during menopause. Estradiol can also help alleviate other common symptoms of low estrogen levels, such as changes to the vaginal tissue, lining, and pH balance. These changes can cause issues like vaginal dryness, atrophic vaginitis, and vulvar atrophy, which in turn can result in  dryness, soreness, inflammation, and irritation that is relieved or improved by estradiol therapy. Women who are experiencing issues with their ovaries may also benefit from estradiol therapy. Female hypogonadism, failure of both ovaries, and removal of the ovaries can be improved by using supplemental estradiol. Estradiol can also help to minimize bone loss, which is more likely to occur after menopause as the risk of osteoporosis increases. Additionally, women taking estradiol have been shown to have lower level of fat within their liver, potentially showing benefits to keep liver disease at bay. 

Are There Any Risks Associated With Estradiol?

Estradiol has numerous benefits and can help relieve the symptoms of hormone imbalances, but it also has numerous risks. Hormone replacement therapy was once the standard treatment for women undergoing menopause, but more recent research has revealed a link between the extended use of hormones and certain medical conditions, such as cancer and heart issues. Four major health risks are linked to usage of estradiol:

  • Birth defects: Miscarriages are more likely to occur in women who become pregnant while taking estradiol or other types of estrogen. If the pregnancy is able to continue through the full term, birth defects in the newborn are common. Women should not take estradiol or other forms of estrogen during pregnancy. 
  • Blood clots: Women taking estradiol and other types of estrogen are more likely to experience blood clots, which can lead to heart attack, stroke, and death.
  • Dense breast tissue: Estrogen hormone replacement therapy can cause dense breast tissue to develop in someone women. The development of dense breast tissue can make the detection of early stage breast cancer more difficult, as mammograms are harder to read. 
  • Cancer: Patients using estradiol and other forms of estrogen are more likely to develop certain types of cancers, including breast cancer and endometrial cancer. Any woman with a family history of these cancers or other types of cancer should be sure to provide their doctor with a complete medical and family history prior to taking estradiol. 

Additionally, estradiol is generally not recommended for breastfeeding women as it has been shown to pass into breast milk. Estradiol is also contraindicated in women with a history of cardiovascular disease, endometriosis, heart disease, and hereditary angioedema. 

References:

https://www.uofmhealth.org/health-library/d00537a1 

https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/estradiol 

https://www.webmd.com/drugs/2/drug-5186/estradiol-oral/details 

https://www.drugs.com/estradiol.html 

https://medlineplus.gov/druginfo/meds/a605041.html 

https://www.healthline.com/health/womens-health/benefits-of-estrogen# 

https://www.mayoclinic.org/diseases-conditions/menopause/symptoms-causes/syc-20353397 

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