Estradiol interactions to avoid

In this article:

• Estradiol drug interactions
• Estradiol food interactions
• When to talk to a healthcare provider

In this article

• Estradiol drug interactions
• Estradiol food interactions
• When to talk to a healthcare provider

Estradiol is a prescription drug containing a form of the female hormone, estrogen. Estradiol comes in several different forms—oral tablets, injections, topical cream, topical patches, and vaginal creams. It’s also sold in various brand names, such as Estrace, Estring, and Vivelle dot. Estradiol is prescribed for people who aren’t producing enough estrogen, such as perimenopausal or postmenopausal women, or women who’ve had their ovaries removed. Estradiol may also be prescribed for gender affirming care for male to female transgender individuals.

Estradiol can interact with other medications, such as CYP3A4 inducers and inhibitors, seizure medications, thyroid medications, and benzodiazepines. While most foods are safe to consume while taking estradiol, doctors agree that people taking estradiol should stay away from grapefruit.

Overall, most medicines and foods pose little risk while you’re taking estradiol. Still, it’s important to be aware of any possible interactions, and exercise caution when needed.

Estradiol drug interactions

Most medications are fine to take while you are taking estradiol. That’s because estradiol is a synthetic form of the hormone estrogen. “It’s important to remember that estradiol is a hormone naturally produced by the body for the majority of a woman’s life—it’s not a foreign substance,” says Suzanne Gilberg, MD, OB-GYN and author of Menopause Bootcamp.

Not only that, but as Dr. Gilberg points out, “the amounts [of estradiol] prescribed during perimenopause or menopause are typically much lower than what the body produces during reproductive years, pregnancy, or even normal menstrual cycles.”

It’s also important to note which form of estradiol you are taking. Research has found that topical estrogen—patches, gels, and creams typically have fewer side effects or interactions with drugs than oral or injectable forms of estradiol. As such, using a topical estrogen (patch or cream) is a good alternative to an oral or injection estrogen.

Here’s what to know about estradiol interactions. 

CYP3A4 inducers or inhibitors

CYP3A4 inducers or inhibitors are drugs that impact your body’s metabolism of the enzyme CYP3A4. According to the FDA, CYP3A4 inducers or inhibitors can affect the way your body metabolizes estrogen, which can result in decreased levels of estrogen in your body. This means that estradiol medication may be less effective. Examples of estradiol inducers that may affect estradiol potency include St. John’s Wort, carbamazepine, phenobarbital, and rifampin. CYP3A4 inhibitors that can reduce estradiol effectiveness include erythromycin, ketoconazole, clarithromycin, and itraconazole.

Benzodiazepines

Benzodiazepines are a family of medicines that slow down your central nervous system.

Mitchell Kramer, MD, OB-GYN, chairman of the department of obstetrics and gynecology at Huntington Hospital says that diazepam (Valium), lorazepam (Ativan), temazepam (Restoril), and triazolam (Halcion) are benzodiazepines to be cautious with if you are taking estradiol. “Effects of these meds can be increased or decreased when taken with estradiol,” he says. It’s important to keep in touch with your healthcare provider, who may need to adjust your benzodiazepines dose, switch to a different medication, or try a different estradiol formulation.

Anticonvulsants

Anticonvulsants are medications used to treat seizures or mood disorders. Lamotrigine is an anticonvulsant often sold under the brand names Lamictal and Lamictal XR. It’s also sometimes prescribed to treat bipolar disorder. According to Erika Gray, Pharm.D., founder and chief medical officer at MyToolBox Genomics, lamotrigine is one medication that may interact poorly with estradiol, especially if you’re taking oral estradiol. Estradiol “can also lower lamotrigine levels, which raises seizure risk,” she warns. Using topical estrogens may be a good alternative for some people.

Thyroid medications

Thyroid medications are used for people who either do not produce enough thyroid hormone (hypothyroid) or too much thyroid hormone (hyperthyroid). Levothyroxine (brand names: Synthroid, Levoxyl, Unithroid, and Tirosint) is used to treat hypothyroidism, which is when you have an underactive thyroid. According to Dr. Kramer, if you’re taking estradiol with levothyroxine, absorption of levothyroxine may be reduced, leading to decreased effectiveness. Some people may need to adjust their levothyroxine levels if this becomes a concern. Levothyroxine should be taken on an empty stomach and not with any other medications. Wait to eat or drink for 30 minutes after levothyroxine is taken. If you’re concerned about interaction between levothyroxine and estradiol, have your provider order and review TSH lab work 6 weeks after estradiol started. 

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Estradiol food interactions

As was the case with medication interactions, there are few food interactions to be concerned with when you’re taking estradiol. “It’s important to emphasize that women taking estradiol don’t need to unnecessarily restrict their diet,” Dr. Gilberg emphasizes. “You can continue enjoying your normal food choices while on estradiol replacement therapy.”

Dr. Kramer recommends an overall healthy diet pattern when taking estradiol. Here’s what he recommends:

• Limit highly processed foods
  Limit high-sugar foods
• Limit foods with excess salt, which can alter or exacerbate the effects of estradiol
• Consider adopting a Mediterranean-style diet, with less red meat and more plant-based foods
• Foods high in antioxidants can be beneficial
• Increased fiber in your diet is also helpful

Estradiol and grapefruit

Although most foods are fine to eat when you’re taking estradiol, grapefruit and grapefruit juice are the one exception. “Grapefruit or grapefruit-containing foods may inhibit liver enzymes that metabolize estradiol,” says Dr. Kramer. “This can elevate estradiol to unsafe levels in the body.” As such, he recommends minimizing or avoiding grapefruit and grapefruit juice altogether.

Other Estradiol interactions

Again, although estradiol interactions are not common, certain additional substances may react poorly with estradiol. Moreover, there are a few medical conditions in which it may be best to avoid or minimize estradiol usage. 

Estradiol and alcohol

You can drink alcohol while taking estradiol, but you should do so moderately. “It is always recommended to limit alcohol use when taking any medication,” says Dr. Gray. “Although a moderate intake of alcohol will not cause any significant harm, excessive alcohol can raise estrogen levels and should be avoided.”

Estradiol and pregnancy/breastfeeding

There are very few situations where estradiol is contraindicated. But if you are planning to be pregnant, are pregnant or are breastfeeding, you will not be prescribed estradiol. “Estradiol isn’t typically prescribed during pregnancy or breastfeeding, as a woman’s body is already producing substantial amounts of natural hormones,” says Dr. Gilberg.

Health conditions

Although you can take estradiol regardless of most health conditions, there are certain conditions where it is not recommended. This is typically for oral or injection estradiol, not the topical versions (patches, creams).

According to Dr. Gilberg, people with the following conditions should not take oral estradiol:

• Individuals with a known blood clotting disorder or a genetic predisposition to a blood clotting disorder
• Women in active treatment for an estrogen-dependent cancer, which may include breast cancer or endometrial cancer
• Anyone with a history of a stroke, heart attack, or unprovoked thromboembolism

How to minimize interactions

To reduce the chance of interactions, Dr. Gray recommends using the lowest effective dose for the shortest duration. “Let your healthcare provider know about new medications, supplements, or symptoms,” she recommends. “Monitoring for side effects can also help identify systemic absorption of estrogen.”

Finally, switching to a different formulation of estradiol may help reduce interactions. Topical versions—such as patches and creams—are less likely to cause systemic reactions in the body as they are more readily available to the body and are not metabolized in the same way. 

When to talk to a healthcare provider about estradiol interactions

This article doesn’t include a complete list of possible estradiol interactions. Not only that, but everyone is different, and their body may have differing responses to estradiol. That’s why it’s vital to stay in touch with your healthcare provider when taking estradiol.

“There’s no one-size-fits-all approach to estradiol,” Dr. Gilberg concludes. “Each patient’s treatment plan should be individualized based on their unique needs and health goals.”