Estriol vs. estradiol: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Estriol (E3) and estradiol (E2) are two different forms of the female hormone known as estrogen (sometimes referred to as oestrogen). These forms of estrogen are steroid hormones that are naturally found in the body. Estriol and estradiol can be used as hormone replacement therapy (HRT) for women after menopause.

Estriol and estradiol are two of the three different types of estrogen hormones. The third type of estrogen is estrone (E1), which is produced in women during menopause and young women who are experiencing their first periods. Estrone is not typically used for HRT because it is considered a weak estrogen.

Estrogens work by binding to estrogen receptors (ERα or ERβ) in the body. While their locations can overlap, estrogen receptor alpha (ERα) is primarily found in the endometrium, breast tissue, and ovaries. Estrogen receptor beta (ERβ) is found in other parts of the body such as the brain, heart, kidneys, bones, and lungs.

What are the main differences between estriol and estradiol?

Estriol (Estriol coupons | Estriol details) is sometimes referred to as E3 or oestriol. It is the weakest form of estrogen in the body. Like estrone, estriol levels naturally increase during pregnancy. Estriol is FDA approved for urinary incontinence in female dogs after removal of the ovaries and uterus. Estriol is not FDA-approved as a prescription drug for humans. However, some compounding pharmacies may sell estriol compounded with other drugs.

Estradiol (Estradiol coupons | Estradiol details), or E2, is the most potent of the three estrogens. Some forms of estradiol can be found in low-dose birth control pills for premenopausal women. It is primarily used as a tablet, patch, or cream for estrogen replacement therapy. Estradiol can be found in FDA-approved products such as Estrace, Vivelle-Dot, Vagifem, and Climara, among others. The FDA has also approved estradiol in bioidentical hormone therapy with progesterone.

Conditions treated by estriol and estradiol

Estrogen is most commonly used as hormone replacement therapy for women experiencing symptoms of menopause. Estrogens are often combined with progesterone or other steroid hormones called progestins. Estradiol is FDA approved to treat symptoms of menopause. These symptoms include vasomotor symptoms such as hot flashes, night sweats, and flushing of the skin. Other menopausal symptoms include vaginal atrophy, or vaginal dryness, inflammation, and thinning.

Estradiol can also be used in late-stage breast cancer that has spread to other parts of the body. It is used to help decrease the severity of the cancer (palliative care). For women with ER-positive (ER+) breast cancer that has metastasized, high dose estradiol may be used as therapy. According to studies from Maturitas, if breast tumors express the ESR1 gene, the cancer may respond well to estradiol therapy.

Estradiol tablets are also approved to treat advanced prostate cancer that is androgen dependent. While estrogen levels can contribute to prostate cancer, estradiol can be used as palliative treatment in some men. Studies show that estradiol is an effective form of therapy for certain types of prostate cancer.

Estriol is not FDA-approved in humans. However, it is sometimes compounded with other medications for hormone replacement therapy. Because it is an estrogen, it can be used as an off-label drug for estrogen-related conditions. The only FDA-approved form of estriol is Incurin, which treats urinary incontinence in female dogs after removal of the ovaries and uterus (ovariohysterectomy).

Other off-label uses of estriol and estradiol include relief of menstrual migraines and prevention of osteoporosis (bone loss) after menopause. Estrogen plays a large role in bone density. Postmenopausal women with an estrogen deficiency may have a lower bone mineral density. Estrogen therapy can also be used to treat postpartum depression. According to some studies, transdermal estradiol has been shown to be useful for relieving depression after giving birth.

Is estriol or estradiol more effective?

Out of the three forms of estrogen, estradiol is the most potent form. It is approved by the U.S. Food and Drug Administration to treat estrogen-related conditions. Estriol and estrone are not approved in the U.S. for women. However, these estrogens may still be used in some compounded medications.

No head-to-head trials have been conducted with estriol and estradiol. Some studies have shown that estriol is safe and effective for symptoms of menopause. When applied topically for vaginal atrophy, estriol has been reported to be effective with other drugs. Because estriol is less potent, it may have fewer adverse effects. Using estriol, like other estrogen therapies, can still increase the risk of breast cancer, endometrial hyperplasia, and endometrial cancer.

Estradiol treatment can be useful as HRT after menopause. In fact, it is the most common estrogen prescribed for symptoms of menopause. All forms of estradiol are approved for hormone replacement therapy. The transdermal patch has been shown to result in steady estrogen levels for optimal therapy.

Consult your healthcare provider to discuss your options if you are considering medications that affect hormone levels. You may be recommended other forms of estrogen such as drugs containing conjugated estrogens (e.g., Premarin, Prempro).

Coverage and cost comparison of estriol vs. estradiol

Currently, there are no FDA-approved drugs containing estriol for humans. Therefore, it is not usually covered by Medicare and insurance plans. Incurin is the brand name for estriol that is approved for dogs with urinary incontinence. The cost can vary depending on the pharmacy you purchase it from. SingleCare discounts for estriol are not currently available.

Estradiol is available as a generic skin patch. Brand names of estradiol include Minivelle, Climara, and Vivelle-Dot. Brand name estradiol average cash price can differ with Medicare and insurance plans but you can purchase a generic version for $33-$63 with a SingleCare discount card.

Get the SingleCare prescription discount card

Side effects of estriol and estradiol

The most common side effects of estrogen therapy include menstrual changes (changes in bleeding patterns), spotting, pain during periods (dysmenorrhea), breast tenderness, nausea, vomiting, and headache. Other side effects of topical and oral estrogens include bloating, weight gain, and hair loss.

Topical estriol or estradiol may cause more direct effects when applied to the vagina. Side effects can include itching and increased secretions. Other more serious side effects may include fungal infections (candidiasis).

Estrogen has been shown to alter or increase the production of melanin, a substance responsible for the skin’s pigment. Estrogen can increase pigment and darken the skin in some cases.

Severe side effects of estrogen use include high blood pressure (hypertension), heart attack, blood clots (thromboembolism), worsening of asthma, gallbladder disease, and low calcium levels. Other severe adverse effects can include the enlargement of fibroids in the uterus as well as the increased risk of breast and cervical cancer.

This may not be a complete list. Consult your doctor or pharmacist for other side effects.
Source: DailyMed (Estriol), DailyMed (Estradiol)

Drug interactions of estriol vs. estradiol

Estrogen is primarily metabolized in the liver by CYP3A4 enzymes. CYP3A4 inhibitors, such as certain antibiotics, antifungals, steroids, and anticonvulsants, can increase the levels of estrogenic drugs in the body. In turn, this can increase the risk of adverse side effects.

CYP3A4 inducers like certain antibiotics, antifungals, and antivirals can decrease the level of estriol or estradiol in the blood. CYP3A4 inducers can ultimately lead to reduced effectiveness with drugs containing estrogen. (See chart for examples)

Estriol and estradiol can also interact with grapefruit juice. Consuming grapefruit juice with estrogen-containing products can increase the risk of side effects. It’s important to discuss your complete medical history with a doctor who specializes in endocrinology.

This may not be a complete list of all possible drug interactions. Consult a doctor with all medications you may be taking.

Warnings of estriol and estradiol

Using estrogen can increase the risk of endometrial cancer, especially when it’s not taken with a progestin. Estriol and estradiol also have an increased risk of heart attack (myocardial infarction), stroke, pulmonary embolism (blood clot in the lungs), and deep vein thrombosis (blood clot in the veins) in postmenopausal women aged 50 to 79 years old. In the same population of women, estrogen use can also lead to an increased breast cancer risk, according to the Women’s Health Initiative. Estrogen may also increase the risk of dementia in some postmenopausal women over 65 years of age.

Consult a doctor if you have risk factors including a medical history of:

• Heart attack
• Stroke
• Blood clots
• Cancer (of any form)
• Abnormal periods
• High blood pressure
• Heart disease
• Asthma
• Gallbladder disease
• Liver disease
• Uterine fibroids
• Endometriosis
• Hypocalcemia

Women who smoke tobacco may be at an increased risk of blood clots. Estrogen-containing products should not be used in these women.

Estriol, estradiol, and other estrogen-related drugs can harm an unborn baby. They should not be used during pregnancy or breastfeeding.

Frequently asked questions about estriol vs. estradiol

What is estriol?

Estriol is a form of estrogen that is naturally produced in the body. Estriol is not FDA approved for hormone replacement therapy in humans. Some compounding pharmacies may sell medications containing estriol which are used for off-label purposes. Estriol is only approved to treat urinary incontinence in female dogs.

What is estradiol?

Estradiol is the most potent form of estrogen. It is available in several different versions of brands and generics. Brand names include Estrace, Climara, and Vivelle-Dot. It can be used as an oral tablet, transdermal patch, or vaginal cream for women with postmenopausal symptoms. It can also be used as palliative treatment for late-stage breast and prostate cancer.

Are estriol and estradiol the same?

No. Estriol and estradiol are not the same. Estriol is a weaker form of estrogen that may only be found in compounded hormone therapy products. Estradiol is more potent than estriol and is FDA approved for hormone replacement therapy.

Is estriol or estradiol better?

Estradiol is stronger and more effective than estriol. Estriol is a weaker form of estrogen and may have a better safety profile compared to estradiol. However, more clinical trials may be needed on the effectiveness and safety of estriol.

Can I use estriol or estradiol while pregnant?

No. Estrogens like estriol and estradiol should be avoided while pregnant. Taking these medications while pregnant can lead to an increased risk of birth defects. Estrogen should not be taken while breast-feeding.

Can I use estriol or estradiol with alcohol?

No. Estriol or estradiol should not be used with alcohol. Alcohol use can increase the levels of estrogen in the blood. Drinking alcohol with estrogen therapy can increase the risk of breast cancer.