Is Bi-Est Cream a Gentler HRT? Here’s What Experts Say

Menopause may be “having a moment,” but reliable information about treatment options can feel as elusive as a good night’s sleep. 

One therapy getting buzz: Bi-Est, a prescription blend of two forms of estrogen that comes in ratios of 50/50 or 80/20. It’s often marketed as a “gentler” alternative to standard hormone replacement therapy (HRT), with fewer side effects. But the truth is more nuanced.

We asked two physicians who specialize in hormone health to unpack Bi-Est, break down the difference  between Bi-Est 80/20 and 50/50, and how to know if it’s right for you.

About the Experts

• Candice Knight, M.D., is a longevity-focused physician who is board-certified in Family Medicine and Integrative Medicine, with additional certifications in Functional Medicine and Quantum Biology.
• Natalie Kunsman, M.D., M.S., is an integrated health advisor and board-certified family physician. She specializes in family medicine, anti-aging and regenerative medicine, and hormonal health in Colorado Springs, CO.

What is Bi-Est?

Bi-Est is a compounded bioidentical hormone replacement therapy (BHRT) that combines estradiol (E2), the strongest form of estrogen, with estriol (E3), a weaker version, to help relieve symptoms of perimenopause and menopause. It comes in topical creams, gels, oral capsules, or lozenges.

• Estradiol (E2) is the most potent and biologically active form of estrogen. Estradiol levels begin to gradually decline during perimenopause, so taking estradiol can ease symptoms like hot flashes, mood swings, fatigue, and vaginal dryness. However, at higher doses, it can lead to side effects such as breast tenderness or bloating. ¹
• Estriol (E3) is a weaker form of estrogen typically produced during pregnancy. Estriol on its own is often too weak to relieve all menopause symptoms, but studies suggest it can enhance outcomes when combined with other estrogens or used for local vaginal support.^{2 3}

Bi-Est, which is derived from plant sources like wild yams or soy, is chemically identical to hormones your body makes naturally. Most modern HRT (also called menopause hormone therapy, or MHT) options are bioidentical too. 

Is Bi-Est milder than other forms of HRT?

Bi-Est may also be gentler than other forms of HRT because each prescription is custom-mixed by a pharmacy to match the personalized ratio and dose prescribed by your doctor. The most common ratios are 80/20 (80 percent estriol, 20 percent estradiol) and 50/50 (equal parts of each).

“Some patients describe Bi-Est as feeling a bit ‘gentler’ than estradiol-only therapy,” says integrative physician Candice Knight, M.D. “That’s largely because estriol—the weaker estrogen—may balance some of estradiol’s intensity while still providing benefits.”

Because it’s compounded, Bi-Est itself isn’t FDA-approved, but both of its ingredients are. Plus,  compounding pharmacies need to meet strict safety standards.

How effective is Bi-Est cream?

While the hormones in Bi-Est—estradiol and estriol—are well-studied for menopause symptom relief, research on Bi-Est cream compared to other formulations is limited. That’s largely because compounded medications vary by pharmacy, which makes large-scale studies difficult. 

It’s also tough to study formulas that are highly individualized. “What feels balanced for one woman may not for another,” says Knight. “Because there is so much biochemical individuality, it’s essential that hormone replacement therapy be customized for each patient—the right ratio, dose, and delivery method should always be based on your symptoms, medical history, and lab values.”

Many women experience significant improvement once their dose and ratio for Bi-Est are dialed in, Knight says—especially when treatment is monitored with follow-up lab testing.

The best way to gauge the effectiveness of any BHRT or HRT is to track your symptoms and work with a healthcare provider to adjust the plan as needed.

Types of Bi-Est Medication

Bi-Est is available in several forms, including:

• Bi-Est cream 
• Bi-Est sublingual troche (a tablet that dissolves under the tongue)
• Bi-Est with progesterone, sometimes called Tri-Est

Natalie Kunsman, M.D., an integrative physician, says she tends to prescribe the cream for its ease and availability. While a 2013 study found that sublingual BHRT can reduce menopause symptoms more quickly than topical versions, Bi-Est troches are not widely available from most compounding pharmacies, according to Kunsman.⁴

If you still have a uterus, you’ll need to take progesterone with Bi-Est, since taking estrogen alone can lead to endometrial hyperplasia, which increases the risk of uterine cancer.⁵

Tri-est medication vs oral progesterone

Tri-est combines Bi-Est with progesterone, but some research shows it might not provide as much uterine protection as Bi-Est combined with oral progesterone, mainly due to absorption issues. ⁶ Talk to a healthcare provider to figure out which combination of estrogen and progesterone is best for you.

Bi-Est 80/20 vs 50/50: Which Ratio Is Right For You?

The numbers in Bi-Est refer to the ratio of estriol (E3) to estradiol (E2).

• Bi-Est 80/20 = 80 percent estriol + 20 percent estradiol
• Bi-Est 50/50 = 50 percent estriol + 50 percent estradiol

Bi-Est 80/20 often works well if you’re consistently experiencing uncomfortable side effects of estrogen therapy. Though there’s no high-quality data on women who use the transdermal patch, which is the most common method of estrogen therapy, it’s estimated that up to 29 percent of women experience breast tenderness and 8–10 percent experience bloating and fluid retention.⁷ Adding estriol to your HRT results in a blend that maximizes estriol’s protective effects while still including enough estradiol for symptom relief, Kunsman says. 

If you’re experiencing intolerable heat flashes or worsening vaginal thinning or dryness, you might need Bi-Est 50/50, which is a stronger dose of estradiol than Bi-Est 80/20.

Typical starting doses for either ratio begin around 1 mg total hormones daily, increasing in 0.5 mg intervals if symptoms persist. Because Bi-Est is customized, your provider can fine-tune both the ratio and dose over time—a key benefit of using Bi-Est, Kunsman says.

Bi-Est Benefits

Bi-Est can relieve a wide range of menopause symptoms, including:

• Hot flashes and night sweats
• Anxiety ⁸
• Mood swings and irritability ⁹
• Insomnia and fatigue 
• Low libido ¹⁰

Bi-Est circulates through the bloodstream to deliver whole-body benefits, which is why some women also notice improvements in joint stiffness, and skin hydration and elasticity, says Knight. She adds that Bi-Est can also improve vaginal tone, lubrication, and sensation.

And because it’s customizable, your provider can adjust the formulation to match your needs. You can change to a stronger ratio (Bi-Est 50/50) if your symptoms aren’t getting better or adjust to a gentler balance (Bi-Est 80/20) if you’re experiencing side effects.e (Bi-Est 80/20) if you’re experiencing unpleasant side effects.

How to Apply Bi-Est Cream

Bi-Est cream is applied once or twice daily ¹¹ to areas of the body with subcutaneous fat, such as:

• Outer thighs
• Buttocks
• Lower abdomen

Avoid applying Bi-Est cream to:

• Breasts
• Genitals
• Cut, scratched, or irritated skin

Absorption can be unpredictable in hormone-sensitive areas or broken skin. To ensure even absorption of Bi-Est cream and prevent hormone transfer, follow these steps:

• Wash hands before and after application, or use clean, disposable gloves.
• Apply at the same time every day.
• Rub the cream in completely.
• Do not bathe or swim for 20-30 minutes after application.
• Prevent transference of the hormones by avoiding skin-to-skin contact with others for 20-30 minutes after application.

Bi-Est Side Effects

Common side effects of Bi-Est cream include:

• Breast tenderness
• Bloating or mild weight gain
• Headaches
• Nausea
• Mood changes
• Spotting or vaginal bleeding

Knight says these side effects, which are similar to what you’d experience with other forms of systemic estrogen therapy, typically fade within weeks as your body adjusts to the medication. 

Bi-Est 50/50 may carry a slightly higher chance of side effects due to its higher estradiol content. If symptoms persist, talk to your provider about adjusting your dose or ratio. 

Mentioned in This Article:

Bi-est cream

Hone’s Bi-est Cream is available as a 50/50 or 80/20 compound of estradiol and estriol, and is used as a topical treatment to balance hormones and alleviate menopausal symptoms like hot flashes and night sweats.

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About the reviewer

Marilyn Lajoie, M.D., is an internist who specializes in hormone therapy for men and women. She holds degrees in integrative medicine from Saba University School of Medicine and chiropractic medicine from Northeast College of Health Sciences.