Biest 50/50 and 80/20 describe the proportion of estriol to estradiol in a compounded estrogen cream: 80/20 is 80% estriol and 20% estradiol, while 50/50 is an equal split. 80/20 leans on the weaker estrogen (estriol) and is the conventional starting ratio. The ratio is separate from the strength.

Key takeaways

  • The two numbers are the ratio of estriol to estradiol, not the dose. 80/20 = 80% estriol / 20% estradiol; 50/50 = equal parts.
  • Estradiol is the more potent estrogen and estriol the weakest, so 50/50 carries a larger relative share of active estradiol than 80/20 at the same strength.
  • Ratio and strength are two separate dials. Strength is written in mg per gram (for example, 2.5 mg/gm) and is set independently of the ratio.
  • 80/20 is the conventional, historically established starting ratio. It became standard by practice, not by trials comparing it head to head against 50/50.
  • Evidence for ratio-specific outcomes is genuinely thin. No good studies show one ratio relieves symptoms better or is safer than the other.
  • Compounded biest is not FDA-approved. The ratio is a physician's decision based on your history, not a self-select option.

If you have compared biest formulas, you have seen 80/20 and 50/50 listed like menu choices. They are not interchangeable, but the difference is also smaller and less studied than most marketing implies. This page explains what each ratio actually changes, why 80/20 is the usual starting point, and where the evidence runs out. For the broader picture on what biest is, safety, and dosing, start with the biest cream overview. Therisse is a physician-led practice, so the goal here is an accurate comparison, not a pitch for one ratio.

What 80/20 and 50/50 actually mean

Biest ("bi-est") is a compounded cream containing two bioidentical estrogens: estriol (E3) and estradiol (E2). The ratio tells you how the total estrogen is split between them.

80/20 50/50
Estriol (E3) 80% 50%
Estradiol (E2) 20% 50%
Leans on The weaker estrogen (estriol) A larger share of the stronger estrogen (estradiol)
Status Conventional starting ratio Less common; a higher relative estradiol share
FDA status Not FDA-approved (compounded) Not FDA-approved (compounded)

Estradiol is the most potent of the body's estrogens and estriol is the weakest, so the practical difference is this: at the same total strength, a 50/50 cream carries more than double the share of active estradiol that an 80/20 cream does. That is the entire reason the two ratios exist as distinct options.

Ratio vs strength: the distinction that trips people up

This is the single most important thing to understand, and it is where a lot of confusion comes from: the ratio is not the dose.

  • Ratio (80/20 or 50/50) = how the estrogen is split between estriol and estradiol.
  • Strength (mg/gm) = how much total estrogen is in each gram of cream.

They are set independently. "Biest 80/20 2.5 mg/gm" means an 80/20 ratio at 2.5 mg of total estrogen per gram. You could hold the ratio fixed and raise the strength, or hold the strength fixed and change the ratio. They are two separate dials a physician can turn.

That matters because people sometimes assume 50/50 is automatically "stronger" than 80/20. It is not stronger in total estrogen: a 50/50 and an 80/20 cream at the same mg/gm contain the same total amount of estrogen. What changes is the mix, specifically the proportion that is the more active estradiol. A higher-strength 80/20 can deliver more estradiol than a lower-strength 50/50. Total dose and ratio have to be read together.

Why 80/20 is the conventional starting ratio

80/20 is the formula most compounding references treat as the default, and it has been the standard since biest was popularized in the 1990s by integrative-medicine practitioners. The rationale was to lean on estriol, the weaker estrogen, while still including enough estradiol for symptom relief.

Two honest caveats:

  • The convention is historical, not trial-based. 80/20 became standard by practice and preference, not because a study compared it against 50/50 and found it superior. There is no head-to-head evidence establishing 80/20 as the "correct" ratio.
  • It is also the ratio with the most pharmacokinetic data, such as it is. The one randomized pharmacokinetic trial most often cited (Sood and colleagues, Maturitas, 2013, a 40-woman study) tested compounded biest at an 80:20 ratio across three strengths (2.0, 2.5, and 3.0 mg) against a standard estradiol patch. It found the lower-strength creams generally delivered less estradiol into the bloodstream than the patch, with blood levels at the highest strength (3.0 mg) not statistically different from the patch. So even for the conventional ratio, lower strengths tended to under-deliver, which is why a conservative starter is titrated upward rather than assumed to be enough.

Therisse's standard starting formulation is biest 80/20 at 2.5 mg/gm, the conventional ratio at a deliberately conservative strength, chosen because with compounded creams the more common problem is under-treatment, not over-treatment. If relief is incomplete, the clinical move is to step the strength up (or, less commonly, revisit the ratio), not to start high.

Does 50/50 work better than 80/20?

Honest answer: there is no good evidence that either ratio relieves symptoms better or is safer than the other. No randomized trial has compared 80/20 against 50/50 for symptom relief, bone protection, or safety outcomes.

What can be said is mechanistic, not outcomes-based: because 50/50 carries a larger share of the more potent estradiol, a 50/50 cream at a given strength delivers a higher proportion of active estrogen than an 80/20 cream at the same strength. Whether that translates into better symptom control for a given person is exactly the kind of individual response a physician tracks and adjusts, not something the ratio predicts on its own.

The deeper reason the evidence is thin is structural. The National Academies of Sciences, Engineering, and Medicine reviewed compounded bioidentical hormone therapy and concluded there is little published information on the bioavailability and pharmacokinetics of these preparations, and that the "sheer diversity and heterogeneity" of compounded products and pharmacy practices makes comparative studies very difficult to conduct. In plain terms: even two pharmacies using the same ratio and strength can produce creams that absorb differently because of their non-active ingredients. That is why no one can hand you a clean, evidence-based ranking of 80/20 versus 50/50.

Who does each ratio suit?

Because the comparative evidence is thin, "who each suits" is a clinical judgment, not a formula. The general framing a physician works from:

  • 80/20 (the usual starting point): A reasonable default for most people beginning biest. It leans on estriol and includes a smaller share of active estradiol, which fits the conservative "start low, then titrate" approach.
  • 50/50 (a higher relative estradiol share): A physician might consider it when an 80/20 cream at an adequate strength is not giving enough relief and the goal is a larger proportion of active estradiol without simply pushing total strength higher. It is a less common starting choice.

For women who still have a uterus, either ratio of estrogen is paired with progesterone to protect the uterine lining, since estrogen alone raises the risk of endometrial overgrowth. That is true regardless of which ratio is used.

The decision belongs with a clinician who has reviewed your history and your response over time, not with a dropdown menu. The ratio is one of several dials (ratio, strength, and the decision to use biest at all), and a website cannot set it for you.

Do the two ratios differ in risk?

There is no evidence that 80/20 and 50/50 carry meaningfully different safety profiles, and no study designed to detect such a difference. Both are estrogen therapy, and both carry the established risks of estrogen therapy: blood clots, stroke, and breast cancer.

On clot risk, the relevant factor is route, not ratio. Large observational research (the ESTHER study) found that oral estrogen raised the risk of venous blood clots while transdermal (through-the-skin) estrogen did not show the same increase, likely because skin-applied estrogen skips the liver "first pass" that drives clotting factors. Both biest ratios are transdermal creams, so both share that more favorable route compared with estrogen pills. This is reassuring context, not a guarantee, and the compounded-cream evidence base specifically is limited. A physician reviews your history (including any personal or family history of clots, stroke, or hormone-sensitive cancers) before prescribing either ratio.

How Therisse handles the ratio

Therisse is physician-led. A board-certified physician reviews your intake and history before anything is prescribed, and the cream is dispensed by a licensed 503A compounding pharmacy. We start at the conventional, defensible formulation (biest 80/20 at 2.5 mg/gm) and adjust strength, or revisit the ratio, based on how you respond, rather than starting high or leaving it to guesswork. The ratio is set by the physician, not chosen from a menu by the patient.

Prescription products require an online consultation with a licensed provider. If a physician does not approve you, your initial consult fee and any medication charge are refunded in full.

Compounded products are not FDA-approved. This page is educational and is not medical advice. Hormone therapy is not right for everyone, and it carries risks including blood clots, stroke, and breast cancer. Talk to a licensed clinician about your individual history.

Frequently asked questions

What is the difference between biest 80/20 and 50/50? The ratio of estriol to estradiol. 80/20 is 80% estriol and 20% estradiol, leaning on the weaker estrogen. 50/50 is an equal split, so it carries a larger relative share of the more potent estradiol. The ratio is separate from the strength (mg/gm).

Is 50/50 biest stronger than 80/20? Not in total estrogen. At the same mg/gm strength, both contain the same total amount of estrogen. 50/50 just has a higher proportion of the more active estradiol. Total strength and ratio have to be read together, since a higher-strength 80/20 can deliver more estradiol than a lower-strength 50/50.

Why is 80/20 the standard ratio? It became the conventional formula by historical practice when biest was popularized in the 1990s, leaning on estriol while including some estradiol for relief. It is the default in most compounding references, but no trial has shown it is superior to 50/50.

Which ratio is better for menopause symptoms? There is no good evidence that either ratio relieves symptoms better. No randomized trial has compared them head to head. The right ratio is a clinical decision based on your history and your response over time.

Can I choose my own biest ratio? No. The ratio is a prescribing decision made by a licensed physician who has reviewed your history, not a self-select option. Compounded biest is not FDA-approved and requires a prescription.

Do 80/20 and 50/50 have different risks? There is no evidence of a meaningful safety difference between the two ratios. Both are estrogen therapy and both carry its established risks (blood clots, stroke, breast cancer). For clot risk, the route (transdermal cream) matters more than the ratio.

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