Updated :27-1–2025 ; Author:David Bauder, Owner & PA-C Weight Loss and Vitality
Bioidentical hormone therapy has become a popular option for many individuals struggling with conditions like menopause, but what does “bioidentical” really mean?
Are these hormones really the same as the ones that naturally circulate throughout your body?
The truth is that yes, bioidentical hormones are structurally the same as your endogenous hormones. Bioidentical hormones just come from plants instead.
To further understand bioidentical hormones, let’s dive into the science of how they’re made and how they compare to natural and FDA-approved hormones.
What does bioidentical really mean?
Bioidentical hormones originate from plant extracts, typically soy or yams. Once extracted, they are altered chemically to become structurally identical to the natural hormones within our bodies (1).
Chemically, these end up being practically the same as common endogenous hormones, such as estradiol, estrone, estriol, and progesterone. A brief overview of these hormones is included below.
Estradiol (E2)
- Synonyms: Estradiol, beta-estradiol, 7beta-estradiol, oestradiol
- Molecular formula: C18H24O2
- Notes: Estradiol is produced by the female body. Additionally, it is available commercially in many hormone therapy products to help manage issues associated with low estrogen.
Estrone (E1)
- Synonyms: Folliculin, theelin, estrovarin
- Molecular formula: C18H22O2
- Notes: Estrone is produced by the placenta, ovaries, and peripheral tissues and plays a role as an estrogen, antineoplastic, and bone density conservation agent. It is converted to estradiol in the peripheral tissues.
Estriol (E3)
- Synonyms: oestriol, trihydroxyestrin, accifemine
- Molecular formula: C18H24O3
- Notes: Estriol is primarily produced by the placenta during pregnancy.
Progesterone (P4)
- Synonyms: agolutin, crinone
- Molecular formula: C21H30O2
- Notes: Progesterone plays a crucial role in embryo implantation, endometrial receptivity, and achieving pregnancy. Low progesterone can result in pregnancy loss or infertility (2).
Compounded medications will include a combination of some of these hormones in a bioidentical form.
History of bioidentical hormones
The history of hormones dates back all the way to the early 1900s, when the first commercial estrogen preparation was created via extraction from placentas.
This product was termed Emmenin, and it was utilised for the treatment of dysmenorrhea, which is painful menstruation.
Afterwards, Ayerst, McKennen, and Harrison, a pharmaceutical company, began producing Emmenin as the first and only female sex hormone to be taken orally.
In 1939, Premarin, or pregnant mare urine (PMU), was developed. This product contained as many as ten estrogens, with the main estrogens including estrone (50 to 60%), equilin (22.5 to 32.5%), and estradiol (5%).
By the time the nineties rolled around, Premarin had become the number one prescribed drug in the US. In 1997, sales grew to more than one billion dollars (3).
In the present day, many different hormone options are available, including bioidentical hormone therapy.
How are bioidentical hormones made?
As aforementioned, compounded bioidentical hormones are derived from plant sources. From there, they are compounded to contain between one to three forms of estrogen that are considered “identical” to those found naturally in our bodies.
These include estradiol, estrone, and estriol, which are combined in different ratios. Frequently used compounded formulations and their respective ratios are included in the table below.
| Preparation | Contents |
| Progesterone | Progesterone |
| Estriol | Estriol |
| Bi-estrogen | Estriol and estradiol in an 8:2 or 9:1 ratio |
| Tri-estrogen | Estriol, estrone, and estradiol in an 8:1:1 ratio |
When compounded, these formulations are typically available in the forms of oral, vaginal, and transdermal preparations (4).
Comparing bioidentical versus synthetic hormones
Because both bioidentical and synthetic hormones are available, you may be wondering the differences between the two. Let’s review some of the differences.
Structure. As we know, bioidentical hormones are structurally identical in terms of their molecular structure compared to endogenous hormones found within the body.
This is different from synthetic hormones, which are structurally modified and thus different from human endogenous hormones.
These modifications can affect things like absorption, metabolism, and duration of action.
Receptor binding. Because synthetic hormones are modified, their binding properties to hormone receptors may be different from endogenous and bioidentical hormones.
Side effects. Additionally, because of differences in receptor binding and duration of action, someone may experience different side effects when using synthetic versus bioidentical hormones.
For example, synthetic hormones are sometimes modified to be active in the body for longer durations, which can affect the side effect profile (5).
Risks. Many people think that because bioidentical hormones are “natural” they are therefore safer. However, there are inherent risks associated with using any hormone therapy, as with most medications.
But the risk profile could potentially differ between synthetic and bioidentical hormones. For example, a meta-analysis indicated that natural estrogen (E2) had a 33 per cent lower risk of venous thromboembolism (VTE) versus synthetic ethinyl estradiol (6).
Other research shows differences in breast tissue effects, mood, and more between the two different types of hormones.
What type of hormone is right for you will depend on a number of factors, including your medical history and assessment by a provider.
Many providers will opt for bioidentical hormones for hormone balance and tissue specificity.
The role of E1, E2, E3, and P4
We previously discussed some high-level differences between E1, E2, and E3, but let’s dive a bit further into how both are used within the body.
Estrone (E1)
Estrone, or E1, is the weakest form out of the three estrogen types. After a woman experiences menopause, estrone is the only form of estrogen that the body continues to produce itself.
Thus, post-menopausal women tend to have high estrone levels versus those who are pre-menopausal.
The adrenal glands, adipose tissue, and ovaries all produce estrone. Low estrone levels are associated with increased osteoporosis risk, fatigue, low libido, and hot flashes (7).
Estradiol (E2)
Unlike estrone, estradiol (E2) is considered the most biologically active estrogen, and it is mainly produced in the ovaries.
It is the most important hormone throughout a woman’s reproductive age, as it is necessary for sexual function and reproduction.
It also impacts several other tissues and organs.
For example, estradiol is essential to growth hormone in the reproductive organs, maintenance of ooctyes, and ovulation.
It also drives the changes that happen during puberty, the menstrual cycle, and pregnancy. Its levels can impact bone health, the brain, blood flow, and risk of disease (8).
Estriol (E3)
Estriol’s function is a bit more limited of the other estrogen hormones. In fact, it only plays a major role during pregnancy.
Throughout pregnancy, estriol contributes to uterine growth to accommodate the fetus and helps prepare the body for labour, delivery, and breastfeeding.
As such, estriol levels start to increase in the eighth week of pregnancy and continue to rise throughout the pregnancy itself (9).
Progesterone (P4)
Progesterone is not an estrogen, but it is important and has a lot of functions. Progesterone helps prepare the endometrium within the uterus for a pregnancy.
It is also involved in aspects of menstruation and pregnancy itself. Low progesterone is associated with mood changes, difficulty sleeping, anxiety, depression, and hot flashes (10).
FDA approved versus compounded hormones
So, all of these hormones are important, and thus, you might be considering hormone therapy. But FDA-approved hormones or compounded hormones – which is right for you?
It is important to note that the clinical data supporting the use of compounded bioidentical hormone therapy (BHT) is growing.
There are several smaller clinical studies and observational research that support BHT’s ability to improve symptoms. However, this research is limited in size, duration, and funding.
But in contrast, FDA-approved hormone therapy must undergo rigorous randomized controlled trials (RCTs) that prove their safety and efficacy.
Thus, there is a lack of evidence supporting BHT versus FDA-approved products.
One benefit of compounded bioidentical hormones, however, is the ability to customize. This differs from FDA-approved formulations, which come in fixed ratios and strengths.
Providers can prescribe individualised ratios (for example, 50/50 or 60/40 E2/E3) of BHT that have demonstrated favourable receptor binding patterns and symptom control in smaller studies.
When it comes to the hormones themselves, hormones like estriol have been shown to improve genitourinary syndrome of menopause (GSM).
This is a condition that affects daily activity, relationships, and sexual function. Low doses of estriol vaginal gel have been shown to reverse vulvovaginal symptoms in postmenopausal women, specifically in women with breast cancer receiving retreatment with non-steroidal aromatase inhibitors (11).
Another example is progesterone. As we know, progesterone is important to maintaining the endometrium, and thus bioidentical progesterone therapy can help support the endometrium. It can also improve sleep quality.
Conclusion
In summary, bioidentical hormones are exactly what the name suggests – practically identical to your body’s natural hormones on a structural level. As such, they can mimic endogenous hormones such as estradiol, estrone, estriol, and progesterone to help alleviate conditions such as menopause.
When comparing bioidentical and synthetic hormones, there are a few key differences in how they are synthesised and what their structure is.
As such, you may notice some differences clinically in how the body responds and tolerates either hormone option.
If you are interested in hormone therapy, visit our clinic at Weight Loss and Vitality or discuss with your provider which option might be right for you. Additionally, you can read more about understanding hormones here on our latest blog.
References
- https://journals.sagepub.com/doi/10.2217/17455057.4.2.163?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
- https://pubchem.ncbi.nlm.nih.gov/
- https://www.urmc.rochester.edu/ob-gyn/ur-medicine-menopause-and-womens-health/menopause-blog/february-2016/the-history-of-estrogen#:~:text=Premarin%C2%AE%20contained%20at%20least,before%20entering%20the%20general%20circulation.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3127562/
- https://www.preventivemedicinedaily.com/healthy-living/womens-health/menopause/bioidentical-hormones-vs-synthetic-which-is-safer-evidence-based-insights/?utm_source=chatgpt.com#definition-and-chemical-properties
- https://www.mdpi.com/2072-6694/17/16/2680?utm_source=chatgpt.com
- https://my.clevelandclinic.org/health/body/22398-estrone
- https://www.news-medical.net/health/What-does-Estradiol-do.aspx
- https://my.clevelandclinic.org/health/articles/22399-estriol
- https://my.clevelandclinic.org/health/body/24562-progesterone
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9452593/