Hormones: Bioidentical, Synthetic and Animal-derived Estrogens and Progesterone

Topic - Hormones: Bioidentical, Synthetic and Animal-derived Estrogens and Progesterone

Essence of the Article:

Dr. Kent Holtorf reviews the scientific literature pertaining use of differing forms of estrogen and progesterone hormones in HRT (Hormone Replacement Therapy).

Dr. Holtorf cites numerous research articles with troubling findings connecting synthetic and animal-derived hormones with increased risk of health issues. Two of those issues are breast cancer and cardiovascular disease.

There are also positive findings connected to bioidentical hormones.

Dr. Holtorf concludes that more research is warranted to further analyze the differences in forms of hormones used in treatment.

Essential Thinking:

Common sense has a place in this discussion. While the FDA and The Endocrine Society both contend there is insufficient evidence that bioidentical hormones, which have the same molecular structure as those found in the human body, are safer or more effective, isn't the question better asked in reverse? What evidence supports the use of synthetic and animal derived products as better, safer choices than naturally occurring substances for hormone replacement?

The main argument against bioidentical hormones is that they are compounded by pharmacists and, as such, not FDA approved like those produced in registered manufacturing facilities. It is worth noting that pharmacists are trained and licensed to compound drugs.

Do you think research on this topic is worthy of public funding?

What would be your choice for hormone replacement?

Would you feel comfortable discussing hormone choices with your doctor?

If you want to look at a differing point of view, here a link for such an article.

Want more information on bioidentical hormones? Here's a link to our friend Dr. David Brownstein's website Dr. Brownstein has written and lectured about hormones extensively.

Another informational website

Finally, we would add that the type of hormone test is also important. We have chosen, in our primary test offerings, to use advanced methodologies for serum testing that are more exacting. This type of testing requires a longer wait for results, but we feel in most cases it is well worth it. There are also hormone tests with fast turnaround when needed.


The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy?

Kent Holtorf, MD

Holtorf Medical Group, Inc.,

Torrance, CA


Background: The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administration and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective.

Objective: This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the commonly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease.

Methods: Published papers were identified from PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords associated with bioidentical hormones, synthetic hormones, and HRT. Papers that compared the effects of bioidentical and synthetic hormones, including clinical outcomes and in vitro results, were selected.

Results: Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized controlled trials have been documented. Synthetic progestins have a variety of negative cardiovascular effects, which may be avoided with progesterone.

Conclusion: Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly.

Menopause. 2004 May-Jun;11(3):356-67.

Bioidentical hormone therapy: a review.

Boothby LA, Doering PL, Kipersztok S.


Columbus Regional Drug Information Center, Columbus, GA, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.



The terms "natural" or "bioidentical" hormone therapy (NHT) are used to describe hormone treatment with individually compounded recipes of certain steroids in various dosage forms, including dehydroepiandrosterone, pregnenolone, testosterone, progesterone, estrone, estradiol, and estriol. Based on the results of a person's salivary hormone levels, the final composition of the compounded dosage form is individualized to that specific person. Proponents claim that NHT is better tolerated than manufactured products. This paper is intended to review the concept of NHT and to determine whether there is sufficient scientific evidence to support its use.


A literature search was performed in Medline using the following MeSH terms and key words: drug combinations; progestational hormones; hormone replacement therapy; endometrium; estrogen replacement therapy; climacteric; menopause; estradiol; estrogens; progesterone; drug monitoring; and drug compounding. Current Contents, International Pharmaceutical Abstracts, Cochrane Database of Systematic Reviews, Lexis Nexis, Google, Medscape, MD Consult, and were searched with key words.


There are a few observational studies and clinical trials comparing conventional hormone therapy with bioidentical hormone therapy. Studies generally lacked adequate study design, including small sample sizes and comparison of inequivalent doses, to prove safety and efficacy. Little evidence was found to support individualized hormone dosing based upon saliva hormone concentrations.


Evidence suggests that, although individualized hormonal products may decrease some symptoms of menopause, it seems they have no proven advantage over conventional hormone therapies and their use is not supported by evidence regarding pharmacokinetics, safety, and efficacy.

Comment in

Comment on "Bioidentical hormone therapy: a review".Moskowitz D. Menopause. 2004 Nov-Dec; 11(6 Pt 1):639; author reply 639-41.

Comment on "Bioidentical hormone therapy: a review".Marks M. Menopause. 2004 Nov-Dec; 11(6 Pt 1):641-2; author reply 642-3.

A review of bioidentical hormones.Curcio JJ, Smolinski D, Dye J. Menopause. 2005 Nov-Dec; 12(6):774-5; author reply 775. Epub 2005 Nov 8.



[PubMed - indexed for MEDLINE]

Holtorf article link