What’s the difference between synthetic vs. bioidentical hormone replacement therapy?
Let’s talk about it.
For years, the only choice menopausal women had was prescription synthetic hormones. Fortunately, since the late 80s, bioidentical hormones have been available.
The Difference Between Synthetic vs. Bioidentical Hormone Replacement Therapy
Synthetic hormone replacement therapy are chemically created in a lab, and have a hormonal effect in the body. For instance, medroxyprogesterone is a synthetic progestin that is derived from a testosterone molecule with fewer carbons than natural progesterone. It does protect the uterus against estrogen’s building effects so that you're less likely to get endometrial cancer. But it does not protect the rest of your body, like your breast tissues. Progestins are not progesterone.
Bioidentical hormones look exactly like what your ovaries would make, so your cells don't know the difference. Bioidentical hormones still have to be synthesized somewhat, which means that you can't eat a yam and get progesterone, or eat soybeans and get estrogen. The precursor molecules of those hormones in these plants can be divided in the lab into estrogen and progesterone, as well as testosterone, pregnenolone, and DHEA.
HRT and BHRT are chemically different.
Synthetics are patentable, man-made chemicals. Bioidenticals are not necessarily patentable, although there are a few bioidenticals in pharmaceuticals that have patented delivery systems. You have choices.
The types of bioidentical hormone replacement therapy include estrogens – estradiol, estrone, and estriol. Sometimes they're combined, and sometimes they're taken separately.
Progesterone is best micronized, meaning a smaller molecule, so that it's absorbed better. Chemically derived testosterone is methylated, which is very toxic to your liver. Bioidentical testosterone is non-methylated.
In perimenopause, I refer to hormone replacement therapy as supplemental, meaning we're just giving you enough of those hormones to help with your symptoms, but not so much that we're replacing all of your needs, because you may be able to still make it. We usually start with progesterone.
By menopause, you need to consider full hormone replacement therapy - both progesterone and estrogen.
If needed for osteoporosis or sarcopenia, testosterone can be added.
Finding the most effective bioidentical hormones can be challenging.
Gen-Pro™
In the early 90s, I began working with a compounding pharmacist to improve upon the existing transdermal delivery of progesterone. At the time, I was focusing on progesterone as hormone replacement therapy, but also for infertility treatments, to prevent miscarriage, as well as to regulate menstrual cycles. At the time progesterone injections were the gold standard, and they're very painful. Then, compounders developed progesterone suppositories, great absorption, but are incredibly messy and can cause uterine cramping as well as some urogenital symptoms like urinary retention.
So, transdermal delivery seemed to be the best option, but not all transdermal bases are created equally.
After years of sharing my clinical experiences with the compounded pharmacist, we came up with an amazing liposomal-based transdermal with a very high absorption, higher than anything any other compounders had created, and higher than anything over the counter. Progesterone is such a large molecule, so it’s very difficult to deliver transdermally. Most creams deposit progesterone into the subcutaneous tissue, which makes it difficult to reach the bloodstream and become systemically absorbed.
Our progesterone formula had very high absorption rates. In fact, I was able to utilize this transdermal cream to replace injectable progesterone as well as progesterone suppositories for my pregnant women trying to prevent miscarriage.
In the fall of 2023, we were finally able to manufacture our highly effective progesterone transdermal cream. Gen-Pro™, the same formula I prescribed for my patients, is now available over the counter.
Gen-Pro™ is the foundation for bioidentical hormone replacement therapy.
Don't forget to join our FREE Hormone Reboot Training!
What is the difference between bioidentical and synthetic hormones?
Bioidentical hormones are molecularly identical to the hormones the human body naturally produces — including estradiol, progesterone, and testosterone. Because they match the body's own hormones exactly, cells recognize and respond to them through the same receptor pathways used for endogenous hormones. Synthetic hormones, by contrast, are chemically modified versions that produce hormonal effects in the body but have a different molecular structure. Medroxyprogesterone acetate (a synthetic progestin) and conjugated equine estrogens are among the most commonly prescribed synthetic hormones. The structural difference matters clinically — it determines how each hormone interacts with receptor sites, how it is metabolized, and what its downstream effects are on tissues like the breast, uterus, and cardiovascular system.
Are bioidentical hormones safer than synthetic hormones?
The safety profile differs meaningfully between the two, particularly for progesterone vs. synthetic progestins. Natural bioidentical progesterone does not carry the same breast cancer risk signal as synthetic progestins — multiple studies, including the large French E3N cohort study, have found that combined therapy using estradiol with bioidentical progesterone does not increase breast cancer risk the way estradiol combined with synthetic progestins does. The 2002 Women's Health Initiative study that generated widespread fear of HRT used synthetic conjugated equine estrogens combined with medroxyprogesterone acetate — its risk findings do not directly apply to bioidentical transdermal estradiol with natural progesterone. Oral synthetic estrogen is also associated with increased clotting risk through first-pass liver metabolism, a risk that transdermal bioidentical estradiol largely avoids. That said, no hormone therapy is without risk, and individual health history, genetics, and monitoring remain important for any HRT decision.
What is the difference between progesterone and progestin?
Progesterone and progestin are frequently used interchangeably but they are chemically and clinically distinct. Bioidentical progesterone is identical to the hormone produced by the ovaries and adrenal glands — it binds to progesterone receptors and also supports GABA production, which has a calming effect on the nervous system, and is involved in bone protection, thyroid function, and neuroprotection. Synthetic progestins, such as medroxyprogesterone acetate, are derived from testosterone molecules with altered carbon structures. They do protect the uterine lining against estrogen-driven overgrowth — which is their primary clinical purpose — but they do not confer the broader protective effects of natural progesterone, and they interact with androgen and glucocorticoid receptors in ways natural progesterone does not, which contributes to their different risk profile for breast tissue and mood.
What types of bioidentical hormones are available?
Bioidentical hormones are available in both FDA-approved pharmaceutical forms and through compounding pharmacies. FDA-approved bioidentical options include estradiol patches, gels, sprays, and rings, as well as micronized progesterone (sold under the brand name Prometrium). These are not unregulated — they have undergone the same approval process as synthetic pharmaceuticals. Compounded bioidentical hormones are custom-formulated by licensed compounding pharmacies and allow for individualized dosing and delivery combinations not available in standard pharmaceutical forms. The three bioidentical estrogens used clinically are estradiol (E2, the primary active form), estrone (E1, dominant in postmenopause), and estriol (E3, a weaker estrogen sometimes used in compounded combinations). Bioidentical testosterone is non-methylated, which distinguishes it from chemically derived testosterone that is methylated and potentially hepatotoxic.
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