The Language of Menopausal Hormone Therapy and Why it Matters.

Do you really know what compounded and "bioidentical" mean?

Recently I’ve been making short videos on TikTok and Instagram about menopause, called Menopause Minutes. Catchy, I know (insert wink emoji). And every time I mention compounded hormones or the nebulous term “bioidentical,” there are many questions and lots of comments. The confusion is understandable as these words are often used to imply safety and superiority, but as far as science is concerned, they have nothing to do with either of those important things. 

“But bioidenticals are safe!” is such a common reply, that I thought it worth discussing here again. I’ve reviewed how the term is medically meaningless before (here), but the terminology is complex and people are up against a flood of disinformation, so it’s worth a recap. 

The other common reply when I post about compounded and “bioidentical” hormones is, “Then what are we supposed to do? Suffer?” The answer to that is no, there are safer, better alternatives.

What I want is for people to know what they are putting into their body and for them to have the correct information to make an informed choice about that medication. If you know what I know about these products and how they are marketed and still want to use them, that is your choice. But I prefer hormones that are regulated, tested and safe, and you really should too. 

I also get a lot of attacks from people who make a living selling so-called “bioidenticals”, many who will call me a shill for Big Pharma. I should just note up front, in my practice, I get paid the same whether I prescribe a drug or not. I also don’t take any money from any pharmaceutical company. People who promote “bioidenticals” and compounded products, on the other hand, are typically profiting from these products. So let’s just put that argument to rest up front.

What is a compounded hormone?

A compounded hormone is made by a compounding pharmacy instead of a traditional pharmaceutical company (think Big Pharma). Pellets are included here. Compounded hormones are often promoted under the guise that they can be tailored for you, often by monitoring hormone levels. This is untrue and there are no credible publications to back up this claim. Compounded hormones are not FDA approved in the United States.

Compounding definitely has a place in medicine. For example, there are some situations where an FDA-approved pharmaceutical doesn’t exist, and so sometimes a compounding pharmacy can fill that void. As the alternative is to go without therapy, this is an important contribution. They can also make liquid forms of some medications for people who can’t swallow pills. Or they can make a product without a certain ingredient if there is an allergy.

But these rare exceptions do not explain the number of prescriptions in the United States for compounded hormones. An estimated 1 million to 2.5 million women in the United States ages 40 years or older use compounded hormones and most are unaware that these hormones have not been studied appropriately or approved by the FDA.

Compounded hormones are typically made in small batches, meaning a pharmacist mixes one or a few prescriptions at a time by grinding the powder and dissolving it with chemicals so the hormone can be suspended in the delivery vehicle (think cream, lotion etc.). In some cases, like pellets, the products are made in larger batches. There is no formal quality control with compounded hormones, meaning we don’t actually know how much hormone is in each dose.

A doctor from the pellet company BioTe has publicly admitted instead of quality control, the company relies on hormone testing (an added expense that you the consumer bears) to “get the dose right”. A pharmaceutical company would be shut down if they operated this way. Imagine a pharmaceutical company saying, “Look, we’re really not sure how much cancer drug is in your infusion, let’s just see how you do, check your labs, and go from there!” There would be outrage, so why is this acceptable for hormones and menopause? 

Pharmaceutical products are precisely formulated and tested for accuracy, so we know what is in each dose. Plus, there are lot numbers, so if doctors see a trend of patients responding in an unforeseen way, say more cancers than expected, investigators can look at the lot number to see if the prescription itself was at fault. None of this back end safety exists with compounded drugs and even more concerning, adverse events often go unreported. 

The hormone delivery vehicle, the process that helps the hormone get absorbed into your body at the proper dosage, matters a lot. Pharmaceutical products are subject to years, and often decades of research in order to get this right. None of this exists with compounded hormones. Big Pharma has to show this data to get approved by the FDA, but because compounded hormones are not FDA approved, they don’t need to prove anything. 

Compounded hormones are huge money makers, so the idea that there is some unforeseen force preventing this research is bullshit. For example BioTe, one of the companies that makes pellets, had $139 million in revenue last year, but apparently they can’t turn any of that cash into clinical studies to prove their product is safe and effective. The answer here is almost certainly because the results would be inconvenient for their profit. But hey, prove me wrong! Spend some of those millions on research!  

What’s even worse is many providers will willingly prescribe and many pharmacies will willingly make products we know can’t work. The one I’m thinking of here is topical progesterone (read more about that here). It cannot be absorbed through the skin (this is not the same as a topical progestin, which is a similar hormone, but not the same thing). Imagine prescribing or making a product that is literally useless. 

What does that say? A lot of things, really. None of them good.

Compounded Hormones are often sold as a “bespoke” product

The raw hormone in a compounded product comes from exactly the same place that Big Pharma gets their raw hormone. I’m going to say that again, the raw hormone is the same as what you get from Big Pharma. So the powdered estradiol that is made into a cream by a compounding pharmacy is the same powdered estradiol used by Big Pharma to make patches or pills. It’s just with a compounded product, you have no idea about the dose and whether it is getting absorbed properly. Remember, they don’t test this.

Imagine you have the raw ingredients for corn flakes and you sell those to a Big Cereal company and sell the same raw ingredients to a bespoke “Mom and Pop” organic cereal company (and here you also have to consider a $140 million company “mom and pop”). The Big Cereal company makes corn flakes in a factory with machines that weigh and measure everything accurately and each day a batch is tested for bacteria as well as the ratio of ingredients. That information is logged and ready to be inspected by the FDA at any time. The nutritional value of a cup of cereal is on the label and it’s verified. If someone who eats the cereal gets food poisoning, it’s reported. The plant is maintained to a specific standard in case the FDA visits. The “Mom and Pop” cereal company makes the corn flakes in their oven as they don’t have equipment that has the precision of Big Cereal. There is no testing for bacteria and the precise ratio of ingredients in the final product is unknown. You have no idea of the nutritional value of each cup, and in fact there isn’t even a proper label. If you get sick from this cereal it is unlikely to be reported. And even if it is, there is no way to trace who else may have been affected. The “Mom and Pop” Cereal is however in a pretty glass jar.

What are bioidentical hormones?

“Bioidentical” is a marketing term for the type of hormone, and it means hormones that are similar to what your body makes, but not identical. If I prescribe pharmaceutical estradiol, the main hormone made by the ovary, or progesterone, those could be considered “bioidentical”, but since the term is used to imply safety where none exists, I won’t use it. Also, many people confuse “bioidentical” with pellets or compounded hormones, but “bioidentical” describes the hormone in the product and pellets, and compounded hormones describe the delivery systems. 

Estradiol made by your body can kill you. It can give you breast cancer and endometrial cancer.  The fact that a hormone is made by your body, meaning exactly identical, does not mean that it is safe. Nothing about “bioidentical” should be taken to imply safety. Also, “bioidentical” hormones aren’t even identical to what the body makes. There is a minor difference based on the source of the carbon atoms (we get our carbon atoms from all the food we eat versus when a hormone is made in the lab the carbon all comes from a single chemical). 

The hormones made by your body that are often used in menopausal hormone therapy are estradiol, estrone, estriol, and progesterone (although in the United States estrone and estriol are not recommended as no safety data has been reported to the FDA). These hormones should not be prescribed just because they are almost identical to what the body makes. Hormones should only be prescribed because they are safe and effective and we only know this through research.

The issue here is people read or hear the term “bioidentical” and they assign goodness and safety to that term. The same is true with the equally grating term that is used in the UK, “body identical.” When I hear these terms I think, “Wow, you must think women are incapable of learning that transdermal estrogen is the safest form of menopausal hormone therapy” (transdermal means applied across the skin, and includes pharmaceutical patches, creams, gels, lotions, and a vaginal ring). This doesn’t mean oral is unsafe, but transdermal is the safest and hence the preferred starting point. That is really all you need to know as far as estrogen is concerned. 

There is one more thing that you need to know, if you have a uterus you also need a progestogen so the estrogen won’t give you cancer. The preferred product is progesterone, which can only be taken orally. There are other regimens with oral estrogens and different progestogens that are not progesterone, and they are all fine choices, but with no other compelling reasons to make a different decision, we recommend starting with transdermal estradiol and if you have a uterus, oral progesterone. It’s a pretty easy message. 

Bioidentical hormones and compounded hormones are not plant-based or natural 

The only natural hormone is Premarin, which is extracted from the urine of pregnant mares. That’s it. If anyone else is advertising their hormones as natural they are an idiot, a grifter, or both. 

All other hormones are made by semi-synthesis in a lab from a chemical found in yams or soybeans that similar in structure to hormones, but is itself not a hormone. This starting chemical is then exposed to multiple chemical processes in a lab to convert it into estradiol or progesterone etc. If your compounding pharmacy is grinding up yams to make your hormone cream, there are many more issues here, but you are most definitely not getting a natural hormone because there is no estrogen or progesterone in yams. 

So whether the estradiol (the estrogen most recommended for menopausal hormone therapy) comes from Big Pharma or a compounding pharmacy, it was made in the same way in a lab by semi-synthesis, meaning a chemical found in nature was converted through chemistry to another chemical. Same for estrone, estriol, progesterone etc. That’s a big stretch to call it plant-based.

Compounded hormones often have multiple hormones mixed together and require lab work

It isn’t uncommon to see compounded hormones that are concoctions, a mix of estradiol and estrone and estriol (sold as Bi-est or Tri-est) or with DHEA or testosterone and this is offered as some kind of “bespoke” mix tailored for your needs. This is a sales tactic. There is zero data that these special mixes do anything, but they are more expensive and give the illusion of customization. 

For those asking about testosterone, it’s not part of menopausal hormone therapy, it is a specific therapy in some situations for women with low libido. If your provider is recommending testosterone for low mood, or hot flashes, or preserving muscle mass they are not following the recommendations from any recognized professional society.

Compounded products are typically paired with lab work that further enhances the illusion of safety. This might be salivary hormone testing (which is useless for menopause in every way as it’s not even accurate, so your provider is literally charging you for a medically worthless test), urine testing, or blood work. And this includes the absolutely useless DUTCH test (read more about that here). What happens here is the provider looks at your levels, hems and haws, and then makes adjustments based on pulling numbers out of their ass or, in the case of pellets, proprietary software that pulls numbers out of a computer’s ass. As none of this has been subject to valid studies, I get to say that. 

I can see how the specialized blood work and the review of the lab work with a provider makes the patient feel heard, and can enhance the placebo effect, but that is all it is. That and wasted money.

Fine, I still like my compounded hormones 

I hear this very often. I hope your provider explained compounded hormones are not recommended by any menopause society anywhere in the world as first or second line therapy. The only time they are considered acceptable is in the case of a true allergy where there is no pharmaceutical option.

I also hope your provider explained that compounded hormones often contain exactly the same raw hormone as the government regulated pharmaceuticals you get from “Big Pharma”, just with inconsistent dosing and no guarantee of sterility. So same thing, less safe. And that some contain hormones that are not recommended for menopausal hormone therapy. 

I also hope they explained how some studies tell us that compounded concoctions often either have too much or too little estrogen. Too much estrogen (estradiol, estrone and estriol) can give you cancer and too little can leave you at risk for osteoporosis. Are you getting too much or too little with a compounded concoction? Who knows, the expensive blood work won’t tell you. Although with pellets you are definitely getting way too much hormone.

If you still want compounded hormones after all that, it’s your body and your choice. 

Fine, I still want “bioidentical” hormones. 

It’s not a great term as it is inaccurate at best and purposefully deceitful at worst, and I don’t use it, but if you want to use that terminology I have great news for you, you can indeed get a well tested and quality assured “bioidentical” hormone from a pharmaceutical company. That is what I personally use, a transdermal estradiol patch and oral micronized progesterone, which is the recommended starting therapy for menopause. But I don’t use these two because they are “bioidentical” (and of course the word is in quotations because as discussed, no estrogen or progesterone can truly be bioidentical), I use them because I want the regimen with the lowest risks and I want to know the exact dose of hormone I am absorbing so I can get the impact I want and protect my uterus from cancer. The combination of transdermal estradiol and oral progesterone have the lowest risk of blood clots, gallbladder disease, and breast cancer. Also, pharmaceutical transdermal estradiol comes in multiple doses and delivery systems, so you can most definitely get a therapy tailored to your needs.

There are also a myriad of other government-regulated options, and depending on your individual needs, another approach may be better for you.

But don’t get hung up on the term “bioidentical”, because it doesn’t mean “safer” or “better”. And don’t fall for the compounded hype, because you are accepting all kinds of risks with no studies that show benefit, while providers and pharmacies are cashing in.

There are indeed safe, tested hormones for menopause and the only place to get them is from a pharmaceutical company. And while I know that lots of people immediately think, “evil Big Pharma”, and there are good reasons for believing that, you also have to remember that sometimes there is value to government regulation and testing, and this is one of those instances.

References:

The 2022 Hormone Therapy Position Statement from the North American Menopause Society. Menopause, 2022;29:767-794.

Pinkerton JV, Santoro N. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women. Menopause. 2015 Sep; 22(9): 926–936.

The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use (2020). The National Academies Press. ISBN 978-0-309-67712-7.

FDA actions against compounding pharmacies https://www.fda.gov/drugs/human-drug-compounding/compounding-inspections-recalls-and-other-actions

Jiang X, Bossert A, Parthasarathy N, et. al. Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women. Menopause 28, 8. DOI: 10.1097/GME.0000000000001782

Davis SR, Baber AR, Panay N, et. al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab 104: 4660–4666, 2019.

Dohm J, Kim J, Woodcock J. Improving Adverse Event Reporting for Compounded Drugs. JAMA Intern Med. 2019;179(11):1461–1462.

Lewis JG, McGill H, Patton VM, Elder PA. Caution on the use of saliva to monitor absorption of progesterone from transdermal creams in post- menopausal women. Maturitas 2002; 41: 1-6.

Leonetti HB, Longo S, Anasti JM. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999; 94: 225-228.

Burry KA, Patton PE, Hermsmayer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol 1999; 180: 1504-1511.

Wren BG, McFarland K, Edwards L, et al. Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern and plasma progesterone and salivary progesterone levels in postmenopausal women. Climacteric 2000; 3: 155-160.

Carey BJ, Carey AH, Patel S, et al. A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women. BJOG 2000; 107: 722-726.

Wren BG, Champion SM, Willets K, et al. Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, mood, and quality of life for postmenopausal women. Menopause 2003; 10: 13-18.