Most women who are interested in using HRT during perimenopause and menopause have heard that bioidentical hormones are better.
Synthetic hormones are artificially created compounds and while they share similarities with the hormones our bodies make, their structure is not identical to our own hormones. Bioidentical hormones on the other hand are structurally identical to our own hormones and are derived from natural sources. This “bioidentical” molecular structure to the hormones our body makes means that these types of hormone medications will more closely mirror the function of the hormones we produce compared to synthetic hormones.
I cover this topic more in this article: Understanding Bioidentical vs. Synthetic Hormone Replacement Therapy
It used to be that to get a bioidentical hormones for HRT you needed to use a compounding pharmacy, as only synthetic versions were available as FDA-regulated products at your local CVS pharmacy or the like. This is no longer the case as there is bioidentical progesterone available as Prometrium (or its generic equivalent) and bioidentical estrogen available in a variety of products, including patches such as the Vivelle Dot or Climera, gels such as Divigel or Elestrin, and even a topical spray (Evamist).
Testosterone on the other hand at the time of this writing, is not available as an FDA-regulated product for women. Currently, testosterone is only FDA approved for use in men.
Hold on Dr Brooke, aren’t many menopause experts out there espousing the benefits of testosterone for women? Yes they are, and while some use compounding pharmacies, many outspoken menopause experts suggest using small doses of the male approved FDA regulated testosterone preparations over compounded formulas. More on why I think that’s not the best approach in a moment.
What Is The Difference Between An FDA Regulated and a Compounded Hormone Prescription?
First, there is unnecessary fear around using compounding pharmacies for your HRT needs. On the flip side, there is the notion that the only way you can get bioidentical hormones is via compounding pharmacy. Both issues are creating a lot of confusion for women and this article will hopefully clear that up.
The simple difference between these two types of hormone preparation is that an FDA regulated product is made in a large batch by a pharmaceutical company and thus each batch is tested and standardized. A compounded preparation is made for you and only you. Just that one bottle per the prescription from your provider to the compounding pharmacist. It is not big batch tested as an FDA product would be because it’s just the one, single product that was custom made for you.
Wait, not tested? Sounds scary right? Less so than you think.
While that one bottle of progesterone capsules or that one tube of estrogen cream were not tested or standardized, the ingredients INSIDE that compounded formula were tested and standardized.
This compounded formula was not made in someone’s basement with ingredients from Target. It was prepared in a compounding pharmacy that is regulated and inspected by both state and federal agencies by a trained and licensed pharmacist. It was made with ingredients that WERE batch tested and standardized and those ingredients are FDA regulated.
So the bottle that gets sent to your home was not individually tested BUT the ingredients in it are available by prescription only, were made by a FDA regulated pharmaceutical company and by a licensed pharmacist in a regulated, licensed pharmacy location.
Why We Have Compounding Pharmacies
Customized Formulations
Compounding pharmacies exist to create unique formulations when a patient’s specific needs make pre-made formulations an issue. Because the ingredients and delivery forms can be tailored to each individual woman, allergies, sensitivities and preferences can be taken into account vs. having a set ingredient list on a prescription you pick up from your regular pharmacy. This gives women so many more options and even an option in some cases where they would otherwise not be able to take a certain medication.
For example, the FDA regulated bioidentical progesterone known as Prometrium contains peanut oil as part of its formulation. If a woman has a peanut sensitivity or allergy then Prometrium would be a no-go. If you have a sensitivity to an ingredient like a carrier oil (i.e. peanut), various fillers or preservatives in an FDA regulated product, then compounded medications are a great option.
Were you told that Provera is the best substitution for Prometrium?
Many doctors will use the term “progesterone” to describe both bioidentical or micronized progesterone (i.e. compounded progesterone or brand name Prometrium) as well as synthetic progestin known as methoxy progesterone acetate (brand name Provera).
These are not the same thing. While synthetic progestin will work to counter estrogens activity on the uterine lining thus protecting your uterus from unopposed estrogen, it will not confer the same sleep and mood benefits that progesterone does.
One of the biggest issues for women during perimenopause and menopause is anxiety, depression and insomnia. All of these are helped by progesterone but not by progestin. In fact, depression is a known side effect of progestins.
Progestins are found in the prescription Provera, certain birth control pills (often called “low dose” pills) and in IUDs such as Merina and Skyla.
Note: it’s important to know that a small subset of women do not respond well to progesterone and their sleep and mood is not improved when they take it. This is not that common but it does happen. These women are likely more progesterone sensitive or have issues with progesterone metabolism. This is seen often in women with PMDD for example. More on why some women don’t tolerate progesterone on this episode of the Dr Brooke Show.
Compounding pharmacies can also be utilized for formations better suited for children or even pets, where a variety of unique needs can be taken into account such as flavors, sensitivities and even texture preferences.
Customized Dosages
Creating custom compounded formulations also allows for women to have more options when it comes to dosages of medications. In the case of say an antibiotic, we know there is a specific dose that is effective for killing a particular bacteria thus sticking with the FDA regulated product as is just makes sense. In the case of HRT however, there is A LOT of variability for women when it comes to dosing – especially during perimenopause.
To use Prometrium as another example, this FDA regulated version is available only in 100mg and 200mg dosages. So if you need 150mg or 175mg of progesterone because the 100mg dose is too little and 200mg feels like too much, a compounded formulation is perfect for you.
As well if you are early in perimenopause or even low progesterone in your 20s or 30s a lower dose topical progesterone or lower dose oral (i.e. 25-50mg) might be very helpful but more than that would be too much. So again a compounded formulation would be ideal.
When we need a unique dosage or a different type of filler or additive (i.e. olive oil vs. peanut oil) or a special delivery form (an estrogen cream vs. a patch that has an adhesive that gives you a rash), then we can turn to compounding pharmacies to give us options.
And if there’s one thing women need during their HRT journey it’s options! Dogma and protocols do not serve women well in general, but particularly not in this case.
Are Compounding Pharmacies Really Unregulated?
Compounding pharmacies are regulated by the FDA as well as state agencies. They are subject to regular inspections and must maintain certain standards. In short, NO, compounding pharmacies are not unregulated.
As well, compounding pharmacists receive specialized training in compounding as part of their education which is typically at the doctorate level. Many who go on to work in compounding after graduation will also do extra training. Pharmacists can also earn a designation as a “board-certified sterile compounding pharmacist” (BCSCP) meaning they meet standards for safety when preparing sterile, compounded medications.
You may not know this about me, but before becoming an ND and functional medicine doctor I was completing my doctor of pharmacy. During my internship, I worked in a large pharmacy that serviced in-patient nursing homes and we did a lot of compounding. Next to the controlled substances, this was the most regulated, regimented, clean and monitored part of our pharmacy. It was also a lot of fun as it really relied on our chemistry and lab training, it was one of my favorite parts of my work there.
Compounding pharmacies have to use pure, pharmaceutical-grade ingredients that must be made at a facility that’s registered with the FDA when making customized, compounded formulas.
Medications are made to the specifics sent by the ordering provider in terms of the medication i.e. estradiol or progesterone, desired dosage, and with any unique bases (i.e. olive oil vs. peanut oil) or preservatives that are better suited to each patient vs. what may come in the FDA regulated equivalent. Thus, they are not batch tested because the capsules or cream in the bottle that arrives to you was not made in a big batch, rather it was made custom for you.
Is This Lack Of Batch Testing A Problem?
Potentially as while this compounded formulation was made by an licensed health care provider, but it was made by a human and humans do make mistakes.
It is important to remember though that most people are caring professionals and are doing a good job. As well, anyone wanting to keep their job or their business open would obviously want to provide a reliable service that encourages you to use their pharmacy. Many checks and balances exist in pharmacy practice to reduce errors, however errors in medicine do happen – but this is hardly a problem exclusive to a compounding pharmacy.
Errors also happen also in the office of your family doctor and in the hospital. In fact medical errors result in death or permanent disability in nearly 800,000 Americans ain 2023.
We sometimes forget that doctors like all professionals are humans too. Your surgeon for example may have been having a very bad day before they operate on you. So too could your mechanic before working on your car or your hairdresser before taking their scissors or color to your tresses. Of course, most of the time all of these professionals can still perform their job well, but even on the best of days and certainly on the worst of days, people do make mistakes.
To me, the human error factor comes up in all manner of jobs and is not a reason to write off a compounding pharmacist, but the potential of a mistake is not something to ignore either. Ideally your provider will have a close working relationship with a compounding pharmacy they trust and use frequently.
So could a compounding pharmacist make an error in your formulation? Yes. Currently there isn’t good data on the rate of errors in hormone prescriptions but with the rising use of HRT again, hopefully we will glean more insight into potential problems in the near future. This could lead to even more oversight for compounding medications and that would be a good thing.
The biggest error potential for compounded formulas is incorrect dosing. My advice is: if you get a new prescription from your compounding pharmacy and you have not changed your dose per your provider and you experience any new symptoms or side effects, consider a dosing error in the formulation and reach out immediately to both the pharmacy and your prescriber.
Still nervous because you’ve heard about compounding pharmacy mistakes?
Compounding pharmacies can create both sterile compounds and non-sterile compounds. Sterile compounds are drugs that will be injected into blood, into tissue or put into your eyes. Hormones such as those used in HRT (oral progesterone, topical progesterone or estrogen) are not considered sterile.
Sterile products made for injection or to be used in the eyes obviously have a higher risk for contamination than non-sterile product like HRT.
A scary headline you may have heard is that in 2012, a compounding pharmacy in New England sent out a compounded batch of a steroid (methylprednisolone acetate) solution to be used for injection. This batch did not contain the proper preservatives and ultimately was found to contain a fungus that went on to infect 753 people, tragically 63 of them died.
This situation is horrible and was due to poor practices no doubt. Again though, HRT is not injected and the likelihood of this lethal type of situation happening your HRT formulation is highly, highly unlikely.
Pros and Cons of FDA Regulated vs. Compounded Prescriptions For HRT
Compounded Prescription Formulations PROS
Customized doses for women that need a different strength vs. what’s available in FDA regulated, pre-set strengths.
Customized formulations for women that have sensitivities or preferences with other ingredients such as carrier oils or preservatives.
Variety of formulations are available including creams, troches and capsules.
Higher levels of hormones for some women are reached more easily on a topical cream vs. an estrogen patch which is sometimes better for alleviating their symptoms. For example, many women find that it’s only using a compounded cream vs. a patch that gets their levels are high enough to address certain thing like brain fog or joint pain.
Cycling of hormones or customization for women that want to vary daily dosing of hormones in order to more closely mimic a 28 day cycle (i.e. more estrogen week 2 vs. week 4) can be done quite easily with a cream whereas a patch is a set dose throughout each week. Patches can be cut to vary dosing but it’s not generally recommended and doesn’t always work well due to the construction of the adhesive on the patch.
Should you be cycling your HRT? See this post
Compounded Prescription Formulation CONS
Not typically covered by insurance so compounded formulas are often an out of pocket expense for most women.
Formulations themselves are not FDA regulated or batch tested before they are sent to you. Do remember though that the ingredients ARE FDA regulated and facilities they are created in are regulated at the state and federal levels. As well, facilities are subject to regular inspection and the pharmacists and technicians making your formula are licensed in their state to practice.
Biest is an estrogen formula that contains both estradiol and estriol (a much weaker estrogen than estradiol) is commonly used by many prescribers that favor compounded hormones for HRT. Many experts do not suggest using biest because the estriol can bind estrogen receptors making them unavailable for the stronger, more active estradiol creating less estrogen effect overall. This can lead to less symptom alleviation and risk reduction. That said, some women do great on biest so it’s not a clear cut answer for each woman. In contrast, FDA regulated products contain the more active estradiol form of estrogen only. NOTE: you can get plain estradiol in a compounded formula as well, this is just noting that many providers that prefer compounding often prescirbe biest.
Formulations are often on autoship (though not always) and this can be considered a pro or a con. Many of my patients love that their prescription just shows up every month with no effort on their part. Others find it tedious that they have to alert their provider that they have too much on hand and these formulas do have much shorter shelf lives than FDA regulated products. As well, if you need to change your dose and you already had a shipment scheudled, you may end up with a dosage you don’t need and thus an extra expense. For example, you might have a stockpile of 150mg progesterone capsules and then your provider changes you dosage to 175mg and now you aren’t sure what to do with the 150s you already paid for. One solution is to ask your doc for 25mg caps to help you finish out your 150mg caps, but again more hassle and more expense.
FDA Regulated Formulations PROS:
Typically covered by insurance resulting in less out of pocket costs.
Ease of use as estrogen patches that are changed 1-2 x per week vs. a compounded estrogen cream which needs to be applied daily.
Estrogen comes in a variety of strengths and dosage forms such as patch, gel and oral (although oral is not typically recommended).
Dosage is set with estrogen patches eliminating human error with applying a cream from a multidose tube.
Can pick up as needed at a local pharmacy, thus there is no waiting for a shipment if you run out.
FDA Regulated Formulations CONS:
Set dosing (i.e patches come typically in 0.0375, 0.05, 0.075, 1.0mg etc) and progesterone is available in 100mg and 200mg capsules only. If a woman finds she needs a slightly different dose, that’s not an option with these formulations. Again to use Prometrium as an example many women find 100mg is too low and 200mg is too high and there are no in between options without using a compounding pharmacy.
Cycling hormone to mimic a typical 28 day cycle is hard as dosages are set.
If there are sensitivities or reactions to other ingredients in oral medications or sensitivities to adhesives in patches there are less options (although bioidentical estradiol is avaialble in an FDA regulated gel).
Patches can be tricky to get adhered properly or they have water interference from swimming or bathing and this can result in some fluctuating estrogen levels.
They are not typically on autoship and mailed to your home, this might be a pro or a con for you.
And This Brings Us To Testosterone….
Testosterone is an important hormone for women and it may very well need to be addressed a part of your HRT plan. I cover testosterone in more detail in this article.
However, as I said above there is no FDA regulated formulation of testosterone for women, it’s a schedule 2 regulated drug by the FDA like opiods. So if you are in need of testosterone like many midlife women are, a proper, female specific physiological dose of testosterone from a compounding pharmacy is available.
What may feel extra confusing for you is that many famous HRT and menopause experts with huge platforms are very anti- compounded estrogen and progesterone and suggest women only use the FDA regulated forms YET in the same breath, many share that they do in fact use compounded testosterone. You’ll see that they use it both personally and in their practice.
In these cases, these docs have found a compounding pharmacy that they trust and use for their testosterone yet they espouse that compounding is a big no no for estrogen and progesterone. If that has you scratching your head, well it does me too.
For testosterone, the other option for women is to use small doses of the FDA regulated preparations approved for men, such as Androgel. While it is an option, a compounded formula with a female appropriate dose makes much more sense to many women and many providers.
The truth is both options are viable options for women and ideally you’re provider would be open to whatever works best for you.
If it’s helpful, I talk about my journey with HRT in this article.
The Other Compounded HRT: Pellets
In short: I hate them and I cover why in this article. While pellets work for some women, there are a lot of problems with pellet therapy and I see women suffering with them every day. Many women that have used pellet therapy for their HRT report that it was presented as the only or best option or even that they felt pressured to use them as that’s what their doctor preferred.
You deserve to hear the other side of pellet therapy so you can make the best decision for you. I cover all that here.
Since It’s So Cusomized, Shouldn’t All Women Use Compounded Formulas?
Do you love being special? Me too.
You may be wondering, since a compounded formulation is created so uniquely for you, isn’t that just the way to go?
Not necessarily.
For starters, if the FDA regulated products work for you it would make sense for most women to utilize this option in order to bill insurance and have no or less out of pocket costs.
As well, most women find that changing a patch twice a week is easier than using a cream that has to be applied daily and you have to be very careful not to get it on other people via close contact or even the towel you dried your hands with after you applied your cream.
That said either due to sensitivities or preferences, need for a unique dosage or that you’re not doing well for any reason on the FDA regulated options for HRT, then exploring compounding preparations is a great next step.
For reference, I personally use a mix of both compounded and FDA regulated HRT. You don’t have to choose between those two options and your provider should be embracing both options and prescribing whatever works best for YOU. What will get you closer to your goals, account for your unique risk factors, honor your preferences, your budget and your sensitivities – that is the way to go.
We can set aside this notion that compounding pharmacies are unregulated or unsafe and work with providers that have the knowledge to know what tools are best for each individual case.