What You Need to Know About Pellet Therapy for Menopause...

But the pellet providers won't tell you

I’ve done several call-in radio shows as part of my book tour for The Menopause Manifesto. It’s always fun to chat with people from different areas across the United States and Canada. However, there can also be difficult moments when someone tells you their story and you realize they are getting substandard care. The most common scenario is a caller reveals they are getting so-called pellet therapy, which is an injection of a pellet made of hormones, typically an estrogen and/or progesterone, that supposedly dissolves slowly over 3-6 months releasing hormone(s) into the bloodstream. I say “supposedly” as pellet therapy is inadequately tested for menopausal hormone therapy (MHT) and the scant data we do have is very concerning. 

As this comes up a lot it’s time for a closer look at the unregulated horrors of pellet therapy.  

Pellets are pushed for MHT by doctors and nurse practitioners who make money inserting them. The pellets cost about $350 per dose and up, but it varies by the brand used and the person inserting the pellet. They aren’t covered by insurance, so it’s a cash only business. Pellet providers typically recommend hormone testing to “manage” the pellet therapy, often using proprietary software to supposedly calculate dosing. This adds to the expense as these tests are also not covered by insurance. As an aside, hormone testing is not recommended to manage menopausal hormone therapy. We ask patients about their symptoms and then start the pharmaceutical therapy, no testing needed.

Pellets are often advertised with medically nonsensical terms, such as “bioabsorbable,” “biosimilar”, and “bioidentical.” I know many of you have heard the term “bioidentical” so much that it feels as if it is a medical term, but it isn’t. No estrogen or testosterone made in a lab can be identical to what is made by the body (for those interested in learning more about this, it is covered in detail in The Menopause Manifesto). But even if we could make a truly identical hormone in the lab that doesn’t make it safe. What matters in medicine is if a therapy is tested and found to be safe and effective, not whether it is similar to what the body makes. After all, the estradiol made by the body causes cancer of the lining of the uterus (endometrial cancer).

So here’s what you need to know about pellets

Hormone Pellets for Menopausal Hormone Therapy are Hard to Make Safely

Making hormones for human use requires research, expertise and the right equipment. Each dose must be identical be it pill, patch, or pellet. In addition, clinical studies are needed so we know how much hormone from each pill, patch, or pellet enters the bloodstream. Change any ingredient in this recipe, even a seemingly inert filler, and everything could change. These aren’t recipes that can be altered on the fly, you aren’t making an omelette, any minor variation requires detailed study and that simply doesn’t happen with pellets. As pellets are inserted into the body they must also be sterile.

It can take years of testing to get pills or patches just right so they are absorbed in a uniform manner. Pellets are even harder to make because the hormone in a pellet is supposed to be specially formulated so it dissolves slowly over time. Get the recipe wrong and too much or too little could be released, causing complications.

Pellets are about the size of a grain of rice, about 3 mm X 8 mm. To make a pellet correctly a pharmacist must have special equipment to mix, dry and package the pellets and this equipment must be incredibly precise as a size difference of even 0.1 or 0.2 mm could change how much hormone there is in the pellet. Most pharmacies do not have this capability.

With any FDA approved medication (think traditional pharmaceutical) you know what each pill or patch contains, how it is absorbed, and the blood levels it produces. This is all unknown with a hormone pellet. 

Many Pharmacies that Make the Pellets have Issues

In California, the Board of Pharmacy took action against University Compounding Pharmacy for making pellets in a non sterile and unsafe manner. You can read the records here. The FDA is investigating at least two of the pharmacies used by the pellet company BioTe, the letters from the FDA detailing all of their concerns about the lack of sterile conditions and other issues can be found here and here.

Pellets Don’t Have Quality Control 

This sounds super boring, but it’s very important. Traditional pharmaceutical hormones are batch tested for uniformity, meaning patches, pills, creams etc made by these companies are routinely subjected to quality control testing so the company and the FDA can be sure each dose contains what the company claims. As medications made by compounding pharmacies aren’t subject to FDA oversight, this testing isn’t required. 

Despite this, some practices that offer pellets make false claims. For example, Family Medicine Centers states on their website that “The estrogen and testosterone in the pellet are FDA approved.” This is not true as compounded medications are not reviewed for safety and efficacy nor approved by FDA.

In 2019 Dr. Dr. Gary S. Donovitz of BioTE, one of the pellet companies, admitted to the National Academies of Sciences, Engineering, and Medicine that BioTE pellets aren’t batch tested for dose and purity and instead providers who insert these pellets rely on the blood levels from the patients to check dosing. This means instead of BioTE making sure each pellet is the right dose, they are making patients pay for their own testing and then somehow working out with their propriety software if the pellet was the right dose. This isn’t an acceptable method of quality control or patient care. This is a bit like an airline asking you about turbulence after the flight to make sure the airplane is sound. That’s not how it’s done. 

Pellets are Inadequately Tested and We Have Evidence of Harm

The Chief Medical Officer of BioTE recently published a dismal retrospective review of their data that I am shocked was published. There is inadequate data about hormone levels and a host of other concerns. There are no clinical trials telling us that pellets are safe or what dose to use. We have countless studies with traditional pharmaceutical hormones, and none with pellets. That speaks volumes. The companies must either be hiding something or they don’t think the patients who receive the pellets deserve to know if their product is safe and effective. Remember, everyone thought DES was safe and amazing and it was released to the general public with essentially no testing to drastic consequences. 

I have seen real harm from pellet therapy as have many of my colleagues. Some of the issues related to pellets, especially testosterone pellets, are vaginitis, hair loss, acne, an enlarged clitoris, abnormal uterine bleeding, blood clots and cancers.  

These anecdotal findings have been confirmed in a recent study that looked at the records of women who received testosterone and estrogen pellets versus those receiving standard menopausal hormone therapy (MHT). Side effects were much more common among the women who received pellets, 58%, versus 15% for those receiving standard MHT. The side effects included mood swings, anxiety, hair loss. acnes, abnormal uterine bleeding, and needing a hysterectomy for abnormal uterine bleeding. 

And once a pellet is inserted it can’t be removed. There are cases of it taking much longer than 6 months for hormone levels to come back into the normal range. If you have a pellet related issue, your only option is to tough it out. 

In 2019 the FDA identified over 4,000 adverse events from the pellets distributed by BioTe that had gone unreported to the FDA. The type of adverse events we’re talking about are cancers, strokes, heart attacks, blood clots, and infections where the pellet was implanted. The number of unreported adverse events likely represents an underestimation. 

Pellets Often Produce Very High Levels of Estrogen and Testosterone

In the study referenced above, the average testosterone level was far higher than recommended for women in menopause: 192 ng/dl, and 38% of women using testosterone pellets had levels of testosterone greater than 200 ng/dl. The normal range for a postmenopausal woman for this study was 3-41 ng/dL. This explains why some women who receive pellets develop acne, lose hair, and get an enlarged clitoris, many are getting levels of testosterone meant for men.

In the same study estradiol levels were also sky high, with an average level of 238 pg/ml for those with pellets versus 93 pg/ml for those receiving standard MHT. The hormone levels for women receiving the standard MHT were as expected, but an average level of 238 pg/ml is far too high, and the potential consequences are an increased risk of cardiovascular disease, blood clots, cancers, gallbladder disease and other complications of MHT not seen with low dose transdermal therapy. 

Women with a uterus face another issue with pellets. Anyone taking MHT with a uterus needs to take a progestogen (progesterone or progesterone like hormone) to protect their uterus from endometrial cancer. With standard MHT we know exactly how much progestogen to use. We have no idea what dose to give to counteract the very high levels of estradiol and testosterone with pellets. 

Multiple Major Medical Societies Do NOT Recommend Testosterone Pellets

Estrogen pellets are not recommended, but there has been less of a formal agreement on this. They are not recommended by the American College of Obstetricians and Gynecologists, the North American Menopause Society, or the National Academies of Sciences, Engineering, and Medicine.

Essentially every major medical group advises against testosterone pellets including American College of Obstetricians and Gynecologists (ACOG), the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women’s Sexual Health, The North American Menopause Society, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The Royal College of Obstetricians and Gynecologists, The International Society of Endocrinology, The Endocrine Society of Australia, and The Royal Australian and New Zealand College of Obstetricians and Gynecologists. 

Most Women Are Unaware of the Dangers of Pellet Therapy

In one survey, only 14% of women knew that compounded hormones, which includes pellets, are not approved by the FDA. Given 94% of women who use pellets have not tried other MHT, these are clearly not women who have tried and failed multiple pharmaceutical products. I suspect many end up with pellets because of the marketing, both by the company and on the advice of physicians who make money doing implants, or because they went to their doctor for MHT and were unfortunately told it was unsafe, and so the “bioidentical” marketing of pellets made them sound like a safer alternative, when in reality they are the opposite. 

But I Am Using Pellets and I Feel Good!

Not everyone who smokes gets cancer or lung disease and many people who smoke feel fine. Not everyone using pellets will have issues, but many will. Using an untested and poorly manufactured product that produces concerning levels of hormones should not reassure anyone. If pellets were so safe, ask yourself why every major medical society recommends against their use?

Pellet therapy for menopause is not recommended by experts, there is no data supporting safe use, they are associated with an increased risk of complications, the actual manufacturing of the product is fraught with issues, and there is no batch testing for purity. Oh, and a safer, tested option in the form of traditional MHT exists.  

If your provider recommends pellets for menopausal hormone therapy, get a new provider. That’s all you really need to know about pellets.

References

1) National Academies of Sciences, Engineering, and Medicine 2020. The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. https://doi.org/10.17226/25791.

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

3) 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

4) 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.

5) Dohm J, Kim J, Woodcock J. Improving Adverse Event Reporting for Compounded Drugs. JAMA Intern Med. 2019;179(11):1461–1462. doi:10.1001/jamainternmed.2019.3830