In Brazil, these hormones, delivered as subcutaneous “pellets,” are commonly referred to as "beauty chips" and are both promoted as treatments for medical conditions like depression and osteoporosis and marketed with aesthetic promises such as fat loss, enhanced libido, and muscle gain. However, this practice carries significant risks. In December 2023, seven Brazilian medical societies issued a joint letter expressing concerns about the inappropriate use of hormonal implants. While some implants have legitimate medical applications, such as contraception or managing endometriosis, they are often marketed with exaggerated claims and sold directly in doctors' offices.
Several issues related to this practice warrant attention:
- A lack of robust scientific evidence supporting its use for various health conditions
- Adverse effects
- Potential failures in the compounding process, which could lead to lower-quality or unsafe products
- Aggressive marketing campaigns that promote the product as a universal cure-all
The Hormone Prophet
While researching this article, I uncovered numerous professionals and companies subtly promoting hormonal implants for a wide range of health conditions. However, one name appeared with striking frequency throughout my research, Gary Donovitz, an obstetrician, gynecologist and hormone specialist. He is the founder of the Institute for Hormonal Balance, a clinic specializing in hormone replacement therapies, and BioTE Medical, the largest provider of hormone implants in the United States and a hormone “optimization” training center.
Consider his research published in 2021 in Therapeutic Advances in Endocrinology and Metabolism.
In this study, Donovitz conducted a retrospective evaluation of the continuity rates and adverse events associated with subcutaneous testosterone and estrogen implants over a seven-year period. The data were collected through BioTracker, a registry where professionals who administered hormone pellets reported potential adverse effects, dosages, pellet manufacturing sources, and related information. More than 70% of professionals adhered to the established protocol, accounting for over 85% of the total procedures reported during the study period. BioTE Medical collected the BioTracker every two weeks throughout the study period.
Over the seven years (2012 to May 2019):
- 376,254 patients underwent subcutaneous implant procedures, resulting in a total of 1,204,012 procedures.
- 85% (1,018,516) of these procedures were performed on women, aged 25 to 92 years.
- 15% (185,496) were performed on men, aged 35 to 85 years.
43% of patients discontinued therapy after their first insertion, although the study did not record specific reasons for discontinuation. However, for those undergoing at least two hormonal insertions continuation rates were high: 89.2% in men and roughly 94% in women.
In over 1.2 million procedures performed, there were only 1% adverse effects reported. Based on these results, Donovitz claims testosterone and estradiol deficiencies can be safely treated with subcutaneous pellets, citing high therapy continuation rates as evidence of the procedure’s ease, tolerability, and safety. He argues that advanced training and certification by BioTE, enable professionals to minimize adverse events and improve acceptance of the therapy.
However, the study’s limitations warrant closer scrutiny.
- Selection bias: Complications were self-assessed by professionals and patients, introducing the risk of selection bias and subsequent underreporting of adverse effects.
- Incomplete analysis: Common testosterone side effects in women—such as body and facial hair growth, acne, and hair thinning—were not examined.
Two broader criticisms of Donovitz's work stand out. Most critically, the high dropout rate of 43%, which Donovitz downplayed by citing over 1.2 million procedures. The study fails to explain why 161,190 participants discontinued care, their motivations are undocumented. And Donovitz, as the founder and director of BioTE Medical, has a financial conflict of interest, which is acknowledged but not necessarily unacted upon.
BioTE’s track record reinforces these concerns. In 2019, Bloomberg Law reported that the FDA had cited BioTE for failing to report over 4,000 adverse events linked to its hormonal medicines. An FDA investigation in 2018 also associated compounded medicines, including hormonal pellets, with serious health risks such as cancer, strokes, heart attacks, thrombosis, extrusion, and cellulitis.
Does Compounding Make a Difference?
Many regulatory agencies and professional councils have pointed out that one of the primary concerns with compounded medicines is the potential for handling errors. Does this concern have a basis in scientific evidence?
One useful source is a 2021 article published in Menopause. The authors conducted a retrospective cohort study to assess the safety and serum concentrations of estradiol and free testosterone in postmenopausal women treated with hormonal therapy. The study compared outcomes between women using pellets (PHT) and those receiving FDA-approved hormone therapy (FHT).
The study involved information from thousands of patients at Reading Hospital in Pennsylvania on:
- Demographics
- Early menopause symptoms (such as hot flashes and decreased libido)
- Side effects (mood changes, breast tenderness, acne, and weight gain)
- Serum estradiol and testosterone levels
- Treatment duration
Interestingly, FDA-approved hormone therapy (FHT), encompassing 24 different brands, was prescribed by all providers offering menopause treatment. In contrast, hormone pellets were used exclusively by two private clinics. These pellets typically consisted of compounded estradiol and testosterone or were sourced from the Sottopelle brand.
The study concluded that women in the PHT group exhibited higher maximum levels of estradiol and testosterone during treatment and experienced a significantly higher incidence of side effects compared to those in the FHT group. The risk of adverse events was approximately 8.9 times higher for the PHT group. Commonly reported symptoms included anxiety, breast tenderness, changes in hair pattern, acne, and weight gain.
One primary limitation of the study is its observational and retrospective design, which did not employ random sampling to select participants. This introduces the potential for sampling error and selection bias, limiting the ability to establish causality. Moreover, there were notable differences in sample characteristics between the two groups, particularly regarding age, which could act as a confounding factor. Finally, it is important to note that most side effects were self-reported, a method that inherently lacks precision in measurement, often favoring under-reporting.
Although the study has several limitations, which, I agree, do not confirm an inherent danger associated with hormonal implants, the study make a valuable observation that highlights potential issues caused by pellets. Major medical societies have raised concerns about the risks associated with excessive doses in compounded pellets, the lack of safety and efficacy data, and the absence of informational leaflets and warnings on the packaging.
The association between menopausal hormone replacement therapy and an increased risk of certain cancers requires patients to carefully weigh the risks and benefits of treatment. This uncertainty has driven many women to explore alternatives, such as "compounded bioidentical hormone therapy (cBHT)," formulations based on prescriptions of a practitioner for an individual patient; a method heavily promoted across various media platforms.
Currently, nearly 50% of menopausal hormone therapy prescriptions in the U.S. fall under the cBHT category, with annual sales estimated at 26 million to 33 million units, generating over $1 billion in revenue.
Despite widespread promotion, many doctors argue that conventional hormone therapy is not inferior to, and safer than, compounded preparations. cBHT products lack the safety warnings mandated for FDA-approved therapies. Prescribing cBHT without first recommending FDA-approved options is both inappropriate and unethical due to insufficient safety evidence.
Additionally, misleading marketing tactics often inflate the perceived benefits of cBHT. By using terms like “bioidentical” and “natural,” marketers create a false dichotomy that portrays FDA-approved therapies as unsafe while positioning their products as superior. Healthcare professionals must take an active role in dispelling these misconceptions and ensuring patients receive accurate information.
What is the current consensus?
In recent years, several international guidelines have addressed the issue of "bioidentical hormone therapy" and the use of hormone pellets. However, the most comprehensive document to date was published in 2020 by the National Academies of Sciences, Engineering, and Medicine (NASEM) in the United States assessing the clinical utility of cBHTs, at the request of the FDA.
NASEM concluded that insufficient data supports cBHT preparations being as safe or effective as FDA-approved hormone therapies. The report also raised concerns about inadequate oversight and the lack of adverse event reporting, which pose public health risks. Current cBHT use largely reflects patient and prescriber preferences, often influenced by marketing and celebrity endorsements.
The committee recommended:
- Restricting the use of cBHT preparations
- Reviewing specific preparations and dosages for potential FDA approval
- Enhancing education for prescribers and pharmacists involved with cBHT
- Increasing federal and state oversight to address safety and effectiveness concerns
- Disclosing conflicts of interest
- Expanding research on cBHT safety and efficacy using rigorous methodologies
I couldn't have thought of better recommendations myself.
Sources: Low complication rates of testosterone and estradiol implants for androgen and estrogen replacement therapy in over 1 million procedures. Therapeutic Advances in Endocrinological Metabolism. DOI: 10.1177/20420188211015238.
Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women. Menopause. DOI: 10.1097/GME.0000000000001782.
