Important Things To Know About Implantable Estrogen Pellets

Patches! Pills! Injections! But, Estrogen Pellets? Of all the ways to get estrogen (estradiol) into the body, pellets are not currently FDA-approved and pellets are not currently manufactured by large pharmaceutical companies. Implantable estradiol pellets are available from compounding pharmacies, but there are some important details that you should know.

We discuss things to know before ordering from a compounding pharmacy in an earlier article. We recommend reading that article for information on how to vet a compounding pharmacy, information on the ones we work with most, and references regarding the pros and cons. We’ll include a quick re-cap here:

The PROs of compounding pharmacies:

• Products individualized to your needs.
  • Got allergies or sensitivities? A compounding pharmacy may be able to make your desired medication without the ingredients that you react to.
  • Need a different strength or form? Compounding pharmacies may be able to create a form that you can use. Compounding pharmacies can even add flavorings to medicines.
  • Multiple medications can sometimes be combined into one formulations.
  • Some medications may be available via compounding pharmacies that aren’t available elsewhere.

The CONs of compounding pharmacies:

• The manufacturing process at compounding pharmacies is not as strictly monitored as at FDA-regulated laboratories. This means that:
  • Products from compounding pharmacies are more likely to vary in strength or concentration between batches or even within one container of product. You may receive differing dosages without knowing.
  • Compounded products may not have been rigorously tested for safety and reliability.
  • Controls to prevent contamination may not be as strong compared to other laboratories. This may mean that the risk of contamination in compounded products is higher. (5)
• Compounded medicines may cost more, and may not be covered by insurance.
• It may take longer to get your prescriptions.

If you are considering a compounding pharmacy, we strongly recommend having a detailed informed consent discussion with your prescriber. In another article, we discuss things to think about before using a compounding pharmacy. The FDA maintains a database of inspections, recalls and other actions for compounding pharmacies and a reporting program for injuries, reactions, or other harms experienced by patients.

Back to Estrogen Pellets!

As mentioned, estrogen pellets are not currently approved by the FDA, however, pellets and implants have been studied in cis populations for a couple of decades.

What’s an Implant and What’s a Pellet?

• Implants generally have a non-biodegradable shell or structure. The material is housed within a structure that supports sustained release of the medicine. Some implants can be removed when no longer needed or desired.
• Pellets are generally fully biodegradable and cannot be removed once inserted into the body.

Like testosterone pellets, estrogen pellets can be very convenient: the insertion requires an office visit, where the pellets will be injected under the skin, usually in the outer buttocks. Once in the body, pellets release hormones for approximately three to six months. (NOTE: the duration of compounded pellets may vary greatly between batches and pharmacies.)

Transhub.au mentions that estrogen pellets are typically available in 50mg or 100mg dosages in Australia, and most people use 1 or 2 pellets at a time, replacing them when desired, but typically between every 6 and 24 months. They also link to the Cairns Sexual Health Service’s two videos:

• Implant interview
• Implant procedure

Important things to think about:

• Insertion requires a medical appointment, any activity restrictions may apply while the insertion point heals.
• Once in the body, it may not be possible to remove pellets.

Complication Rates

A 2021 research article (1) found that overall complication rates for inserted hormone pellets in cis women was less than 1%. The most common complication was pellets migrating out of the body. This study separated the cis women participating into receiving T pellets only or T and E pellets. No individuals received only estrogen pellets. The estrogen pellets were made from estradiol powder and steric acid.

We do have a recent study of estrogen implants in transgender women!

It isn’t large – 38 individuals total – but there is a study of estrogen implant use by transgender women in Australia between April 2019 and November 2022. (2) This study states that target blood serum levels of estrogen (250-600 pmol/L) were achieved following the insertion of a 100mg implant and maintained at the one, three, six, nine, and 12-month blood checks, with a median insertion frequency of just shorter than nine months. Surveys received from seventeen participants indicated that they preferred implants to other forms of estrogen therapy. (2)

A 1993 study in thirty-six postmenopausal cis women identified that a dosage of three implanted pellets was equivalent to wearing an estradiol patch dosed at 0.05 mg/day. (3) (note – we were not able to access the full article, so we do not know the dosage of each implant.)

There are multiple studies of pellets or implants in cisgender women, but many of them were done in the 1980s and 90s and are not very applicable to today’s technologies or hormone formulations.

What Does This All Mean?

The biggest takeaways are:

• We don’t have good research for knowing how much estrogen should be implanted to achieve desired effects, or how long they may be effective, especially when sourced from compounding pharmacies.
• It may be difficult to remove pellets to lower the dosage or stop treatment if estradiol pellets turn out to be an unpleasant experience. Manufactured implants with a non-biodegradable structure may be removed, but biodegradable pellets might not be removable. (4)
• Overall, people who try them seem to like them. (1, 2)

If you are interested in estrogen pellets, we strongly recommend having a detailed informed consent discussion with your provider to go over the risks and benefits of pellets. We also recommend vetting your compounding pharmacy for accreditation and any history of complaints or violations. What should I know before using a compounding pharmacy?

Citations

1. Donovitz GS. Low complication rates of testosterone and estradiol implants for androgen and estrogen replacement therapy in over 1 million procedures. Ther Adv Endocrinol Metab. 2021 May 27;12:20420188211015238. doi: 10.1177/20420188211015238. PMID: 34104398; PMCID: PMC8165877.
2. Mesure Joanna, Afrin Sarjana, Fitzgerald Sandra, Luu Judy, Gibberd Alison, Leigh Lucy, Wynne Katie (2023) Oestradiol implants for gender-affirming hormone therapy: an observational study of serum oestradiol levels and consumer survey. Sexual Health 20, 550-557. https://doi.org/10.1071/SH23126
3. Suhonen SP, Allonen HO, Lähteenmäki P. Sustained-release subdermal estradiol implants: a new alternative in estrogen replacement therapy. Am J Obstet Gynecol 1993; 169(5): 1248-1254.
4. Satu P. Suhonen, Hannu O. Allonen, Pekka Lähteenmäki, Sustained-release estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy, American Journal of Obstetrics and Gynecology, Volume 172, Issue 2, Part 1, 1995, Pages 562-567, ISSN 0002-9378, https://doi.org/10.1016/0002-9378(95)90573-1.
5. Shehab N, Brown MN, Kallen AJ, Perz JF. U.S. Compounding Pharmacy-Related Outbreaks, 2001-2013: Public Health and Patient Safety Lessons Learned. J Patient Saf. 2018;14(3):164-173. doi:10.1097/PTS.0000000000000188