Hormone Pellet Therapy

Implanted testosterone pellets

A 2015 historical article in Urology is titled as describing Robert Benjamin Greenblatt, a gynecologist, as an unlikely founder of the testosterone pellet. PubMed lists no abstract for it, and its subject headings are drug implants, gynecology, obstetrics, Canada and twentieth-century history. The sources reviewed here therefore do not give the dates or details of his work, and this page does not date the first use of implanted testosterone.

A 2018 retrospective study of men states in its abstract that implantable testosterone pellets have been used since 1972. The same abstract reports that earlier literature gave a very wide range for secondary polycythemia on any form of testosterone replacement, from 0.4% to 40%, with the lowest figure attributed to pellets.

Implanted estradiol

A 2025 critical narrative review states that subcutaneous estradiol pellets have been documented since the 1940s and that its literature search covered 1949 to 2024. The authors report that a commercially manufactured estradiol implant was available in several countries until its global discontinuation in 2011, which they describe as a commercial decision. They add that pellets have since remained available through compounding pharmacies in countries including Brazil, the United States and the United Kingdom.

Compounded hormones after 2002

The Endocrine Society position statement links interest in compounded bioidentical hormones to the 2002 Women's Health Initiative findings. It says that many clinicians and women stopped hormone therapy afterward, which created an environment for the unproven idea that compounded preparations might be safer or more effective than approved ones. The sources reviewed do not document the growth of clinic franchises offering pellets in the 2010s and 2020s, so this page makes no claim about it.

Pellets, implants and pellet therapy

Sources use several overlapping terms for the same general format. Studies of men describe subcutaneous testosterone pellets, abbreviated STP in one survey, while a review of menopausal treatment uses estradiol pellets and estradiol implants interchangeably. Case reports and a 2024 psychiatric case report use the phrase testosterone pellet therapy. The phrase hormone pellet therapy on this page covers testosterone, estradiol or combined implants.

Testopel is named as the pellet product in a 2013 survey title and among the keywords of a 2017 open-label study, whose authors include employees of the product's manufacturer. Other product names appear in the sources only as quoted brand examples, and this page does not endorse any of them.

Bioidentical and compounded

The Endocrine Society defines bioidentical hormones as substances with the same chemical and molecular structure as hormones the body produces, and notes that many approved products meet that description. It says the term has also been used for compounded formulations of estrogens, progesterone and androgens. The American College of Obstetricians and Gynecologists says many compounding pharmacies use bioidentical as a marketing term implying that preparations are natural and therefore safer or more effective.

The Food and Drug Administration states that compounded bioidentical hormone products, such as progesterone and testosterone, are sometimes used in place of approved drugs. A National Academies report page adds that the agency does not review compounded preparations for safety, quality or effectiveness. Compounded pellets are therefore a subset of the wider topic covered on the Machipedia page Bioidentical Hormone Replacement.

General format

Sources describe pellets as small solid implants placed in the tissue under the skin, where they dissolve slowly and release hormone into the circulation over months. A review of estradiol pellets says this bypasses first-pass metabolism in the liver and that the procedure is a minor surgical one. The same review states that the implant cannot be easily removed after insertion, so dose adjustment is limited until the next procedure. This page does not describe how pellets are prepared or inserted.

Treatment is repeated over time. A survey of 113 men reported a mean of 2.8 implant procedures per respondent, and a 2023 case report describes a man receiving implantations every six months for three years.

Hormones and products

Pellets are reported with testosterone alone in studies of men, and with estradiol alone or with testosterone in studies of women. A review of estradiol pellets states that the active ingredient is 17-beta estradiol, the same hormone as in approved transdermal and oral products. The Endocrine Society says compounded preparations are not subject to FDA monitoring for dose, purity, safety or efficacy, and that post-market surveys have found inconsistencies in dose and quality.

Who delivers it

The 2013 survey was conducted at an academic urology clinic, while a 2024 case report describes pellets prescribed to a woman by a holistic practitioner. A critical review argues that safety depends mainly on the prescriber's conduct, including dose control, laboratory monitoring and endometrial protection. The sources reviewed identify no professional-body training standard or register specific to pellet insertion, and this page does not cover laws or enforcement.

In men

Studies of men describe pellets as a form of testosterone replacement for androgen deficiency or hypogonadism, with symptoms such as reduced sexual function and low mood measured by questionnaires. In the 2013 survey, convenience was the most important reason men gave for starting pellets, cited by 68.8% of respondents, and cost was the main reason for stopping, given by half of the 32 men who discontinued. The related Machipedia page Testosterone Replacement Therapy (TRT) covers the wider topic.

In women

A review of estradiol pellets reports use for menopausal vasomotor symptoms, bone density, mood and, with testosterone, sexual desire, and describes use mainly in women whose symptoms persisted on other routes, with low skin absorption, or after surgical menopause. A 2012 pilot study tested testosterone implants for migraine in 27 women. Machipedia covers the broader topic on the pages Hormone Replacement Therapy and Testosterone Therapy in Women.

Claims that professional bodies do not support

The Menopause Society statement on hormone therapy misinformation says estrogen-containing hormone therapy is not recommended for prevention of aging or for hair loss, skin changes or weight gain. It says testosterone therapy is recommended for hypoactive sexual desire disorder in select, screened postmenopausal women, and is not recommended for age-related conditions such as sarcopenia or osteoporosis, or for mood changes, brain fog or general well-being. The statement does not mention pellets by name.

Studies in men

A 2017 open-label study followed 15 men with androgen deficiency for 113 days and reported that testosterone concentrations stayed at or above the 300 ng/dL threshold, that questionnaire scores improved, and that pellet extrusion and polycythemia each occurred in one participant. The authors state that the uncontrolled design and small, ethnically non-diverse sample limit interpretation, and call for randomized trials.

A retrospective chart review of 228 men found secondary polycythemia, defined as a hematocrit above 50%, in an estimated 10.4% at six months, 17.3% at twelve months and 30.2% at 24 months. A single-clinic retrospective series of 168 men reported that complication rates varied with the insertion approach used. Both are observational designs from single centers.

Estradiol implants in women

A critical narrative review of studies from 1949 to 2024 summarizes randomized trials, cohort studies and case series on estradiol pellets. It reports symptom relief and bone density gains in the studies it covers, and describes more predictable blood levels than transdermal products in women with poor skin absorption. The authors also state that larger randomized trials with long follow-up comparing pellets with other routes are lacking, and that quality control of compounded formulations needs study.

Testosterone in women

The 2012 migraine pilot reported that 92% of 27 women rated their headaches as improved three months after implants, with no control group and self-rated outcomes. A clinical practice guideline for hypoactive sexual desire disorder reports a moderate benefit from systemic testosterone in the studies reviewed, but recommends transdermal use and states that compounded products cannot be recommended for lack of efficacy and safety data.

Gaps in the evidence

The Endocrine Society states that no comprehensive trial has examined the safety or efficacy of compounded bioidentical hormones and that no clinical outcomes trials have been completed. The American College of Obstetricians and Gynecologists says placebo-controlled randomized trials with long follow-up, comparing custom-compounded products with approved hormone therapy, are needed. PubMed title searches for hormone pellet therapy, subcutaneous testosterone pellets and estradiol implants in menopause returned only a small set of mostly case-level, observational or narrative papers.

Compounded hormone therapy

The American College of Obstetricians and Gynecologists, in a clinical consensus document reaffirmed in 2026 and endorsed by the American Society for Reproductive Medicine, states that compounded bioidentical menopausal hormone therapy should not be prescribed routinely when approved formulations exist. The Endocrine Society says there is no evidence-based medical need for compounded hormone therapy when an approved preparation is available, and advises caution and counseling about the controversy.

The Food and Drug Administration states that because compounded bioidentical products are not approved, there is no assurance of safety and efficacy, and encourages reporting of adverse events. This page summarizes these statements as public-health information only.

Pellets and testosterone in women

A 2025 position statement of the Latin American Association of Gynecological Endocrinology states that subcutaneous pellets and compounded bioidentical testosterone are not recommended, citing the risk of supraphysiological dosing and insufficient evidence, and graded the recommendation as low. It prefers transdermal formulations. The International Society for the Study of Women's Sexual Health guideline notes that testosterone is not approved for women by most regulatory agencies. The Menopause Society position on pellets specifically was not found in the sources opened for this page.

Procedure-related complications

A single-clinic series reported pellet extrusion in a range of 0.8% to 7.5% of procedures, infection in 1.2% to 5%, and hematoma in 1.2% of one subgroup, depending on the approach used. None of the infections or bleeds required further surgery, and 58 insertions in men taking blood thinners had no significant hematoma.

Case reports describe more serious events. One describes granulomatous panniculitis with fat necrosis, a draining sinus tract and undissolved pellets in a man with repeated implantations. Another describes cellulitis, soft-tissue infection and an enlarging hematoma at the implant site of a woman, who was then diagnosed with von Willebrand disease. Case reports show that such events can occur but cannot give their frequency.

Hormone-level effects

The retrospective study of 228 men described above reported secondary polycythemia rising over time on pellet therapy. For estradiol, the critical review describes supraphysiologic levels, tachyphylaxis, which it defines as early return of symptoms despite adequate or high levels, and uterine bleeding or endometrial stimulation when estrogen is not opposed by a progestogen. It attributes these mainly to excessive dosing, premature reimplantation or missing endometrial protection, a view that the sources reviewed do not test in a trial.

The Endocrine Society cites a study of blood levels well above the anticipated range in women using compounded pellet therapy. A 2024 case report describes severe psychiatric symptoms in a postmenopausal woman that clinicians linked to prolonged testosterone pellet therapy, and a 2026 case report describes repeated recurrences of endometriosis in a woman on estrogen pellets that the authors link to unopposed and potentially supraphysiologic estrogen.

Dose variability and reversibility

The Endocrine Society says customization of hormone dose is difficult because blood levels vary and available assays have limits. Because pellets keep releasing hormone and cannot be removed easily, the critical review says patient selection matters and that adverse effects or intolerance cannot be stopped abruptly, unlike with a patch or oral tablet.

Contraindications and care boundaries

For estradiol pellets, the critical review lists the same absolute contraindications as for other systemic estrogen: undiagnosed abnormal genital bleeding, known or suspected breast cancer, active deep vein thrombosis or pulmonary embolism, and active liver disease. A bleeding disorder was identified after a complicated insertion in one case report. The testosterone guideline advises baseline testing and monitoring for signs of androgen excess.

This page is not medical advice and does not replace assessment by a qualified clinician. Anyone with symptoms of menopause, androgen deficiency or an implant site problem should seek conventional medical care rather than delay it. Related Machipedia pages include Hormone Replacement Therapy, Bioidentical Hormone Replacement and Peptide Therapy, which is a separate topic not covered here.