Pellets for Men and Women:

A Thoughtful, Evidence-Based Approach to Hormone Therapy

 

By Dr. Carla Russo FACOG, Dip ABLM 

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Hormone therapy is one of the most nuanced—and often misunderstood—areas in modern medicine.

 

For patients, it can feel overwhelming. Conflicting headlines, outdated interpretations of landmark studies, and strong opinions on all sides have created an environment where even highly motivated individuals are left asking:

 

What actually works—and what is truly safe?

 

Among the most debated options is hormone pellet therapy. While some view it as an outdated or unproven approach, others recognize its physiologic advantages and long-standing use in clinical practice.

 

As a physician dedicated to hormone optimization for both men and women, I believe this topic deserves a more balanced and intellectually honest discussion—one that respects not only randomized trials, but also decades of pharmacologic data, clinical outcomes, and international experience.

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Understanding Hormone Pellets

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Hormone pellets are small, subcutaneous implants—approximately the size of a grain of rice—that deliver continuous, low-dose hormone therapy over several months. Typically, they contain testosterone and/or estradiol, depending on patient needs.

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In men, the FDA-approved product Testopel has been used for decades to treat hypogonadism, providing sustained testosterone levels for three to six months [1].

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In women, pellet therapy is most commonly compounded. While this distinction is frequently cited as a limitation, it reflects regulatory pathways rather than a lack of scientific foundation—a point that warrants deeper consideration.

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The Pharmacologic Rationale: Stability Over Fluctuation

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At its core, pellet therapy offers a fundamental pharmacologic advantage: STABILITY.

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Unlike injections, which can produce supraphysiologic peaks followed by rapid decline, or topical therapies that depend on variable skin absorption, pellets provide near zero-order release kinetics—a steady, predictable delivery of hormone over time.

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This has meaningful clinical implications:

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• Testosterone pellets maintain physiologic levels for four to six months in men [2-4]

• Early pharmacokinetic studies demonstrate consistent serum concentrations without large fluctuations [2,3]

• Estradiol pellets in women have been shown to maintain levels within physiologic ranges (~50–80 pg/mL) when appropriately dosed [5]

 

For patients, this often translates into something tangible:

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More consistent energy, mood, sleep, and sexual health—without the variability that can accompany other delivery methods.

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The Evidence Base: A Broader Perspective

 

One of the most persistent misconceptions surrounding pellet therapy is that it lacks meaningful scientific support.

 

In reality, the literature spans more than three decades, with significant contributions from the United Kingdom, Australia, and Europe.

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Across these studies, findings are remarkably consistent:

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• Significant improvement in menopausal symptoms, including vasomotor instability, mood, and libido [7-9]

• Sustained physiologic hormone levels over extended periods

• High rates of patient satisfaction and preference

• Acceptable safety profiles when dosing is appropriate

 

For example:

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• Early UK studies demonstrated near-complete resolution of climacteric symptoms with estradiol and testosterone implants [8,9]

• Australian studies confirmed prolonged testosterone stability in men, with strong patient preference for pellet therapy [3,4]

• Contemporary pharmacokinetic data continues to support predictable hormone delivery within physiologic ranges [5]

 

This raises an important question:

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Should decades of consistent international evidence be discounted simply because it was not generated within the United States or through large-scale randomized trials of compounded formulations?

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The FDA Distinction: Context Matters

 

In the United States, Testopel is FDA-approved for testosterone replacement in men [1]. There are, however, no FDA-approved pellet formulations for women, and most are compounded.

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This distinction is often interpreted as a safety concern. In practice, it more accurately reflects:

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• The cost and complexity of the FDA approval process

• Limited pharmaceutical incentive for investment

• Historical prescribing patterns

 

Importantly, absence of FDA approval does not equate to absence of safety or efficacy—particularly when a therapy is supported by decades of pharmacologic and clinical data [6,31].

 

 

 

 

 

 

 

 

 

Testosterone in Women: Challenging Outdated Assumptions

 

Perhaps no aspect of hormone therapy is more misunderstood than the role of testosterone in women.

 

Testosterone is not simply a “male hormone.” In fact:

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It is one of the most biologically active hormones in women, playing a central role in libido, mood, cognition, musculoskeletal health, and metabolic function [26,27].

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Yet the framework used to define “normal” testosterone levels in women is deeply flawed.

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The Problem With “Normal” Testosterone Ranges

 

Most laboratory reference ranges are derived from:

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• ​Small or non-representative populations

• Older assay technologies with limited accuracy at low concentrations

• Lack of menstrual cycle standardization

• Minimal consideration for age-related decline

 

More precise measurement techniques, such as LC-MS/MS, have revealed that:

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• Testosterone levels are often lower than previously reported using older assays

• Healthy women may exhibit higher physiologic peaks, particularly mid-cycle

• There is substantial inter-individual variability, even among healthy populations [10-18]

 

Even leading endocrine guidelines acknowledge:

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There are no universally accepted reference ranges for testosterone in women [13,29].

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This introduces a critical limitation:

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If the reference population is already hormonally depleted, then “normal” may not reflect optimal physiology.

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Rethinking Physiologic Androgen Levels

 

Emerging perspectives suggest that:

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• Conventional reference ranges may underestimate physiologic androgen exposure in women

• Testosterone levels exceeding standard laboratory norms may still be clinically appropriate in selected patients

• The balance between testosterone and estradiol may be more relevant than absolute values alone [26]

 

Long-term observational data adds further context:

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• Women treated with testosterone implants have demonstrated lower-than-expected breast cancer incidence compared to population norms [19–21]

• No consistent signal of increased risk has been observed in these cohorts over extended follow-up

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At the same time, large epidemiologic studies show mixed associations between endogenous testosterone and breast cancer risk—many limited by:

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• Inaccurate hormone measurement methods

• Lack of adjustment for estradiol levels

• Failure to account for aromatization [22–25]

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Taken together, the data suggests a more nuanced conclusion:

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The relationship between testosterone and women’s health is complex—and cannot be reduced to a single laboratory value.

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Addressing Common Concerns

 

Supraphysiologic Levels

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Elevated hormone levels can occur—but most often reflect dosing practices, not the delivery system itself. When therapy is individualized and monitored, levels can remain within appropriate ranges [6,31].

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Irreversibility

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While pellets cannot be immediately discontinued, most side effects are dose-dependent and manageable, and proper monitoring significantly reduces risk.

 

Lack of Randomized Trials

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Although large U.S.-based randomized trials are limited, the breadth of international data and long-term clinical experience is substantial.

It is also worth noting that even landmark studies—such as the Women's Health Initiative—have undergone significant reinterpretation over time [28,32], highlighting the importance of context in evaluating evidence.

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Compliance: An Underappreciated Advantage

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One of the most practical strengths of pellet therapy is adherence.

 

With no daily dosing, no weekly injections, and no variability in application:

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Patients receiving pellet therapy are, by definition, fully compliant during the dosing interval.

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In contrast, adherence to traditional hormone therapies declines significantly over time.

 

The Central Issue: Not the Therapy, but the Practice

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Ultimately, the most important variable in hormone therapy outcomes is not the delivery method—it is how the therapy is practiced.

Safe, effective pellet therapy requires:

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• Careful patient selection

• Individualized dosing strategies

• High-quality sourcing and compounding standards

• Regular laboratory monitoring

• Thoughtful follow-up and adjustment

 

When these elements are in place, many of the commonly cited concerns become manageable—and often preventable.

 

A Clinical Perspective

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In my practice, I care for both men and women seeking to restore hormonal balance and improve quality of life.

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The goal is not to advocate for one therapy over another, but to:

• Understand the underlying physiology

• Evaluate the full body of evidence

• Individualize treatment based on each patient’s needs

 

Hormone pellet therapy is not appropriate for every patient. But when used thoughtfully, it represents a pharmacologically sound, clinically effective option that deserves a place in the broader conversation.

 

To learn more about my approach to hormone health, visit: Hormone & Sexual Health 
 

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Final Thoughts

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Medicine evolves—and so must our interpretation of evidence.

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Pellet therapy challenges us to move beyond simplified narratives and engage with complexity: physiology, pharmacology, and long-term clinical outcomes.

 

For both men and women, the objective remains the same:

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Restore balance. Improve function. Enhance quality of life.

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And above all, practice medicine with curiosity, rigor, and respect for the patient in front of us.

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​​If you’re considering hormone therapy and want a thoughtful, individualized approach, I invite you to learn more or schedule a consultation.

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References:

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FDA / Foundational

 1. Testopel® (testosterone pellets) Prescribing Information. Food and Drug Administration.

 

Pellet Pharmacokinetics & Clinical Data

 2.  Jockenhövel F, Vogel E, Kreutzer M, et al. Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men. Clinical      Endocrinology. 1996;45(1):61-71.

 3.  Handelsman DJ, Conway AJ, Boylan LM. Pharmacokinetics of testosterone pellets in man. Journal of Clinical Endocrinology & Metabolism. 1990.

 4.  McMahon CG, et al. Efficacy and safety of testosterone implants in men with hypogonadism. Journal of Sexual Medicine. 2017.

 5.  Jacobsen L, Fernandes DM, Nagel ML, et al. Subcutaneous estradiol pellets as hormone therapy in menopause. Journal of Clinical Medicine. 2025.

 6.  Jiang X, et al. Safety assessment of compounded vs FDA-approved hormone therapy. Menopause. 2021.

 

UK / European Pellet Studies 

 7.  Studd J, et al. Oestradiol and testosterone implants in the treatment of menopausal symptoms.

 8.  Brincat M, et al. Hormone implants and climacteric symptom control. Lancet. 1984.

 9.  Cardozo L, et al. Subcutaneous hormone implants and menopausal symptom relief. Maturitas. 1984.

 

Testosterone Physiology & Reference Ranges in Women

 10.  Davison SL, et al. Androgen levels in adult females. JCEM. 2005.

 11.  Braunstein GD, et al. Testosterone reference ranges in healthy premenopausal women. J Sex Med. 2011.

 12.  Haring R, et al. LC-MS/MS testosterone reference ranges in women. JCEM. 2012.

 13.  Skiba MA, et al. Androgens during reproductive years. JCEM. 2019.

 14.  Bui HN, et al. Testosterone and free androgen index in women. Clin Chim Acta. 2015.

 15.  Mezzullo M, et al. Steroid reference intervals in women. Eur J Endocrinol. 2021.

 16.  Rothman MS, et al. Hormone variation across menstrual cycle. Steroids. 2011.

 17.  Huang G, et al. Testosterone and DHT variation across cycle. Fertil Steril. 2022.

 18.  Wang Y, et al. Testosterone by age and menopausal stage. EBioMedicine. 2025.

 

Testosterone & Breast Cancer Data

 19.  Glaser RL, Dimitrakakis C. Reduced breast cancer incidence with testosterone therapy. Maturitas. 2013.

 20.  Glaser RL, et al. 10-year cohort of testosterone implant therapy. BMC Cancer. 2019.

 21.  Glaser R, Dimitrakakis C. Testosterone and breast cancer prevention. Maturitas. 2015.

 22.  Kaaks R, et al. Sex hormones and breast cancer risk (EPIC). Int J Cancer. 2014.

 23.  Schernhammer ES, et al. ORDET cohort (premenopausal). Breast Cancer Res. 2013.

 24.  Sieri S, et al. ORDET cohort (postmenopausal). Cancer Epidemiol Biomarkers Prev. 2009.

 25.  Tin Tin S, et al. UK Biobank hormone data. Br J Cancer. 2021.

 

Testosterone Therapy in Women (Reviews)

 26.  Davis SR, Wahlin-Jacobsen S. Testosterone in women—clinical significance. Lancet Diabetes Endocrinol. 2015.

 27.  Somboonporn W, et al. Testosterone for peri/postmenopausal women. Cochrane Review. 2005.

 

Hormone Therapy (Broader Evidence & Guidelines)

 28.  Bofill Rodriguez M, et al. Long-term hormone therapy. Cochrane Review. 2025.

 29.  Wierman ME, et al. Endocrine Society guideline—Androgen therapy in women. JCEM. 2014.

 30.  Elhassan YS, et al. Society for Endocrinology guideline. Clin Endocrinol. 2025.

 31.  ACOG Clinical Consensus No. 6. Compounded bioidentical hormone therapy. Obstet Gynecol. 2023.

32.  Belchetz PE. Hormonal treatment of postmenopausal women. NEJM. 1994.