Testosterone deficiency—commonly referred to as hypogonadism—affects millions of men, and its prevalence increases with age. Standardized testosterone replacement therapy (TRT) protocols have long provided symptom relief, yet they often fail to consider individual variations in hormone metabolism, lifestyle and health status. As a result, many patients experience suboptimal outcomes or unnecessary side effects. In 2025, personalization is rapidly becoming the new frontier of testosterone care. This shift encompasses advanced diagnostics, precision dosing, innovative delivery systems and data‑driven tools that tailor treatment to each patient’s unique physiological profile. By integrating artificial intelligence (AI) with evolving hormone delivery technologies—such as microdosing protocols, hydrogel microbeads and selective estrogen receptor modulators—clinicians can optimize therapy for safety, efficacy and adherence. This article explores the landscape of personalized testosterone therapy and explains why individualized care is poised to transform how hypogonadism is managed.

Why Personalization Matters in Testosterone Therapy

Traditional TRT typically involves prescribing a standard dosage of testosterone injections, gels or patches and adjusting based on serum levels. However, this approach fails to account for variables such as genetic differences in hormone metabolism, body composition, lifestyle factors and comorbidities. Men may metabolize testosterone at different rates, experience side effects at different thresholds or have varying goals—such as fertility preservation. MenMD emphasizes that a one‑size‑fits‑all strategy can discourage treatment because older delivery methods have drawbacks like injection discomfort, risk of skin transfer or inconvenient administration.

Personalization acknowledges that each patient’s hormonal milieu and physiology are unique. Tailored therapy aims to deliver the right dose at the right time using the optimal delivery system. This can enhance efficacy, reduce side effects and improve adherence. Moreover, personalized care aligns with broader trends in medicine, where targeted therapies and individualized protocols are increasingly standard.

Comprehensive Assessment: The Foundation of Personalization

Personalized TRT begins with a thorough evaluation. The Cleveland Clinic recommends confirming low testosterone with two morning blood tests and performing additional assessments—hemoglobin, hematocrit, liver function tests, LH and PSA—to determine the underlying cause and ensure that TRT is appropriate. Physicians also consider symptoms such as fatigue, low libido, mood changes and decreased muscle mass. A detailed medical history, including comorbidities (e.g., cardiovascular disease, sleep apnea), medications, fertility goals and lifestyle factors, informs individualized treatment. The American Urological Association (AUA) guidelines emphasize shared decision‑making and regular monitoring to adjust therapy to each patient’s needs.

Precision Dosing: Microdosing and Extended‑Release Injections

One dimension of personalization involves adjusting the dose and frequency of testosterone administration. Standard intramuscular injections often produce peaks and troughs in serum testosterone; some patients experience mood swings or polycythemia when levels spike. Microdosing protocols, highlighted by MenMD, address this by administering smaller amounts more frequently. Subcutaneous injections, which can be self‑administered, reduce pain and maintain more stable levels, minimizing side effects. For patients who prefer fewer injections, extended‑release formulations are available that slowly release testosterone drive over several weeks. These approaches enable clinicians to calibrate dosing based on how patients metabolize the hormone and respond symptomatically.

Tailored Delivery Systems: Gels, Patches, Pellets and Hydrogel Microbeads

Choosing the right delivery system is integral to personalized care. Some men may prefer daily gels or patches, while others favor periodic injections or implants. Advances in 2025 expand these options:

• Improved transdermal systems: Modern gels offer better absorption and reduced transfer risk, and patches use materials that reduce skin irritation. Men who prefer daily application can select the formulation that best suits their skin and lifestyle.
  
• Pellet implants: Advances in pellet technology include smaller pellet sizes and modified release kinetics that provide consistent hormone levels. Pellets remain ideal for men who desire long-term steady delivery without daily or weekly maintenance.
  
• Hydrogel microbeads: One of the most intriguing developments involves core shell spherification (CSS) to encapsulate testosterone in hydrogel microspheres. Drug Target Review notes that these microbeads are fully aqueous, avoiding non-biocompatible oils, and they enable slow, extended release after a monthly self‑injection. Hydrogel microbeads are similar to micropellets but require no surgical implantation; as the hydrogel degrades, the hormone diffuses gradually into the bloodstream. Early preclinical studies show that encapsulated hormones maintain steady release, potentially lengthening the dosing interval to monthly or even longer. The hydrogel material—often hyaluronic acid—has a well-established safety profile. Patients seeking minimal maintenance and fewer office visits may benefit from such technology once it becomes clinically available.
  

Personalization means evaluating each option’s advantages and drawbacks in the context of an individual’s lifestyle, preferences and risk tolerance. For example, someone with skin sensitivity might avoid gels in favor of subcutaneous injections, while a busy professional might opt for pellet implants or microbead injections to minimize dosing frequency.

AI‑Driven Personalized Protocols

Artificial intelligence is revolutionizing testosterone care by analyzing complex datasets to optimize dosing and monitor progress. The Fountain of Youth (FOY) clinic reports that AI systems analyze patient-specific variables—such as hormone levels, genetics, body mass index and lifestyle—to propose customized dosing strategies. Machine learning models can predict how an individual metabolizes testosterone and adjust dose and timing accordingly, reducing trial-and-error approaches. Wearable devices and health apps feed real-time hormone and biometric data into AI systems, enabling dynamic adjustments. This continuous feedback loop ensures that therapy remains aligned with the patient’s current physiological state, enhancing safety and efficacy.

AI-driven protocols also improve clinical efficiency. Physicians can focus on patient counseling and care while AI handles data analysis and provides evidence-based recommendations. Such systems may incorporate pharmacokinetic models, genetic information (e.g., polymorphisms affecting testosterone metabolism), and comorbidity profiles to create comprehensive personalized plans. However, implementing AI requires robust data privacy and security measures, regular validation of algorithms to ensure reliability, and human oversight to prevent automated decisions from overlooking individual nuances.

Personalized Alternatives: SERMs and Fertility Preservation

Personalization extends beyond exogenous testosterone. For men wishing to maintain fertility or stimulate their own testosterone production, selective estrogen receptor modulators (SERMs) such as clomiphene citrate and enclomiphene offer individualized alternatives. These drugs block estrogen receptors and stimulate the hypothalamic‑pituitary‑gonadal axis, leading to increased endogenous testosterone and sperm production. A 2024 study found that enclomiphene increased testosterone levels more than clomiphene and produced fewer side effects. Men concerned about estrogenic side effects or testicular atrophy may opt for enclomiphene as a personalized treatment. SERMs illustrate that personalization involves not only adjusting existing therapies but also choosing the right class of therapy based on patient goals.

Gene Therapy and Genetic Personalization

Although gene therapy remains experimental, it hints at a future where treatment could be tailored to the genetic root of hypogonadism. Research using AAVDJ vectors to deliver the Lhcgr gene to Leydig cell progenitors restored testosterone production and fertility in mice. If translated to humans, such therapies could provide long-term or permanent solutions for men with genetic forms of hypogonadism. Genetic testing may also identify polymorphisms affecting testosterone metabolism or receptor sensitivity, guiding dose selection and therapy type. As genomics integrates with endocrine care, clinicians will be able to personalize TRT at a molecular level.

Telehealth and Remote Monitoring

Personalized testosterone care also leverages telehealth to increase accessibility. Remote clinics offer virtual consultations, at-home blood sample collection kits and mail-order medications. AI-driven platforms, such as those described by some telemedicine services, provide personalized treatment plans and ship medications directly to patients. Wearable devices track vital signs and send data to healthcare providers, enabling adjustments without frequent office visits. This model is particularly appealing to men in rural areas or those seeking discreet care.

Factors Influencing Personalization

When designing a personalized TRT plan, clinicians consider multiple factors:

• Patient preference and lifestyle: Some men prioritize convenience (e.g., monthly or semi-annual dosing), while others desire fine control over their hormone levels.
  
• Comorbidities: Conditions like cardiovascular disease, polycythemia, sleep apnea or prostate disease may influence therapy selection and monitoring frequency.
  
• Fertility goals: Men wishing to conceive or preserve fertility may choose SERMs over exogenous testosterone.
  
• Metabolism and body composition: Genetic variations can affect how a patient metabolizes testosterone, guiding dosing frequency and amount.
  
• Insurance coverage and cost: Different delivery methods and medications vary in cost and insurance reimbursement.
  
• Monitoring requirements: Some therapies require frequent lab work, while others may need only periodic checks.
  

A personalized approach weighs these factors to create a treatment plan that optimally balances efficacy, safety, convenience and cost.

Challenges and Ethical Considerations

While personalization promises better outcomes, it introduces challenges:

• Data privacy: AI-driven personalization relies on sensitive health data. Robust encryption, secure data storage and ethical use of information are essential.
  
• Algorithmic bias: AI models trained on limited or homogenous data may produce biased recommendations. Continuous validation and diverse data sets are necessary.
  
• Accessibility and equity: Personalized therapies may be more expensive or require access to technology (wearables, smartphones). Ensuring equitable access is critical.
  
• Regulatory compliance: As new delivery systems and gene therapies emerge, regulatory agencies must evaluate safety and efficacy.
  
• Patient education: Patients need clear explanations of personalized protocols to understand benefits, risks and the importance of adherence.
  

Healthcare providers and policymakers must address these challenges to ensure that personalized testosterone care is safe, ethical and available to all who need it.

Conclusion

The future of testosterone care lies in personalization. Rather than relying on standardized dosing and delivery, clinicians now have an expanding arsenal of tools—microdosing strategies, subcutaneous injections, improved gels and patches, pellets, hydrogel microbeads, AI-driven dosing algorithms, SERMs, gene therapy research and telehealth platforms—to tailor therapy to each patient. Data-driven protocols ensure precision and reduce side effects, while innovative delivery systems offer convenience and consistency. By considering individual physiology, lifestyle, fertility goals and risk factors, personalized TRT maximizes benefits and minimizes harm. As technology advances and research deepens our understanding, testosterone care will continue to evolve toward truly individualized treatment, improving the quality of life for men with hypogonadism.

What does “personalized testosterone therapy” mean?

 Personalized testosterone therapy refers to tailoring treatment to an individual’s unique hormonal profile, metabolism, lifestyle and health goals. This includes selecting the optimal delivery method (e.g., injections, gels, pellets), dosing schedule (microdosing vs. extended-release), and considering alternatives like SERMs for fertility preservation. It also involves regular monitoring and adjustments based on laboratory tests and symptoms.

How does artificial intelligence improve testosterone therapy?

AI systems analyze a patient’s hormone levels, genetics, weight, lifestyle factors and real-time data from wearable devices to recommend precise dosing and scheduling. Machine learning algorithms predict how individuals metabolize testosterone and adjust doses to maintain stable levels, reducing trial-and-error and minimizing side effects. AI also enables continuous monitoring, allowing physicians to refine treatment plans dynamically.

What are hydrogel microbeads, and why are they significant?

Hydrogel microbeads are tiny spheres containing compressed testosterone encapsulated in a biocompatible hydrogel matrix. According to Drug Target Review, core shell spherification produces fully aqueous microspheres that release hormone gradually after a self-administered injection. As the hydrogel degrades, testosterone diffuses steadily into the bloodstream, allowing dosing as infrequently as once per month. These microbeads avoid the surgical implantation required for pellets and offer consistent levels with minimal local irritation.

Can AI replace physicians in managing testosterone therapy?

 No. AI is a tool to assist clinicians, not replace them. While AI can analyze data and suggest dosing adjustments, human oversight ensures that decisions consider nuances not captured by algorithms and address ethical considerations. Physicians interpret AI recommendations in the context of patient preferences, comorbidities and overall care plans.

Are selective estrogen receptor modulators (SERMs) part of personalized care?

 Yes. SERMs like clomiphene citrate and enclomiphene stimulate the body’s own testosterone production and are useful when preserving fertility is important. A study found that enclomiphene increased testosterone levels while reducing estradiol and had fewer adverse effects than clomiphene. Clinicians may recommend SERMs to men who wish to avoid exogenous testosterone or those who experience side effects on standard TRT.

How do clinicians decide which delivery method to use?

 Clinicians evaluate multiple factors: patient preference (e.g., desire for fewer injections), lifestyle, comorbidities, fertility goals, cost and insurance coverage, and monitoring requirements. For instance, men concerned about daily maintenance may choose pellets or hydrogel microbeads, while those needing fine control might choose subcutaneous microdosing. Allergies, skin conditions and comfort with self-injection also influence selection.

Is gene therapy currently available for testosterone deficiency?

 Gene therapy is still experimental. Researchers have used AAVDJ vectors to deliver the Lhcgr gene to Leydig cells in mice, restoring testosterone production and fertility. While promising, these therapies are not yet approved for human use. Clinical trials will be required to assess safety and efficacy before gene therapy becomes an option.

What are the main challenges of personalized TRT?

1. Challenges include protecting patient data used by AI systems, avoiding algorithmic bias, ensuring equitable access to advanced treatments, navigating insurance coverage and regulatory approvals, and educating patients about complex protocols. Moreover, personalized therapies may cost more or rely on technology (wearables, smartphone apps) that not all patients can access.
   

Personalization is transforming testosterone care, making therapies more precise, effective and aligned with individual needs. By integrating AI, innovative delivery systems and patient-centered decision-making, the future of TRT promises better outcomes and improved quality of life.