A comprehensive retrospective study presented at the ENDO 2026 annual meeting has revealed significant gaps in the diagnostic procedures preceding the prescription of testosterone therapy for men. Led by researchers from the University of Michigan, the study indicates that only a small fraction of patients receive the full battery of guideline-concordant testing required to ensure that testosterone replacement therapy (TRT) is both clinically necessary and safe. The findings, presented by Sophia Hemmrich Sinha, MD, and senior author Maria Papaleontiou, MD, suggest that the current landscape of testosterone prescribing is characterized by incomplete laboratory evaluations and a failure to adequately screen for contraindications that could pose serious health risks to patients.
The research comes at a time when the use of testosterone supplements has seen a dramatic global increase, driven by aging populations and heightened public awareness of male hypogonadism. However, the University of Michigan study suggests that the clinical rigor applied to these prescriptions may not be keeping pace with the volume of treatment. According to the data, a vast majority of men are initiated on hormone therapy without the comprehensive diagnostic confirmation recommended by major medical organizations, such as the Endocrine Society and the American Urological Association.
Methodology and Study Population
The study utilized a retrospective chart review of 200 males assigned at birth who were patients within the Michigan Medicine system. To be included in the sample, participants had to have a documented diagnosis of hypogonadism and have received an initial testosterone prescription between the years 2020 and 2025. The researchers focused on primary care settings, ensuring that each participant had at least one outpatient visit within the year preceding their prescription.
The mean age of the study population was 52.5 years, a demographic typically associated with the onset of age-related testosterone decline. However, the researchers noted a high prevalence of comorbid conditions among the participants. Specifically, 63% of the men were classified as obese, 52% suffered from hypertension, and 40% had a diagnosis of depression. Additionally, diabetes and arthritis each affected 28% of the cohort. These comorbidities are significant because they often present with symptoms—such as fatigue, low libido, and mood changes—that overlap with those of clinical hypogonadism, potentially complicating the diagnostic process and leading to inappropriate prescribing if objective laboratory standards are not strictly met.
The Gap in Guideline-Concordant Testing
Clinical guidelines for the treatment of hypogonadism are designed to distinguish between a transient dip in hormone levels and a true clinical deficiency. Standards typically require at least two separate morning testosterone measurements (total testosterone below 300 ng/dL) taken between 5 a.m. and 10 a.m., when levels are at their peak. Furthermore, clinicians are encouraged to measure Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) to determine whether the hypogonadism is primary (testicular failure) or secondary (pituitary or hypothalamic issues).
The University of Michigan study found that only 12% of the men who received an initial testosterone prescription met the full criteria for guideline-concordant care. This 12% threshold required the patient to have two low morning testosterone levels (or specific low free/bioavailable levels), a measurement of LH and/or FSH, and a complete absence of medical contraindications.
"The majority of men had incomplete laboratory evaluation prior to their first testosterone prescription, and some had counterindications to testosterone therapy," stated Dr. Sinha during her presentation. The data revealed that while 77% of patients had a complete blood count (CBC) measured and 62% had a prostate-specific antigen (PSA) test within the year prior to treatment, these individual tests do not constitute a full diagnostic workup when performed in isolation.
Identifying Clinical Risks and Contraindications
One of the most concerning aspects of the study involves the prescription of testosterone to patients with pre-existing conditions that are generally considered contraindications or risks for the therapy. Testosterone therapy can exacerbate certain conditions, such as erythrocytosis (an abnormal increase in red blood cells) and obstructive sleep apnea (OSA).
The study found that 55% of the men prescribed testosterone already suffered from obstructive sleep apnea. Testosterone is known to potentially worsen OSA by altering the ventilatory response to carbon dioxide or changing the physical structure of the upper airway. Furthermore, the researchers found that 4% of the patients had a history of prostate cancer, and 1.5% had a PSA level greater than 4 ng/mL before the initiation of therapy. Because testosterone can stimulate the growth of prostate tissue, guidelines generally advise extreme caution or avoidance in patients with active or high-risk prostate malignancies.
The presence of these conditions in more than half of the study population highlights a potential disconnect between specialist guidelines and the practical application of those guidelines in a clinical setting. The researchers emphasized that failing to screen for these conditions before starting TRT could lead to avoidable adverse events, including cardiovascular complications and the progression of undiagnosed prostate issues.
Provider Distribution and Treatment Modalities
The study also examined the professional background of the prescribing clinicians. The data showed a diverse range of providers involved in testosterone management:
- Primary Care Physicians: 45%
- Urologists: 35.5%
- Endocrinologists: 18%
- Other Specialists: 1.5%
The high percentage of prescriptions originating from primary care physicians (PCPs) suggests that these providers are on the front lines of hypogonadism management. However, it also suggests that PCPs may require more robust support tools to navigate the complexities of hormone replacement guidelines, which are often more familiar to specialists like endocrinologists and urologists.
Regarding the method of delivery, topical formulations were the most common choice, accounting for 68.5% of the prescriptions. Topical gels and patches are often preferred for their ease of use and ability to maintain more stable physiological levels of testosterone compared to some injectable forms, but they also require strict adherence to safety protocols to prevent accidental transfer to women or children.
Chronology of Research and Future Interventions
The timeframe of the study, spanning from 2020 to 2025, captures a period of significant evolution in telehealth and outpatient care. The researchers noted that the retrospective nature of the chart review allowed for a realistic look at how "real-world" clinical decisions are made outside of a controlled trial environment.
Dr. Maria Papaleontiou emphasized that the findings should serve as a catalyst for systemic change within healthcare institutions. “Our study findings highlight opportunities to improve patient care and reduce inappropriate testosterone prescribing,” Papaleontiou said. She suggested that the path forward involves the development of clinical decision support (CDS) tools—digital prompts within electronic health record systems that can alert a physician if they are attempting to prescribe testosterone without the required laboratory results or in the presence of a documented contraindication.
The research team plans to follow this study with evaluations of targeted interventions. These may include educational modules for primary care providers and the implementation of standardized diagnostic templates. The goal is to move the 12% compliance rate significantly higher, ensuring that TRT is reserved for those who will truly benefit from it while protecting those for whom the risks outweigh the rewards.
Broader Implications for the Healthcare System
The implications of the Michigan Medicine study extend beyond individual patient safety to the broader issues of healthcare quality and cost-effectiveness. Inappropriate prescribing of testosterone therapy contributes to unnecessary healthcare spending, both for the medication itself and for the subsequent monitoring and treatment of side effects.
Furthermore, the study touches on the psychological impact of medicalization. When men are prescribed testosterone based on incomplete data, there is a risk that the underlying causes of their symptoms—such as obesity-related fatigue or clinical depression—remain inadequately addressed. By focusing on a "quick fix" hormone prescription, the healthcare system may miss opportunities for more effective lifestyle interventions or mental health support.
The medical community’s reaction to such findings typically involves a call for more integrated care. Experts suggest that while primary care physicians are essential for identifying symptoms, a multidisciplinary approach involving urology and endocrinology could standardize the diagnostic process. The data from ENDO 2026 underscores that the current "siloed" approach to prescribing may be contributing to the high rates of non-concordance.
Conclusion
The University of Michigan’s research presents a sobering look at the state of testosterone prescribing in a modern academic medical setting. With only 12% of patients receiving guideline-concordant care, the study serves as a clear indication that current diagnostic protocols are frequently bypassed.
As Dr. Papaleontiou and Dr. Sinha noted, the long-term goal is to foster an environment where testosterone is prescribed with the same diagnostic rigor as any other high-impact medication. Through quality-improvement efforts, better provider education, and the integration of smart clinical tools, the medical community can ensure that testosterone therapy remains a valuable tool for those with genuine clinical need, while minimizing the risks associated with inappropriate use. The findings from ENDO 2026 provide a necessary roadmap for these essential improvements in men’s health and endocrinology.
