A comprehensive retrospective chart review led by researchers at the University of Michigan has identified a critical deficiency in the adherence to established clinical guidelines for prescribing testosterone therapy. The study, presented at the ENDO 2026 annual meeting, reveals that a vast majority of men initiated on testosterone replacement therapy (TRT) did not receive the full battery of diagnostic tests or screenings recommended by major medical societies. The findings raise significant concerns regarding patient safety, the potential for over-prescribing, and the necessity for enhanced clinical decision-support tools within primary and specialized care settings.
The research, spearheaded by Sophia Hemmrich Sinha, MD, and senior author Maria Papaleontiou, MD, an associate professor at the University of Michigan, analyzed the records of 200 males assigned at birth who were diagnosed with hypogonadism and prescribed testosterone between 2020 and 2025. The data indicates that only 12% of these patients underwent a diagnostic process that fully aligned with the standards set forth by organizations such as the Endocrine Society and the American Urological Association. These guidelines are designed to ensure that testosterone is only administered to those with a documented biological deficiency and no underlying health conditions that could be exacerbated by the hormone.
Methodology and Patient Demographics
The study utilized a random sample of patients from Michigan Medicine who had at least one outpatient primary care visit within the year prior to receiving their initial testosterone prescription. The mean age of the study participants was 52.5 years, a demographic typically associated with the onset of age-related testosterone decline, often colloquially referred to as "andropause."
The patient population exhibited a high prevalence of comorbidities, which complicates both the diagnosis of hypogonadism and the safety profile of testosterone therapy. Among the participants:
- 63% were classified as obese.
- 52% suffered from hypertension.
- 40% had a diagnosis of depression.
- 28% were managing diabetes.
- 28% were treated for arthritis.
These comorbidities are significant because conditions like obesity and type 2 diabetes can naturally lower total testosterone levels by reducing sex hormone-binding globulin (SHBG), without necessarily indicating a failure of the hypothalamic-pituitary-testicular axis. Consequently, guidelines emphasize the need for rigorous, multi-step testing to differentiate between transiently low levels and clinical hypogonadism.
The Diagnostic Gap: Failure to Meet Clinical Standards
The most striking finding of the Michigan Medicine study was the lack of comprehensive laboratory evaluation prior to the commencement of therapy. Clinical guidelines stipulate that a diagnosis of hypogonadism should only be made after at least two separate morning testosterone measurements show levels below 300 ng/dL. These tests must be conducted between 5:00 a.m. and 10:00 a.m. to account for the natural diurnal rhythm of testosterone production, which peaks in the early morning hours.
The researchers found that the 12% of patients who met the "guideline-concordant" criteria were the only ones who had:
- Two confirmed low morning testosterone levels (total testosterone < 300 ng/dL, free testosterone < 70 pg/mL, or low bioavailable testosterone).
- Measurements of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) to determine if the hypogonadism was primary (testicular) or secondary (pituitary/hypothalamic).
- A clear absence of contraindications to the therapy.
Furthermore, the study highlighted gaps in baseline screenings for potential side effects. While 77% of patients had a complete blood count (CBC) and 62% had a prostate-specific antigen (PSA) test in the year preceding their prescription, a significant portion of the cohort began treatment without these baseline metrics. Testosterone therapy can increase red blood cell count (polycythemia), which raises the risk of blood clots and stroke, making CBC monitoring a vital safety requirement.
Identification of Contraindications and Risks
The University of Michigan researchers expressed particular concern over the number of patients prescribed testosterone despite having documented contraindications. The study found that 55% of the men had obstructive sleep apnea (OSA), a condition that can be significantly worsened by testosterone therapy as the hormone may alter the drive to breathe or change airway muscle tone.
Additionally, 4% of the study participants had a history of prostate cancer, and 1.5% had a PSA level greater than 4 ng/mL prior to the prescription. Because testosterone can stimulate the growth of prostate tissue, it is traditionally contraindicated in men with active or high-risk prostate cancer. The inclusion of these patients in the prescription pool suggests a breakdown in the screening process or a lack of awareness regarding the potential risks of hormone supplementation in the presence of prostatic malignancies.
"The majority of men had incomplete laboratory evaluation prior to their first testosterone prescription, and some had counterindications to testosterone therapy," noted Dr. Sinha. This sentiment was echoed by Dr. Papaleontiou, who emphasized that improving adherence to guidelines is essential to prevent avoidable risks in individuals who may not have a genuine clinical need for the hormone.
Prescriber Profiles and Treatment Modalities
The study also examined the sources of these prescriptions, revealing that primary care physicians (PCPs) are the leading providers of testosterone therapy, accounting for 45% of the initial prescriptions in the sample. Urologists followed at 35.5%, while endocrinologists—the specialists most closely associated with hormonal disorders—accounted for only 18% of the prescriptions. Other specialists made up the remaining 1.5%.
The high percentage of prescriptions originating from primary care highlights the pressure on general practitioners to manage complex hormonal cases. It also suggests that quality-improvement efforts should be primarily targeted at the primary care level. Regarding the method of administration, topical formulations were the most common, prescribed to 68.5% of the patients. Topical gels and patches are often preferred for their ease of use and ability to maintain more stable serum levels compared to cyclical injections, though they carry risks of accidental transfer to women or children.
Contextual Background: The "Low T" Surge
The findings of this study arrive amid a decade-long surge in the popularity of testosterone replacement therapy. Following aggressive direct-to-consumer marketing campaigns in the early 2010s that branded various symptoms of aging—such as fatigue, decreased libido, and mood changes—as "Low T," the market for testosterone products expanded rapidly.
In 2014 and 2015, the U.S. Food and Drug Administration (FDA) issued safety communications requiring manufacturers to change labeling to clarify that testosterone is approved only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, or brain. The FDA also mandated the inclusion of warnings regarding a possible increased risk of heart attacks and strokes. Despite these regulatory actions, the University of Michigan study suggests that the clinical application of these warnings and the rigorous diagnostic steps required to justify therapy remain inconsistent.
Implications for Clinical Practice and Future Research
The implications of this research are twofold: it identifies a need for better physician education and suggests a role for technological intervention. Dr. Papaleontiou noted that these findings could lead to the development of clinical decision support (CDS) tools. These tools, integrated into electronic health record systems, could prompt physicians to order the necessary follow-up tests (like LH/FSH) or flag contraindications (like severe sleep apnea) before a prescription can be finalized.
"Our study findings highlight opportunities to improve patient care and reduce inappropriate testosterone prescribing," Dr. Papaleontiou stated. "Long-term, these findings can lead to quality-improvement efforts and clinical decision support tools that promote consistent, guideline-concordant testosterone prescribing."
The study also calls for a shift in how "low testosterone" is perceived in the clinical setting. Rather than treating a single low lab value as a definitive diagnosis, clinicians are encouraged to view it as a signal for further investigation into the patient’s overall metabolic and cardiovascular health. Given that 63% of the study’s subjects were obese, lifestyle interventions—such as weight loss and exercise—might have addressed the hormonal imbalance without the need for lifelong pharmaceutical intervention.
Conclusion
The University of Michigan’s retrospective review serves as a cautionary report for the medical community. With only 12% of patients receiving guideline-concordant care, the study exposes a significant gap between medical evidence and clinical practice. As testosterone therapy continues to be a widely sought-after treatment for aging men, the necessity for standardized diagnostic protocols becomes increasingly urgent.
Future research will likely focus on whether targeted interventions, such as mandatory "repeat-testing" alerts or specialist consultations for high-risk patients, can successfully bridge this gap. For now, the data suggests that for thousands of men, the path to testosterone therapy may be missing the vital guardrails intended to ensure their long-term health and safety.
