A comprehensive retrospective study led by researchers at the University of Michigan has revealed a stark disconnect between established clinical guidelines and the actual prescribing practices for testosterone therapy in men. Presented as part of the ENDO 2026 research initiatives, the study conducted by Sophia Sinha, MD, and senior author Maria Papaleontiou, MD, found that only a small fraction of men diagnosed with hypogonadism received the full battery of diagnostic tests and screenings recommended by medical societies before beginning treatment. The findings suggest a widespread pattern of incomplete laboratory evaluations and the prescription of testosterone to patients with clear medical contraindications, raising concerns about patient safety and the long-term efficacy of such interventions.
According to the research team, the primary objective of the study was to quantify the frequency of guideline-concordant care within a major academic medical center. By analyzing the electronic health records of patients at Michigan Medicine, the researchers sought to identify opportunities for quality improvement and the development of clinical decision support tools. The implications of the study are significant, as inappropriate testosterone prescribing can lead to avoidable health risks, including cardiovascular issues, polycythemia, and the exacerbation of pre-existing conditions like obstructive sleep apnea and prostate cancer.
Study Methodology and Patient Demographics
The research utilized a retrospective chart review of a random sample of 200 males assigned at birth who had a diagnosis of hypogonadism and received an initial testosterone prescription between 2020 and 2025. To ensure the data reflected contemporary primary care practices, the inclusion criteria required each patient to have had at least one outpatient primary care visit at Michigan Medicine within the year prior to their prescription.
The study population had a mean age of 52.5 years, representing a demographic typically targeted for "Low T" evaluations. The researchers also documented a high prevalence of comorbid conditions within this group, which often complicate the diagnosis and treatment of testosterone deficiency. Among the 200 men studied:
- 63% were classified as obese.
- 52% suffered from hypertension.
- 40% had a diagnosis of depression.
- 28% were managing diabetes.
- 28% suffered from arthritis.
These comorbidities are noteworthy because conditions such as obesity and type 2 diabetes are known to naturally lower total testosterone levels through various metabolic pathways. In many cases, addressing the underlying lifestyle or metabolic factors is recommended before or alongside hormonal intervention. The high rate of depression also highlights the overlap in symptoms between mental health disorders and hypogonadism, such as fatigue and low libido, which can sometimes lead to misdiagnosis.
The Gap in Guideline-Concordant Care
The most striking finding of the study was that only 12% of the men who received an initial testosterone prescription met the full criteria for guideline-concordant diagnostic testing. Medical guidelines, such as those provided by the Endocrine Society and the American Urological Association, stipulate a rigorous testing protocol to ensure that testosterone therapy is both necessary and safe.
To be considered guideline-concordant in this study, a patient had to meet several specific criteria:
- Repeat Testing: Documentation of two separate low morning testosterone levels (total testosterone < 300 ng/dL, free testosterone < 70 pg/mL, or low bioavailable testosterone).
- Timing: The blood samples must have been drawn between 5 a.m. and 10 a.m. to account for the natural diurnal rhythm of testosterone production, which peaks in the early morning.
- Pituitary Evaluation: Measurement of Luteinizing Hormone (LH) and/or Follicle-Stimulating Hormone (FSH) to determine if the hypogonadism is primary (testicular failure) or secondary (pituitary or hypothalamic issues).
- Absence of Contraindications: Ensuring the patient does not have conditions that would make testosterone therapy dangerous.
The data revealed that the majority of patients began therapy without this complete picture. While 77% of patients had a complete blood count (CBC) measured and 62% had a prostate-specific antigen (PSA) test in the year preceding their prescription, other vital diagnostic steps were frequently skipped. The failure to measure LH and FSH levels is particularly concerning to specialists, as it prevents clinicians from identifying potentially serious underlying issues in the pituitary gland.
Identifying Contraindications and Safety Risks
A significant portion of the study focused on the presence of contraindications—medical reasons why a patient should not receive testosterone. Dr. Sophia Hemmrich Sinha noted that some men were prescribed the hormone despite having conditions that are traditionally considered red flags.
One of the most prevalent concerns was obstructive sleep apnea (OSA). The study found that 55% of the men prescribed testosterone had a pre-existing diagnosis of OSA. Testosterone therapy is known to worsen sleep apnea by potentially affecting the central drive to breathe and relaxing the muscles of the upper airway. Without careful monitoring and management of OSA, testosterone therapy can lead to severe nocturnal hypoxia.
Furthermore, the study identified risks related to prostate health. Approximately 4% of the men in the sample had a history of prostate cancer, and 1.5% had a PSA level greater than 4 ng/mL before the prescription was written. Because testosterone can stimulate the growth of prostate tissue, its use in patients with active or high-risk prostate cancer is generally restricted or requires extremely close oncological supervision.
The researchers also emphasized the importance of the 77% CBC screening rate. Testosterone therapy can cause erythrocytosis—an abnormal increase in red blood cell production—which thickens the blood and increases the risk of blood clots, strokes, and heart attacks. While the majority of patients received a baseline CBC, the lack of universal adherence to this safety check remains a point of concern for the research team.
Prescribing Patterns Across Specialties
The study also examined which types of healthcare providers were initiating testosterone therapy. The distribution of prescriptions across specialties was as follows:
- Primary Care Physicians: 45%
- Urologists: 35.5%
- Endocrinologists: 18%
- Other Specialists: 1.5%
The fact that nearly half of all prescriptions originated in primary care highlights the central role of general practitioners in managing men’s hormonal health. However, it also suggests that primary care offices may be the areas where the most support is needed to ensure guideline adherence. Specialists like urologists and endocrinologists, who are often more familiar with the nuances of hormonal feedback loops, accounted for a smaller combined percentage of the initial prescriptions.
Regarding the method of administration, topical formulations were the most common, accounting for 68.5% of the prescriptions. Topical gels and creams are often preferred for their ease of use and ability to maintain more stable physiological levels of testosterone compared to infrequent, high-dose injections. However, they also carry risks of accidental transfer to women and children, requiring specific patient education that may be overlooked if the initial diagnostic process is rushed.
Analysis of Implications and Future Directions
The results of the Michigan Medicine study point to a systemic issue in how "Low T" is managed in clinical settings. Dr. Maria Papaleontiou emphasized that these findings should serve as a catalyst for quality-improvement efforts. The goal is not necessarily to reduce the number of prescriptions, but to ensure that those who receive them are the ones who truly need them and can safely tolerate them.
"Our study findings highlight opportunities to improve patient care and reduce inappropriate testosterone prescribing," Papaleontiou stated. "Long-term, these findings can lead to quality-improvement efforts and clinical decision support tools that promote consistent, guideline-concordant testosterone prescribing."
One proposed solution is the integration of clinical decision support (CDS) tools within electronic health record systems. These tools could act as digital "guardrails," prompting physicians to order a second morning testosterone test or check LH/FSH levels before the system allows a prescription to be finalized. They could also flag patients with high PSA levels or untreated sleep apnea, forcing a manual override or a documented justification for the therapy.
The rise in testosterone prescriptions over the last decade has been attributed to several factors, including direct-to-consumer advertising and a growing societal focus on anti-aging medicine. However, as Dr. Sinha pointed out, improving adherence to guidelines helps prevent avoidable risks in people who may not have a true clinical need for the hormone. For many men, symptoms like fatigue and low libido may be better addressed through weight loss, improved sleep hygiene, or the management of chronic diseases like diabetes and depression.
Chronology of the Research and Context
The study covers a critical five-year window from 2020 to 2025, a period characterized by significant shifts in healthcare delivery, including the expansion of telehealth. While the study focused on a traditional academic medical center (Michigan Medicine), the timeframe reflects an era where testosterone therapy has become increasingly accessible through various channels.
The presentation of this data at the ENDO 2026 forum marks a milestone in the ongoing effort by the Endocrine Society to standardize care for male hypogonadism. Previous studies in the early 2010s suggested similar trends in over-prescribing, but the Sinha and Papaleontiou study provides a modern update, showing that despite a decade of updated guidelines, the gap between recommendation and practice remains wide.
As the medical community moves forward, the focus will likely shift toward targeted interventions. Dr. Papaleontiou noted that future studies should evaluate whether these interventions—such as provider education workshops or automated EHR alerts—can effectively move the needle from the current 12% compliance rate toward a much higher standard of care.
In conclusion, the research underscores a vital need for a more disciplined approach to male hormonal health. By ensuring that every patient undergoes a thorough, guideline-based evaluation, clinicians can better distinguish between the natural effects of aging and comorbid illness versus true clinical hypogonadism, ultimately protecting patient safety and optimizing therapeutic outcomes.
