New Endocrine Society statement reinforces diagnostic standards for testosterone therapy

The statement follows a December 2025 FDA expert panel review of testosterone eligibility criteria and new ENDO 2026 data showing gaps in guideline-concordant prescribing.

A new Endocrine Society statement has reinforced the importance of accurate diagnosis and appropriate clinical assessment before testosterone replacement therapy (TRT) is initiated in men with hypogonadism.¹ Published July 16, 2026, the statement reiterates that treatment should not be based on symptoms alone and highlights continuing uncertainties around the long-term safety of TRT. It follows an FDA expert panel that reviewed testosterone eligibility criteria in December 2025, Society comments submitted to the FDA in February 2026, and new prescribing-pattern data presented at ENDO 2026, the Society’s annual meeting, in June.

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Male hypogonadism is diagnosed in men with symptoms and signs consistent with testosterone deficiency together with unequivocally and consistently low testosterone concentrations. Diagnosis can be challenging because features such as reduced libido, low energy, and unexplained anemia may overlap with normal aging, obesity, depression, and other potentially reversible conditions. Testosterone measurements may also vary substantially between laboratories and assays, increasing the risk of inaccurate diagnosis.

The Society’s formal guidance practice guideline was published in 2028, and recommends diagnosing hypogonadism only in men with compatible symptoms and signs and consistently low testosterone concentrations confirmed by repeat morning testing. It also advises against routine population-level screening.² The July 2026 statement reinforces these existing recommendations rather than introducing a new clinical practice guideline.

On diagnosis, the statement cautions that terms such as age-related, late-onset, or functional hypogonadism are poorly defined and may blur the distinction between a treatable endocrine disorder and changes associated with aging.¹ It recommends confirming hypogonadism using at least 2 early-morning, fasting testosterone measurements, with assays certified under the Hormone Standardization (HoST) program administered by the US Centers for Disease Control and Prevention, because non-standardized assays can produce inconsistent results from the same sample.¹

For men with appropriately diagnosed hypogonadism attributable to being overweight or obese — defined in the statement as a body mass index above 27 kg/m² — with no other identified cause, weight loss should generally be considered first-line treatment rather than TRT.¹

The statement also reviews recent safety evidence. The phase 4 TRAVERSE trial (NCT03518034) enrolled more than 5,200 middle-aged and older men with hypogonadism and pre-existing or elevated cardiovascular risk and found that TRT was noninferior to placebo for major adverse cardiovascular events over 1 to 4 years of follow-up.³

However, pulmonary embolism occurred more frequently in the testosterone group, and a separate, prespecified TRAVERSE substudy found that testosterone treatment did not reduce fracture risk: the 3-year cumulative incidence of clinical fractures was about 4% with testosterone compared with 2.8% with placebo.^1,3,4 Long-term safety, including the possible effect of treatment on prostate cancer risk, remains uncertain. The Society called for a long-term Men’s Health Initiative, modeled on the Women’s Health Initiative, to help address these evidence gaps.¹

The statement follows an FDA expert panel on testosterone replacement therapy for men, held December 10, 2025.⁵ Panelists at that meeting expressed support for expanding treatment eligibility beyond hypogonadism with a confirmed testicular, pituitary, or hypothalamic cause, eliminating some current contraindications and prostate-related warnings, and removing testosterone’s status as a Schedule III controlled substance.⁶ The Endocrine Society submitted comments to the FDA docket in February 2026, addressing questions relevant to men’s health and prescribing practice.⁷ The Society’s July 2026 statement, emphasizing rigorous diagnostic criteria, comes as this regulatory conversation continues.

Evidence of a gap between guideline recommendations and clinical practice was highlighted in a presentation at ENDO 2026 by Dr Sophia Sinha and senior author Dr Maria Papaleontiou, both of the University of Michigan, Ann Arbor, MI, USA.⁸

In a retrospective review of a random sample of 200 patients with a hypogonadism diagnosis who received an initial testosterone prescription at Michigan Medicine between 2020 and 2025, only 12% had undergone the full diagnostic workup assessed by the researchers.⁸ This included 2 qualifying low morning testosterone results, luteinizing hormone and/or follicle-stimulating hormone testing, and confirmation that no contraindications to treatment were present.⁸ Prostate-specific antigen and complete blood count testing had been performed in 62% and 77% of patients, respectively. Prescriptions were most commonly written by primary care physicians, accounting for 45%, followed by urologists at 35.5% and endocrinologists at 18%.⁸

“Our study findings highlight opportunities to improve patient care and reduce inappropriate testosterone prescribing,” said Dr Papaleontiou, the study’s senior author, in a press release. “Long-term, these findings can lead to quality-improvement efforts and clinical decision support tools that promote consistent, guideline-concordant testosterone prescribing.”⁸

The new statement emphasizes that clinicians should continue to confirm the diagnosis using repeated, standardized testosterone measurements, assess potential contraindications, and discuss the known benefits, uncertainties, and emerging safety signals with patients before starting treatment.

References

1. The Endocrine Society. Statement on Testosterone Replacement Therapy [Press release]. July 16, 2026. Available at: https://www.endocrine.org/news-and-advocacy/news-room/2026/statement-on-testosterone-replacement-therapy
2. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–44.
3. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389:107–17. ClinicalTrials.gov Identifier: NCT03518034.
4. Snyder PJ, Bauer DC, Ellenberg SS, et al. Testosterone treatment and fractures in men with hypogonadism. N Engl J Med. 2024;390:203–11.
5. US Food and Drug Administration. FDA Expert Panel on Testosterone Replacement Therapy for Men. Meeting. December 10, 2025. Available at: https://www.fda.gov/patients/fda-expert-panels/fda-expert-panel-testosterone-replacement-therapy-men-12102025
6. Healio. FDA panel supports expanding population indicated for testosterone therapy. December 10, 2025. Available at: https://www.healio.com/news/endocrinology/20251210/fda-panel-supports-expanding-population-indicated-for-testosterone-therapy
7. The Endocrine Society. Society Submits Comments to FDA Expert Panel on Testosterone Replacement Therapy for Men. Society letter. February 11, 2026. Available at: https://www.endocrine.org/advocacy/society-letters/2026/fda-testosterone
8. The Endocrine Society. Testosterone therapy in men may be overprescribed, inconsistent with clinical guidelines [Press release]. June 13, 2026. Available at: https://www.endocrine.org/news-and-advocacy/news-room/2026/papaleontiou-press-release-endo-2026