The Endocrine Society’s clinical practice guidelines for the diagnosis of hypogonadism recommend evaluating only those men who show signs and symptoms of testosterone deficiency. However, the signs and symptoms of hypogonadism (which include erectile dysfunction, depressed mood, decreased libido, lethargy, sleep disturbances, decreased muscle mass and strength, and loss of body hair) are non-specific and can be attributed to other causes, explains Ezgi Caliskan Guzelce, MD. Furthermore, even when testing is initiated, there may be issues regarding imprecision that can hinder a proper diagnosis.

Dr. Guzelce recently spoke with Physicians’ Weekly about the difficulties of diagnosis and management of hypogonadism to help provide a clear picture of how these obstacles can be addressed in the field.

PW: In your opinion, what is the greatest challenge in treating hypogonadism?

Dr. Guzelce: The greatest challenge is the diagnosis of hypogonadism. A paper my colleagues and I recently had published in Best Practice & Research Clinical Endocrinology & Metabolism emphasizes the importance of the diagnosis of hypogonadism in men and focuses on the accurate measurement of testosterone.

The evaluation of men suspected of hypogonadism is conceptually uncomplicated; however, the non-specificity of symptoms, variations in the circulating testosterone levels over time due to biological factors, the inaccuracy and imprecision of some commonly used assays for the measurement of total and free testosterone levels, and the discordance of reference ranges among assays and laboratories can contribute to diagnostic inaccuracy. Once a diagnosis of hypogonadism is made, the treatment involves testosterone replacement and searching for the causes.

Another challenge is that only a small proportion of men receiving testosterone therapy undergo appropriate evaluation and monitoring. Patients treated with testosterone should be monitored to determine that normal serum testosterone concentrations are achieved. There are desirable effects of testosterone administration, such as developing or maintaining secondary sexual characteristics and increases in libido, muscle strength, fat-free mass, and bone density. There are also undesirable effects related directly to testosterone treatment, such as acne, prostate disorders (eg, benign prostatic hyperplasia symptoms), sleep apnea, and erythrocytosis. Therefore, the goal of treatment is to achieve normal testosterone levels.

PW: What should physicians incorporate into their practice based on your research?

Dr. Guzelce: Accurate measurement of total and free testosterone concentrations is central to the accurate diagnosis of hypogonadism and other androgen disorders. Testosterone levels should be measured preferably in a CDC-certified laboratory using validated assays, and men receiving testosterone therapy should undergo appropriate evaluation and monitoring to achieve optimal outcomes.

PW: What would you like future research to be focused on? What still needs to be explored?

Dr. Guzelce: The risk for misdiagnosing testosterone deficiency is high when testosterone levels are close to the lower limit of the normal range. Validation of additional biomarkers of testosterone deficiency is needed to improve the diagnostic accuracy, especially in men with testosterone levels that are only slightly below or slightly above the lower limit of the normal range.