Symptom-Based Testosterone Therapy in Japanese Men With Late-Onset Hypogonadism Syndrome: A Real-World Single-Arm Study Following the 2022 Guideline.

Abstract

Objectives: Following the 2022 revision of the Japanese clinical practice guidelines for late-onset hypogonadism, more flexible diagnostic criteria have been recommended, emphasizing both clinical symptoms and testosterone levels. This study aimed to evaluate the clinical characteristics of late-onset hypogonadism syndrome and the effectiveness of testosterone replacement therapy combined with daily phosphodiesterase-5 inhibitors in symptomatic men, including those with normal testosterone levels.

Methods: From 2019 to 2023, 704 men presenting with late-onset hypogonadism-related symptoms were assessed for serum testosterone levels and symptom profiles. Of these, 227 received combination therapy with testosterone replacement therapy and daily phosphodiesterase-5 inhibitors. Changes in mood, vitality, sexual function and lower urinary tract symptoms were evaluated using validated questionnaires.

Results: The most frequent symptoms were depressive mood, loss of energy, and easy fatigue, which may represent core features of late-onset hypogonadism syndrome. No significant association was found between testosterone levels and symptom severity. Combination therapy significantly improved symptom scores, as well as subjective feelings of vigor, confidence, and masculinity. Among the patients, 48.4% reported feeling "better" or "much better," 47.2% reported feeling "slightly better," and 4.4% experienced "no change" or "worsening." Patients with normal testosterone levels showed greater improvement in symptom scores. Recovery of morning erections independently predicted overall improvement.

Conclusions: Testosterone replacement therapy combined with daily phosphodiesterase-5 inhibitors is effective for late-onset hypogonadism-related symptoms, even in patients with normal testosterone levels. These findings support the revised Japanese guidelines, which promote a symptom-oriented treatment strategy alongside biochemical evaluation.