Endocrine Abstracts

Background: Testosterone replacement therapy (TRT) is prescribed for hypogonadotrophic hypogonadism, but inappropriate initiation has major implications for fertility. Discontinuation of TRT is associated with variable recovery times for the hypothalamic–pituitary–gonadal axis and spermatogenesis, typically 6–18 months in published series. Shift work may further alter circadian testosterone rhythms and complicate interpretation.

Case: A 33-year-old male was referred for reassessment of a historical diagnosis of hypogonadotrophic hypogonadism. He had been on long-term TRT with Nebido injections for 8 years. His main concern was fertility. Semen analysis revealed azoospermia, and gonadotrophins were suppressed (FSH <0.3 IU/l, LH <0.1 IU/l). Trough serum testosterone on treatment was normal, with low SHBG.

Investigations: TRT was withdrawn to reassess endogenous pituitary–gonadal function. Over the following 6 months, pituitary hormones normalised, serum testosterone reached 10.4 nmol/l, and calculated free testosterone was reassuring despite low SHBG. The role of shift work in lowering testosterone was discussed, and daytime working was encouraged to support recovery.

Outcome: Hypogonadism resolved within 6 months, with spontaneous partner pregnancy reported. This recovery period is at the shorter end of the expected global range (6–18 months; WHO Task Force, 1990; Liu et al., J Clin Endocrinol Metab, 2006). Fertility was restored without the need for gonadotrophin induction therapy.

Conclusion: This case highlights recovery of the hypothalamic–pituitary–gonadal axis after prolonged TRT use, the risk of azoospermia from unnecessary therapy, and the impact of circadian disruption from shift work. It underscores the importance of critically re-evaluating historical diagnoses of hypogonadism and providing tailored management for men seeking fertility. 1. Diagnosis and Type of Hypogonadism: It is critical to establish the diagnosis and type of hypogonadism using a combination of clinical history, physical examination, and biochemical tests. This helps in determining whether the condition is primary (testicular) or secondary (pituitary or hypothalamic) hypogonadism. 2. Recovery of spermatogenesis after discontinuing TRT varies; published studies suggest 6–18 months, though some men may take up to 24 months. 3. Calculated Free Testosterone in Low SHBG: 1. When SHBG (sex hormone-binding globulin) is low, the calculation of free testosterone becomes essential for an accurate assessment of testosterone status. This helps to better understand the bioavailable testosterone in the body. 2. However, there is ongoing uncertainty in the medical community about reference ranges and their correlation with symptoms. This is an area that needs further research to clarify. 4. Shift work can alter circadian testosterone secretion and should be considered in interpretation and management.