Long-term trajectories of reproductive and pituitary-adrenal-thyroid hormones in young males following Omicron BA.2 infection: a two-year prospective cohort study

Objective: To investigate the longitudinal changes and temporal patterns of reproductive, thyroid, and adrenal hormones in young males following SARS-CoV-2 Omicron BA.2 infection, using a 3-month post-infection convalescent reference point. Methods: A prospective cohort of 71 young male university students with confirmed Omicron BA.2 infection was followed for 24 months. Fasting blood samples were collected at 3 (early convalescent reference), 6, 12, and 24 months post-infection. Serum levels of 15 hormones across the hypothalamic-pituitary-gonadal (HPG), thyroid (HPT), and adrenal (HPA) axes were measured. Linear mixed-effects models were utilized to assess longitudinal changes over time. Persistent symptoms were recorded at each visit. Results: At the 3-month post-infection convalescent reference point, 8 of 71 participants (11.3%) reported mild persistent symptoms, which decreased to 4.3% by 24 months. Testosterone remained stable throughout the follow-up (all P > 0.05). Relative to the 3-month reference, prolactin declined progressively from an initially elevated mean of 22.55 ng/mL to 14.73 ng/mL at 24 months, gradually normalizing within the clinical reference range (4.04-15.2 ng/mL). Estradiol decreased at all follow-up points (P < 0.0001), while FSH and TSH demonstrated continuous, progressive increases (P < 0.001). TT4 and FT4 showed biphasic fluctuations. Adrenal markers (ACTH, cortisol) generally declined after 6 months (P < 0.0001). Ultimately, most mean hormone values remained within normal clinical reference ranges. Conclusion: Among young males, testosterone remained robustly stable over two years following Omicron BA.2 infection, while other endocrine markers displayed measurable longitudinal dynamics relative to the 3-month post-infection convalescent reference point. These findings highlight temporal post-infection patterns rather than definitive endocrine injury. While routine extensive endocrine screening may not be necessary for asymptomatic young males, targeted evaluation is recommended for individuals with persistent symptoms.