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.