2023 Volume 70 Issue 7 Pages 755-756
【State-of-the-Art Review in Endocrinology】 EJ22-0604, endocrj 70: 655-662.
Browse “Advance online publication” versionDear Editor;
We read the review regarding the impact of testosterone in men’s health [1]. This review indicated the importance of testicular function and showed that lifestyle improvements prevent aging-related decline of testosterone and its related symptoms defined as late-onset hypogonadism (LOH) [1]. Symptoms of LOH include fatigue, poor concentration, insomnia, and headache. We have been interested in the relationship between COVID-19 and LOH and particularly the relationship of LOH with persistent symptoms in patients who visited our COVID-19 aftercare clinic (CAC) [2].
Although the mechanisms of long COVID have yet to be elucidated, it is known that SARS-CoV-2 targets ACE2, which is abundantly expressed in the testis and Leydig cells [3]. We reported that male hypogonadism is partly involved in the symptoms of long COVID [4]. Here, we analyzed androgen levels in male long COVID based on the infected phases of viral variants. Among 310 male long COVID patients who visited the CAC between February 22, 2021 and April 30, 2023 due to symptoms that had persisted for more than one month after infection, serum free testosterone (FT) concentration was examined by a radioimmunoassay in 157 patients (50.6%) due to suspicion of hypogonadism (Fig. 1A). Eighty-two patients (26%), 52% of the examined patients, met the earlier criterion of serum FT <8.5 pg/mL (Fig. 1B). The detection rates of LOH gradually increased from the Preceding phase (47%) to the Delta (51%) and to the Omicron phases (54%). In the LOH patients complaining of long COVID symptoms, the most frequent symptoms in patients infected in the Preceding and Delta phases were fatigue, dysgeusia and dysosmia, whereas the major symptoms in patients infected in the Omicron phase were fatigue, headache and insomnia. The proportions of LOH patients under 50 years of age in the Delta phase were increased up to 78% (FT <8.5 pg/mL: Fig. 1B upper) and 81% (FT <7.5 pg/mL: Fig. 1B lower) compared with the proportions of such patients in the Preceding and Omicron phases, though the proportion of younger patients in whom FT was examined was not increased (Fig. 1C), and those proportions were much higher than the detection rate of LOH in young patients in general practice (31%) [5].
Trend changes of LOH in long COVID. A) Numbers of long COVID males and FT examination; B) Percentages of LOH patients ≧50 years of age and <50 years of age and with FT levels under 8.5 pg/mL and 7.5 pg/mL; C) Population in which serum FT was examined. Preceding phase: from the ancestral to Alpha strains before July 18, 2021; Delta phase: from July 19, 2021 to December 31, 2021; Omicron phase: after January 1, 2022. *p < 0.05 by Fisher’s exact test.
Here we showed a phase-dependent trend of long COVID indicating that LOH in young patients was transiently increased in long COVID patients who were infected in the Delta phase. Serum androgen and gonadotropin levels are useful for detecting occult LOH in patients with long COVID symptoms. Prospective studies on treatments and prognosis are needed for establishing clinical significance of long COVID-related LOH.
COVID-19, Coronavirus disease 2019; CAC, COVID-19 aftercare clinic; FT, free testosterone; LOH, late-onset hypogonadism
This research was in part supported by Ryobi Teien Memory Foundation (2022) in Japan.
This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Okayama University Hospital (No. 2105-030).
We are sincerely grateful to the clinical staff at the Department of General Medicine who contributed to the present work.
The authors declare no conflict of interest.
