Seasonal changes of serum gonadotropins and testosterone in men: a reappraisal from a large data set of real-world observations over eight years Giorgia Spaggiari 1 , Antonio RM Granata 1 , Monica Setti 2 , Simonetta Tagliavini 3 , Tommaso Trenti 3 , Manuela Simoni 1, 4 & Daniele Santi 1, 4

1 Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile of Baggiovara, Modena, Italy; 2 Service of Clinical Engineering, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy; 3 Department of Laboratory Medicine and Anatomy Pathology, Azienda USL of Modena, Italy; 4 Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Objective: Environmental rhythmicity seems able to affect the hypothalamic-pituitary-gonadal axis in animals, but the extent of its influence in humans is still controversial. This study was designed to evaluate seasonal fluctuations of the main hormones involved in the hypothalamic-pituitary-gonadal axis in men, using a big data approach.

Methods: An observational, retrospective, big data trial was carried out, including all testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements performed in a single laboratory between January 2010 and January 2019. Subjects presenting any factor interfering with the hypothalamic-pituitary-gonadal axis were excluded. The trend and seasonal distributions were analysed using autoregressive integrated moving average models.

Results: A total of 12,033 data were included, accounting for 7,491 men (mean age 47.46±13.51 years, range 1891 years). Mean testosterone serum levels (5.34±2.06 ng/dl, range 1.7015.80 ng/dl) showed a seasonal distribution with higher levels in summer (P=0.008) and a direct relationship with environmental temperatures and daylight duration. LH (mean 4.64±2.54 IU/l, range 1.0015.00 IU/l) presented 2 peaks of secretion in autumn and spring (P=0.001), independently from temperatures and daylight duration. FSH levels did not show any seasonal distribution.

Conclusions: A clear seasonal fluctuation of both LH and testosterone was demonstrated in a large cohort of adult men, although a circannual seasonality of hypothalamic-pituitary-gonadal hormones in humans could be not strictly evolutionarily required. Testosterone seasonality seems independent from LH fluctuations, which could be regulated by cyclic central genes expression, and more sensible to environmental temperatures and daylight duration.