Abstract

Environmental rhythmicity is able to affect the hypothalamic-pituitary-gonadal axis in several animals to achieve reproductive advantages. However, conflicting results were obtained when assessing the environmental-dependent rhythmicity on reproductive hormone secretion in humans. 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. 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 using Chemiluminescent Microparticle Immunoassay. Subjects presenting any factor interfering with the hypothalamic-pituitary-gonadal axis were excluded. The trend and seasonal distributions were analyzed using autoregressive integrated moving average (ARIMA) models. A total of 12,033 data, accounting for 7,491 men (mean age 47.46 ± 13.51 years, range 18–91 years) were included. Testosterone serum levels (mean 5.34 ± 2.06 ng/dL, range 1.70–15.80 ng/dL) showed a seasonal distribution with higher levels in summer and a direct correlation to environmental temperatures and daylight duration. LH levels (mean 4.64 ± 2.54 IU/L, range 1.00–15.00 IU/L) presented 2 peaks of secretion in autumn and spring, independently from environmental parameters. FSH levels (mean 5.51 ± 3.24 IU/L) did not show any seasonal distribution. 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.

Highlights

  • Life is strictly embedded in cyclic changes and several organisms have developed circadian and circannual clocks to adapt their physiological functions to external environmental changes

  • We demonstrate a clear seasonal fluctuation of both luteinizing hormone (LH) and testosterone in a large sample of adult human males

  • The testosterone annual change shows a wider variability in annual values compared to LH, evident including levels below and above the laboratory reference ranges, while LH fluctuations remain irrespective of the reference range

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Summary

Introduction

Life is strictly embedded in cyclic changes and several organisms have developed circadian and circannual clocks to adapt their physiological functions to external environmental changes. The hypothalamic-pituitary-gonadal axis seems to be extremely susceptible to environmental rhythmicity [3], since annual hormone fluctuations are needed for several animals to optimize reproduction timing [4]. This physiological mechanism has a genetic substrate, and several clock genes regulate the circadian hormone rhythmicity in a large number of organisms, including mammals [5,6,7,8,9]. A circannual seasonality of sexual hormones in the human species could not be, evolutionarily, strictly required

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