Hormone seasonality in medical records suggests circannual endocrine circuits

Abstract

Significance We provide a dataset of millions of hormone tests from medical records that shows seasonality with a winter−spring peak in hormones for reproduction, growth, metabolism, and stress adaptation. Together with a long history of studies on a winter−spring peak in human function and growth, the hormone seasonality indicates that, like other animals, humans may have a physiological peak season for basic biological functions. We further use the specific seasonal phases of the hormones to suggest a model for a circannual clock in humans and animals that can keep track of the seasons, similar in spirit to the circadian clock that keeps track of time of day. Hormones control the major biological functions of stress response, growth, metabolism, and reproduction. In animals, these hormones show pronounced seasonality, with different set-points for different seasons. In humans, the seasonality of these hormones remains unclear, due to a lack of datasets large enough to discern common patterns and cover all hormones. Here, we analyze an Israeli health record on 46 million person-years, including millions of hormone blood tests. We find clear seasonal patterns: The effector hormones peak in winter−spring, whereas most of their upstream regulating pituitary hormones peak only months later, in summer. This delay of months is unexpected because known delays in the hormone circuits last hours. We explain the precise delays and amplitudes by proposing and testing a mechanism for the circannual clock: The gland masses grow with a timescale of months due to trophic effects of the hormones, generating a feedback circuit with a natural frequency of about a year that can entrain to the seasons. Thus, humans may show coordinated seasonal set-points with a winter−spring peak in the growth, stress, metabolism, and reproduction axes.