Endocrine Abstracts

Context: Several previous studeis suggested seasonal variation in testosterone levels. However, these studies were limited by either their small sample size or by variability in baseline characteristics and confounders such as: differences in age and weight distribution, co-existent illness, time in the day in which testosterone was measured and by differences in geographic location and climate conditions. Ultraviolet (UV) exposure is one of the main environmental stimuli. In a recent study (Parikh R, et al, Cell Rep. 2021, 36(8): 109579), we explored a novel skin-brain-gonad axis triggered by UV and mediated by skin p53. Through the use of various mouse models, we found that UV exposure led in male and female mice to increased hypothalamus-pituitary-gonadal axis hormone levels and to increased sexual responsiveness and attractiveness. These data provide for the first time an underlying mechanism for seasonal variability in testosterone levels.

Objectives: To evaluate in a large cohort of males with a wide-range of age, metabolic status and co-existent morbidities, whether month of blood test performance was associated with total and bioavailable testosterone levels independent of age, body-mass index (BMI), existing cardiovascular disease (CVD) and CVD risk factors.

Methods: Cross-sectional study including data from computerized medical records of 27,328 men aged 20-70, treated by the largest health care organization in Israel, who underwent testosterone measurement. In 7,940 subjects with available sex-hormone-binding globulin levels, bioavailable testosterone was calculated.

Results: Total and bioavailable testosterone levels gradually decreased with age and BMI (P<0.001) and were significantly lower in men with diabetes, hypertension, hyperlipidemia and known CVD (P<0.001). Intrigungly, testosterone levels were higher in current smokers compared with non-smokers (P<0.001). We stratified total and bioavailable testosterone levels according to the month in which the test was performed and observed a peak of total and bioavailable testosterone levels during August to October. After October, total testosterone and bioavailable testosterone started to decline reaching a nadir in March. Overall, total and bioavailable testosterone levels were significantly lower in March compared to August-October (P<0.001). In a linear regression analysis, age, BMI, current smoking, and month of testing were independently associated with both total (P<0.001) and bioavailable testosterone levels (P=0.002).

Conclusion: In a large cohort of men with a wide-range of age, BMI and co-morbidities, month of testing was independently associated with total and bioavailable testosterone levels. These data provide compelling evidence that seasonal variation has to be considered in clinical practice.