At age 21, at testosterone peak level, levels declined from 19.68 in 2006–9 to 17.76 in 2016–19. Age-specific testosterone levels over the observation period are depicted in Fig. No meaningful differences in BMI (η 2 = 0.001) or in exact age (η 2 = 0.004) between study periods were observed. The final analysis was performed on a total of 102,334 eligible patients (mean age 45.6, SD = 17.3, Table 1). R Foundation for Statistical Computing, Vienna, Austria. 25, MATLAB, and R (R: A language and environment for statistical computing. All analyses were conducted using IBM-SPSS ver. To test the significance of the year as a contributing factor to the testosterone level beyond age we fit a quadratic model for the age and a linear model for the measurement year ( testosterone level = 1 + age + age 2 + age 3 + age 4 + year, the quadratic model was used for age due to the strictly non-linear behavior of testosterone as a function of age in the range 13–80). Differences in age-specific mean BMI between decades were compared using η 2, a measure of effect size using analysis of variance (ANOVA). The study protocol has been approved by the Maccabi Healthcare Service’s institutional review board. We additionally filtered the data such that all included samples have the same lab norms (8.4–28.7 nanomole/liter), to ensure that all the samples were measured using the same lab methods (all the blood tests in Maccabi are analyzed at a single central lab). Included in the analysis were only the first blood sample taken from each patient ever since 2000. We pulled data on all the blood test measures of total testosterone ( Current Procedural Terminology, 4th Edition code 84002) performed on men aged 13–80 between the years 1/2006–3/2019. Membership retention rate in MHS is very high (less than 1% is leaving the organization annually) allowing for a long retrospective follow-up with a minimal lost to follow-up. Thus, all sectors of the Israeli population are represented in MHS, except for young adults aged 18–21, since a high percentage of them are enlisted in the Israeli Defense Forces (IDF), and receive medical care there. According to the 1994 Israel National Health Act, MHS may not bar applicants on any grounds, including age or state of health. This cross sectional study was conducted in Maccabi Healthcare Services (MHS), the second largest health organization maintenance in Israel, serving 25% of the total population countrywide (2.3 million members). Since the decline in testosterone levels seem to be affected by modifiable risk factors, the objectives of the current study were to assess long term trends over recent decades in total testosterone lab results using data from a stable, population-based cohort of male members of a large state-mandated health provider in Israel. Changes in lifestyle and health indices have been associated with declining testosterone, free testosterone, and SHBG levels, including body weight gain and smoking cessation. However, to the best of our knowledge, no such data were published after 2004. Several studies from the US and Nordic countries have shown a significant decline in serum testosterone among men from 1970s to early 2000s. Testosterone plays a major role in male reproductive function, including stimulating Sertoli cell function and spermatogenesis, as well as affecting non-reproductive organs such as muscle growth, stimulating bone mineralization, erythropoiesis, and cognitive function.
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