Nelson Vergel
Founder, ExcelMale.com
Source: http://www.ncbi.nlm.nih.gov/m/pubmed/23294933/#fft
Seasonal variations in testosterone: the evidence
In one of the earliest manuscripts on the topic, Reinberg et al. [8] demonstrated circannual variation in plasma T in five Parisian males with peak plasma levels and sexual activity occurring in the month of October. Shortly thereafter, Smals et al. [9]examined a group of 15 healthy male subjects and found statistically significant seasonal patterns in T levels. The authors recorded peaks in the summer and early autumn and a nadir in the winter and early spring [9]. Since that time, seasonal variation has been confirmed in several cross-sectional studies of ethnically, socially, and geographically varied populations of men [10], [11], [12], [13], [14], [15] and [16]. Others however, have not shown similar circannual variations [17], [18], [19] and [20]. Inconsistent variations have also been identified in a number of longitudinal studies on seasonal patterns of T[9], [15], [21], [22] and [23].
Svartberg et al. [24] cross-sectionally examined the seasonal variations in total and free testosterone (TT and FT), luteinizing hormone (LH), and sex hormone binding globulin (SHBG) levels amongst 1548 men living in northern Norway. A population selected based on its exposure to a wide seasonal variation in both temperature and daylight. Among these men, TT showed bimodal seasonal variation with peak values in October–November and a nadir in June. Similar results were seen in patterns of FT demonstrating peaks in December and a nadir in August. Notably, the lowest T levels occurred in months with the highest temperatures and longest hours of daylight. The variations in hormone levels were large, with a 19% and 31% difference between the lowest and highest monthly mean levels of TT and FT respectively. The authors hypothesized that these fluctuations could be explained by the variation in daylight exposure and temperature [24].
While the study had a significant confounder in that a large length of time (i.e. 0800–1600) was deemed suitable for the laboratory T collection, a substantial seasonal effect on T was still highlighted [24]. A follow-up cross-sectional study [7] was conducted on men exposed to less extreme seasonal changes in sunlight and temperature (San Diego, California) to determine whether seasonal variations of T persisted in this population. In the 915 men studied, neither TT nor bioavailable T (BT) varied by season [7]. These results were independent of age as well as anthropometric measurements and no association with air temperature or duration of sunlight exposure was documented [7]. The conflicting results obtained in the study set in California and the original Norwegian study were postulated to be due to differences in climate and sleep patterns [7] and [24].
In a population with a similar photoperiod and climate (Denmark), Andersson et al. [25], obtained monthly blood samples on 27 men during a 17-month period. Measurements of inhibin B, follicle stimulating hormone (FSH), LH, TT, and estradiol (E2) levels were recorded. The authors found seasonal variation in LH and T levels, but not in the levels of other sex hormones. The seasonal variation in TT paralleled the variation seen in LH with peak levels in the summer (June–July) and nadirs in the winter and early spring [25]. This data reported by Andersson et al. [25] is in contrast to the Svartberg study [24], which showed peaks in the fall and a nadir in the summer. The lack of concordant seasonal changes in hormone patterns in these two geographically similar populations calls into question the clinical significance of these findings.
Whereas the aforementioned studies had limited study populations, Moskovic et al. examined serum TT, E2, SHBG, FSH, LH and dehydroepiandrosterone (DHEA) in 11,000 men in the southwestern United States [26]. Given the previous finding by Crawford et al. [4] which suggested that diurnal variation diminished after age 60, men in the Moskovic study were divided into cohorts of less than 60 years of age and those greater than 60 years of age. This division was to control for potential physiologic differences in age-related hormonal regulation. Moskovic et al. [26] subsequently found statistically significant differences in E2, testosterone: estrogen ratio (T:E), FSH, and SHBG between seasons. The magnitude of these differences was only significant in the younger cohort of patients, although the younger cohort was also larger (N = 9669 versus 1954). Peak to trough variations were 16.5% for T: E ratio, with a peak in the spring and nadir in the fall. The difference between T:E ratio in the two cohorts was hypothesized to be due in part to increased physical activity in the younger cohort and evidence to suggest that the HPG axis is more sensitive in younger men [27]. Whereas no significant change in TT was observed, a 10% change was noted in FT between peak (summer) and trough (fall) values; however, this was not clinically significant.
Despite its sample size, the Moskovic study [26] still failed to show statistically significant differences in TT, LH, FT and DHEA in either cohort. This study was also limited in that samples were collected between 0900 and 1900 and was based on initial, single patient observations as opposed to longitudinal data [26]. Along with the prior Svartberg study in San Diego [7], this represented the second investigation in the southwestern United States which failed to show significant seasonal TT variation. This suggests that the prior Scandinavian studies were demonstrating a regional effect. Further research in dissimilar climates and populations is required to replicate the variability in these prior studies and substantiate their findings.
One such study by Brambilla et al. [20] was based in Boston, Massachusetts and therefore contrasts with the prior Moskovic study [26] in the potential regional effects of climate and epidemiology. The authors examined seasonal fluctuations in androgens, including serum TT, FT, BT, dihydrotestosterone (DHT), SHBG, LH, DHEA, dehydroepiandrosterone sulfate (DHEA-S), E2, and cortisol. One hundred and twenty-one men, aged 30–79, completed six morning blood draws at 0, 3, and 6 months [20]. Time of enrollment was random in order to capture data from all twelve months. Aside from cortisol, there was no evidence of seasonal variation in hormone levels [20]. Peak levels were within 4% of the mean level for all hormones examined. The authors found that intra-individual variation was greater for each hormone evaluated when compared with seasonal variation. Brambilla et al. [20] concluded, therefore, that seasonal effects are likely not an important source of significant variation clinically.
Whereas regional influences may account for some of the observed patterns of seasonal variation, age within the study population also has the potential to confound these results. For instance, Moskovic et al. [26] found more significant seasonal variation in T:E ratio in younger men whereas Svartberg [7] found neither TT nor BT varied by season and these results were independent of age. Similarly, Tancredi et al. [19], in a study of 5028 men aged 50 and over, showed that monthly variations in serum FT values did not show significant seasonal variation (<15%) [19]. Dai et al., in an epidemiologic study, demonstrated that age and obesity correlated with T levels in 243 men; however, while diurnal variation was noted, seasonal variation of T was not [17].
Based on the substantial heterogeneity within these studies, the evidence for seasonal variation of androgens can only be characterized as inconsistent at this time.
Seasonal variations in testosterone: the evidence
In one of the earliest manuscripts on the topic, Reinberg et al. [8] demonstrated circannual variation in plasma T in five Parisian males with peak plasma levels and sexual activity occurring in the month of October. Shortly thereafter, Smals et al. [9]examined a group of 15 healthy male subjects and found statistically significant seasonal patterns in T levels. The authors recorded peaks in the summer and early autumn and a nadir in the winter and early spring [9]. Since that time, seasonal variation has been confirmed in several cross-sectional studies of ethnically, socially, and geographically varied populations of men [10], [11], [12], [13], [14], [15] and [16]. Others however, have not shown similar circannual variations [17], [18], [19] and [20]. Inconsistent variations have also been identified in a number of longitudinal studies on seasonal patterns of T[9], [15], [21], [22] and [23].
Svartberg et al. [24] cross-sectionally examined the seasonal variations in total and free testosterone (TT and FT), luteinizing hormone (LH), and sex hormone binding globulin (SHBG) levels amongst 1548 men living in northern Norway. A population selected based on its exposure to a wide seasonal variation in both temperature and daylight. Among these men, TT showed bimodal seasonal variation with peak values in October–November and a nadir in June. Similar results were seen in patterns of FT demonstrating peaks in December and a nadir in August. Notably, the lowest T levels occurred in months with the highest temperatures and longest hours of daylight. The variations in hormone levels were large, with a 19% and 31% difference between the lowest and highest monthly mean levels of TT and FT respectively. The authors hypothesized that these fluctuations could be explained by the variation in daylight exposure and temperature [24].
While the study had a significant confounder in that a large length of time (i.e. 0800–1600) was deemed suitable for the laboratory T collection, a substantial seasonal effect on T was still highlighted [24]. A follow-up cross-sectional study [7] was conducted on men exposed to less extreme seasonal changes in sunlight and temperature (San Diego, California) to determine whether seasonal variations of T persisted in this population. In the 915 men studied, neither TT nor bioavailable T (BT) varied by season [7]. These results were independent of age as well as anthropometric measurements and no association with air temperature or duration of sunlight exposure was documented [7]. The conflicting results obtained in the study set in California and the original Norwegian study were postulated to be due to differences in climate and sleep patterns [7] and [24].
In a population with a similar photoperiod and climate (Denmark), Andersson et al. [25], obtained monthly blood samples on 27 men during a 17-month period. Measurements of inhibin B, follicle stimulating hormone (FSH), LH, TT, and estradiol (E2) levels were recorded. The authors found seasonal variation in LH and T levels, but not in the levels of other sex hormones. The seasonal variation in TT paralleled the variation seen in LH with peak levels in the summer (June–July) and nadirs in the winter and early spring [25]. This data reported by Andersson et al. [25] is in contrast to the Svartberg study [24], which showed peaks in the fall and a nadir in the summer. The lack of concordant seasonal changes in hormone patterns in these two geographically similar populations calls into question the clinical significance of these findings.
Whereas the aforementioned studies had limited study populations, Moskovic et al. examined serum TT, E2, SHBG, FSH, LH and dehydroepiandrosterone (DHEA) in 11,000 men in the southwestern United States [26]. Given the previous finding by Crawford et al. [4] which suggested that diurnal variation diminished after age 60, men in the Moskovic study were divided into cohorts of less than 60 years of age and those greater than 60 years of age. This division was to control for potential physiologic differences in age-related hormonal regulation. Moskovic et al. [26] subsequently found statistically significant differences in E2, testosterone: estrogen ratio (T:E), FSH, and SHBG between seasons. The magnitude of these differences was only significant in the younger cohort of patients, although the younger cohort was also larger (N = 9669 versus 1954). Peak to trough variations were 16.5% for T: E ratio, with a peak in the spring and nadir in the fall. The difference between T:E ratio in the two cohorts was hypothesized to be due in part to increased physical activity in the younger cohort and evidence to suggest that the HPG axis is more sensitive in younger men [27]. Whereas no significant change in TT was observed, a 10% change was noted in FT between peak (summer) and trough (fall) values; however, this was not clinically significant.
Despite its sample size, the Moskovic study [26] still failed to show statistically significant differences in TT, LH, FT and DHEA in either cohort. This study was also limited in that samples were collected between 0900 and 1900 and was based on initial, single patient observations as opposed to longitudinal data [26]. Along with the prior Svartberg study in San Diego [7], this represented the second investigation in the southwestern United States which failed to show significant seasonal TT variation. This suggests that the prior Scandinavian studies were demonstrating a regional effect. Further research in dissimilar climates and populations is required to replicate the variability in these prior studies and substantiate their findings.
One such study by Brambilla et al. [20] was based in Boston, Massachusetts and therefore contrasts with the prior Moskovic study [26] in the potential regional effects of climate and epidemiology. The authors examined seasonal fluctuations in androgens, including serum TT, FT, BT, dihydrotestosterone (DHT), SHBG, LH, DHEA, dehydroepiandrosterone sulfate (DHEA-S), E2, and cortisol. One hundred and twenty-one men, aged 30–79, completed six morning blood draws at 0, 3, and 6 months [20]. Time of enrollment was random in order to capture data from all twelve months. Aside from cortisol, there was no evidence of seasonal variation in hormone levels [20]. Peak levels were within 4% of the mean level for all hormones examined. The authors found that intra-individual variation was greater for each hormone evaluated when compared with seasonal variation. Brambilla et al. [20] concluded, therefore, that seasonal effects are likely not an important source of significant variation clinically.
Whereas regional influences may account for some of the observed patterns of seasonal variation, age within the study population also has the potential to confound these results. For instance, Moskovic et al. [26] found more significant seasonal variation in T:E ratio in younger men whereas Svartberg [7] found neither TT nor BT varied by season and these results were independent of age. Similarly, Tancredi et al. [19], in a study of 5028 men aged 50 and over, showed that monthly variations in serum FT values did not show significant seasonal variation (<15%) [19]. Dai et al., in an epidemiologic study, demonstrated that age and obesity correlated with T levels in 243 men; however, while diurnal variation was noted, seasonal variation of T was not [17].
Based on the substantial heterogeneity within these studies, the evidence for seasonal variation of androgens can only be characterized as inconsistent at this time.
