madman
Super Moderator
We have been preaching on the forum for years that natty men need to have their testosterone levels tested in the early am (peak) in a fasted state otherwise your results will be skewed even when using the most accurate assays for TT (LC/MS-MS) and FT (Equilibrium Dialysis/Equilibrium Ultrafiltration).
Many frequenting the forum are still unaware of this.
We have also stressed that there is no need to test your TT/FT in a fasted state when on testosterone replacement therapy.
Hopefully this study gives reassurance to those still unaware!
Abstract
Oral calorie intake causes an acute and transient decline in serum testosterone concentrations. It is not known whether this decline occurs in men on testosterone therapy. In this study, we evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy. This is a secondary analysis of samples previously collected from a study of hypogonadal men with type 2 diabetes who received testosterone therapy. Study participants (n=14) ingested 75 grams of oral glucose and blood samples were collected over two hours. The test was repeated after 23 weeks of intramuscular testosterone therapy. The mean age and BMI of study volunteers were 53±8 years and 38±7 kg/m2 respectively. Following glucose intake, testosterone concentrations fell significantly prior to testosterone therapy (week 0, P=0.04). The nadir of testosterone concentration was at one hour, followed by recovery to baseline by two hours. In contrast, there was no change in testosterone concentrations at week 23. The change in serum testosterone concentrations at 60 minutes was significantly more at week 0 than week 23 (-11±10% versus 0±16%, P=0.05). We conclude that oral glucose intake has no impact on testosterone concentrations in men on testosterone therapy. Endocrinology societies should consider clarifying in their recommendations that fasting testosterone concentrations are required for diagnosis of hypogonadism, but not for monitoring testosterone therapy.
Oral calorie intake causes an acute and transient decline in serum testosterone concentrations (1). This fall in testosterone is usually evident within 20 minutes of the food intake, plateaus in 60 minutes and recovers by 4 hours (1). This phenomenon has been observed after any type of macronutrient intake (glucose, fat, protein) (1-3). In contrast, testosterone concentrations do not change acutely after ingestion of water, in the absence of food intake. Sex hormone binding globulin (SHBG) concentrations do not change in the short term after meal intake (2, 4). Therefore, free and bioavailable testosterone concentrations also decline. The mechanism of this decline in testosterone following a meal is not known. Two possibilities are 1) reduction in synthesis or secretion of testosterone, and 2) increased metabolism/clearance/tissue uptake of testosterone. If the former is true, then the decline in testosterone concentrations would not be observed in hypogonadal men on exogenous testosterone replacement. If the latter is true, then the decline would be observed regardless of whether the serum testosterone is produced endogenously or derived from an exogenous source.
Endocrine Society guidelines recommend that testosterone measurements in men should be performed in a fasting state (5). It is not known whether this recommendation applies to men on testosterone therapy as well. We evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy.
Discussion
Our study clearly show that oral glucose intake has no impact on testosterone concentrations in men on testosterone therapy. Therefore, it is not necessary to obtain a fasting blood sample to monitor testosterone concentrations in men on testosterone therapy.
It has been well documented that serum testosterone concentrations fall acutely and transiently after calorie intake (1-4, 8). While the mechanism is not known, the decline could be due to either decreased secretion or increased clearance of testosterone from the blood postprandially. Our data provide conclusive evidence against the latter. If the post prandial decline in testosterone was related to increased clearance or metabolism, there should be a fall in serum testosterone regardless of whether testosterone was produced endogenously or supplied exogenously. In the presence of adequate testosterone therapy, endogenous testosterone secretion is minimal to none. Since there was no change in testosterone concentrations after oral glucose intake in men taking testosterone therapy in our study, it seems that the cause of post-prandial decline in testosterone is decreased synthesis or secretion of testosterone.
As previously mentioned, SHBG does not change acutely after meal intake (2, 4, 9). Estradiol also does not change (10). If the decline in testosterone following a meal was related to a decrease in SHBG or enhanced conversion to estradiol, it would have a similar impact regardless of whether the testosterone was endogenous or provided from an external source. Thus, our study provides corroborative evidence against these mechanisms.
Ours is also the first study to have evaluated the change in testosterone in untreated hypogonadal men. Previous studies have studied the meal induced decline in testosterone in healthy men. Some studies have included men with comorbidities which are associated with a high prevalence of hypogonadism, such as diabetes or lung disease (11, 12). However, no study had previously investigated a group of hypogonadal men. We found that testosterone concentrations declined by 11% after oral glucose ingestion in hypogonadal men. This is somewhat less than the decline previously reported in eugonadal men (11-34%) following glucose intake (1, 9). This may be because of a lower baseline testosterone in hypogonadal men, and/or limited ability of their gonadal axis to be modulated by physiologic challenges.159 Interestingly, we found that higher BMI was associated with a lesser postprandial decline in testosterone concentrations. It is well known that obesity has a suppressive effect on the gonadal axis (13). It also appears that obesity impacts the response of gonadal axis to meal intake. Our data are partly consistent with a prior study which showed that elderly and obese men had a smaller decline in testosterone after mixed meal consumption as compared to younger and lean men (8).
It is not clear how meal intake reduces secretion of testosterone, and whether the effect is centrally mediated or by a direct effect on testicular production. Prior studies have not shown a consistent effect on gonadotropins. In one study, LH pulses were little lower, but mean LH was not affected (14). Other studies have found an increase (12), decrease (15) or no change in LH concentrations in the post prandial setting (1, 2, 4, 9, 10, 16). Prolactin either decreases or does not change after macronutrient intake (1). A small rise in cortisol concentrations has occasionally been observed after meal intake (17). In one study, testosterone declined but cortisol did not change after glucose ingestion (9). No relation has been noticed between the post prandial decline in testosterone and changes in glucose, insulin, leptin, or adiponectin (8, 9, 14, 16).
We and others have shown that macronutrient intake leads to post prandial inflammation and oxidative stress (18-22). Inflammatory mediators, such as Interleukin-1 and tumor necrosis factor-α have a suppressive effect on the gonadal axis (23). However, the decline in testosterone postprandially seems to occur earlier than the induction of inflammation. In one study, the decline in testosterone preceded the rise in interleukin-6 and 17 by over an hour (10). Many meal studies also show that inflammation and oxidative stress are mostly seen after two hours of meal ingestion. Furthermore, meal induced inflammation varies according to the type of macronutrient (24). In contrast, the decline in testosterone is largely similar, regardless of the type of macronutrient ingested (1). Thus, it is not likely that inflammation is the driver of post-prandial decline in testosterone.
It has been observed that intravenous glucose or lipid infusion does not lower testosterone (10, 25). The effect is only after oral macronutrient intake. It is possible that the release of incretins following oral food intake may have a role in mediating the postprandial decline in testosterone. While only a handful of studies have investigated this possibility, the results do not seem supportive. In one study, glucagon like peptide (GLP)-1 rise after meal did not correlate with the decline in testosterone (15). Infusion of GLP-1 was found to decrease the number of testosterone pulses and increase the duration of pulses, but it did not change the testosterone concentrations (16). Treatment with GLP-1 agonists also does not lower testosterone (26, 27). It is possible that postprandial decline in testosterone is autonomic/neural mediated. It is not known if this phenomenon is observed in men with altered gut anatomy, such as gastric bypass surgery.
*In conclusion, our data show that oral glucose ingestion does not lower testosterone concentrations in men on testosterone therapy. Hypogonadism is common in men, and testosterone therapy is prescribed on a regular basis by endocrinologists, urologists, and primary care providers. Endocrinology societies should consider clarifying in their recommendations that fasting testosterone concentrations are required for diagnosis of hypogonadism, but not for monitoring testosterone therapy.
Many frequenting the forum are still unaware of this.
We have also stressed that there is no need to test your TT/FT in a fasted state when on testosterone replacement therapy.
Hopefully this study gives reassurance to those still unaware!
Abstract
Oral calorie intake causes an acute and transient decline in serum testosterone concentrations. It is not known whether this decline occurs in men on testosterone therapy. In this study, we evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy. This is a secondary analysis of samples previously collected from a study of hypogonadal men with type 2 diabetes who received testosterone therapy. Study participants (n=14) ingested 75 grams of oral glucose and blood samples were collected over two hours. The test was repeated after 23 weeks of intramuscular testosterone therapy. The mean age and BMI of study volunteers were 53±8 years and 38±7 kg/m2 respectively. Following glucose intake, testosterone concentrations fell significantly prior to testosterone therapy (week 0, P=0.04). The nadir of testosterone concentration was at one hour, followed by recovery to baseline by two hours. In contrast, there was no change in testosterone concentrations at week 23. The change in serum testosterone concentrations at 60 minutes was significantly more at week 0 than week 23 (-11±10% versus 0±16%, P=0.05). We conclude that oral glucose intake has no impact on testosterone concentrations in men on testosterone therapy. Endocrinology societies should consider clarifying in their recommendations that fasting testosterone concentrations are required for diagnosis of hypogonadism, but not for monitoring testosterone therapy.
Oral calorie intake causes an acute and transient decline in serum testosterone concentrations (1). This fall in testosterone is usually evident within 20 minutes of the food intake, plateaus in 60 minutes and recovers by 4 hours (1). This phenomenon has been observed after any type of macronutrient intake (glucose, fat, protein) (1-3). In contrast, testosterone concentrations do not change acutely after ingestion of water, in the absence of food intake. Sex hormone binding globulin (SHBG) concentrations do not change in the short term after meal intake (2, 4). Therefore, free and bioavailable testosterone concentrations also decline. The mechanism of this decline in testosterone following a meal is not known. Two possibilities are 1) reduction in synthesis or secretion of testosterone, and 2) increased metabolism/clearance/tissue uptake of testosterone. If the former is true, then the decline in testosterone concentrations would not be observed in hypogonadal men on exogenous testosterone replacement. If the latter is true, then the decline would be observed regardless of whether the serum testosterone is produced endogenously or derived from an exogenous source.
Endocrine Society guidelines recommend that testosterone measurements in men should be performed in a fasting state (5). It is not known whether this recommendation applies to men on testosterone therapy as well. We evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy.
Discussion
Our study clearly show that oral glucose intake has no impact on testosterone concentrations in men on testosterone therapy. Therefore, it is not necessary to obtain a fasting blood sample to monitor testosterone concentrations in men on testosterone therapy.
It has been well documented that serum testosterone concentrations fall acutely and transiently after calorie intake (1-4, 8). While the mechanism is not known, the decline could be due to either decreased secretion or increased clearance of testosterone from the blood postprandially. Our data provide conclusive evidence against the latter. If the post prandial decline in testosterone was related to increased clearance or metabolism, there should be a fall in serum testosterone regardless of whether testosterone was produced endogenously or supplied exogenously. In the presence of adequate testosterone therapy, endogenous testosterone secretion is minimal to none. Since there was no change in testosterone concentrations after oral glucose intake in men taking testosterone therapy in our study, it seems that the cause of post-prandial decline in testosterone is decreased synthesis or secretion of testosterone.
As previously mentioned, SHBG does not change acutely after meal intake (2, 4, 9). Estradiol also does not change (10). If the decline in testosterone following a meal was related to a decrease in SHBG or enhanced conversion to estradiol, it would have a similar impact regardless of whether the testosterone was endogenous or provided from an external source. Thus, our study provides corroborative evidence against these mechanisms.
Ours is also the first study to have evaluated the change in testosterone in untreated hypogonadal men. Previous studies have studied the meal induced decline in testosterone in healthy men. Some studies have included men with comorbidities which are associated with a high prevalence of hypogonadism, such as diabetes or lung disease (11, 12). However, no study had previously investigated a group of hypogonadal men. We found that testosterone concentrations declined by 11% after oral glucose ingestion in hypogonadal men. This is somewhat less than the decline previously reported in eugonadal men (11-34%) following glucose intake (1, 9). This may be because of a lower baseline testosterone in hypogonadal men, and/or limited ability of their gonadal axis to be modulated by physiologic challenges.159 Interestingly, we found that higher BMI was associated with a lesser postprandial decline in testosterone concentrations. It is well known that obesity has a suppressive effect on the gonadal axis (13). It also appears that obesity impacts the response of gonadal axis to meal intake. Our data are partly consistent with a prior study which showed that elderly and obese men had a smaller decline in testosterone after mixed meal consumption as compared to younger and lean men (8).
It is not clear how meal intake reduces secretion of testosterone, and whether the effect is centrally mediated or by a direct effect on testicular production. Prior studies have not shown a consistent effect on gonadotropins. In one study, LH pulses were little lower, but mean LH was not affected (14). Other studies have found an increase (12), decrease (15) or no change in LH concentrations in the post prandial setting (1, 2, 4, 9, 10, 16). Prolactin either decreases or does not change after macronutrient intake (1). A small rise in cortisol concentrations has occasionally been observed after meal intake (17). In one study, testosterone declined but cortisol did not change after glucose ingestion (9). No relation has been noticed between the post prandial decline in testosterone and changes in glucose, insulin, leptin, or adiponectin (8, 9, 14, 16).
We and others have shown that macronutrient intake leads to post prandial inflammation and oxidative stress (18-22). Inflammatory mediators, such as Interleukin-1 and tumor necrosis factor-α have a suppressive effect on the gonadal axis (23). However, the decline in testosterone postprandially seems to occur earlier than the induction of inflammation. In one study, the decline in testosterone preceded the rise in interleukin-6 and 17 by over an hour (10). Many meal studies also show that inflammation and oxidative stress are mostly seen after two hours of meal ingestion. Furthermore, meal induced inflammation varies according to the type of macronutrient (24). In contrast, the decline in testosterone is largely similar, regardless of the type of macronutrient ingested (1). Thus, it is not likely that inflammation is the driver of post-prandial decline in testosterone.
It has been observed that intravenous glucose or lipid infusion does not lower testosterone (10, 25). The effect is only after oral macronutrient intake. It is possible that the release of incretins following oral food intake may have a role in mediating the postprandial decline in testosterone. While only a handful of studies have investigated this possibility, the results do not seem supportive. In one study, glucagon like peptide (GLP)-1 rise after meal did not correlate with the decline in testosterone (15). Infusion of GLP-1 was found to decrease the number of testosterone pulses and increase the duration of pulses, but it did not change the testosterone concentrations (16). Treatment with GLP-1 agonists also does not lower testosterone (26, 27). It is possible that postprandial decline in testosterone is autonomic/neural mediated. It is not known if this phenomenon is observed in men with altered gut anatomy, such as gastric bypass surgery.
*In conclusion, our data show that oral glucose ingestion does not lower testosterone concentrations in men on testosterone therapy. Hypogonadism is common in men, and testosterone therapy is prescribed on a regular basis by endocrinologists, urologists, and primary care providers. Endocrinology societies should consider clarifying in their recommendations that fasting testosterone concentrations are required for diagnosis of hypogonadism, but not for monitoring testosterone therapy.
