Oral glucose load and mixed meal feeding lowers testosterone levels in healthy eugonadal men

Thiago Gagliano-Jucá, Zhuoying Li, Karol M. Pencina, Yusnie M. Beleva, Olga D. Carlson, Josephine M. Egan, Shehzad Basaria

Precise evaluation of serum testosterone levels is important in making an accurate diagnosis of androgen deficiency. Recent practice guidelines on male androgen deficiency recommend that testosterone be measured in the morning while fasting. Although there is ample evidence regarding morning measurement of testosterone, studies that evaluated the effect of glucose load or meals were limited by inclusion of hypogonadal or diabetic men, and measurement of testosterone was not performed using mass spectrometry. Sixty men (23-97 years) without pre-diabetes or diabetes who had normal total testosterone (TT) levels underwent either an oral glucose tolerance test (OGTT) or a mixed meal tolerance test (MMTT) after an overnight fast. Serum samples were collected before and at regular intervals for 2 h (OGTT cohort) or 3 h (MMTT cohort). TT was measured by LC-MS/MS. LH and prolactin were also measured. TT decreased after a glucose load (mean drop at nadir = 100 ng/dL) and after a mixed meal (drop at nadir = 123 ng/dL). Approximately 11% of men undergoing OGTT and 56% undergoing MMTT experienced a transient decrease in TT below 300 ng/dL, the lower normal limit. Testosterone started declining 20 min into the tests, with average maximum decline at 60 min. Most men still had TT lower than baseline at 120 min. This effect was independent of changes in LH or prolactin. A glucose load or a mixed meal transiently, but significantly, lowers TT levels in healthy, non-diabetic eugonadal men. These findings support the recommendations that measurement of serum testosterone to diagnose androgen deficiency should be performed while fasting.