Serum levels of sex hormone‐binding globulin (SHBG) are not associated with lower levels of non‐SHBG‐bound testosterone in male newborns and healthy adult men

Abstract

SummaryObjective It is generally accepted that SHBG decreases the bioavailability and activity of testosterone (T). In in vitro experiments increased levels of SHBG will be associated with decreased levels of non-SHBG bound testosterone (non-SHBG-T). However, in vivo SHBG can alter both production and clearance rates and thus plasma levels of T. Design and patients In order to study the effect of SHBG on the levels of non-SHBG-T in vivo in the presence of an active hypothalamo-pituitary-gonadal (HPG) axis we conducted a cross sectional study in 400 healthy adult men with an age range of 40 -80 years and in 106 newborn boys. Measurements In both groups, regression coefficients ( β ) and partial correlation coefficients (r) were calculated for the relationship between SHBG and T or non-SHBG-T. Adult men were divided into age groups per decade (40 -50 years, 51-60 years, 61-70 years and 71-80 years) to study possible differences in the impact of SHBG on the level of non-SHBG-T throughout ageing. Results Higher levels of SHBG were associated with higher levels of total testosterone in neonates ( β = 0·02 ± 0·004, r = 0·44, P < 0·001) but not with non-SHBG-T ( β = − 0·001 ± 0·001, r = 0·05, P = 0·52). In adult men there was a significant age related increase in levels of SHBG and an age-related decrease of both total and non-SHBG-T. Higher SHBG was strongly associated with higher total testosterone in all age groups ( β = 0·26, 0·26, 0·26 and 0·23 for 40 -50 years, 51-60 years, 61-70 years and 71-80 years, respectively, P < 0·001 for all age groups). Higher SHBG was not or only slightly associated with higher non-SHBG-T β = 0·02 ( P = 0·32), β = 0·04 ( P = 0·03), β = 0·04 ( P = 0·02) and β = 0·02 ( P = 0·16) for 40 -50 years, 51-60 years, 61-70 years and 71-80 years, respectively. Conclusions In contrast to general belief, SHBG levels barely influence levels of non-SHBG-bound testosterone both in male newborns and healthy adult men: the influence, if any, is positive. Consequently the age related increase of SHBG does not account for the age related decline in non-SHBG-T in healthy adult men.

Salivary Testosterone during the Minipuberty of Infancy

“…It is clear from our data, that free T levels in infants were well below the pubertal range (1.02-18.6 pg/ mL) when compared with adolescent boys (19.5-66 pg/ mL), which explains the absence of virilization in infants. Although we did not measure serum SHBG, previous reports have shown elevation of SHBG during the first postnatal months in infants [6,14], which supports the hypothesis that lower free T is a reason for the absence of virilization even in the presence of elevated serum total T. Taken together, based on our results and previous reports, it is clear that these infants are exposed to high circulating T levels for only a short period in contrast to pubertal boys, who have a prolonged and continued exposure to high levels of T and thus manifest some physical changes of puberty. It is also important to mention that even though free T levels are low in infants, they are higher than in prepubertal children [2], which could be the reason for the small increase in penile length and testicular size [15,16].…”

“…Assays in saliva provide us with a noninvasive way of monitoring steroid hormone levels, and are, therefore, a more direct indicator of biologically active hormone secretion. Earlier reports of unbound T values in early infancy that were calculated [2,6,8] or measured by RIA [9] are inconsistent. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has higher sensitivity and precision when measuring low levels of steroids.…”

“…The high serum total T in the early neonatal stage is reflected physically by a significant increase in testicular volume due to seminiferous tubule elongation and Sertoli cell proliferation [4], and by only a slight increase in penile length [5] without any evidence of virilization. Sex hormone-binding globulin (SHBG) levels are known to be elevated during this phase of development, and thus the circulating T is for the most part SHBG bound [6], which may explain the lack of virilization. One would, therefore, anticipate low levels of free T.…”

Calculation of Bioavailable and Free Testosterone in Men: A Comparison of 5 Published Algorithms

“…In aging men, total testosterone concentrations tend to decrease and SHBG concentrations increase (11 ); therefore, measurements of FT and bioT are advocated to support the diagnosis of hypogonadism, which has nonspecific signs and symptoms in elderly men (12,13 ).…”

Postnatal Testosterone Levels and Temperament in Early Infancy

“…At their peak between 1 and 3 months of age, plasma testosterone levels in male infants approach the adult male range before falling to typical low childhood values around 6 months of age (Andersson et al, 1998;Forest, Sizonenko, Cathiard, & Bertrand, 1974). Although the biologically active proportion of testosterone in male neonates is well below that observed in adult men (de Ronde et al, 2005), as in other primates (Dixson, Brown, & Nevison, 1998), the postnatal increase in testosterone levels is critical for the normal development of male genitalia and reproductive function (Main, Schmidt, & Skakkebaek, 2005). For example, in a large prospective study of penile growth in male infants from birth to three years of age, higher levels of total and free testosterone at 3 months of age were associated with greater penile growth across the three years of development (Boas et al, 2006).…”