@Nelson Vergel and
@Cataceous
Can you find evidence for both theories/explanations (shbg on TRT etc)?
The references were inbedded in the content:
NO TRT (normal physiology):
Sex hormone-binding globulin profoundly influences the distribution of testosterone between bound (inactive) and free (active) forms. Under normal physiological conditions,
SHBG helps determine an individual’s total testosterone requirement by binding a consistent fraction of the hormone – if SHBG levels rise, the body elevates total T production to maintain adequate free T, and if SHBG falls, the body curtails production to prevent free T excess
pure.amsterdamumc.nl In healthy men, this feedback mechanism leads to an inverse relationship between SHBG and endogenous T output, ensuring relative stability of free testosterone
pure.amsterdamumc.nl clindiabetesendo.biomedcentral.com.
First PDF Attached Summary:
Summary of "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"
Objective:
The study challenges the widely held belief that higher levels of sex hormone-binding globulin (SHBG) reduce the bioavailability of testosterone by lowering non-SHBG-bound testosterone (non-SHBG-T, i.e., free plus albumin-bound testosterone) in vivo. While in vitro models predict that increased SHBG should lower non-SHBG-T, the authors hypothesized that in living humans, especially those with an intact hypothalamo-pituitary-gonadal (HPG) axis, the relationship may be different due to feedback mechanisms affecting testosterone production and clearance.
Study Design and Participants:
Cross-sectional study of:
400 healthy adult men aged 40–80 years (divided into age decades)
106 male newborns (aged 1–6 months)
Both groups had measurements of SHBG, total testosterone, and calculated non-SHBG-T.
Key Methods:
Hormone levels measured using validated immunoassays.
Non-SHBG-T calculated using established formulas, assuming a fixed albumin concentration.
Linear regression and correlation analyses assessed relationships between SHBG, total testosterone, and non-SHBG-T, adjusting for age and BMI where appropriate.
Main Results:
In Newborns:
SHBG levels were much higher, and both total and non-SHBG-T were much lower than in adults.
SHBG was significantly
positively associated with total testosterone but
not associated with non-SHBG-T.
After adjusting for age, the association with non-SHBG-T remained statistically insignificant.
In Adult Men:
SHBG increased with age; both total and non-SHBG-T decreased with age.
SHBG was
strongly positively associated with total testosterone across all age groups.
SHBG was
not or only weakly positively associated with non-SHBG-T; any associations were minimal and sometimes statistically insignificant after adjustment for age and BMI.
The age-related increase in SHBG did
not account for the age-related decline in non-SHBG-T.
Interpretation and Discussion:
Contrary to mathematical models, higher SHBG in vivo does
not reduce non-SHBG-T in healthy males (newborns or adults); if anything, the association is slightly positive.
The HPG axis appears to compensate for changes in SHBG by adjusting testosterone production, maintaining non-SHBG-T within a narrow range.
The age-related decline in non-SHBG-T is
not due to increased SHBG but likely due to other age-related changes in the HPG axis, such as altered feedback sensitivity and reduced Leydig cell responsiveness.
In neonates, the lack of association between SHBG and non-SHBG-T suggests a highly sensitive and functional HPG axis during early life.
Limitations:
Cross-sectional design limits causal inference.
Potential health selection bias in older adult participants.
Hormone assays in neonates may be less accurate at low concentrations, but findings are consistent with other studies.
Conclusion:
In both male newborns and healthy adult men, SHBG levels do
not meaningfully reduce non-SHBG-bound testosterone levels.
The widespread assumption that higher SHBG lowers bioavailable testosterone in vivo is not supported in populations with an intact HPG axis.
Age-related increases in SHBG do
not explain the decline of non-SHBG-T with age in healthy men.
Implications:
Clinical assessment of androgen status in men should consider that SHBG variations may not significantly impact bioavailable testosterone, especially in those with a healthy HPG axis.
Further research is needed to clarify the mechanisms behind age-related changes in testosterone bioavailability and HPG axis function.
