Low SHBG

[GoinPlatinum]

I've asked this question a few times but never really get an answer.

My SHBG level was low last time I tested a few weeks ago 15.3 (16.5 - 55.9)

This was before I began my TRT. Should I worry about this # being low? Should I do something to try to raise it? I'm not really sure what SHBG is responsible for... Your help is appreciated.

 

[Frustrated1]

That's the perfect number. This means a lower total t level brings a higher free t level.

 

[Packgus]

agree its a great #. dont worry about it.

 

[Frustrated1]

More than you wanted to know

In a nutshell you have excellent metabolism.

This chart shows how the relationship works to free Testosterone. Notice the lower the SHBG the higher the Free Testosterone.
View attachment 542892

 

[THE-DET-OAK]

I've asked this question a few times but never really get an answer.

My SHBG level was low last time I tested a few weeks ago 15.3 (16.5 - 55.9)

This was before I began my TRT. Should I worry about this # being low? Should I do something to try to raise it? I'm not really sure what SHBG is responsible for... Your help is appreciated.

this was originally posted by Scally on MESO. Not to alarm anyone cause you would have to have a low low shbg for long periods to have this affect you.


Endogenous sex hormones are associated with the development of cardiovascular events and its risk factors. Sex hormone- binding globulin (SHBG), the binding globulin of sex hormones, can regulate the levels of free sex hormones and has been found to be biologically active recently. In other words, SHBG may exert biological functions through itself and regulation of the levels of free sex hormones. In human studies, serum SHBG was negatively correlated with obesity, dyslipidemia, metabolic syndrome (MetS), insulin resistance, and type 2 diabetes.

Recently, inflammation has been found to be an important mechanism for the development of cardiovascular diseases (CVD). Serum C-reactive protein (CRP), a marker for inflammation, can predict cardiovascular events in the future. Besides, various reports suggest that CRP also participates in the pathogenesis of CVD. There were many studies reporting the association between endogenous sex hormones and serum CRP concentrations. However, the findings were not consistent, which may result from different study populations, different menopause status, and different confounders used in the statistic models. Therefore, researchers conducted a cross- sectional study to investigate the association among serum sex hormones, SHBG, and CRP concentrations in men, pre-menopausal and post-menopausal women. In the statistic models, they included all potential confounders including gender difference, menopause status, insulin resistance, liver enzyme, lipid profiles, components of MetS, and sex hormones.

In summary, they found that serum SHBG was inversely correlated with serum CRP concentration, after comprehensive adjustment for age, MetS components, insulin resistance, LDL-C, and sex hormone levels in men, pre-menopausal women, and postmenopausal women.


Liao CH, Li HY, Yu HJ, et al. Low serum sex hormone-binding globulin: Marker of inflammation? Clin Chim Acta. Low serum sex hormone-binding globulin: Marker of inflammation? http://www.sciencedirect.com/science/article/pii/S0009898112000423

BACKGROUND: Low sex hormone-binding globulin (SHBG) is associated with metabolic syndrome (MetS), but its relationship with inflammation is unclear.

METHODS: This cross-sectional study included 696 subjects (255 men, 235 pre-menopausal women, and 206 postmenopausal women). Body mass index, waist circumference, blood pressure, lipid profiles, plasma glucose, insulin, FSH, LH, total testosterone (TT), estradiol, SHBG, dehydroepiandrosterone sulfate (DHEA-S), and hs-CRP concentrations were measured. MetS was defined according to the updated National Cholesterol Education Program criteria with modification of waist circumference for Asians.

RESULTS: Serum hs-CRP and SHBG were negatively correlated in men (r=-0.29, p<0.001), pre-menopausal women (r=-0.38, p<0.001), and postmenopausal women (r=-0.27, p<0.001). In men, TT and hs-CRP showed a negative association (r=-0.25, p<0.001), but the association was attenuated after adjusting for SHBG (r=-0.14, p=0.039). Multivariate regression models showed that SHBG was independently associated with hs-CRP in men (r=-0.18, p=0.009), pre-menopausal women (r=-0.15, p=0.025), and postmenopausal women (r=-0.21, p=0.005), adjusted for age, MetS components, insulin resistance, low-density lipoprotein-cholesterol, and serum sex hormone levels.

CONCLUSIONS: Serum SHBG and hs-CRP concentrations were inversely correlated in men, pre-menoposal, and post-menopausal women independently.

 

[THE-DET-OAK]

Molecular Mechanism of TNF Induced Down-Regulation of SHBG Expression

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein produced and secreted by the human liver. In blood, SHBG acts as a carrier of androgens and estrogens regulating their bioavailability. Body mass index is considered a major determinant of SHBG concentrations in the blood of both men and women. Obese individuals of all ages have low plasma SHBG levels, and high serum SHBG levels are found in children and women with anorexia nervosa.

Patients suffering from obesity, a low-grade chronic inflammatory disease, are characterized among other features by high plasma levels of TNF. In obese subjects TNF is mainly produced by macrophages that infiltrate the expanded adipose tissue, and its levels correlate to the degree of adiposity and insulin resistance. The actions of TNF in the liver mainly occur through TNF recptor 1 (TNF-R1), and they are mediated by nuclear factor-kB (NF-kB), c-Jun N-terminal kinase (JNK), and p38. JNK and p38 are Mitogen-Activated Protein Kinases (MAPK) that activate c-jun and activating transcription factors (ATF), respectively.

The molecular mechanisms of the SHBG regulation have been studied in the last decade, and the human SHBG promoter has been characterized. Apart from defining the footprint regions (FP) of the human SHBG promoter, several works have identified the transcription factors that bind to these regions. In this regard, it has been described that hepatocyte nuclear factor (HNF) 4 transcription factors can bind to FP1 and/or FP3, peroxisome proliferator activated receptor can bind to the FP3, and upstream stimulatory factor can bind to the FP4 region of the SHBG promoter. Moreover, in the last few years several works have described that affecting the HNF4 protein levels is another mechanism by which hepatic SHBG production can be regulated. Thyroid hormones and carbohydrate-induced de novo lipogenesis can regulate the SHBG production by increasing or decreasing hepatic HNF4 protein levels, respectively.

Given that an inverse relationship has been reported between TNF and SHBG plasma levels in several chronic inflammatory diseases, researchers have addressed the question of whether human SHBG expression in the liver is regulated by TNF and which mechanism(s) are involved. Because rodents do not express SHBG in their livers, they have addressed these studies using the human hepatoblastoma HepG2 cell line, which they have used previously to study human SHBG production and regulation by the liver.

In conclusion, their studies suggest that TNF plays a role in the down-regulation of SHBG production by decreasing hepatic production of HNF-4 through NF-kB activation. Further studies addressed to exploring whether measurements of plasma SHBG might represent a biomarker of chronic low-inflammatory states and could be used to monitor treatment to alleviate this clinical conditions are warranted.