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Low SHBG

Many men have learned that SHBG binds to a little over half of their testosterone molecules and renders them "inactive".  Because of this, as SHBG goes up, unbound testosterone goes down.  Many physicians like to focus on free testosterone, which is your T that is not bound to SHBG or another protein called albumin.  And the rule is simple:  as SHBG goes down, free testosterone goes up.  And free testosterone is considered the form of testosterone that is active and available to act on tissues.

NOTE:  It is actually a little more complicated than that as testosterone bound to albumin can be easily unbound and used as well.  But the point remains the same.

So clearly a man wants low SHBG, since it indicates that his free testosterone would be improved, right? 

Wrong!  As it turns out, low SHBG is often a sign of many of the worst chronic diseases that we face in modern, civlized societies.   

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1.  Obesity and Being Overweight.  Low SHBG is associated with obesity. [1] The reason is probably due to a loss of insulin sensitivity as we'll discuss below. 

2.  Lower Insulin Levels.  There is evidence that increasing insulin lowers SHBG. [2]  Studies have found this both in vitor and in vivo as well, i.e. on human subjects and male ones at that. [3] Therefore, SHBG is often a flag or warning signal of insulin and blood sugar issues. In other words, SHBG does not cause insulin resistance but does indicate it.

NOTE:  You may also want to read my link on The Causes of High SHBG.

3.  Cardiovascular Disease, Diabetes, Metabolic Syndrome and Decreased Longevity. Due to #1 and #2, mumerous studies have shown that low SHBG can actually indicate decreased longevity.  For example, one study found:

"Low SHBG and IGFBP-1 were both associated with an increased prevalence of abnormal glucose tolerance and the metabolic syndrome, but only SHBG was associated with diabetes mellitus. SHBG was less influenced by body mass index than IGFBP-1. Low SHBG indicated increased cardiovascular and coronary disease mortality; the association remained after adjustment for abnormal glucose tolerance, but not after adjustment for prevalent cardiovascular disease." [1]

 

This is about as ugly as it gets.  Low SHBG is correlated with three of the biggest killers of  men:  heart disease, diabetes and Metabolic Syndrome.  A more recent and larger scale study verified the above results but did find that all mortality risk was due to its association with diabetes, lowered HDL and weight gain. So SHBG does not seem causative, but rather often a sign that something else is wrong.  By the way, it was "ischemic heart disease" risk that was associated with lowered SHBG in this case, which basically means accelerated arteriosclerosis and decreased blood supply to the heart.

4. Apnea.  I document in my link on Apnea and Testosterone how apnea can affect your baseline testosterone levels by 30 percent or more. Other studies have shown that apnea significantly lowers SHBG as well. [7] So if you have low testosterone and low SHBG, this is something to consider.

5. Obesity.  Because weight gain can lead to loss of insulin sensitivity, low SHBG values are correlated to extra weight. 

6. Inflammation.  One study (in women) found that lowered SHBG was associated with elevated CRP (C-Reactive Protein), one of the "gold standard" markers of systemic inflammation that is linked to heart disease, dementia and autoimmune disorders. [8]

7. Hypothyroidism.  One study found that low SHBG was associated with hypothyroidism and could even be reversed by correcting the underlying thyroid issue. [9]

8. Elevated Triglycerides. Several studies have found that elevated triglycerides, which are a risk factor for both heart disease and erectile dysfunction, are also tied in with low SHBG. [10] Of course, this should be no shock since elevated triglycerides usually come from eating meals with an overly high glycemic load and refined carbohydrates.

NOTE:  HRT will lower SHBG some and steroid usage even moreso.

 

Low SHBG Solutions

So, as you can see, having low SHBG and the supposedly elevated free testosterone that accompanies it, is usually nothing to brag about. This means that, in general, if you have low SHBG, you should find the underlying cause and correct it.

This may not be as easy to do as you might think, because most doctors are very unlikely to do anything about a lowish value of SHBG, because the lab ranges are VERY wide.  On the Peak Testosterone Forum I have seen ranges such as 7-47 nmol/l, 10-50 nmol/l or even 10-80 nmol/l. In all cases the lower value for SHBG is extremely low and so will not even be on your doctor's radar. However, values below about 20 can be indications of underlying issues and should not be ignored in my opinion.

Hopefully, one way or another you can get your doctor to consider doing the following:

1. Monitor. Test you for any of the (appropriate) conditions above.  Many of these you can get as part of a standard physical or well-being check, so you may want to ask your physicain about that possibility.

2. Correct Medical Conditions. Correct any issues found in #1.  Work with your doctor and do what you have to do:  treat your thyroid dysfunction; exercise; lower the glycemic load of your diet;  lose those extra pounds; get a CPAP machine.

3. Natural Cure #1.  The root cause for low shbg is generally the beginnings of fatty liver and insulin resistance and, as mentioned above, low SHBG is good predictor of future diabetes.  One of our posters went after his low SHBG with a vengeance in this regard and exercised (heavily), took berberine and liver cleanses, lost weight and did other things to get rid of the fatty liver and insulin resistance.  He actually more than doubled his SHBG and is one of the very few men I know that have done so.  You can read his story here in my page on How to Cure Low SHBG.

4. Natural Cure #2 (For Men With High Estradiol)?  I had a report from a long time poster who was suffering with low SHBG and high estradiol levels.  This man actually took an AI (aromatase inhibitor which lowers estradiol) and found that his SHBG increased significantly, an outcome that is counterintuitive in my mind.  This is a little scary, because I think the original poster did estradiol conversions incorrectly and the man did not have high estradiol.  Thus an AI could drive his estradiol too low and possibly lead to bone loss if done long enough.

In any event, it seem to have cured this man's low SHBG.   The description and possible explanation is as follows: 

"A young male presented with chronically elevated E2 [estradiol] and low SHBG. Physicians prescribed testosterone, which only exacerbated the SHBG/E2 imbalance. His problems persisted for years. His entire youth, in fact. I suggested that he try an AI-only mode of treatment.

This worked to bring his E2 within normal range, and ... surprisingly, his SHBG increased to from the single digits and low teens to 30! SHBG has remained at 30, even though AI has been discontinued. He claims that he is "85% cured." His FT is now a bit low (FAI of 0.65) and I have suggested that with T supplementation, he might actually bring himself to a completely normal hormonal profile.

It seems like he was able to wake up dormant SHBG expression by simply starving E2. I have no other explanation for this case. I have never, in 10+ years of reading about these kinds of cases, seen a liver completely correct itself with regard to SHBG expression. Perhaps, like insulin receptors, receptors in the liver can become increasingly desensitized to estrogen? In these cases, a course of AI over a 3 month period can completely resensitize them... or so it seems." [17]

NOTE:  Be sure to measure your estradiol with the correct test (LC-MS/MS) for men. 

There are also many natural ways to raise SHBG as well.  I have a few ideas below.  Of course, it is most important to correct underlying medical conditions, but here are some other methods that can help which perhaps could be combined synergistically to really raise SHBG:

5. Coffee.  Several studies on women showed that coffee raised SHBG.  Finally, this was verified in a study on men as well. [12]

6. Green Tea. A couple of studies, admittedly on women, have shown that green tea increases SHBG levels. [13]

7. Lower Fat Diets and Fiber. One study on men showed that low fat diets increased SHBG, probably due to the fact that they increase insulin sensitivity. [14] So one simply way to likely raise your SHBG a little is to eat a low glycemic, low fat diet.  I discuss in my link on Low Fat Diets and Diabetes that this way of eating will likely reverse any prediabetes or diabetes that you have and lower arterial plaque at the same time.  A smiliar study echoed the same result and suggested that fiber may play a role as well. [15]

8. T3 and T4 (If Hypothyroid). One study found that "Thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) increase SHBG accumulation in HepG2 cell culture medium over 5 days, and increase cellular SHBG mRNA levels." [16] A hypothyroid man that goes on thyroid medication will often see his low SHBG rise.

NOTE:  If you actually have high SHBG and not low, see my link on the Causes of High SHBG and Natural Solutions.

 

What about HRT and Low SHBG?

The concerns here are that 1) adding HRT may lower an already low SHBG even further, 2) may sidetrack a man from dealing with underlying medical issues and 3) will simply create an overabundance of free estradiol.

Now I definitely agree with 2.  All reasonable underlying issues should be tracked and investigatedby by or with your doctor.  Argument 1, however, may be weak.  To test this hypothesis, it would be best to look for research with participants that are likely to have low SHBG.  One such study was done on senior men with Metabolic Syndrome (prediabetes) and the researchers found that giving these men testosterone gel did indeed lower their SHBG a little.  However, this was for a very small net change in testosterone. [12]

The same study boosted men's testosteorne much more significantly with testosterone undecanoate and actually found that the particpants' SHBG rose.  Thus in this case, the testosterone actually helped.  Why did the undecanoate do the trick where the gel did not?  The reason is probably the fact that the undecanoate gave over a 100% increase in testosterone and testeosterone lowers insulin.

As far as #3, one has to realize that the difference in, say, free testosterone from low to midrange SHBG is not that great.  For example, let's say you were a lowish testosteorne guy with total testosterone of 400 ng/dl and had SHBG of 32, which is a very "normal amount".  That SHBG of 32 nmol/l would give you a free testosterone level of 8.31 ng/dl.  A man with SHBG of 20 and total T of 400 would have free testosterone of 10.5.  

This is an increase of 26% in free T. Now this is a bump, admittedly, but it is not the kind of bump that is going to make that much difference. Thus SHBG does matter, but it is not the force of nature that many men think it is when it comes to elavating testosterone levels.  However, it does matter in the sense that it can foreshadown many medical conditions that need to be dealt with.

However, what I hear "on the streets" is that men who are low SHBG or just high converters to estrogen tend to do better with 3X weekly subQ injections.  I believe the reason for this is that with smaller doses of testosterone cypionate more often, you get a smoother ride with lower estradiol peaks.  The reason this is probably important is that if you are low SHBG, then you are going to be higher free estradiol. And, of course, elevated free estradiol causes many issues for us men.

 

REFERENCES:

1)   The Journal of Clinical Endocrinology & Metabolism, Mar 1 2005, 90(3):1550-1556, "Sex Hormone-Binding Globulin and Insulin-Like Growth Factor-Binding Protein-1 as Indicators of Metabolic Syndrome, Cardiovascular Risk, and Mortality in Elderly Men"

2) The Journal of Steroid Biochemistry and Molecular Biology, Jun 1995, 53(1-6): "Interrelations between sex hormone-binding globulin (SHBG), plasma lipoproteins and cardiovascular risk"

3) The Journal of Clinical Endocrinology & Metabolism, Jul 1 1996, 81(7):2515-2519, "Acute and chronic regulation of serum sex hormone-binding globulin levels by plasma insulin concentrations in male noninsulin-dependent diabetes mellitus patients"

4) Diabetes Care, May 2004, 27(5):1036-1041, "Testosterone and Sex Hormone–Binding Globulin Predict the Metabolic Syndrome and Diabetes in Middle-Aged Men"

5) Arch Intern Med. 2007; 167(12):1252-1260, "Sex Steroids and All-Cause and Cause-Specific Mortality in Men"

6) International Journal of Impotence Research, 2003, 15(Suppl 4):S14–S20, "Hypogonadism and diabetes"

7) J Clin Endocrinol Metab, 1989 Feb, 68(2):352-8, "Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy"

8) Ann Epidemiol, 2006 Feb, 16(2):105-12, Epub 2005 Oct 10, "Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease"

9) Horm Res, 1990,34:215–218, "Reproductive Endocrine Functions in Men with Primary Hypothyroidism: Effect of Thyroxine Replacement"

10) Am J Clin Nutr, l996, 63:22-3l, "Association of dietary factors and selected plasma variables with sex hormone-binding globulin in rural Chinese women"

11) Journal of Andrology, 29(1):102–105, January-February 2008"A Dose-Response Study of Testosterone on Sexual Dysfunction and Features of the Metabolic Syndrome Using Testosterone Gel and Parenteral Testosterone Undecanoate"

12) Eur J Endocrinol, Aug 1 2003, 149:145-152, "The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study"

13) Reproductive Sciences, Jan 2006, 13(1):63-68, "Effects of Chinese Green Tea on Weight, and Hormonal and Biochemical Profiles in Obese Patients With Polycystic Ovary Syndrome—A Randomized Placebo-Controlled Trial"

14) The Journal of Clinical Endocrinology & Metabolism, May 1 1987, 64(5):1083-1085, "DIETARY LIPIDS : AN ADDITIONAL REGULATOR OF PLASMA LEVELS OF SEX HORMONE BINDING GLOBULIN"

15) Am J Clin Nutr, Dec 1996 64(6):850-855, "Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study"

16) Journal of Molecular Endocrinology, 2009, 43, 19–27, "Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4a"

17) http://www.peaktestosterone.com/forum/index.php?topic=5794.0

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