Low SHBG ! Good or bad?

Found this article which says .. '' low SHBG is often a sign of many of the worst chronic diseases that we face in modern, civlized societies.

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.


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 SHBG 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.''


My SHBG is currently 6.95 nmol/L (14.5-48.4) nmol/L , my endocrinologist checked my thyroid,said it`s all good , I have never been overweight,tiglycerides last time checked were 0.6mmol/L (0.00-2.30mmol/L) ,haven't check the other ones : diabetes ,etc..

What are your toughts on this one please? Any help appreciated.

SHBG is one of those hormones that finds its own level and is hard to adjust.

Low SHBG has many unwanted side effects unfortunately.

Any tips for increasing SHBG ? Since I've started TRT it decreased more,should I stop the therapy ? Thanks Gene.

What about the so called theory of '' less SHBG , more Free T available '' ?

The fact of the matter is, eating animal protein, increases a hormone in your body called insulin-like-growth-factor-1 (IGF-1), which is the most powerful growth hormone in the body!(The effects of dietary protein on serum IGF-1 levels in adult huma
Kevin Donnelly, Tianna Beare, Joan Clapper and Bonny Specker http://www.fasebj.org/cgi/content/meeti ... acts/883.8)

The way to increase S.H.B.G. is through diet and exercise.

Q. "What causes low S.H.B.G.?"

A. "High levels of IGF-1"

Q. "What causes high levels of IGF-1?"

A. "Protein"

Interesting, it is true that I am eating a lot of animal protein ,so would be wise to cut a bit ...thank you Vince!

Okian, I also eat a lot of protein and I have no plans to cut back.

Cool , so from what I've read on different sources , the ideal way for low SHBG issue,would be a protocol of frequent injections ,EOD (every other day) ?? because men who are low SHBG are high converters to estrogen ?, therefore smaller doses more often to get a smoother ride with lower estradiol peaks . Anyone else facing this problem ?

Okian said:

Any tips for increasing SHBG ? Since I've started TRT it decreased more,should I stop the therapy ? Thanks Gene.

Click to expand...

Exogenous testosterone can lower SHBG. If you have mid to low levels it's best to do two or even three smaller dosed injections per week as one larger injection really can suppress levels.

I tested at 16 a few months ago on a once a week schedule, ive bern considering the EOD sched from the 3.5D im on now.

Avoid vitamin D. Vitamin D raises free T, higher free T lowers SHBG.

Gene Devine said:

Exogenous testosterone can lower SHBG. If you have mid to low levels it's best to do two or even three smaller dosed injections per week as one larger injection really can suppress levels.

Click to expand...

Done blood work 3 days ago : Total Testosterone : 15.98 nmol/L (9.9 - 27.8) nmol/L

Free Testosterone : 0.068 nmol/L (0.015 - 0.145) nmol/L

SHBG : 6.95 nmol/L (14.5 - 48.4) nmol/L

Estradiol : 120.2 pmol/L (28 -156) pmol/L

My goal for Total T is to be on the range of 17.4 - 24.3 nmol/L (9.9 - 27.8) nmol/L or 500 - 700 ng/dL ( 300 - 1000 ) ng/dL as Dr. Michael Scally recommends in the interview with Nelson Vergel, and to discuss with my doctor about a HPTA restart or eventually move from gels to an injection protocol (x2 ,x3 times/week) + HCG + A.I (aromatase inhibitor) for estrogen if needed! But this is another subject for a different thread,sorry!

The strange thing is that my doctor told me to test only Total T , SHBG and FSH (wasted money on this one from what I've read,because once you introduce exogenous Testosterone FSH goes down no matter what? correct me if I am wrong please ) , and because of this amazing info on this forum I've decided that I need to test Free T and Estradiol as well . Let's see tomorrow at the appointment what he decides.

Bass said:

Avoid vitamin D. Vitamin D raises free T, higher free T lowers SHBG.

Click to expand...

Thanks Bass , @ 4 months ago I've done a test for Serum Vitamin D : 59 nmol/L ( 50 - 140 ) nmol/L , and after the result I have bought a bottle of 1000iu ,finish that ,after bought another one 5000iu , finish this one as well ,and the third one was 2000 iu .. I think it's time to stop now.. in this case!

Another interesting article .. which says that by eating a lot of meat and dairy , SHBG goes down . It is shown in the study that a high protein diet decreases SHBG and Total T while increasing Free T . While a high carbohydrate diet increases SHBG . http://www.thinkmuscle.com/articles/incledon/diet-01.htm

That makes sense,because that's exactly what I've done in the last few years , I've followed a high protein + low carbohydrates diet.. so maybe it's time to change something in the diet and let's see if SHBG goes up!

I'm a big believer in vitamin D3, so I thought I would add this

vitamin D deficient subjects. Both animal and human studies have found that vitamin D directly affects muscle. That is, vitamin D increases muscle mass. For example, Birge and Haddad found that vitamin D caused new protein synthesis in rat muscle.Birge SJ, Haddad JG. 25-hydroxycholecalciferol stimulation of muscle metabolism. J Clin Invest. 1975 Nov;56(5):1100-7. What about humans? In 1981, Young performed muscle biopsies on 12 severely vitamin D deficient patients before and after vitamin D treatment. They found type-II (fast-twitch) muscle fibers were small before treatment and significantly enlarged after treatment. Sorensen performed muscle biopsies on eleven older patients with osteoporosis before and after treatment with vitamin D. The percentage and area of fast twitch fibers increased significantly after treatment, despite the lack of any physical training. Young A, Edwards R, Jones D, Brenton D. Quadriceps muscle strength and fibre size during treatment of osteomalacia. In: Stokes IAF (ed) Mechanical factors and the skeleton. 1981. pp 137-145. Sorensen OH, Lund B, Saltin B, Lund B, Andersen RB, Hjorth L, Melsen F, Mosekilde L. Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Lond). 1979 Feb;56(2):157-61. Sato reported that two years of treatment with 1,000 IU of vitamin D per day significantly increased muscle strength, doubled the mean diameter, and tripled the percentage of fast-twitch muscle fibers, in the functional limbs of 48 severely vitamin D deficient elderly stroke patients. The placebo control group suffered declines in muscle strength, and in the size and percentage of fast-twitch muscle fibers. Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial. Cerebrovasc Dis. 2005 Jul 27;20(3):187-192 [Epub ahead of print] These studies clearly show that vitamin D when administered to vitamin D deficient people stimulates the growth and number of those muscle fibers critical to athletic ability, type-2, or "fast twitch," muscle fibers. 4. Many studies have found direct associations between physical performance and vitamin D levels. That is, the higher your vitamin D level, the better your athletic performance.

That's fine if you have no problem with shbg, but if you do then D would do more harm than good.

Low SHBG - by Dr. Mariano , Physician, Psychiatrist


'' Testosterone, itself, will drive SHBG down.

Estrogen will increase SHBG.

Thus controlling estradiol will lower SHBG.

Insulin also will drive SHBG down. Insulin has the strongest effect on SHBG, compared to any other factor.

Low SHBG is a good sign that a person has insulin resistance or diabetes - with lowers testosterone production.

Insulin resistance or diabetes greatly increases the risk for cardiovascular disease.

Realize that SHBG is determined by multiple hormones: Estrogen, Progesterone, Thyroid hormone, Testosterone, DHEA, Growth Hormone, Insulin, etc.

Thus, whatever SHBG one has - outside of a low level, for which problems with insulin need to be assess, does not tell if something is wrong since the effects of these hormones may cancel each other out.

Thus, a specific SHBG, outside of diabetes, does not tell much about what is happening with a person.

I generally do not like driving SHBG too low since testosterone and estrogen won't last long in the body.

The lower the SHBG, the more likely testosterone level is going to be low since free testosterone has a half-life of only 10 to 100 minutes.

Without SHBG, nearly all testosterone (unless it is continuously produced) would be gone from the body in less than about 50 minutes to 8 hours, being destroyed by degradative enzymes, such as by those in the liver.

SHBG makes testosterone last longer.

The higher the SHBG, the lower the dose of testosterone is needed in treatment.

Insulin, by reducing SHBG, contributes to hypogonadism in diabetes.

The lower the SHBG, the more frequent testosterone dosing needs to be done to maintain a given testosterone level.

The lower the SHBG, the more rollercoaster a person's experience with testosterone.

Let's look at what influences SHBG:

Increases SHBG:

Estrogens (particularly Estradiol)
Progesterone (by increasing Estrogen receptors)
Thyroid Hormone (particularly Hyperthyroidism)
Liver Disease
Anorexia, Starvation
Hypoglycemia (low insulin)

Reduces SHBG:

Insulin (and insulin resistance)
Testosterone
Growth Hormone
DHEA
Other Androgens
Obesity
Hypothyroidism
Excessive Cortisol (Cushing's Syndrome or Disease)
Progestins (such as by blocking progesterone's effects)
Excessively high SHBG may indicate factors increasing SHBG may be in excess in thus should be addressed. For example, an excess of Estrogen to testosterone may result in high SHBG.

Since SHBG is determined by several hormones, it is not generally a good component to address directly.

Rather the influences affecting SHBG should be addressed independently of SHBG.

Testosterone replacement alone will drive down SHBG.

Low SHBG, high free testosterone but LOW total testosterone is common in diabetes.

From my point of view, overly focusing on SHBG when trying to improve libido once total testosterone is raised to at least 650 ng/dL is a fairly narrow point of view.

Free Testosterone is only a fraction of Testosterone signaling.

Free Testosterone too often does not determine libido.

One can use Bioavailable Testosterone as a measure of testosterone's signaling strength.

I, myself, consider total testosterone more important.

Testosterone which isn't free - but is bound to SHBG - also has signaling function on SHBG receptors.

To take this function into account, I use total testosterone as a clearer measure of testosterone signaling.

If one focuses on the factors that determine SHBG and focus on optimizing them or treating the disease condition involved, then one hardly needs to measure SHBG at all.

High or low, SHBG indicates something is wrong but does not tell you what is wrong. Thus, alone, it is not a useful measure.

SHBG within the reference range also doesn't tell if something is wrong. Factors that influence SHBG can cancel each other out, thus SHBG will be in the reference range.

Thus, one still has to optimize each factor that influences SHBG separately.

As a result of these considerations, SHBG is a minor player. I would look at the other issues that influence SHBG instead in their own right as more important considerations. ''

'' Low SHBG strongly predicts risk for Type 2 diabetesBy Helen Albert
06 August 2009

N Engl J Med 2009; Advance online publication
MedWire News:

Low levels of circulating sex hormone-binding globulin (SHBG) are strongly predictive for Type 2 diabetes in women and men, report researchers in the New England Journal of Medicine.
“Circulating SHBG levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing Type 2 diabetes is uncertain,” say Simin Liu (University of California Los Angeles, USA) and colleagues.
The investigators carried out a nested case-control study of postmenopausal women in the Women’s Health Study who were not using hormone therapy at baseline. They included 359 individuals who developed Type 2 diabetes over a 10-year follow-up period and 359 controls from the same study who did not.
A replica study of an independent cohort of men from the Physicians Health Study II was also carried out, from which 170 men who developed Type 2 diabetes over 8-years of follow-up were included as well as 170 controls who did not.
The Women’s Health Study group was divided according to baseline levels of SHBG into quartiles, which ranged from a median of 17.1 to 55.8 nmol/l from the lowest to the highest quartiles, respectively. The Physicians Health Study II of men cohort was stratified in a similar fashion.
Liu et al found that higher levels of SHBG were strongly associated with a lower risk for Type 2 diabetes, as well as lower body mass index (BMI), lower risk for hypertension, a better lipid profile, and more favorable levels of C-reactive protein.
Compared with the lowest quartile of SHBG, women and men in the highest quartiles of circulating SHBG had a 91% and 90% reduced risk for Type 2 diabetes, respectively.
Of note, the team found that carriers of the risk allele of the SHBG gene (SHBG) variant rs6259 had 10% higher SHBG levels than non carriers, whereas carriers of the minor allele of the SHBG variant rs6257 had 10% lower plasma levels of SHBG than non carriers.
In agreement with the other findings, the rs6259 allele was associated with a lower risk and the rs6257 allele with a higher risk for Type 2 diabetes.
“These strong and consistent findings, obtained with the use of multiple analytic approaches and subgroup analyses in two independent cohorts, support the notion that SHBG may play an important role in the development of Type 2 diabetes at both the genomic and phenotypic levels,” conclude the authors.
“SHBG could be an important target in stratification for the risk of Type 2 diabetes and early intervention.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

http://www.medwirenews.com/57/83834...rongly_predicts_risk_for_Type_2_diabetes.html

I have low SHBG (I range from 7 to 13, with the normal scale usually being between 20-70) and I have been on TRT for 4 years. It has been very disappointing, as I never really feel the benefits of TRT. I do have a bit more energy but I still have low libido, ED, I am unable to gain muscle, etc...Also it should be noted that I am not a lot overweight, (I could stand to loose 10 pounds), diabetic or pre-diabetic and I have tried every protocol out there, with the exception of pellet injections and Nebido, which I believe is only available in Europe. Daily injections, twice weekly injections, weekly injections, with HCG, without HCG, with Anastrozol, without - it all feels the same, which mostly feels the same as having low T overall. Oh, and my E2 is in range as is my Prolactin. I am in good heath overall and not on any BP meds, have never smoked and I workout 5-6 days a week, every week.