What is Sex Hormone Binding Globulin?
Sex Hormone Binding Globulin (SHBG) is a protein that binds to and transports sex hormones, like testosterone and estrogen, through the bloodstream. It safeguards these hormones so that they are not eliminated by the body too quickly.
When SHBG is bound to testosterone or estrogen, these hormones cannot exert their effects on the body. In this state, they are not active or not bioavailable. When not bound to SHBG or other protein carriers, these sex hormones are active or bioavailable. In this state, they can exert their effects on the body. Other proteins, like albumin, also help transport testosterone through the bloodstream and act in the same way.
Why is sex hormone binding globulin important? In the case of testosterone, SHBG levels determine free testosterone levels. Most testosterone is bound (not active) in the bloodstream. Normally, 45% of testosterone is bound to SHBG and 53% is bound to albumin.1 The remaining 2% of testosterone exists in a free (unbound) active state. Therefore, only a very small amount of testosterone is biologically active at any given time.
(Advanced Note: Historically only the free T was thought to be the bioavailable component. However, testosterone that is bound to albumin dissociates easily. As a result, it is readily available for tissue uptake. Therefore, all non-SHBG bound testosterone is considered bioavailable. Based on this definition, approximately 55% is bioavailable at any given time.)
Relationship Between SHBG and Free Testosterone
The amount of testosterone that is free depends on the level of sex hormone binding globulin. With all else being equal, higher levels result in lower free T levels. Conversely, lower levels result in higher free T levels. This relationship is important because free, unbound testosterone is the active form of testosterone. As a result, men with normal total testosterone levels but high SHBG levels may experience symptoms of low testosterone.
Normal Sex Hormone Binding Globulin Levels
Normal sex hormone binding globulin levels in adult men fall between 20 to 60 nmol/L. A value below 20 nmol/L is considered low. A value above 60 nmol/L is considered high.2
Normal SHBG Levels in Adult Men (nmol/L) |
Description |
| <20 | Low |
| 20-60 | Normal |
| >60 | High |
As mentioned above, high sex hormone binding globulin levels are not ideal. Too much SHBG will reduce the amount of free, unbound testosterone. In this state, most testosterone will be unavailable for healthy tissues. If this is the case, a man may have normal total testosterone levels but less than normal free T levels.3
Low sex hormone binding globulin levels are also not ideal. In men, low total testosterone and low SHBG are associated with higher rates of obesity and diabetes (insulin resistance).4-6 Insulin plays an important role in the management of SHBG levels, and insulin resistance lowers these levels.7-8
Sex Hormone Binding Globulin and Aging
Unfortunately, as a man ages, sex hormone binding globulin levels increase by a little over 1% per year after early adulthood.9-14 This increase decreases free T levels. Coupled with the fact that total testosterone levels decrease with aging, free T levels decrease even more.
Total testosterone decrease by about 30% in healthy men between the ages of 25 and 75, while free T levels decline by about 50%. This more dramatic decline in free T levels is directly linked to the increase in SHBG.15-23 As a result of this increase, aging men may potentially experience signs of feminization. The increased SHBG levels prevent testosterone from exerting its effects. Also, since SHBG binds testosterone better than estrogen, this increase also leaves estrogen’s physiological impact on the male physiology unchecked.
What Causes SHBG Levels to Increase?
The exact reason why sex hormone binding globulin levels typically increase with age is unknown. It is known that SHBG levels decrease with high levels of growth hormone (GH) and insulin growth factor (IGF-1). One possibility is that the age-related decline in GH and IGF-1 levels might contribute to the increase.7 It is also known that low levels of estrogen and thyroid hormones decrease SHBG levels. Therefore, high levels of estrogen and thyroid hormones likely increase SHBG.
Interestingly, obese men tend to have lower sex hormone binding globulin levels than non-obese men because these men often have some level of insulin resistance. Insulin plays an important role in the management of SHBG levels, and insulin resistance lowers these levels.7-8 While obese men have lower SHBG levels, they do not necessarily have higher free T levels. Because obesity significantly reduces total testosterone levels, they still have less free, unbound testosterone than their non-obese counterparts.
| Conditions associated with decreased SHBG concentrations | Conditions associated with increased SHBG concentrations |
| Moderate obesity | Aging |
| Nephrotic syndrome | Hepatic cirrhosis and hepatitis |
| Hypothyroidism | Hyperthyroidism |
| Use of glucocorticoids, progestins, and androgenic steroids | Use of anticonvulsants |
| Acromegaly | Use of estrogens |
| Diabetes mellitus | HIV disease |
Should SHBG Levels Be Lowered?
The amount of testosterone that is bioavailable depends on the level of sex hormone binding globulin. Thus, it would seem like any man would always want to lower his SHBG. However, low levels are correlated with heart disease, diabetes, and obesity. While high levels are certainly not good either, the medical community does not treat high levels directly. Rather, the standard approach is to address any underlying causes associated with either increased or decreased concentrations. If high levels are contributing to lower than normal free T levels, the standard protocol is to treat the low testosterone directly via testosterone replacement therapy.
External Resource: Wikipedia: Sex Hormone Binding Globulin
Updated: April 26, 2015
1. Llewellyn W. Anabolics. 6th Edition. 2007. Body of Science.
2. http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=91215.
3. Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Williams Textbook of Endocrinology. Philadelphia, PA: Elsevier; 2008.
4. Saad F, Gooren L. The role of testosterone in the metabolic syndrome: a review. J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):40-3.
5. Li C, Ford ES, Li B, Giles WH, Liu S. Association of testosterone and sex hormone binding globulin with metabolic syndrome and insulin resistance in men. Diabetes Care. 2010 Jul;33(7):1618-24.
6. Brand JS, Wareham NJ, Dowsett M, et al. Associations of endogenous testosterone and sex hormone binding globulin with glycated haemoglobin in middle-aged and older men. Clin Endocrinol (Oxf). 2010 Dec 15.
7. Steppan CM. Lazar MA. Resistin and obesity-associtaed insulin resistance. Trends Endocrinol Metab. 2002: 13: 18-23.
8. Chubb SAP, Hyde Z, Almeida O, Flicker L, Norman, PE, Jamrozik, K, Hankey, GJ, Yeap, BB. Lower sex hormone binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study. Eur J Endocrinol June 1, 2008 158 785-792.
9. Ferrini RL & Barret-Connor E. Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community dwelling men. American Journal of Epidemiology 1998; 147: 750 – 754.
10. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. Journal of Clinical Endocrinology and Metabolism 2002; 87: 589 – 598.
11. Simon D, Preziosi P, Barrett-Connor E, Roger M, Saint-Paul M, Nahoul K et al. The influence of aging on plasma sex hormones in men: the Telecom Study. American Journal of Epidemiology 1992; 135: 783 – 791.
12. Vermeulen A, Kaufman JM & Giagulli VA. Influence of some biological indexes on sex hormone binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism 1996; 81: 1821 – 1826.
13. Leifke E, Gorenoi V, Wichers C, Von Zur MA, Von Buren E & Brabant G. Age-related changes of serum sex hormones, insulin-like growth factor-I and sex hormone binding globulin levels in men: cross-sectional data from a healthy male cohort. Clinical Endocrinology 2000; 53: 689 – 695.
14. Zumoff B, Strain GW, Kream J, O’Connor J, Rosenfeld RS, Levin J et al. Age variation of the 24-hour mean plasma concentrations of androgens, estrogens, and gonadotropins in normal adult men. Journal of Clinical Endocrinology and Metabolism 1982; 54: 534 – 538.
15. Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. Nov 2002; 87 (11): 5001-5007.
16. Morley JE, Kaiser FE, Perry HM, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. Apr 1997 ;46 (4): 410-413.
17. Araujo AB, O’Donnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. Dec 2004; 89 (12): 5920-5926.
18. Muller M, Den Tonkelaar I, Thijssen JH, Grobbee DE, van der Schouw YT. Endogenous sex hormone levels in men aged 40-80 years. Eur. J. Endocrinol. 2000: 149: 583-9.
19. Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Hum. Biol. 1981; 57: 71.
20. Vermeulen A. Androgens in the aging male – clinical review 24. J. Clin. Endocrinol. Metab. 1991: 73 221-4.
21. Harman SM, Metter EJ, Tobin JD, Pearson J & Blackman MR. Longitudinal effects of aging on serum testosterone levels in healthy men. Journal of Clinical Endocrinology and Metabolism2001;86:724–731.
22. Orwoll E, Lambert LC, Marshall LM, Phipps K, Blank J, Barrett-Connor E, Cauley J, Ensrud K & Cummings S. Testosterone and estradiol in older men. Journal of Clinical Endocrinology and Metabolism2006; 91: 1336–1344.
23. Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K & Flicker L. In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health In Men Study. European Journal of Endocrinology 2007; 156: 585–594.
