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Home > Anti-aging Research > SHBG

Sex Hormone Binding Globulin (SHBG)

Alternative News:

  • Men’s Sexual Health: Testosterone & Nitric Oxide Modulation - Huntington University of Health Sciences - "it is significant to note that the human clinical research has been done on a specific proprietary extract known as LJ100. This is important since the LJ100 extract of E. longifolia has been standardized for ... eurypeptides, naturally-occurring compounds which may be the active phytochemicals in E. longifolia, or at least serve as a marker for extract quality ... Human clinical studies on LJ100 have ... been conducted at different dosage levels, but 200 mg/day showed the most benefits. Studies included both controlled trials and open-label trials. It will not be possible to provide a detailed review all of the studies; however, here ...is a synopsis of the research results: Depending on the study, T increased 16.4-71.5 percent 11-13 ... Depending on the study, cortisol decreased 16-32 percent14,11 ... DHEA increased 47 percent9 ... Sexual health scores improved significantly10,15, as much as 91 percent9 ... It appears that at least one of the mechanisms of action for LJ100 is the reduction of sex hormone-binding globulin (SHBG) levels. SHBG is a glycoprotein that binds to sex hormones. While bound to SHBG, T cannot bind to cellular androgen receptors—which means that it won’t have any of the valuable effects of T in this form. Of course, SHBG-bound T can be unbound, but it can take a while for this to happen. Furthermore, SHBG levels increase as we age.2 In one of the studies, LJ100 was shown to reduce SHBG levels in 36 percent of the cases after one week, and 66 percent after three weeks" - See LJ100 at Amazon.com.
  • Male Hormonal Health and the Role of Eurycoma longifolia Herb in Enhancing Free Testosterone in Ageing Men - Rainforest Herbs, 8/13/17 - "In their follow-up study the effects of Tongkat Ali extract on testosterone, dehydroepiandrosterone (DHEA) and sex hormone binding globulin (SHBG) were investigated over a 3 week period using an intermediate dosage of 50 mg extract capsules, with 4 capsules taken each day. Also a questionnaire to determine improvement in quality of life and sexual response was given to the participants. The final results showed that 82% of the participants experienced improvements in physical, sexual and psychological well-being. While total testosterone was not significantly different, the DHEA levels had increased by 26% after one week to 47% after 3 weeks. SHBG levels had reduced in 66% of cases after 3 weeks. When SHBG decreases the free testosterone index (FTI) increases. The FTI analysis showed an increase in 39% of participants after 1 week and 73% of participants after 3 weeks."
  • Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects - J Int Soc Sports Nutr. 2013; 10: 28 - "The effects of tongkat ali in restoring normal testosterone levels appears to be less due to actually “stimulating” testosterone synthesis, but rather by increasing the release rate of “free” testosterone from its binding hormone, sex-hormone-binding-globulin (SHBG) [17,18]. In this way, eurycoma may be considered not so much a testosterone “booster” (such as an anabolic steroid), but rather a “maintainer” of normal testosterone levels and a “restorer” of normal testosterone levels (from “low” back “up” to normal ranges) [19]. This would make eurycoma particularly beneficial for individuals with sub-normal testosterone levels, including those who are dieting for weight loss, middle-aged individuals suffering with fatigue or depression, and intensely training athletes who may be at risk for overtraining ... Salivary cortisol levels were significantly lower (−16% compared to placebo, PL) following tongkat ali (TA) supplementation (200 mg/day for 4 weeks) ... Daily supplementation (200 mg/day for 4 weeks) with tongkat ali (TA) resulted in significant improvements compared to placebo (PL) for indices of Tension (−11%), Anger (−12%), and Confusion (−15%) in moderately stressed adults ... Tongkat ali has been referred to as Malaysia’s “home-grown Viagra” [4] with the Malaysian government investing considerable effort to license, develop, and sustain research into the potential health benefits of Eurycoma longifolia through a variety of governmental organizations, including the Forest Research Institute of Malaysia" - See tongkat at Amazon.com.
  • Cross-Sectional Association of Coffee and Caffeine Consumption With Sex Hormone-Binding Globulin in Healthy Nondiabetic Women - Medscape, 1/23/18 - "High coffee (≥3 cups/day) and caffeine (≥265 mg/day) intakes were associated with a reduced risk of being in the 1st quartile of the SHBG level distribution (<46.3 nmol/L) in a multivariate adjusted model (OR: 0.72 ... Consumption of high coffee and caffeine is associated with a reduced risk of low SHBG, an established risk marker for T2DM, which might contribute to the protective effects of coffee for type 2 diabetes"
  • Vitamin D Supplements May Raise Sex Hormone Levels in Men - Medscape, 6/1/17 - "Testosterone is converted to estradiol, and SHBG binds testosterone and estradiol, Dr Lerchbaum observed, but only the unbound fraction of hormones is biologically active. Effectively, the lower SHBG levels result in more bioavailable testosterone. "We think that low SHBG levels should be an advantage for these men because they have more biologically active hormone." ... Maybe. Sufficient estradiol levels are important for the feedback mechanism with hypothalamus and the pituitary gland (LH and FSH levels) ... It may be speculated that the decrease in SHBG and the resultant increases in free testosterone levels might help improve the hypogonadism problem and fertility in these" - See vitamin D at Amazon.com.
  • Oleic acid increases hepatic sex hormone binding globulin production in men - Mol Nutr Food Res. 2013 Oct 20 - "Low circulating sex hormone-binding globulin (SHBG) is an independent risk factor for cardiovascular disease ... A total of 315 men were included. In these patients, nutrition data and plasma samples for SHBG assessment were obtained. In vitro studies to examine the effects of oleic and linoleic acid on SHBG production using HepG2 cells were performed. We provided evidence that SHBG serum levels were significantly higher in subjects using olive oil for cooking in comparison with subjects using sunflower oil ... MUFA were independently associated with SHBG levels and accounted for the 20.4% of SHBG variance ... Olive oil consumption is associated with elevated SHBG serum levels"
  • Tongkat Ali as a Potential Herbal Supplement for Physically Active Male and Female Seniors-A Pilot Study - Phytother Res. 2013 Jun 11 - "Tongkat Ali (Eurycoma longifolia; TA) is known to increase testosterone levels and alleviate aging males' symptoms. This study aimed at investigating TA as an ergogenic supplement for elderly people. Thirteen physically active male and 12 physically active female seniors (57-72 years) were supplemented with 400-mg TA extract daily for 5 weeks ... Treatment resulted in significant increases in total and free testosterone concentrations and muscular force in men and women. The increase in free testosterone in women is thought to be due to the significant decline in sex hormone-binding globulin concentrations" - See Tongkat Ali products at iHerb.
  • Association of vitamin D status with serum androgen levels in men - Clin Endocrinol (Oxf). 2009 Dec 29 - "Men with sufficient 25(OH)D levels (>/=30 mug/l) had significantly higher levels of testosterone and FAI and significantly lower levels of SHBG when compared to 25(OH)D insufficient (20-29.9 mug/l) and 25(OH)D deficient (<20 mug/l) men (p<0.05 for all). In linear regression analyses adjusted for possible confounders, we found significant associations of 25(OH)D levels with testosterone, FAI, and SHBG levels (p<0.05 for all). 25(OH)D, testosterone, and FAI levels followed a similar seasonal pattern with a nadir in March (12.2 mug/l, 15.9 nmol/l, and 40.8, respectively) and peak levels in August (23.4 mug/l, 18.7 nmol/l, and 49.7, respectively) (p<0.05 for all). Conclusion: Androgen levels and 25(OH)D levels are associated in men and reveal a concordant seasonal variation" - See vitamin D at Amazon.com.

News & Research:

  • Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men - J Clin Endocrinol Metab 2020 Oct 16 - "Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related and cancer-related mortality"
  • Testosterone, Dihydrotestosterone, Bone Density, and Hip Fracture Risk among Older Men: The Cardiovascular Health Study - Metabolism 2020 Oct 12 - "In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not"
  • Serum SHBG is associated with the development and regression of non-alcoholic fatty liver disease: a prospective study - J Clin Endocrinol Metab. 2019 Dec 3 - "Sex hormone-binding globulin (SHBG), a homodimeric glycoprotein produced by hepatocytes has been shown to be associated with metabolic disorders. Whether circulating SHBG levels are predictive of later risk of non-alcoholic fatty liver disease (NAFLD) remains unknown ... Basal SHBG was negatively associated with NAFLD development, with a fully adjusted odds ratio (OR) and its 95% confidence interval (CI) of 0.22 (0.12-0.40) (P-trend < 0.001). In contrast, basal SHBG was positively associated with NAFLD regression, with a fully adjusted OR of 4.83 (2.38-9.81) (P-trend < 0.001). Multiple-stepwise logistic regression analysis showed that SHBG concentration was an independent predictor of NAFLD development (OR, 0.28 [0.18-0.45]; P < 0.001) and regression (OR, 3.89 [2.43-6.22]; P < 0.001). In addition, the area under the receiver operating characteristic curves were 0.764 (95% CI, 0.740-0.787) and 0.762 (95% CI, 0.738-0.785) for the prediction models of NAFLD development and regression, respectively"
  • SHBG, Sex Steroids and Kyphosis in Older Men: The MrOS Study - J Bone Miner Res. 2016 Jun 29 - "Accentuated kyphosis is associated with adverse health outcomes including falls and fractures. Low bone density is a risk factor for hyperkyphosis, and each vertebral fracture adds roughly 4 degrees to forward spine curvature. Sex steroids, in particular low bioavailable estradiol and high SHBG, are associated with bone loss and high SHBG is associated with vertebral fractures in older men ... After adjustment for age and other confounding variables, no association was found between bioavailable estradiol or testosterone and Cobb angle, either when kyphosis was analyzed as a continuous variable or dichotomized into highest vs. lower three quartiles. In linear regression models adjusted for age and clinic site, there was a significant association between SHBG and kyphosis (parameter estimate = 0.76 per SD increase, p = 0.01). In the fully adjusted model, this association was weakened and of only borderline statistical significance ... High SHBG is associated with bone loss and vertebral fractures. Our results suggest that high SHBG may also be a risk factor for hyperkyphosis"
  • Sex steroids, sex hormone-binding globulin and cardiovascular health in men and postmenopausal women: the Rotterdam Study - J Clin Endocrinol Metab. 2016 May 10 - "estradiol (E2), testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index (FAI) ... optimal cardiovascular health (OCH ... After adjustment for confounders, OCH was associated with lower T [OR (95%CI): 0.69 (0.48-1.00)] and lower FAI [0.43 (0.32-0.57)] and higher levels of SHBG [4.55 (2.99-6.94)] among women and with higher levels of SHBG [2.56 (1.45-4.49)] in men"
  • Sex steroids, sex hormone-binding globulin and cardiovascular health in men and postmenopausal women: the Rotterdam Study - J Clin Endocrinol Metab. 2016 May 10 - "estradiol (E2), testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index (FAI) ... optimal cardiovascular health (OCH ... After adjustment for confounders, OCH was associated with lower T [OR (95%CI): 0.69 (0.48-1.00)] and lower FAI [0.43 (0.32-0.57)] and higher levels of SHBG [4.55 (2.99-6.94)] among women and with higher levels of SHBG [2.56 (1.45-4.49)] in men"
  • Association of Sex Hormone Binding Globulin and Free Testosterone with Mortality in Men with Type 2 Diabetes Mellitus - Eur J Endocrinol. 2015 Oct 19 - "Low circulating testosterone levels have been associated with increased mortality in men. We hypothesized that the prognostic role of testosterone in men with type 2 diabetes mellitus (T2DM) is influenced by its carrier protein sex hormone binding globulin (SHBG) ... higher SHBG (Hazard Ratio (HR) 1.012 [95% Confidence Interval (CI) 1.002-1.022], p=0.02) and lower calculated free testosterone (cFT) (HR 0.995 [95% CI 0.993-0.998], p=0.001) were risk factors for all cause mortality ... By contrast, the inverse association of total testosterone (TT) with mortality weakened after these adjustments (p=0.11). SHBG remained associated with mortality (p<0.001) both if substituted for or added to TT in the multivariable model. In the fully adjusted model, an increase of SHBG by 17.3 nmol/L (1 SD) increased mortality by 22% and a decrease in cFT by 81 pmol/L (1 SD) increased mortality by 45%"
  • The Association of Obesity with Sex Hormone Binding Globulin is Stronger than the Association with Aging - Implications for the Interpretation of Total Testosterone Measurements - Clin Endocrinol (Oxf). 2015 Mar 16 - "Total testosterone concentrations are influenced by sex hormone binding globulin (SHBG) concentrations, which are decreased by obesity and increased with aging ... the association between obesity and lowered SHBG is greater than the association of aging with increased SHBG. These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men"
  • Genetic and environmental influence on the association between testosterone, sex hormone binding globulin, and body composition in Korean men - Clin Endocrinol (Oxf). 2015 Jan 19 - "Each 1-SD increase in age-adjusted levels of TT, cFT, and SHBG were associated with lower levels of adiposity measures and absolute measures of lean body mass. On the other hand, percentage total lean mass increased with increasing levels of TT, cFT, and SHBG (P <0.05)"
  • Low serum sex hormone-binding globulin is associated with nonalcoholic fatty liver disease in type 2 diabetic patients - Clin Endocrinol (Oxf). 2013 Nov 4 - "One hundred and twenty patients with NAFLD and 120 age-, sex- and BMI-matched patients with non-NAFLD were enrolled into a case-control study ... Serum SHBG levels were significantly lower in NAFLD group than in non-NAFLD group (24.5 ± 11.0 vs 37.6 ± 14.4 nm, P < 0.001)"
  • Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy - Ann Pharmacother. 2014 Jul 2 - "Older men who were treated with intramuscular testosterone did not appear to have an increased risk of MI. For men with high MI risk, testosterone use was modestly protective against MI"
  • Total testosterone is the most valuable indicator of metabolic syndrome among various testosterone values in middle-aged Japanese men - Endocr J. 2014 Oct 23 - "TT and SHBG were significantly lower in men with MetS than in men without MetS. All testosterone values gradually decreased as the number of MetS components increased"
  • Both total testosterone and sex hormone-binding globulin are independent risk factors of metabolic syndrome: results from Fangchenggang Area Male Health and Examination Survey in China - Diabetes Metab Res Rev. 2013 Mar 6 - "Men with MetS had a lower level of TT, BT, FT or SHBG than those without MetS (all p < 0.001). Both TT and SHBG were inversely correlated with body mass index (BMI) or homeostasis model assessment of insulin resistance (HOMA-IR) (all age-adjusted p < 0.001). Men within the lowest quartile of TT (OR = 4.86, 95%CI = 2.72-8.68), BT (OR = 3.04, 95%CI = 1.81-5.10), FT (OR = 3.08, 95%CI = 1.81-5.27) or SHBG (OR = 4.28, 95%CI = 2.52-7.27) had a risk of MetS after adjusting for age, smoking, HOMA-IR and BMI. TT remained inversely associated with MetS after further adjusting for SHBG (OR = 0.95, 95%CI = 0.92-0.99), while SHBG remained inversely associated with MetS after further adjusting for TT (OR = 0.99, 95%CI = 0.97-1.00)"
  • The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons - Atherosclerosis. 2012 Oct 3 - "Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively"
  • Blood hormone levels predicted long-term breast cancer risk for postmenopausal women - Science Daily, 10/18/12 - "Women with hormone levels in the highest 25 percent for estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) had a 50 percent to 107 percent greater chance for developing breast cancer compared with women in the lowest 25 percent. Relative risks for developing breast cancer were similar at one to 10 years versus 11 to 20 years (also 16 to 20 years) after blood collection ... Women in the highest 25 percent of SHBG levels had a 30 percent lower risk for breast cancer compared with women in the lowest 25 percent for SHBG levels"
  • High Serum Testosterone Is Associated With Reduced Risk of Cardiovascular Events in Elderly Men The MrOS (Osteoporotic Fractures in Men) Study in Sweden - J Am Coll Cardiol. 2011 Oct 11;58(16):1674-81 - "During a median 5-year follow-up, 485 CV events occurred. Both total testosterone and SHBG levels were inversely associated with the risk of CV events (trend over quartiles: p = 0.009 and p = 0.012, respectively). Men in the highest quartile of testosterone (≥550 ng/dl) had a lower risk of CV events compared with men in the 3 lower quartiles (hazard ratio: 0.70, 95% confidence interval: 0.56 to 0.88). This association remained after adjustment for traditional CV risk factors and was not materially changed in analyses excluding men with known CV disease at baseline (hazard ratio: 0.71, 95% confidence interval: 0.53 to 0.95). In models that included both testosterone and SHBG, testosterone but not SHBG predicted CV risk"
  • Sex Hormone-Binding Globulin, But Not Testosterone, Is Associated Prospectively and Independently With Incident Metabolic Syndrome in Men: The Framingham Heart Study - Diabetes Care. 2011 Sep 16 - "Cross-sectionally, testosterone and SHBG were more strongly associated with metabolic syndrome than free testosterone in the training sample. SHBG, but not testosterone or free testosterone, was significantly associated with metabolic syndrome after adjusting for age, smoking, BMI, and insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR]). These findings were confirmed in a validation sample. Longitudinally, SHBG at examination 7, but not testosterone or free testosterone, was associated with incident metabolic syndrome at examination 8 after adjusting for age, smoking, BMI, and HOMA-IR. Multivariable analyses suggested that age, BMI, and insulin sensitivity independently affect SHBG and testosterone levels and the risk of metabolic syndrome and its components"
  • Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in patients with type 2 diabetes - Diabetes Res Clin Pract. 2011 Aug 19
  • SHBG, Sex Hormones, and Inflammatory Markers in Older Women - J Clin Endocrinol Metab. 2011 Jan 14 - "In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation ... SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 +/- 0.08; P = 0.006) and E2 (0.21 +/- 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. Conclusion: In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state"
  • Why coffee protects against diabetes - Science Daily, 1/12/11 - "A protein called sex hormone-binding globulin (SHBG) regulates the biological activity of the body's sex hormones, testosterone and estrogen, which have long been thought to play a role in the development of type 2 diabetes. And coffee consumption, it turns out, increases plasma levels of SHBG"
  • Sex Hormones and the Risk of Incident Prostate Cancer - Urology. 2010 May 6 - "Serum testosterone, estradiol, estrone, and sex hormone-binding globulin were assayed at baseline ... the mean age was 73 years. Higher serum estrone was strongly related to an increased risk of prostate cancer: compared with men in the lower quartile, the risk of prostate cancer among those in the highest 3 quartiles (>24.9 pg/dL) was nearly 4-fold higher (adjusted heart rate = 3.93, CI: 1.61-9.57). Other sex hormones were not associated with the risk of prostate cancer" - The following results for estrone are for women.   I didn't find any results for men but see the "For Aromatization (in males):" section on my letrozole page.
  • Association of Testosterone and Sex Hormone-Binding Globulin with Metabolic Syndrome and Insulin Resistance in Men - Diabetes Care. 2010 Apr 5 - "men in the first quartile (lowest) (PR, 2.16; 95% CI, 1.53-3.06) and second quartile of total testosterone (PR, 2.51; 95% CI, 1.86-3.37) were more likely to have metabolic syndrome than men in the fourth quartile ... Similarly, men in the first quartile of SHBG (PR, 2.17; 95% CI, 1.32-3.56) were more likely to have metabolic syndrome than men in the fourth quartile ... Low concentrations of total testosterone and SHBG were strongly associated with increased likelihood of having metabolic syndrome, independent of traditional cardiovascular risk factors and insulin resistance"
  • Low testosterone levels and SHBG levels and high estradiol levels are independent predictors of type 2 diabetes in men - Eur J Endocrinol. 2010 Jan 8 - "There was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per SD increase (HR 0.71, CI 0.54-0.92) and in the higher quartiles of total testosterone compared to the lowest (HR 0.53, CI 0.33-0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher SHBG levels, both linearly per SD increase (HR 0.55, CI 0.39-0.79) and when comparing the third (HR 0.38, CI 0.18-0.81) and the fourth quartile (HR 0.37, 0.17-0.82) to the lowest. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol was positively associated with incident diabetes after multivariate adjustments including waist circumference, when comparing the second (HR 0.49, CI 0.26-0.93) and the third (HR 0.51, CI 0.27-0.96) quartile to the highest Conclusion. Men with higher estradiol levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared dependent of obesity"
  • Association of sex hormones and C-reactive protein levels in men - Clin Endocrinol (Oxf). 2009 Sep 21 - "A robust, inverse dose-response correlation between testosterone and SHBG levels with CRP levels provides further evidence of a potential role of androgens in inflammatory processes"
  • New Sign of Diabetes Risk - WebMD, 9/16/09 - "People with the lowest SHBG levels have a tenfold higher risk of type 2 diabetes than those with the highest SHBG levels"
  • Sex Hormones Associated With Broken Bones In Older Men - Science Daily, 8/3/09 - "Low levels of estradiol or high levels of sex hormone binding globulin (SHBG) are associated with an increased risk of osteoporotic fracture in older men"