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Sex Hormone Binding Globulin (SHBG)

My formula for lowering SHBG (search this webpage for the nutrient/medication for the studies on it):

• One gram of fish oil four times per day (fish oil page)
• 50 mg DHEA twice per day (DHEA page)
• 50 mg of danazol per day from an overseas pharmacy.
• 5 mg twice per day boron (boron page)
• 300 mg twice per day of LJ100 Tongkat ali (Tongkat page)
• Vitamin D, 10,000 IU (vitamin D page)
• 2 capsules stinging nettle (stinging nettle page)
• 1.25 mg (half a table) of letrozole every other per day (letrozole page)
• 1000 mg of royal jelly (royal jelly page)
• Magnesium l-threonate 3 capsules per day (magnesium page)

Alternative News:

• A doctor on YouTube claims that he sees a lot of cases of high total testosterone and high SBHG in older men and he blames it on liver damage in the past.  I went to at least two endocrinologists about my high SHBG. Both basically told me that there was nothing they could do. That said, I was ready for them the second time. I asked them to follow up on the formula I was taking to lower it. That formula worked plus it actually lowered my liver enzymes. The formula is at the top of my SHBG page.

   

• • Association of Sex Hormone Binding Globulin and Free Testosterone with Mortality in Men with Type 2 Diabetes Mellitus - Eur J Endocrinol. 2015 Oct 19 - "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%"
  • Testosterone, Dihydrotestosterone, Bone Density, and Hip Fracture Risk among Older Men: The Cardiovascular Health Study - Metabolism 2020 Oct 12 - "SHBG was positively associated with hip fracture risk"
  • SHBG, Sex Steroids and Kyphosis in Older Men: The MrOS Study - J Bone Miner Res. 2016 Jun 29 - "High SHBG is associated with bone loss and vertebral fractures. Our results suggest that high SHBG may also be a risk factor for hyperkyphosis"
    • Hyperkyphosis Definition - spine-health.com - "Hyperkyphosis refers to an excessive curvature of the thoracic spine, commonly referred to as hunchback"
  • Sex Hormones Associated With Broken Bones In Older Men - Science Daily, 8/3/09 - "high levels of sex hormone binding globulin (SHBG) are associated with an increased risk of osteoporotic fracture in older men"
• Effect of Resveratrol Content in Red Wine on Circulating Sex Hormone-Binding Globulin: Lessons from a Pilot Clinical Trial - Mol Nutr Food Res 2022 Jun 25 - "Low sex hormone-binding globulin (SHBG) levels are associated with higher risk of developing cardiovascular disease. Epidemiological studies have shown that red wine has beneficial effects on cardiovascular disease. In this work we explored if resveratrol content in red wine increases SHBG levels. ... Red wine rich in resveratrol reduced total cholesterol in men and women and increased SHBG only in women. Further research aimed at investigating the potential SHBG role enhancement mediated by resveratrol regarding cardiovascular protection that presents women in comparison with men seems warranted" - See resveratrol products at Amazon.com.
• Sex hormone-binding globulin: a new marker of disease severity and prognosis in men with chronic heart failure - Rev Esp Cardiol 2009 Dec - "Sex hormone-binding globulin (SHBG) is a key regulator of the actions of anabolic steroids. Chronic heart failure (HF) has been associated with anabolic steroid deficiency, but its relationship with SHBG is not known ... At enrolment, the SHBG level (median 34.5 nmol/L, IQR 27-50 nmol/L) was correlated with the N-terminal probrain natriuretic peptide level (r=0.271, P=.005), LVEF (r=-0.263, P=.007), body mass index (r=-0.199, P=.020) and total testosterone level (r=0.332, P=.001). The median SHBG level was higher in the 16 patients (15.4%) who died, at 48.5 nmol/L (IQR 36-69.5 nmol/L) vs. 33 nmol/L (IQR 25.3-48.7 nmol/L; P=.001), and a high level was associated with an increased risk of death (hazard ratio [HR]=1.045, 95% confidence interval [CI] 1.021-1.069; P< .001). The association remained significant after adjustment in Cox multivariate regression modeling, at HR=1.049 (95% CI 1.020-1.079; P=.001). Analysis by SHBG tertiles showed mortality was 30% in the third tertile, 14% in the second, and 4% in the first (log rank 0.007; HR=3.25 ... The SHBG level correlated with measures of HF severity and was associated with a higher risk of cardiac death"
• Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition - JCEM, 1/10/05 - "In both the young and elderly group, SHBG levels decreased during letrozole treatment (P = 0.003 and <0.001, respectively; P value for young vs. elderly was not significant). The ratios T/E2 and FT/FE2 were significantly higher after letrozole treatment in both groups" - See letrozole at inhousepharmacy.vu.
• Dietary and serum omega-3 polyunsaturated fatty acids and PCOS: A matched case-control study - Br J Nutr 2021 Aug 10 - "omega-3 PUFAs in serum phospholipids were inversely associated with PCOS prevalence, including total, long-chain and individual PUFAs (e.g., docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). Compared to the lowest tertile (T1), the adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for the highest tertile (T3) were 0.63 (0.40, 0.93) for total omega-3 PUFAs, 0.60 (0.38, 0.92) for long-chain omega-3 PUFAs, 0.68 (0.45, 1.01) for DHA, 0.70 (0.45, 1.05) for EPA and 0.72 (0.45, 1.08) for DPA. For dietary intake of omega-3 PUFAs, significant inverse associations were found only for long-chain omega-3 PUFAs (p trend = 0.001), EPA (p trend = 0.047) and DHA (p trend = 0.030). Both dietary and serum omega-3 PUFAs, mainly EPA and DPA, were negatively correlated with PCOS-related parameters, such as BMI, fasting insulin, total testosterone and high-sensitivity C-reactive protein (hs-CRP), but positively correlated with follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG)" - See omega-3 supplements at Amazon.com and iHerb.
• The effect of Eurycoma Longifolia on the regulation of reproductive hormones in young males - Andrologia 2021 May - "Eurycoma longifolia supplementation increases testosterone levels in humans via activation of the hypothalamic-pituitary-gonadal axis and/or the hypothalamic-pituitary-adrenal axis mainly in older adults and nonhealthy populations ... Thirty-two males (24.4 ± 4.7 years; 1.74 ± 0.07 m; 73.7 ± 8.4 kg) in a placebo-controlled, double-blind, matched-paired study received 600 mg/day Eurycoma longifolia or placebo for two weeks. Blood analysis using repeated measures analysis of variance showed significant interaction and time effects for testosterone (F1,30 = 9.04, p = .005), free testosterone (F1,30 = 7.13, p = .012) and estradiol (F1,30 = 8.07, p = .008) levels in favour of the treatment group, while luteinising hormone, follicle-stimulating hormone and sexual hormone-binding globulin did not. The lack of changes in luteinising hormone and follicle-stimulating hormone levels suggests that a lesser role played by Eurycoma longifolia in activating the hypothalamic-pituitary-gonadal axis in the young adults. The raised testosterone level may be due to a greater rate of hormone production via the hypothalamic-pituitary-adrenal axis. The supplementation of Eurycoma longifolia for two weeks demonstrates steroidogenic effects on young men were dose-related. Consequently, the raised testosterone following Eurycoma longifolia supplementations could benefit muscle and strength gain in young adults" - [Nutra USA] - I take Eurycoma longifolia to lower SHBG. SHBG bines with total testosterone causing lower free testosterone. My SHBG was really high so I came up with my own formula: Tongkat Ali (Eurycoma longifolia), stinging nettle, boron, DHEA and 50 mg (a very low dose) of prescription danazol that I purchased from an overseas pharmacy. It makes a big difference in your sex life and getting rid of your gut.  See Tongkat (Eurycoma Longifolia) at Amazon.com and also the LJ 100 Tongkat used in this trial.
• 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:

• Testosterone "Mystery Molecule" 2: SHBG - YouTube - Doctor claims that he sees a lot of high total testosterone
• SHBG - Sex Hormone Binding Globulin Effects on Testosterone Levels - Doctor's Analysis - YouTube
• How I Manage Men on Testosterone Replacement Therapy (TRT) - YouTube
• Dealing with Hep C and low Testosterone - YouTube
• Serum testosterone and sex hormone-binding globulin are inversely associated with leucocyte telomere length in men: a cross-sectional analysis of the UK Biobank Study - Eur J Endocrinol 2023 Feb 8 - "Older men on average have lower testosterone concentrations compared with younger men, and more age-related comorbidities. Whether lower testosterone concentrations contribute to biological ageing remains unclear. Shorter telomeres are a marker for biological age. We tested the hypothesis that testosterone concentrations are associated with leucocyte telomere length (LTL), in middle to older aged men ... Total testosterone and SHBG were independently and inversely associated with LTL. Men with higher testosterone or SHBG had shorter telomeres, arguing against a role for testosterone to slow biological ageing in men" - But what about the argument for lowering SHBG?
• Increased Morbidity in Males Diagnosed with Gynecomastia: A nationwide register-based cohort study - J Clin Endocrinol Metab 2023 Jan 31 - "A total of 16,253 (69.4%) males in the cohort were identified with idiopathic gynecomastia. These males had a statistically significant higher risk of future disease across all included disease chapters (HR range: 1.19 to 1.89), with endocrine diseases representing the greatest disease risk (HR 1.89, 95% CI: 1.76 to 2.03). The highest sub-chapter disease risk was observed for disorders of endocrine glands (OR 7.27, 95% CI: 6.19 to 8.54). Similarly, the odds ratios of comorbidities were higher across all included disease chapters (OR range 1.05 to 1.51), except for psychiatric disease (OR 0.72, 95% CI: 0.68 to 0.78), with the highest association with musculoskeletal/connective tissue (OR 1.51, 95% CI: 1.46 to 1.57) and circulatory (OR 1.36, 95% CI: 1.29 to 1.43) diseases" - Note: High SHBG is a cause of gynecomastia and also has about the same mortality rate. Connection?
• Sex-specific differences in bone mineral density loss after sleeve gastrectomy - Front Med (Lausanne) 2022 Oct 26 - "High levels of sex hormone-binding globulin (SHBG) have been documented to be a risk factor of bone mineral density (BMD) loss with different effects observed between sexes ... In the multivariate model, SHBG was significantly associated with total hip BMD loss in men (adjusted β = -0.533, P = 0.019) but not women while total estrogen was significantly associated with total hip BMD loss in women"
• TOTAL TESTOSTERONE VS. BIOAVAILABLE TESTOSTERONE: WHY SHBG MATTERS - Core New England - "recent research suggests that high levels of SHBG bind to estrogen and reduce bone mass in both men and women- potentially leading to osteoporosis. Thus, optimal SHBG levels are crucial in maintaining proper bone health and some experts are now suggesting routine measurement of SHBG as a useful new marker for predicting severe bone diseases"
• SHBG Blood Test, Symptoms of High Levels & How to Lower - Written by Carlos Tello, PhD (Molecular Biology) - "Symptoms of High SHBG Levels ... In men, they include [19, 20]: ... Arrested sexual development (in teenagers) ... Infertility ... Decreased sperm concentration and motility ... Decreased sex drive ... Impotence ... Reduced testicle size ... Breast growth ... Decreased body hair ... Hot flashes ... Reduced bone and muscle mass ... Decreased energy and motivation"
• Associations of bioavailable serum testosterone with cognitive function in older men: results from the National Health and Nutrition Examination Survey - J Gerontol A Biol Sci Med Sci 2022 Aug 5 - "with no signs of a plateau effect ... Calculated bioavailable testosterone presented a significant positive association with processing speed, sustained attention and working memory in older men above 60 years of age. Further research is warranted to elucidate the impact of the inevitable age-related decline in testosterone on cognitive function in older men"
• When to Treat Low Testosterone in Diabetes and Obesity - Medscape, 7/15/22 - "Typical symptoms are reduced libido, erectile dysfunction, lack of morning erections, feeling of tightness in the chest area, gynecomastia, reduced secondary hair growth and a decrease in shaving frequency, testicular involution, infertility, hot flashes, excessive sweating, and signs of osteoporosis ... Nonspecifically, testosterone deficiency can express itself as decreased energy, reduced endurance and muscular strength, depression, lack of ability to concentrate, decrease in memory capacity, fatigue, and increased fat mass ... To determine testosterone levels, Petersenn recommended that the sex hormone–binding globulin (SHBG) level be incorporated during interpretation or that BMI-dependent testosterone threshold values be considered. The basis for this is that free testosterone only accounts for about 0.5%-3% of the total testosterone; the predominant share is bound to albumin and SHBG ... Reduced SHBG levels are an observed symptom in obesity, diabetes, nephrotic syndrome, hypothyroidism, and acromegaly, as well as during glucocorticoid therapy. Increased SHBG levels are detected in later life, with hepatitis and HIV, with hyperthyroidism, and during therapy with certain anticonvulsants ... If the total level of testosterone is reduced, free testosterone should be calculated, considering the SHBG. After determining total testosterone, albumin, and SHBG, free testosterone can be estimated using approximation formulae such as the Vermeulen formula"
• Circulating free testosterone and risk of aggressive prostate cancer: prospective and Mendelian randomization analyses in international consortia - Int J Cancer 2022 May 17 - "In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI=1.02-1.28; Phet =0.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR:1.20,1.08-1.34; blood-based:1.03,1.01-1.05) and early-onset prostate cancer (MR:1.37,1.09-1.73; blood-based:1.08,0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups"
• Can we rely on total testosterone measurement to exclude hypogonadism in erectile dysfunction? - Int J Impot Res 2022 Mar 28 - "Although male hypogonadism (MH) is a prevalent comorbidity in patients presenting for erectile dysfunction (ED), its screening relies solely on total testosterone (TT). Ageing and other conditions can increase sex hormone-binding globulin (SHBG) and lower free testosterone (FT) causing symptomatic MH despite normal TT. The primary objective was to measure the prevalence of normal TT/low FT among patients presenting for ED ... Normal TT/low cFT is frequent and can be missed by current screening recommendations for MH in patients presenting for ED. Ageing seems to be the main culprit as elevated SHBG prevalence increases steeply after the sixth decade. TT cannot solely be relied on to exclude biochemical MH in patients presenting for ED, especially in patients over 60 years old"
• SHBG, bone mineral density and physical function among injection drug users with and without HIV and HCV - J Clin Endocrinol Metab 2022 Mar 16 - "Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates the bioavailability of sex hormones and is higher in people with HIV (PWH) and hepatitis C (HCV). SHBG is associated with aging-related diseases, including osteoporosis and frailty in the general population. However, the relationship between SHBG concentration and bone mineral density (BMD) and physical function among PWH and HCV is unclear ... Higher SHBG concentrations are associated with the presence of HIV and HCV viremia. Among women, but not men, higher SHBG concentrations were associated with lower grip strength, higher odds of frailty, and lower lumbar spine BMD" - Note: The thing is, SBHG binds to testosterone, DHT and estrogen. I believe the binding to estrogen is what contributes to bone loss. I haven't found an endocrinologist yet that will treat it. I have one more appointment with one more doctor at UCSD and if that doesn't work, I'm taking it to small claims court to see if they can force them to treat it. It's treatable. See the formula on my SHBG page but they refuse to even work with me on it. It's like pulling teeth just to get them to check it. They've got a bad case of thinking that they're God. When you tell an endocrinologist that you have high SHBG, it's like you said leprosy and they treat you like a disease. I look at General Petraeus and I'm betting that's what happened to him.
  • Sex hormone-binding globulin in osteoporosis - Joint Bone Spine 2010 Jul - "Together with estradiol, SHBG plays a key role in the genesis of bone loss and osteoporotic fractures"
• Aging, cardiovascular risk and SHBG levels in men and women from the general population - J Clin Endocrinol Metab 2021 Jul 1 - "Among men, a linear increase in SHBG levels with age and among women a U-shaped pattern was observed. Participants with larger number of cardiovascular risk factors had lower SHBG levels. When stratified by age, older participants had higher SHBG levels. A multivariate model including total testosterone and triglyceride levels in men and total testosterone, triglycerides, BMI, and fasting insulin in women explained, respectively, 46.2% and 31.8% of the variance in SHBG levels"
• Sociodemographic, Lifestyle and Medical Influences on Serum Testosterone and Sex Hormone–Binding Globulin in Men From UK Biobank - Medscape, 3/12/21 - "When considering SHBG, older, slim, White, unpartnered, qualified below A levels (high school), fish eating and sufficiently physically active men had levels more than double those in middle-aged, Asian, obese, partnered, college/university qualified, red meat eating and insufficiently physically active men." - Note:  So you have to be overweight to lower your SHBG?  I guess it makes sense because they claim that aerobic exercise also raises SHBG and aerobic exercise can make you slim.
• 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 - "The odds ratios (ORs) predicting the presence of high-grade NAFLD in men and women decreased significantly with increasing SHBG tertile"
• 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.
  • Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer - J Clin Oncol. 2008 Apr 1;26(10):1671-6 - "Letrozole reduces plasma E2 and E1S levels to a significantly greater extent than anastrozole" - See Femara (letrozole)at OffshoreRX.
  • Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study - J Clin Oncol. 2002 Feb 1;20(3):751-7 - "estrone (E(1)), estradiol (E(2)), and estrone sulfate (E(1)S) ... Treatment with anastrozole suppressed plasma levels of E(1), E(2), and E(1)S by a mean of 81.0%, 84.9%, and 93.5%, respectively, whereas treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and 98.0%, respectively. The suppression of E(1) and E(1)S was found to be significantly better during treatment with letrozole compared with anastrozole"
• 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"
• Sex hormone-binding globulin: a new marker of disease severity and prognosis in men with chronic heart failure - Rev Esp Cardiol 2009 Dec - "Sex hormone-binding globulin (SHBG) is a key regulator of the actions of anabolic steroids. Chronic heart failure (HF) has been associated with anabolic steroid deficiency, but its relationship with SHBG is not known ... At enrolment, the SHBG level (median 34.5 nmol/L, IQR 27-50 nmol/L) was correlated with the N-terminal probrain natriuretic peptide level (r=0.271, P=.005), LVEF (r=-0.263, P=.007), body mass index (r=-0.199, P=.020) and total testosterone level (r=0.332, P=.001). The median SHBG level was higher in the 16 patients (15.4%) who died, at 48.5 nmol/L (IQR 36-69.5 nmol/L) vs. 33 nmol/L (IQR 25.3-48.7 nmol/L; P=.001), and a high level was associated with an increased risk of death (hazard ratio [HR]=1.045, 95% confidence interval [CI] 1.021-1.069; P< .001). The association remained significant after adjustment in Cox multivariate regression modeling, at HR=1.049 (95% CI 1.020-1.079; P=.001). Analysis by SHBG tertiles showed mortality was 30% in the third tertile, 14% in the second, and 4% in the first (log rank 0.007; HR=3.25 ... The SHBG level correlated with measures of HF severity and was associated with a higher risk of cardiac death"
• 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"
• Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition - JCEM, 10/1/05 - "In both the young and elderly group, SHBG levels decreased during letrozole treatment (P = 0.003 and <0.001, respectively; P value for young vs. elderly was not significant)"