Inflammation is a hot topic button these days. It is hard to read any medical or Health related publications and not read something about inflammation and its contribution to medical problems, disease, and the obstacle it provides to Health. Increased inflammation is found in people with low vitamin D. Increased inflammation results from imbalanced gut bacteria and contributes to extreme metabolic dysfunction and eventually metabolic syndrome. Good nutrition can reduce inflammation; a lack of good nutrition results in inflammation. Obesity is associated with increased systemic inflammation and the result is increased risk of diabetes and cardiovascular disease. Inflammation is critical to the environment that favors cancer development. Whatever the headline, inflammation’s impact on health and disease is hard to miss.
What Does inflammation have to do with Testosterone in men? Quit a bit actually.
In case you have missed the connection in my previous posts, low Testosterone can have quit the negative physiologic impact in men. Low Testosterone and inflammation is no different. Low Testosterone in men is associated with increased inflammation–No opinion here , just science. The evidence that low Testosterone is associated with increased inflammation is very strong:
- Bobjer J et al. Negative association between Testosterone concentration and Inflammatory markers in young men: A nested cross-sectional study. PLOSone. April 18 2013. DOI:10.1371/journal.pone.0061466.
- Bhatia V et al. Low Testosterone and high C-Reactive Protein concentrations predict low hematocrit in type 2 Diabetes. Diabetes Care. Oct 2006;29(10):2289-2294.
- Lyengar RL et al. Low Total Testosterone is associated with inflammation and dyslipidemia in a large population of asymptomatic middle aged men. Circulation. 2011;124:A17951.
- Nettleship JE et al. Inverse relationship between serum levels of interleukin-1beta and Testosterone in men with stable coronary artery disease. Hormone and Metabolic Research. May 2007;39(5):366-71.
- Hall J et al. Testosterone and pro-inflammatory cytokines in men with chronic heart failure. Endocrine Abstracts. 2002;3:250.
The studies highlighted above show that low Testosterone in men is associated with increased inflammatory cytokine signaling–particularly TNF-alpha, IL-1beta, MIP-1alpha, CRP, IL-6, and IL-10. This is just a sampling of the evidence available that low Testosterone in men is associated with increased inflammation in men. When it comes to women and Testosterone, the opposite seems to apply.
How does low Testosterone come to exist in men? I review the 8 most common causes of low Testosterone found in men in my first book Man Boob Nation. One of the most common causes of low Testosterone that I see in men today is the result of excess Estrogen production. Figure 1 shows the linear relationship between increasing Estrogen and inflammation in men. For men, 80% of Estrogen production comes from abdominal fat. Yes, that unsightly mid-section bulge is biologically active. In this case, increasing Estrogen production inhibits Testosterone production. The evidence that excess Estrogen production increases inflammatory cytokine signaling in men is equally strong:
- Mogri M et al. Testosterone concentrations in Young pubertal and post-pubertal obese males. Clin Endocrinol. 2012 Apr;78(4):593-9.
- Tsilidis KK et al. Associations between endogenous sex steroid hormones and inflammatory biomarkers in US men. Andrology. Sep 30 2013. 2047-2927.
- Barud W et al. Relation between markers of inflammation and estradiol in older men. Med Sci Monit. 2010 Dec;16(12):CR593-7.
- Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly Men. Aging Male. 2002 Jun;5(2):98-102.
- Harris MT et al. Expression of proinflammatory genes during estrogen-induced inflammation of the rat prostate. Prostate.200;44:19-25.
- Wilson MJ et al. Matrix metalloproteinases in the pathogenesis of estradiol-induced nonbacterial prostatitis in the lateral prostate lobe of the Wistar rat. Exp Mol Pathol.2004;77:7-17.
Don’t think that the elimination of Estrogen in men will be the panacea. Hormones appear to have a “U” shaped curve. One can lower Estrogen levels to low in men. A man with low Estrogen level can have symptoms similar to men with high levels of Estrogen, though men with higher Estrogen levels have worse metabolic dysfunction and much worse symptoms. The same applies to Testosterone. Figure 2 (right) shows how low Testosterone and high Testosterone levels in men are both associated with increased probability of dying–classic “U” shaped physiologic window. The same applied to DHT and Estradiol, though less significant. In between the high and low hormone levels, optimal and physiologic levels of Estrogen and Testosterone are where optimal hormone balance and Wellness is achieved in men. This appears to be the case with most hormones–physiologic “U” shaped windows with too little associated with metabolic dysfunction and too much equally associated with increased metabolic dysfunction and disease risk.
Elevated Estrogen levels in men increases inflammation. Elevated Estrogen levels in men has been shown to decrease Testosterone levels in men. Low Testosterone is associated with increased inflammation in men. The next logical question should be: does the addition of Testosterone to men with low Testosterone reduce inflammation? The answer is yes. As with elevated Estrogen and low Testosterone, the evidence linking Testosterone therapy in men with low Testosterone to a reduction in inflammation is strong:
- Svetlana YK et al. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double blinded placebo-controlled Moscow study. Clinical Endocrinology. 2010 Nov;73(5):602-612.
- Malkin CJ et al. Testosterone replacement in hypogonadal men with angina improves threshold and quality of life. Heart. 2004 August;90(8):871-876.
- Malkin CJ et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004 Jul;89(7):3313-8.
- Cutolo M et al. Androgen replacement therapy in male patients with rheumatoid arthritis. JArthritis Rheum 34:1-5.
- Bizzarro A et al. Influence of testosterone therapy on clinical and immunological features of autoimmune diseases associated with Klinefelter’s syndrome. J Clin Endocrinol Metab 64:32-36.
- Yalinchenko SY et al. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clinical Endocrinology. Nov 2010;73(5): 602-612.
These studies, with provided links, are just a sampling of the evidence that low Testosterone and high Estrogen levels in men results in increased inflammatory signaling. In addition, Testosterone therapy in men with low Testosterone will reduce inflammatory signaling in men. No opinion, just science.