Know the disease risks of low testosterone

There are certain disease risks for those with low testosterone levels. But if you are suffering from the effects of low testosterone, you’ll be pleased to know that peer-reviewed scientific literature has shown the benefits, indications, and safety of testosterone replacement therapy.

Thankfully, the diagnosis of testosterone deficiency is not limited to laboratory test values. In this article you’ll learn these criteria and some contraindications of which you should be aware.

Along with the scare that testosterone replacement increases heart health risks, as I told you last week in “Testosterone supplementation: Looking at controversial studies,” you first need to be aware that testosterone deficiency poses its own health risks. There is an abundance of studies and meta-analyses that clearly show the association of low testosterone levels in men with cardiovascular disease. [1] [2] [3] [4] [5] [6] There is also a strong association between low testosterone levels and all-cause mortality. [7] [8] [9] [10] [11] [12] [13] In fact, researchers conclude that a decrease of 2.1 standard deviations from normal levels of total serum testosterone is associated with a 25 percent increase in mortality.

Furthermore, low testosterone is found in up to 40 percent of patients with type 2 diabetes. [14] The Endocrine society [15] recommends routinely screening for low testosterone in men with metabolic syndrome (now nearly one in three American adults have this) and type 2 diabetes. They also recommend screening for low testosterone in men with chronic lung disease, osteoporosis, HIV infection, infertility, alcohol abuse, and prolonged treatment with steroids, opiate pain relievers or anticonvulsants.

Low testosterone correlates with many other illnesses

There are more conditions that seem to be associated with low testosterone, indicated by the fact that testosterone replacement therapy improves all these conditions:

  • It improves skeletal muscle mass and strength and builds bones. It decreases pain and death resulting from sarcopenia (degenerative loss of skeletal muscle mass) and osteoporosis (loss of bone density). [16]
  • It improves cognitive function: Higher endogenous testosterone correlates with improved memory, executive function and spatial ability, reduced Alzheimer’s disease and increased cerebral blood flow. [17] Furthermore, testosterone supplementation improves spatial cognition and verbal fluency. [18]
  • Testosterone replacement lowers inflammation and lowers inflammatory cytokines TNF and IL-1 beta; lowers total cholesterol. [19]
  • It improves prostate health (if non-cancerous). Testosterone replacement has no adverse effect on prostate hypertrophy [20] and no increased risk of prostate cancer. [21] [22] [23]
  • It improves libido, sexual appetite, frequency and firmness of erections.
  • It increases energy and feeling of well-being (improves mood). It improves anxiety/fear/depression and loss of self-confidence. Treats anemia.
  • It strengthens the heart and blood vessels and lowers blood pressure, reduces blood clots and improves tissue oxygenation.

Who gets to have testosterone replacement therapy?

Clinical practice guidelines state: “We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels.”  Agreed—however, the definition of “androgen deficiency” varies, as does the cut-off level of “low” serum testosterone.

There is disagreement as to whether a person has androgen deficiency solely based on the laboratory measurement. The international experts (International Society for Study of the Aging Male, European Association of Urology, and the British Society for Sexual Medicine Association) define androgen deficiency by not only a low level, but also clinical symptoms.

They will give a six months trial of therapy if it is a borderline low testosterone level and a man has any symptoms of low testosterone. In fact, a recent poll of expert endocrinologists [24] revealed that in clinical practice, they don’t limit the diagnosis of “androgen deficiency” based on a lab value only. They say that symptoms and signs are “paramount” and recognize that in many men the testosterone that is circulating in the blood does not function because of low receptor uptake and resistance to the hormone. That’s why a therapeutic trial is used in symptomatic cases, not a strict adherence to the serum testosterone concentrations.

In the U.S., doctors are agreeing with the international community more, even though labs report the normal total testosterone range to be from 250 to 350 up to 1,200 nanograms per deciliter (ng/dl). However, for optimal levels many experts argue for treatment at a much higher threshold level.

Experts in the U.S. agree that, “Fatigue, loss of libido and erectile dysfunction are commonly reported, but non-specific symptoms of low testosterone (T) and laboratory verification of low testosterone is an important part of evaluation in addition to a detailed history and physical exam.” That’s because there are significant intra-individual fluctuations in serum testosterone levels, biological variation of testosterone action on end organs, and a wide range of testosterone levels in serum samples. Thus, “laboratory results have to be interpreted in the appropriate clinical setting.” [25]

In my next article I’ll discuss safe and effective methods of testosterone replacement therapy.

To feeling good for health,

Michael Cutler, M.D.
Easy Health Options

[1] Muller M, et al. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 2004. May 4;109(17):2074-9.

[2] English KM, et al. Low-dose transdermal therapy improves angina threshold in men with chronic stable angina. Circulation 2000 Oct 17;102(16):1906-11.

[3] Khaw K-T, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) prospective population study. Circulation 2007; 116(23):2694–2701. [PubMed]

[4] Vikan T, Schirmer H, Njølstad I, Svartberg J. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromsø study. European Journal of Endocrinology. 2009;161(3):435–442. [PubMed]

[5] Hyde Z, Norman PE, Flicker L, et al. Low free testosterone predicts mortality from cardiovascular disease but not other causes: the health in men study. Journal of Clinical Endocrinology & Metabolism.2012;97(1):179–189. [PubMed]

[6] Yeap BB, Hyde Z, Almeida OP, et al. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. Journal of Clinical Endocrinology & Metabolism. 2009;94(7):2353–2359. [PubMed]

[7] Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Archives of Internal Medicine. 2006;166(15):1660–1665. [PubMed]

[8] Hackett G, Kirby M, Sinclair AJ. Testosterone deficiency, cardiac health, and older men. Int J Endocrinol. 2014;2014:143763.

[9] Laughlin GA, et al. “Androgen Deficiency and All-cause Mortality in Older Men: The Rancho Bernardo Study.” Abstract 55-2 presented June 5, 2007. Endocrine Society Annual Meeting.

[10] Tivesten Å, Vandenput L, Labrie F, et al. Low serum testosterone and estradiol predict mortality in elderly men. Journal of Clinical Endocrinology & Metabolism  2009; 94(7):2482–2488. [PubMed]

[11] Maggio M, Lauretani F, Ceda GP, et al. Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the chianti area (InCHIANTI) study. Archives of Internal Medicine. 2007;167(20):2249–2254 [PubMed]

[12] Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Endogenous testosterone and mortality in men: a systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism. 2011;96(10):3007–3019. [PubMed]

[13] Haring R, Völzke HV, Steveling A, et al. Association of low testosterone levels with all-cause mortality by different cut-offs from recent studies. European Heart Journal  2010; 31:1494–1501.[PubMed]

[14] Oh J-Y, Barrett-Connor E, Wedick NM, Wingard DL. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care.2002;25(1):55–60. [PubMed]

[15] Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 2006;91(6):1995–2010.

[16] Harman SM, et al. Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Clin Endocrinol Metab. 2001;86:724-731.

[17] Moffat SD, Resnick SM. Long-term measures of free testosterone predict regional cerebral blood flow patterns in elderly men. Neurobiol Aging. 2007 Jun;28(6):914-20.

[18] Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009 Jun;5(3):427-48.

[19] Malkin CJ, et al. The effect of testosterone replacement on on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004 Jul;89(7):3313-8.

[20] Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009 Jun;5(3):427-48.

[21] Gould DC, Kirby RS. Testosterone replacement therapy for late onset hypogonadism: what is the risk of inducing prostate cancer? Prostate Cancer Prostatic Dis. 2006;9(1):14-18.

[22] Morgentaler A. Testosterone therapy and prostate risks: where’s the beef? Can J. Urol. 2006 Feb;13 Suppl 1: 40-43.

[23] Roden E, et al. A medical progress: risks of testosterone replacement therapy and recommendations for monitoring. NEJM 2004; 350:482-92.

[24] Morgentaler A, Khera M, Maggi M, Zitzmann M. Commentary: Who is a candidate for testosterone therapy? A synthesis of international expert opinions. J Sex Med. 2014 Jul;11(7):1636-45.



Dr. Michael Cutler

By Dr. Michael Cutler

Dr. Michael Cutler is a graduate of Tulane University School of Medicine and is a board-certified family physician with more than 20 years of experience. He serves as a medical liaison to alternative and traditional practicing physicians. His practice focuses on an integrative solution to health problems. Dr. Cutler is a sought-after speaker and lecturer on experiencing optimum health through natural medicines and founder of the original Easy Health Options™ newsletter — an advisory on natural healing therapies and nutrients. His current practice is San Diego Integrative Medicine, near San Diego, California.