Your older patients struggling with obesity, research shows, are possibly suffering from low testosterone linked to a host of other health issues
Testosterone is an anabolic steroid synthesized from cholesterol that elicits a range of physiological processes modulating the physiology and function of multiple organ systems, including muscle, fat, bone, brain, vascular, peripheral nerves, male genital and reproductive systems.1
Serum testosterone levels are controlled by the hypothalamic-pituitary-gonadal (HPG) axis, whereas a negative feedback system is in place to prevent the overproduction of testosterone (see Figure 1). Here we will explore what exactly occurs when there is an underproduction of testosterone.
Testosterone deficiency, also known as hypogonadism, affects about 30 percent of men 40-79 years of age, declining at a rate of 0.5 to 2 percent per year from the age of 30. This decline can be caused by normal physiological changes of aging including testicular dysfunction, or hypothalamus or pituitary gland pathology. We will focus on the former, in particular concomitant changes that occur in obesogenic males. As men age, Leydig cells in the testes begin to deteriorate, decreasing negative feedback and prompting the pituitary gland to surge the gonadotropin luteinizing hormone (LH). This physiological response is termed subclinical compensatory hypogonadism. As the aging male’s body composition changes (commonly seen with sarcopenia) the LH surge becomes inhibited, ultimately disrupting this compensatory response, leading to secondary hypogonadism and its associated physiological decline.
Andropause and clinical manifestation
Testosterone lowering below the normal range is associated with a decrease in quality of life in addition to accelerated aging and several clinical disorders such as diabetes, depression, sexual dysfunction, cognitive decline, dyslipidemia, hypertension, frailty and cardiovascular disease.
As our society has increasingly adopted a more Westernized diet featuring excessive macronutrient consumption, while simultaneously engaging in less frequent physical activity and diminished sleep quality, obesity rates have steadily risen, particularly in the last two decades. This confirms the significant inverse correlation between testosterone and fat (see Figure 2). The hormone leptin is involved in the regulation of energy homeostasis, neuroendocrine function, immunity, lipid and glucose homeostasis, and fatty acid oxidation. Human obesity appears to be the important variable because adipocytes upregulate the hormone leptin, causing “leptin resistance,” which diminishes testosterone levels. In fact, leptin is the best hormonal predictor of a reduction to androgen response related to obesity.
Consequently, low testosterone appears to be both a cause and effect of obesity-induced androgen deficiency and hypogonadism-induced obesity. The prime target here is at the enzymatic activity of aromatase, responsible for converting testosterone to estradiol, that is upregulated by adipocyte expression. The aromatization of testosterone or aromatase activity upregulation has been detected in males with centralized fat accumulation via increased estrogen and androgen receptor activity. Reduced plasma testosterone exacerbates obesity since it promotes changes in body composition, such as enhanced abdominal fat, creating a negative cycle termed hypogonadism-obesity cycle.
Ectopic fat contains a plethora of pro-inflammatory mediators: adipokines such as leptin, resistin, adiponectin, visfatin, and cytokines such as tumor necrosis factor, interleuken-1, and interleukin-6 that not only contribute to insulin resistance and vascular dysfunction but in addition inhibit hypothalamic production of testosterone release (see Figure 1).
It is imperative to distinguish between subcutaneous fat and visceral fat. Visceral fat is present mainly in the omentum and mesentery and drains directly through portal circulation to the liver. Visceral fat compared to subcutaneous fat is more metabolically active, and contains a large number of inflammatory and immune cells, or macrophages, in addition to being more sensitive to lipolysis and more insulin resistant. Thus, visceral fat carries a better prediction of mortality than subcutaneous fat. With observational and epidemiological data suggesting that obesity is the single most powerful contributor to low testosterone, addressing obesity is the most crucial step in a viable treatment option.
Intermittent energy restriction
Circulating elevated levels of insulin and leptin positively correlate with overfeeding and subsequent fat mass gain within the body and impaired long-term regulation of energy balance. Although a decreased eating/feeding frequency lifestyle is often a polarizing topic of discussion, current research is increasingly exploring this implementation.
Intermittent energy restriction (IER), defined as periods of energy restriction followed by periods of normal energy intake, has been investigated as a promising intervention in reducing metabolic disease and centralized fat deposition. Unlike the standard approach to fat loss: continuous energy restriction (CER), which is associated with poor long-term compliance, IER appears to be significantly more achievable due to greater adherence. The primary distinction between CER and IER centers on the stomach’s production of the peptide hormone ghrelin.
Since ghrelin levels are strictly dependent on recent food intake, continuous and substantial reduced food intake increases the concentration of ghrelin. Chronic underfeeding simply facilitates chronic overfeeding. Ghrelin (upregulation) as a potent orexigenic hormone will further enhance feelings of hunger and consequently food intake. Inversely, with IER food intake quantity is not modified in any way, at least initially — modification is made solely to the period of time that feeding is “allowed.” The underlying physiological mechanisms occurring during periods of energy restriction may account for the vast array of positive vascular, metabolic and psychological effects.
Depending on the level of physical activity, a 12- to 24-hour fast typically results in a 20 percent or greater decrease in serum glucose and depletion of hepatic glycogen, accompanied by the switch to a metabolic mode in which non-hepatic glucose, fat-derived ketone bodies and free fatty acids are used as energy sources. Overall, the hormonal changes that typify hypogonadism in over-fat males are altered for the better: improving insulin and leptin sensitivity, and elevating growth hormone, adinopectin and ghrelin levels. In addition, there is a decrease in blood lipids, triglycerides and low-density lipoproteins, and a reduction in inflammatory markers IL-6, TNF-alpha, CRP and homocysteine.
Patient lifestyle modification
Many health clinics tout the benefits of testosterone replacement for people with “low T,” but rarely do physicians explore the role that central adiposity plays in hypogonadism. With a better understanding of clinical nutrition, you may now offer patients another reason to modify their lifestyle.
Louis Miller, DC, MS, DACN, is the owner and operator of Advanced Chiropractic of South Florida and Healthy Weight Solutions. He is currently writing his first book about the many nutritional
cases he’s been presented during practice. He can be contacted at
561-432-1399 or through healthyweightsolutions.org.
Doug Shapiro is a medical student at Lincoln Memorial University with a graduation date in 2020.
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