Hypogonadism and Obesity Have Strong Bidirectional Association
Obesity causes substantial morbidity and mortality. When indicated, TRT significantly improves weight loss without compromising lean muscle mass.
Throughout his life, my father struggled with obesity and endured severe back pain from a serious injury he suffered while serving in the Vietnam War. His physically demanding job as a roofing contractor further compounded his pain. On more than one occasion, I observed my dad arrive home from work and have to crawl from his truck into the house. In addition, he was morbidly obese his entire life. He successfully lost over 100 pounds many times but always regained the weight.
Most of the time, my dad would "tough it out" and live with his pain, but sometimes he had to see his physician because he could barely walk. He rarely could heed his doctor’s advice and rest because work was how he put food on the table for his family. He sought ways to ease his pain, like a cortisone shot, pain medication, or maybe a referral to a back specialist; he needed to be able to climb up a ladder, walk around a steep roof and perform heavy labor.
Despite my father’s dedication and lack of options, his doctor showed little compassion or patience, frustrated that he hadn’t lost weight as advised. The implication was that my dad had more significant problems than getting pain relief. Since he was obese, had high blood pressure, and continued to work a physically demanding, stressful job, it wouldn't be long before he would have a massive heart attack.
Like most people who suffer from severe obesity, my dad was well aware of his increased risk of high cholesterol, hypertension, and arthritis. He had been tested for type 2 diabetes several times, knew he was at a disadvantage metabolically, and was sure his obesity wasn't solely because he ate more than other folks. His testosterone level was never tested.
Stories like my dad's aren't unique but are a regular aspect of life for people of size. A 2012 study surveyed 2,000 medical providers and revealed that physicians have similar levels of anti-fat bias as the general population. Moreover, in most Western cultures, people have been conditioned to condemn people who are obese.
Lilia Graue, MD, LMFT, believes obesity bias has repercussions, and doctors commonly "fail to provide adequate and timely diagnosis and treatment due to all kinds of assumptions, which affect patients along the full weight spectrum." Patients with obesity learn that doctors recommend scans, blood tests, and physical therapy for average-weight patients but repeatedly advise them to lose weight. When doctors body-shame, they risk harming patients' sense of self-efficacy, adversely affecting well-being and quality of life and often leading them to avoid medical care.
Another study of 3,000 adults found that weight discrimination may lead to weight gain from the stress response that can increase appetite for unhealthy food. Compassion and support are more effective than tough love.
Obesity is a chronic multifactorial disease triggered by genetic, psychological, lifestyle, nutritional, environmental, and hormonal factors. Obesity is considered a complex physiological disorder with many causes and comorbidities. It isn't the result of a lack of willpower or moral failure.
Based on the National Survey of Children's Health, one in six youth in the U.S. are obese. Moreover, childhood obesity has tripled in adolescents and more than doubled in children in the past three decades.
Obesity is easy to recognize but very difficult to treat. According to the American Academy of Child and Adolescent Psychiatry, unhealthy weight gain due to poor diet and lack of exercise is responsible for over 300,000 U.S. deaths annually; societal costs related to obesity are around $100 billion annually.
Obesity is strongly associated with increased all-cause mortality and cardiovascular and cancer mortality. Chronic disorders related to obesity include type 2 diabetes, cardiovascular disease, metabolic syndrome, some forms of cancer, arthritis, gallbladder disease, acute pancreatitis, nonalcoholic fatty liver disease, obstructive sleep apnea, and depression. Weight loss can significantly reduce the risk for most of these comorbidities.
Testosterone plays a vital role in men's wellness, and adequate testosterone levels are required for muscle and strength, bone density and mass, red blood cell production, sex drive, sperm production, and sexual function. Serum testosterone levels peak between puberty and early adulthood, then decrease at about 1% per year. Anything that speeds up this process, such as obesity, can lead to testosterone deficiency.
Hypogonadism is diagnosed when total testosterone levels are below 300 ng/dL, and symptoms are present, such as decreased libido and erectile dysfunction. Testosterone replacement therapy (TRT) is a standard, lifelong treatment for low testosterone.
Several studies have demonstrated an association between low testosterone and obesity:
· A landmark 2007 study of 1167 men 40 to 70 years old examined how lifestyle factors and health changes affected the testosterone decline rate. This study gave the first compelling evidence that alterations in health and lifestyle, such as increased body mass index (BMI), are accompanied by accelerated loss of testosterone.
· A 2008 study of 1,862 men ages 30 and above compared waist circumference and BMI, revealing that waist circumference was a stronger predictor of low testosterone than BMI. In addition, a waist size increase of 4 inches increased the odds of having low testosterone by 75%; 10 years of aging increased the odds of having low testosterone by 36%. Waist circumference has been the strongest predictor of low testosterone in multiple studies.
In addition, several studies demonstrate that TRT decreases body fat and facilitates weight loss in patients who are obese:
· Results of a study of 411 obese, hypogonadal men receiving long-term (up to 5 years) testosterone replacement therapy (TRT) showed progressive and sustainable weight loss. The subjects in the study represented all three obesity classes. Based on this study, TRT appears to be a practical approach to sustained weight loss for obese, hypogonadal men, irrespective of obesity severity.
· A 2016 study of 100 hypogonadal men with obesity compared calorie restriction with calorie restriction plus TRT in total weight loss, maintenance of weight loss, and body composition. The average age of the subjects was 53. Patients were randomly assigned to receive 56 weeks of testosterone undecanoate or placebo. Both groups spent ten weeks on a low-energy diet and 46 weeks on weight maintenance. At the calorie-restricted ten weeks, there were no differences in weight loss or changes in body composition between the testosterone group and placebo. However, the testosterone group maintained weight loss through the maintenance phase, while there was a slight weight gain in the control group.
In addition, at the end of the study, the testosterone group had greater fat mass and visceral fat reductions compared to placebo. Also, the testosterone subjects regained lean muscle mass compared with placebo. The overall results showed that the placebo group initially lost fat and muscle during the diet phase, while TRT shifted the weight loss to almost exclusively fat loss. There were no differences in adverse events between groups.
· A 2019 study followed 462 patients in their 50s and 60s with hypogonadism and obesity who were given the choice of whether to start long-term TRT. Of these, 273 patients elected to receive testosterone, and the 189 patients who declined served as the control group. The study showed that over ten years, the testosterone group lost 20.3% of their baseline weight, their waist circumferences decreased by 12.5 cm. and their BMI decreased by 7.3 kg/m2. In contrast, the control group gained 3.9% of their baseline weight, their waist circumference increased by 4.6 cm. and their BMI increased by 0.9 kg/m2. There were no increases in prostate cancer or cardiovascular events in the testosterone group. There was, however, a much higher mortality rate and incidence of major cardiovascular events in the untreated control group.
These are just a sample of the multiple studies demonstrating the correlation between obesity and low testosterone and the weight loss benefits TRT presents for patients with obesity and hypogonadism.
Obesity Hypogonadism Mechanisms
The generally accepted leading reasons obesity leads to decreased testosterone are aromatase overproduction and sex hormone-binding globulin (SHBG) inhibition. First, as you gain more fat cells, aromatase, the enzyme that converts testosterone to estrogen, increases. In obese men with excess fat accumulation, the increased aromatase irreversibly converts testosterone to estradiol, which leads to decreased testosterone and increased estrogen levels.
A second reason obesity can decrease testosterone is the reduced release of the protein SHBG. The function of SHBG is to bind with testosterone and carry it to the bloodstream. However, there is an inverse relationship between high fat and the release of SHBG proteins. Obesity, specifically visceral fat, is associated with decreased testosterone and SHBG.
The mechanism whereby obesity decreases testosterone appears to differ based on obesity severity. For example, modest obesity is primarily associated with reduced total testosterone due to insulin resistance and reduced SHBG. However, severe obesity (BMI >35) appears to decrease testosterone by suppressing the hypothalamic-pituitary-gonadal (HPG) axis. It is postulated that obesity suppresses the HPG axis through leptin resistance, dysregulated insulin signaling, and elevations in pro-inflammatory cytokines.
Low testosterone and obesity are related, and obesity, specifically waist circumference, is the strongest predictor of testosterone deficiency. Also, obesity is one of the strongest predictors of whom will be treated with TRT.
While the obesity-hypogonadal relationship is bidirectional, the influence obesity has on testosterone concentrations is more substantial than testosterone's influence on obesity.
A vicious cycle whereby obesity lowers testosterone levels which can lead to more weight gain. The cycle can compound the problem, potentially leading to continued weight gain and testosterone level reduction.
Obesity has reached epidemic levels and continues to increase, causing significant morbidity and mortality. People with obesity, such as my dad, must be met with compassion and an understanding that weight loss by diet and exercise alone fails 95% of the time. The dire outcomes related to obesity demand that physicians are willing to recommend surgery, prescribe anti-obesity medications, and utilize TRT when indicated.