AACE and ACE clinical practice guidelines on obesity call for testosterone testing and treatment

15 January 20172

American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Garvey WT, Mechanick JI, Brett EM, et al. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2016;22 Suppl 3:1-203.

The combined prevalence of overweight and obesity is 71% in adults1, and up to 50 - 80% of obese men have testosterone deficiency (also known as hypogonadism).2,3 The most common comorbidity among the growing obese population is type 2 diabetes4; about half of all men with type 2 diabetes have hypogonadism.3,5

Recent clinical guidelines on hypogonadism state that increased visceral body fat and obesity are signs of hypogonadism, and that testosterone should be assessed in men with obesity, metabolic syndrome and diabetes.6-8 However, due to the epidemic prevalence of overweight/obesity and related metabolic diseases, the large majority of hypogonadal men will see a primary care physician and/or a diabetologist or cardiologist, who is likely not aware of the clinical guidelines on hypogonadism.

It is therefore laudable that The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) Clinical Practice Guidelines for Comprehensive Medical Care of Patients with Obesity in their 2016 revision dedicated two comprehensive sections on testosterone deficiency and treatment. Here we summarize these AACE / ACE recommendations.9

KEY POINTS

  • All men who have an increased waist circumference (≥102 cm) or who have obesity (BMI ≥30) should be assessed for hypogonadism by history and physical examination and be tested for testosterone deficiency; all men with hypogonadism should be evaluated for the presence of overweight or obesity.
  • All men with type 2 diabetes should be tested to exclude testosterone deficiency.
  • Treatment of hypogonadism in men with increased waist circumference or obesity should include weight-loss therapy. Weight loss of more than 5 to 10% is needed for significant improvement in serum testosterone.
  • Bariatric surgery should be considered as a treatment approach that improves hypogonadism in most patients with obesity, including patients with severe obesity (BMI >50 kg/m2) and type 2 diabetes.
  • Men with hypogonadism and obesity who are not seeking fertility should be considered for testosterone therapy in addition to lifestyle intervention, since testosterone in these patients results in weight loss, decreased waist circumference, and improvements in metabolic parameters glucose, HbA1C, lipids, and blood pressure).

What is known

The prevalence of obesity1,10 and the metabolic syndrome11 continues to rise, and so does the common obesity related comorbidity type 2 diabetes.12 Nearly 35% of all adults and 50% of those aged 60 years or older have the metabolic syndrome11, and 38% are obese.1 In Western countries diabetes prevalence is 12%.13 Alarmingly, nearly 28% of the population has undiagnosed diabetes.13

While the prevalence of hypogonadism in primary care has been reported to be 10 - 39% 3,14, among obese men testosterone deficiency is up to 8 times more common.2,3 Obese men with or without the metabolic syndrome have around 150 and 300 ng/dL (5.2 and 10.4 nmol/L) lower testosterone levels compared to same aged lean men without metabolic syndrome.15 Based on these analyses, the presence of diabetes or fasting serum glucose greater than 110 mg/dL, BMI 30 kg/m2 or greater, and triglycerides 150 mg/dL or greater, each have a clinically relevant association with low serum testosterone.15

The Multidisciplinary Guidelines Task Force on Testosterone, Deficiency underscores that increased visceral body fat/obesity and decreased muscle mass are signs associated with testosterone deficiency.7 The 2016 EAU Guidelines on hypogonadism recommend assessment of testosterone in men with:6

  • Type 2 diabetes
  • Metabolic syndrome
  • Obesity

Physicians in primary care, diabetologists and cardiologists are unlikely to read hypogonadism specific guidelines. Therefore, the 2016 AACE/ACE clinical practice guideline – which targets health care professionals who are more likely to first encounter hypogonadal men - is a landmark publication.9

What the new AACE and ACE Clinical Practice Guideline recommends

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) Clinical Practice Guidelines for Comprehensive Medical Care of Patients with Obesity point out that there are strong associations between obesity, hypogonadism, and cardiometabolic disease, and conclude that sufficient evidence exists to include measurement of serum testosterone in the diagnostic evaluation of metabolic syndrome and type 2 diabetes.9 Obesity is covered in their executive summary:9

  • All men who have an increased waist circumference (≥102 cm) or who have obesity (BMI ≥30 kg/m2) should be assessed for hypogonadism by history and physical examination and be tested for testosterone deficiency; all men with hypogonadism should be evaluated for the presence of overweight or obesity.
  • All men with type 2 diabetes should be tested to exclude testosterone deficiency.

Regarding treatment, the AACE/ACE guideline states:9

  • Treatment of hypogonadism in men with increased waist circumference or obesity should include weight-loss therapy. Weight loss of more than 5 to 10% is needed for significant improvement in serum testosterone.
  • Bariatric surgery should be considered as a treatment approach that improves hypogonadism in most patients with obesity, including patients with severe obesity (BMI >50 kg/m2) and type 2 diabetes.
  • Men with hypogonadism and obesity who are not seeking fertility should be considered for testosterone therapy in addition to lifestyle intervention, since testosterone in these patients results in weight loss, decreased waist circumference, and improvements in metabolic parameters glucose, HbA1C, lipids, and blood pressure).

Comments

It is particularly notable that the AACE/ACE guideline recommends obese men with hypogonadism should be considered for testosterone therapy9, as this acknowledges the relatively unknown vicious circle between obesity and hypogonadism.16,17

Bariatric surgery increases testosterone levels and may reverse hypogonadism.2 After bariatric surgery, the mean weight loss (baseline BMI 42 kg/m2) is maximal after 1 to 2 years (gastric bypass, 3%; vertical-banded gastroplasty, 25%; and banding, 20%). After 10 years, the weight losses is 25% for gastric bypass, 16% for vertical-banded gastroplasty, and 14% for banding, as compared with baseline eight.18 However, bariatric surgery is an invasive and expensive procedure that is not available to most patient. Bariatric surgery also confers a risk for serious complications.

In contrast, testosterone therapy – which is ubiquitously available at a fraction of the cost of bariatric surgery - safely reverses hypogonadism and results, if performed long-term and adequately, in a similar weight loss as bariatric surgery.19-27 A rapidly accumulating body of evidence is showing that testosterone therapy reduces fat mass and increases lean body mass, and in obese hypogonadal men results in concomitant weight loss with reduction in waist circumference and BMI.20,28-35 Long-term testosterone therapy for up to 10 years in obese men with testosterone deficiency results in a significant and marked sustained weight loss, and reduced waist circumference and BMI, without weight regain.20-27 A notable observational study of testosterone therapy in obese hypogonadal men found marked weight loss of 16.78%, 21.62% and 23.59% in obesity class I, class II and class III,  respectively (figure 1).19

Percent weight loss in 411 hypogonadal men receiving long-term testosterone treatment for up to 8 years

Figure 1: Percent weight loss in 411 hypogonadal men receiving long-term testosterone treatment for up to 8 years.19

Note: Obesity class I = BMI 30 - 34.9; class II = BMI 35 - 39.9; class III = BMI ⩾ 40

The 8 year long-term data of testosterone therapy in obese hypogonadal men19 favorably compare with the 10 year data after bariatric surgery.18 Considering that bariatric surgery is an invasive and expensive procedure that can only treat a minority of the growing obese population, non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives.36

Further support for using testosterone therapy to treat obese hypogonadal men comes from research showing that long-term testosterone therapy for up to 10 years is safe and significantly and sustainably improves cardiometabolic parameters such as lipid profile, glycemic control, blood pressure, heart rate, and pulse pressure.20-22,27,37-40

References

  • Centers for Disease Control and Prevention. Obesity and Overweight. Available at https://www.cdc.gov/nchs/fastats/obesity-overweight.htm (accessed Dec 23, 2016). Return to content
  • Pellitero S, Olaizola I, Alastrue A, et al. Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery. Obes Surg. 2012;22(12):1835-1842. Return to content
  • Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60(7):762-769. Return to content
  • Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC public health. 2009;9:88. Return to content
  • Biswas M, Hampton D, Newcombe RG, Rees DA. Total and free testosterone concentrations are strongly influenced by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and diabetes-related quality of life. Clin Endocrinol (Oxf). 2012;76(5):665-673. Return to content
  • Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S, Punab M. 2016 EAU Guidelines on Male Hypogonadism, available at http://uroweb.org/wp-content/uploads/EAU-Guidelines-Male-Hypogonadism-2016.pdf (accessed January 11, 2017). Return to content
  • Morales A, Bebb RA, Manjoo P, et al. Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. Appendix available at: http://www.cmaj.ca/content/suppl/2015/10/26/cmaj.150033.DC1/15-0033-1-at.pdf (accessed Jan 10, 2016). CMAJ. 2015;187(18):1369-1377. Return to content
  • Dean JD, McMahon CG, Guay AT, et al. The International Society for Sexual Medicines Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men. The journal of sexual medicine. 2015;12(8):1660-1686. Return to content
  • Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Available at http://journals.aace.com/doi/pdf/10.4158/EP161365.GL (accessed December 30, 2016). Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2016;22 Suppl 3:1-203. Return to content
  • Collaboration NCDRF. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387(10026):1377-1396.. Return to content
  • Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. JAMA. 2015;313(19):1973-1974. Return to content
  • World Health Organization (WHO). Global report on diabetes. Geneva2016. Return to content
  • Centers for Disease Control and Prevention (CDC). National Diabetes Statistics Report. Available at https://www.cdc.gov/diabetes/data/statistics/statistics-report.html (accessed Apr, 15th, 2020). Return to content
  • Araujo AB, ODonnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004;89(12):5920- 5926. Return to content
  • Kaplan SA, Meehan AG, Shah A. The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men? J Urol. 2006;176(4 Pt 1):1524-1527; discussion 1527-1528. Return to content
  • Ng Tang Fui M, Dupuis P, Grossmann M. Lowered testosterone in male obesity: mechanisms, morbidity and management. Asian journal of andrology. 2014;16(2):223-231. Return to content
  • Tishova Y, Kalinchenko SY. Breaking the vicious circle of obesity: the metabolic syndrome and low testosterone by administration of testosterone to a young man with morbid obesity. Arq Bras Endocrinol Metabol. 2009;53(8):1047-1051. Return to content
  • Sjöström L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-752. Return to content
  • Saad F, Yassin A, Doros G, Haider A. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity Classes I-III: Observational data from two registry studies. Int J Obes (Lond). 2015;Jul 29 [Epub ahead of print]. Return to content
  • Francomano D, Lenzi A, Aversa A. Effects of five-year treatment with testosterone undecanoate on metabolic and hormonal parameters in aging men with metabolic syndrome. International journal of endocrinology. 2014;2014:527470. Return to content
  • Haider A, Saad F, Doros G, Gooren L. Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone: An observational study. Obes Res Clin Pract. 2014;8(4):e339-349. Return to content
  • Haider A, Yassin A, Doros G, Saad F. Effects of long-term testosterone therapy on patients with diabesity: results of observational studies of pooled analyses in obese hypogonadal men with type 2 diabetes. International journal of endocrinology. 2014;2014:683515. Return to content
  • Saad F, Haider A, Doros G, Traish A. Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obesity (Silver Spring). 2013;21(10):1975−1981. Return to content
  • Yassin A, Doros G. Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss. Clinical obesity. 2013;3(3-4):73-83. Return to content
  • Saad F, Yassin A, Doros G, Haider A. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies. Int J Obes (Lond). 2016;40(1):162-170. Return to content
  • Yassin A, Almehmadi Y, Saad F, Doros G, Gooren L. Effects of intermission and resumption of long-term testosterone therapy on body weight and metabolic parameters in hypogonadal in middle-aged and elderly men. Clin Endocrinol (Oxf). 2016;84(1):107-114. Return to content
  • Yassin AA, Nettleship J, Almehmadi Y, Salman M, Saad F. Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadal elderly men: real-life experience from an observational registry study. Andrologia. 2016:Jan 14. doi: 10.1111/and.12514. [Epub ahead of print]. Return to content
  • Francomano D, Bruzziches R, Barbaro G, Lenzi A, Aversa A. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study. J Endocrinol Invest. 2014;37:401-411. Return to content
  • Behre HM, Tammela TL, Arver S, et al. A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up. The aging male : the official journal of the International Society for the Study of the Aging Male. 2012;15(4):198-207. Return to content
  • Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006;154(6):899-906. Return to content
  • Bhattacharya RK, Khera M, Blick G, Kushner H, Nguyen D, Miner MM. Effect of 12 months of testosterone therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS). BMC endocrine disorders. 2011;11:18. Return to content
  • Wang C, Cunningham G, Dobs A, et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004;89(5):2085-2098. Return to content
  • Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab. 2000;85(8):2839- 2853. Return to content
  • Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci. 2003;58(7):618-625. Return to content
  • Srinivas-Shankar U, Roberts SA, Connolly MJ, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010;95(2):639-650. Return to content
  • Miras AD, le Roux CW. Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery? Int J Obes (Lond). 2014;38(3):325-333. Return to content
  • Haider A, Yassin A, Haider KS, Doros G, Saad F, Rosano GM. Men with testosterone deficiency and a history of cardiovascular diseases benefit from long-term testosterone therapy: observational, real-life data from a registry study. Vascular health and risk management. 2016;12:251-261. Return to content
  • Haider A, Zitzmann M, Doros G, Isbarn H, Hammerer P, Yassin A. Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from Five Year-median Follow-up of Three Registries. J Urol. 2015;193(1):80-86. Return to content
  • Traish AM, Haider A, Doros G, Saad F. Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study. Int J Clin Pract. 2014;68(3):314-329. Return to content
  • Yassin DJ, Doros G, Hammerer PG, Yassin AA. Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. The journal of sexual medicine. 2014;11(6):1567-1576. Return to content