Table 3.

Effects of testosterone replacement therapy in patients with cardiometabolic syndrome

Ref.	Design (n)	Cohort	TRT method/duration	Results
45	Observational prospective (n = 850)	Hypogonadal men	T treatment for 12 years	• Improvements in cardiometabolic risk factors, erectile dysfunction, urinary function
54	Observational prospective (n = 656)	Hypogonadal men	T undecanoate (1,000 mg/12w) for 10 years	• Decreased systolic and diastolic blood pressure, levels of triglycerides, LDL and HDL, HbA1c levels, blood glucose levels, and body weight
57	Observational (n = 77)	Hypogonadal men with CVD	T undecanoate (1,000 mg/12w) for 8 years	• Decreased body weight, waist circumference, and BMI • Improved cardiometabolic parameters such as lipid pattern, glycemic control, blood pressure, heart rate, and pulse pressure
70	Observational prospective (n = 850)	Hypogonadal men	T undecanoate (1,000 mg/12w) for 8 years	• Considerable improvements in anthropometric parameters, lipids and glycemic control, blood pressure, C-reactive protein, and quality of life
131	Multicenter DBPC-RT (n = 220)	Hypogonadal men with T2DM and/or MetS	T gel 2%, TTS, for 12 months	• Reduced insulin resistance • Improvements in glycemic control, total and LDL cholesterol, body composition, libido, and sexual function
137	Multicenter DBPC-RT	Obese men with T2DM and serum T ≤ 14 nmol/L	T undecanoate (1,000 mg/12w) for 2 years	• Normalization in blood glucose and improved body composition. • Decrease in total and or abdominal fat mass and increase in lean mass and muscle strength
225	Crossover DBPC-RT (n = 24)	Hypogonadal men with T2DM	Intramuscular T injections (200 mg/3w) for 3 months	• Reduced HOMA-IR, glycated hemoglobin, and fasting blood glucose, visceral adiposity, waist circumference, total cholesterol, and no changes in blood pressure
258	DBPC-RT (n = 788)	Men ≥65 y and serum T levels <275 ng/dL	T gel 1%, for 12 months	• Decrease in total cholesterol, HDL, and LDL, fasting insulin, and HOMA-IR, and no alterations in triglycerides, d-dimer, C-reactive protein, interleukin 6, troponin, glucose, or HbA1c levels
276	RCT (n = 80)	Hypogonadal men with T2DM	T-gel (50 mg/day) for 9 months	• Significant decrease in waist circumference, HOMA-IR and HbA1c, concentrations of resistin, ICAM-1, p-selectin and C-reactive protein, leptin
277	CT (n = 102)	Hypogonadal men with T2DM & ischemic stroke	T undecanoate (1,000 mg/12w) for 2 years, re-evaluation at 5 years	• Reductions in BMI, the levels of cholesterol, triglycerides, LDL, and HDL and systolic and diastolic arterial pressures
278	DBPC-RT (n = 55)	Hypogonadal men with T2DM and obesity	T undecanoate (1,000 mg/10w) for 1 year	• Reductions in HOMA-IR and HbA1c • An increase in flow-mediated dilatation
279	CT (n = 42)	Hypogonadal men >40 years, with chronic heart failure and BMI>30 kg/m2	T undecanoate (1,000 mg/2 injections), evaluation after 24 w	• Decline in insulin and serum glucose and a slight increase in LDL cholesterol and a decrease in triglycerides • No changes in other variables of metabolic syndrome and other biochemical variables, as well as echocardiographic variables, blood pressure
280	DBPC-RT (n = 39)	50- to 70 year-old men with T2DM and T levels <7.3 nmol/L	T gel for 24	• Decrease in high subcutaneous fat area, levels of adiponectin, leptin, leptin/adiponectin ratio, and HDL cholesterol and no change in hepatic fat content and visceral adipose tissue
281	Observational (n = 120)	Men with late-onset hypogonadism	T undecanoate (1,000 mg/10-14w) for 8 years	• Decreased waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, LDL and no changes in BMI, HDL, triglyceride
282	Observational prospective (n = 115)	Hypogonadal men	T undecanoate (1,000 mg/10-14w) for up to 10 years	• A decrease in WC, body weight and BMI, fasting glucose, insulin resistance and HbA1c levels, the ratio of triglycerides: HDL, total cholesterol: HDL ratio and non–HDL cholesterol, systolic and diastolic blood pressure, C-reactive protein, and an increase in HDL levels
283	Observational (n = 58)	Men with mild symptoms of T deficiency and subnormal T levels (<2.35 ng/ml)	T undecanoate (1,000 mg/12 w)	• A reduction in total cholesterol, components of metabolic syndrome • Increase in whole blood viscosity, hemoglobin, and hematocrit levels
284	RCT (n = 857)	Men with T2DM	TRT	• TRT was not associated with improvements in cardiovascular disease risk factors.
267	Meta-analysis of observational studies (n = 4,513)	Men receiving TS in 32 observational studies which evaluate body mass composition and glycometabolic parameters	TS	• Body mass composition: decline in body fat, increase in lean mass • T2DM parameters: decline in fasting glycemia, HOMA-IR index • Obesity parameters: decline in BW, WC, and BMI • Blood pressure: decline in systolic and diastolic BP • Lipid profile: decline in total cholesterol, triglyceride and increase in HDL
266	Meta-analysis of RCTs (n = 5,078)	Men in TS and control groups of 59 RCTs which evaluate body mass composition and glycometabolic parameters	TS	• Body mass composition: decline in body fat, increase in lean mass • T2DM parameters: decline in fasting glycemia, HOMA-IR index • Obesity parameters: no changes in BW, WC, and BMI • Blood pressure: no changes in systolic and diastolic BP • Lipid profile: no changes in total cholesterol, triglyceride, HDL

BMI = body mass index; BW = body weight; CT = controlled trial; DBPC-RT = double-blind placebo-controlled randomized trial; HbA1c = hemoglobin A1c; HDL = high-density lipoprotein HOMA-IR = homeostatic model assessment insulin resistance; LDL = low-density lipoprotein; RCT = randomized controlled trial; T = testosterone; T2DM = type 2 diabetes mellitus; BP = blood pressure; TRT = testosterone replacement therapy; TS = testosterone supplementation; WC = waist circumference; HOMA-IR = homeostatic model assessment insulin resistance.