Long-term testosterone therapy is associated with a reduction in obesity parameters, improved metabolic syndrome and health-related quality of life in men with hypogonadism
Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss. Yassin AA, Doros G. Clinical Obesity 2013;3:73−83.
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. Yassin DJ, Doros G, Hammerer PG, et al. J Sex Med 2014;11:1567–76.
This editorial summarises two papers based on the same observational study of 261 hypogonadal men: the first focused specifically on obesity and assessed the long-term effects of normalising testosterone (T) levels on obesity parameters.1 The second paper focused on parameters associated with the metabolic syndrome (MetS) as well as obesity measures.2
Hypogonadism is associated with several clinical symptoms, including increased adiposity, reduced muscle mass, reduced bone density, obesity, diabetes, and erectile dysfunction (ED).3 Diabetes and obesity are of particular concern as they are well known risk factors for cardiovascular disorders.4 Although, several studies have found that treatment with T can ameliorate these symptoms,5,6 it is not known if these improvements can be sustained in the long-term. The studies summarised in this editorial investigated the long-term effects of testosterone undecanoate (TU) on a number of these symptoms.
Both papers analysed the same registry of 261 hypogonadal men (aged 59.5 ± 8.4 years), all of whom had sought treatment for ED at a single urologist’s office. Patients received parenteral TU 1000 mg at baseline, week 6 and every 12 weeks thereafter for up to 5 years. All 261 patients were followed for ≥1 year, 260 patients for 2 years, 237 for 3 years, 195 for 4 years and 163 for 5 years. Adherence to treatment was excellent and the decline in patient numbers each year represented duration of treatment rather than drop-out rates.1,2
The first paper measured anthropometric parameters. Patient height, body weight, body mass index (BMI) and waist circumference (WC) were measured at baseline, and weight, BMI and WC were measured at least once a year. Blood samples were taken prior to the next TU injection, consequently this meant that T levels measured were trough levels.1
The second paper also measured (at baseline and at every visit) body weight, WC and BMI as well as parameters associated with the MetS; total cholesterol, LDL, HDL, triglycerides, glucose, HbA1c (glycated hemoglobin), blood pressure (BP) and total T concentrations.2
What is known
Between 29.3% and 52.6% of obese men have T levels below the recommended levels.7,8 Treatment with T is associated with an increase in muscle mass and an overall decrease in weight due to loss of fat mass, this weight loss contributes to a positive feedback loop by increasing T levels.9 In addition to a reduction of fat mass in hypogonadal men, treatment with TU is associated with an increase in mood and motivation which may contribute to a more active lifestyle facilitating further weight loss.10
Low T levels also contribute to an increased risk of MetS by increasing insulin resistance, LDL, total cholesterol, triglycerides and reducing HDL levels. Treatment with TU in patients with symptoms of the MetS is associated with a reversal of these changes as T levels reach normal concentrations.5,6
However, as there have been few studies with TU over a long treatment period (>2 years),10-12 it is unknown if the improvements in parameters associated with obesity and the MetS can be sustained in the long term.
What these studies add
Long-term treatment with TU in hypogonadal men resulted in improvements in obesity parameters.1 A significant (p<0.0001), sustained and gradual weight loss of approximately 11 kg occurred in 96% of hypogonadal men treated with TU. This weight reduction was also associated with a decrease in BMI and WC, both of which were sustained over the 5-year treatment period. In the obese subgroup, this reduction was more prominent in patients with baseline BMI ≥30 kg/m2.
Parameters affected by the MetS also improved, including lipid and glucose parameters and BP, that were sustained across the 5-year treatment period.2Patient’s health-related quality of life also improved in the long-term, as demonstrated by a sustained improvement in erectile function (p<0.0001) and muscle and joint pain with long-term TU treatment.
The length of these studies allowed for the optimal effects of TU treatment to be seen, thus providing a timescale for symptom improvements in hypogonadal men treated with T. Indeed, lipid parameters and quality of life improved after only 4 weeks. Nevertheless, it should be noted that it can take more than 12 months for the maximum benefits of T therapy to be observed.
Neither analysis found evidence that long-term treatment with TU increases the risk of prostate carcinoma. They reported that only 2.3% of men observed developed prostate cancer. This equates to an incidence of 55.4 per 10,000 patient-years, whereas other trials examining prostate cancer found an incidence of 116 per 10,000 patient-years13and 96.6 per 10,000 patient-years.14
These findings suggest that long-term treatment with TU in hypogonadal men is well tolerated and effective in reducing both anthropometric parameters of obesity and individual parameters affected by the MetS, and is associated with an increase in patients’ health-related quality of life.
Table 1. Mean % weight change from baseline to study end in hypogonadal men treatded with testosterone undecanoate.1
| ||Year 1|
|Weight change from baseline, % (mean ± SD)||–3.2 ± 0.3*||–5.6 ± 0.3*†||–7.5 ± 0.3*†||–9.1 ± 0.3*†||–10.5 ± 0.4*†|
SD, standard deviation.*p<0.0001 vs. baseline, †p<0.0001 vs. previous year
Table 2. Change in lipid parameters from baseline to study end in hypogonadal men treated with testosterone undecanoate.2
|End of 5-year study period|
|Total cholesterol||256.24 ± 51.06||212.2 ± 40.88*|
|Triglycerides||252.05 ± 95.23||199.04 ± 52.34*|
|LDL||157.09 ± 28.43||126.41 ± 33.7*|
|HDL||41.34 ± 12.15||55.62 ± 14.66†|
All data are given as mg/dL, mean ± SD.
HDL, high-density lipoprotein; LDL, low-density lipoprotein; SD, standard deviation. *p<.0001 vs. baseline, †p<0.05 vs. baseline