Testosterone Augments Erectile Function in Men with Diabetes

Pam Harrison

May 21, 2015

In hypogonadal men with type 2 diabetes, long-term testosterone therapy significantly improves erectile function, corrects metabolic abnormalities, and changes body composition, two long-term registry studies suggest.

Testosterone is not a toxic hormone, said Abdulmaged Traish, PhD, from the Boston University School of Medicine. "As a physiological machine, the human body has a factory called testes that produces testosterone throughout life."

When levels of the natural hormone are returned to normal, "it improves cognition, mood, energy, and sexual function; it reduces visceral fat and lipid deposition; and I think it's absolutely protective for cardiovascular risk," he told Medscape Medical News. "This is what the history of testosterone therapy and research tells us."

Dr Traish presented results from one study at the American Urological Association (AUA) 2015 Annual Meeting in New Orleans.

Results from the other study were presented by Aksam Yassin, MD, from the Institute of Urology and Andrology in Norderstedt-Hamburg, Germany.

"In men with type 2 diabetes, erectile dysfunction has a multifactorial pathophysiology. However, hypogonadism is a major issue and, sooner or later, every other man with diabetes is at risk for erectile dysfunction," Dr Yassin told Medscape Medical News.

Hypogonadism is a major issue and, sooner or later, every other man with diabetes is at risk for erectile dysfunction.

His team conducted an observational registry study of 262 hypogonadal men with erectile dysfunction, 77 (29%) of whom had type 2 diabetes. All men had a total testosterone level of at least 12 nmol/L.

At enrollment, 12% of the patients with type 2 diabetes were overweight and 88% were obese.

Although the study participants received testosterone undecanoate injections for up to 11 years, Dr Yassin presented 8-year data.

Total testosterone levels increased from 7.6 nmol/L at baseline to 17 to 20 nmol/L at 8-year follow-up. And free testosterone levels increased from 150 pmol/L at baseline to 400 to 500 pmol/L at 8-year follow-up.

There was a marked improvement in body composition during the follow-up period, and a mean weight loss of at least 18%. There were also significant reductions in inflammatory markers, such as C-reactive protein.

Table 1. Improvements During the 8-Year Follow-up Period

Outcome Baseline 8-Year Follow-up P Value
Mean body mass index (kg/m²) 34.7 27.7 <.0001
Mean waist circumference (cm) 115.0 96.4 <.0001
Fasting glucose level (mg/dL) 146.0 83.7 <.001
Hemoglobin A1c (%) 7.8 5.9 <.001


"Increasing muscle mass, along with activity levels, with testosterone leads to higher basic metabolic rates, which require more calories to burn," Dr Yassin explained.

"Others have also noted that testosterone has direct effects on blood sugar control and hyperinsulinemia."

Dr Yassin and colleagues assessed patients with the erectile function domain of the International Index of Erectile Function (IIEF-EF). Mean scores increased steadily during the study period — from 6.1 at baseline to 11.4 after 1 year of treatment, 14.4 after 2 years, 16.2 after 3 years, and 16.7 after 4 years. Thereafter, scores remained at approximately 17.0 until year 8, when the mean score was 18.2.

Second Registry

The observational registry study conducted by Dr Traish and his team involved 340 hypogonadal men, 120 (35%) of whom had type 2 diabetes. At enrollment, almost 90% of the men with diabetes were obese.

All men received testosterone undecanoate injections for up to 7 years.

During the follow-up period, testosterone levels rose from 10 nmol/L at baseline to 15 to 18 nmol/L at 7 years. There was a corresponding increase in IIEF-EF score — from 19.7 at baseline to 25.2 at 7 years.

As in the study by Dr Yassin's team, men lost approximately 18% of their body weight during the follow-up period. There were also significant improvements in lipid profile and in diastolic and systolic blood pressure.

Table 2. Improvements During the 7-Year Follow-up Period

Outcome Baseline 7-Year Follow-up P Value
Mean body mass index (kg/m²) 35.6 29.0 <.0001
Mean waist circumference (cm) 109.3 99.9 <.0001
Fasting glucose level (mg/dL) 113.5 95.9 <.0001
Hemoglobin A1c (%) 8.0 5.9 <.0001


At baseline, only 11% of the men had hemoglobin A1c levels in the range of 7%; after 7 years, all the men did.

Dr Traish said he is not surprised by these results. Previous studies have shown that when men are made deficient in androgen, their insulin resistance goes up.

"Androgens are important for regulating fuel metabolism. They regulate protein metabolism, they regulate fat metabolism, and they regulate carbohydrate metabolism. Alterations in carbohydrate metabolism and transport contribute to the onset of diabetes," he explained.

Therefore, "it's not surprising that with androgen deficiency there is an increase in the prevalence of diabetes, and with androgen treatment, we lower plasma glucose, we lower HbA1c, there is an improvement in overall metabolic function and anthropometric parameters, and, of course, an improvement in erectile dysfunction."

The advent of the phosphodiesterase type 5 inhibitors, with their high therapeutic success rate, has deflected attention away from a more global perspective, said Louis Gooren, MD, from VU University in Amsterdam.

Complaints of erectile dysfunction should invite a thorough assessment of vascular, neurologic, and hormonal systems, he told Medscape Medical News.

Type 2 diabetes "is almost always an expression of the metabolic syndrome — increased blood pressure, a high blood glucose level, excess body fat around the waist, and abnormal cholesterol levels," he pointed out.

"Adiposity has a suppressive effect on serum testosterone, whereas low testosterone induces symptoms of the metabolic syndrome," he explained. "This vicious circle can be interrupted by correcting low testosterone levels."

Dr Gooren said he agrees with Dr Traish that the role of testosterone in the metabolic syndrome and its sequelae, such as erectile dysfunction, deserves more attention, particularly from the medical disciplines that deal with the metabolic syndrome but might be unfamiliar with the latest insights in testosterone physiology.

The study authors and Dr Gooren have disclosed no relevant financial relationships.

American Urological Association (AUA) 2015 Annual Meeting: Abstracts D45-06 and D45-03. Presented May 18, 2015.


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