HOUSTON – Long-term testosterone replacement therapy in men with hypogonadism brought impressive reductions in body weight and waist circumference in a 5-year observational study.
"This is an amazing response. I don’t know of many other therapies where you have more than 90% of treated patients respond in a positive way," observed Farid Saad, Ph.D. He referred to the fact that 90% of the 255 men treated for hypogonadism lost at least 5 kg from their initial body weight and 97% experienced shrinkage in waist circumference, with a 10-cm or greater reduction in 46% of men. That’s a lot of belt notches.
This 5-year study of testosterone replacement in hypogonadal men features what’s easily the longest follow-up reported anywhere to date. The average 36-pound weight loss and substantial waist shrinkage were "unintended and unexpected," because prior 1- to 2-year-long studies showed less impressive changes, explained Dr. Saad, at the annual meeting of the Endocrine Society.
The 255 study participants averaged just under 61 years of age. Nearly all were obese or overweight, as is typical in male hypogonadism. All had a serum testosterone level below 350 ng/dL, along with testosterone deficiency–related symptoms. Serum testosterone levels normalized within the first 6-9 months of treatment with slow-acting intramuscular testosterone undecanoate and remained in the normal range thereafter.
"If you can’t motivate men to deal with their subclinical coronary artery disease, they will definitely be motivated to deal with their erections and their frequent night urination."
The men went from a mean baseline body weight of 106 kg to 90 kg over the course of 5 years. A total of 76% of participants lost 10 kg or more of their initial body weight, 53% lost at least 15 kg, and 31% dropped at least 20 kg. The weight loss was continuous; the men lost a mean of 4% of their initial body weight at 1 year, 9% at 3 years, and 13.2% after 5 years. Only 5% of men gained weight during follow-up.
Waist circumference declined by a mean of 8.8 cm from 107.2 cm at baseline. And mean body mass index dropped from 34 to 29 kg/m2.
Study participants were not placed on a structured diet or exercise program, although they did receive advice on the importance of making lifestyle changes.
Three men have developed prostate cancer, but that’s less than the background rate in the general population.
"I think now the general understanding at the major urologic conferences is that testosterone does not increase the risk of prostate cancer. And I wouldn’t expect other side effects because testosterone is a natural substance and we don’t use supraphysiologic doses, we just bring testosterone levels in these hypogonadal men back to normal. I say, in a maybe not very scientific way, that if testosterone [were] harmful to men, then nature would have made a major mistake," according to Dr. Saad, head of global medical affairs–andrology at Bayer Pharma in Berlin.
He added that it would be nice to confirm the findings of this observational study in a prospective randomized controlled trial, but no ethics committee in the world would approve such a study because testosterone deficiency carries elevated risks of osteoporosis, cardiovascular disease, and diabetes. And the treatment for testosterone deficiency as spelled out in Endocrine Society guidelines is testosterone replacement to normal physiologic levels.
Two other studies presented at the conference confirmed Dr. Saad’s weight loss and waist circumference shrinkage findings. Dr. Youssef El Douaihy of Maimonides Medical Center, New York, reported that during a median 6.7-year follow-up of 130 hypogonadal men on testosterone replacement therapy, the subjects lost a mean of 14.3 kg or 13% of their initial body weight. They also experienced a mean 11-cm decrease in waist circumference.
And Dr. Michael Zitzmann of the University of Munster, Germany, presented a series of 334 patients with male hypogonadism treated for up to 15 years with intramuscular testosterone undecanoate. The prevalence of metabolic syndrome dropped from 88% to 52% within the first 2 years. Highly significant reductions in blood pressure, resting heart rate, body weight, body mass index, waist circumference, fasting blood glucose, LDL cholesterol, and triglycerides were documented, all highly significant differences.
Why the big weight loss in patients on long-term testosterone replacement therapy? Dr. Saad speculated that the explanation might lie in the combined improvements in vitality, virility, and motivation to change, all of which in recent studies have been shown to be triggered by normalization of testosterone levels.
"Testosterone may be of value as a facilitator of lifestyle change," he asserted.