Studies Suggest Testosterone Replacement Therapy Improves Risk Factors For Cardiovascular Disease And Diabetes

Dr. Enrique Jacome

Testosterone deficiency becomes more common with age, occurring in 18 percent of 70-year-olds, said a coauthor of both studies, Farid Saad, PhD, of Berlin-headquartered Bayer Schering Pharma. Low testosterone levels are linked to the metabolic syndrome--a cluster of metabolic risk factors that increase the chances of developing heart disease, stroke, and type 2 diabetes--and other health problems, including loss of bone and muscle mass, depression, and decreased libido.

Saad's research showed that restoring testosterone to normal levels in hypogonadal, or testosterone-deficient, men led to major and progressive improvements in features of the metabolic syndrome. Furthermore, men older than 63 benefited as much as younger men, they found. Treatment lasted a year and used a slow-release, injectable form of the hormone (testosterone undecanoate) that is not yet available in the United States.

All 95 men in the studies (ages 34 to 69 years) had the metabolic syndrome. To receive this diagnosis, patients must have three of the following five risk factors: increased waist circumference (abdominal fat), low HDL ("good") cholesterol, high triglycerides (fats in the blood), high blood pressure, and high blood sugar.

The first study showed that testosterone treatment significantly reduced waist circumference, total cholesterol, LDL ("bad") cholesterol, triglycerides, and body mass index (a measure of body fat). Treatment also increased "good" cholesterol. Improvements were progressive over 12 months, indicating that benefits may continue past a year, Saad said.

In the second study, the researchers divided the patient population into three groups by age: less than 57 years, 57 to 63 years, and more than 63 years. They found that the oldest men had similar improvements in metabolic risk factors to the youngest men.

Additionally, the investigators looked at the degree of testosterone deficiency before treatment. This beginning level of testosterone deficiency did not predict the beneficial outcome, they found. Men whose subnormal testosterone levels were not as low as the others had similar improvements in metabolic risk factors to men with the lowest levels, according to Saad.

"We conclude that if elderly men have a deficiency of testosterone, it is worthwhile to treat them with testosterone," he said.

Researchers from The Netherlands and Germany collaborated on these studies. Study participants received treatment in a hospital clinic in Bremerhaven, Germany, which provided free care and testosterone through the German social health care system.

Disclosure: Bayer Schering makes a brand of testosterone undecanoate. Saad is an employee of Bayer Schering and contributed to the study design, he reported.

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Healthy Lifestyle During Menopause May Decrease Breast Cancer Risk Later

Dr. Enrique Jacome

Obese, postmenopausal women are at greater risk for developing breast cancer and their cancers tend to be more aggressive than those in lean counterparts. A University of Colorado Cancer Center study published in the December issue of the journal Cancer Research shows how this risk might be prevented. 

"By using nutrient tracers for fat and sugar, we tracked where the body stored excess calories. In lean models, excess fat and glucose were taken up by the liver, mammary and skeletal tissues. In obese models, excess fat and glucose were taken up by tumors, fueling their growth," says Erin Giles, PhD, postdoctoral researcher at the CU Cancer Center and the paper's lead author. 

In short, if you are lean, excess calories go to healthy tissue. If you are obese, excess calories feed the tumor. 

"This implies that the menopausal window may be an opportunity for women to control their breast cancer risk through weight management," Giles says. 

In this study, Giles worked with a team of scientists including postdoctoral fellows Elizabeth Wellberg and Sonali Jindal, as well as faculty members Steve Anderson, Pepper Schedin, Ann Thor and Paul Maclean. Their study also showed that tumors from obese animals had increased levels of the progesterone receptor, and this receptor appears to give tumors a metabolic advantage for growth. To extend their findings to humans, they recruited gene analysis experts David Astling and Aik-Choon Tan who analyzed 585 human breast cancers and found that human tumors expressing the progesterone receptor had the same metabolic advantage. 

"Basically, we saw an abnormal metabolic response to fat and sugar in the obese that, in many ways, mirrors the response to fat and sugar in Type II diabetes," Giles says. Noticing this similarity, the group tested the use of the common Type II diabetes drug, Metformin, in their model of postmenopausal breast cancer. 

"With treatment, tumor size was dramatically decreased in the obese, and tumors showed reduced expression of the progesterone receptor," Giles says. 

Using a pre-clinical model, the investigators found that weight gain during menopause is particularly bad for those who are obese when entering menopause. Together, the results of this study suggest that the combination of obesity and weight gain during menopause can impact breast cancer in two ways. First, tumors that arise in obese women appear to have a metabolic advantage, and second, the inability to store excess calories in healthy tissues may further fuel tumor growth. 

"While drugs may be useful in controlling breast cancer risk in obese, postmenopausal women, our results imply that a combination of diet and exercise may be equally if not more beneficial," Giles says. 

The group's ongoing studies are testing whether interventions such as diet and exercise, during the period of menopausal weight gain, can improve tumor outcomes. 

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