Testosterone and Metabolic Syndrome

Unfortunately this is a “chicken or the egg” situation.  Men who have metabolic syndrome (which includes many components, especially insulin resistance), tend to have an increased activity of an enzyme – aromatase – that is found in fat cells of both men and women.  Aromatase converts testosterone to estrogen.  For women this process is important especially after menopause, however for men it is much less desirable when it is in excess.

Another way to interpret this study is that men’s testosterone levels are low because their estrogen levels are increased due to the up-regulated activity of the aromatase enzyme.

Instead of treating the supposed “testosterone deficiency” a more appropriate treatment would be to address the underlying condition – what is driving the upregulation of the aromatase and how can we improve insulin sensitivity?  (Testosterone injections like those used in this study will have a “honeymoon period” where the patients will feel better for a short time, however if the mechanism that drives the aromatase activity is not addressed the injected “magic bullet” testosterone is going to be converted to estrogen too).

Functional medicine and nutrition aim to address the underlying processes and address them with diet and lifestyle modifications.  Supplements and nutritional protocols are often used to support the metabolic processes.  Talk to Dr. Slavin about your recent blood work results if you have increased blood sugar, insulin resistance, high cholesterol, high triglycerides or blood pressure.  If you have experienced increased fat storage on your body, decreased libido, fatigue after meals it is important to address your metabolic processes right away

CODHy: Testosterone Improves Metabolic Syndrome

By John Gever, Senior Editor, MedPage Today

May 15, 2010

Read Article on MedPage

* Explain to interested patients that the testosterone product used in the study is not available or FDA approved in the U.S.

* Explain that testosterone levels tend to be depressed in men with diabetes and the metabolic syndrome, but it is not yet proven that testosterone supplements are an effective treatment for these conditions.

* Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.


PRAGUE — Depot testosterone injections in men with metabolic syndrome and hypogonadism led to improvements in several important components of their disease, including significant weight loss and reduced glucose dysregulation, a researcher said here.

Interim results from a randomized, placebo-controlled trial showed that men receiving the hormone injections lost more than 4 kg (9 lb) in the first 30 weeks of a planned three-year study versus almost no change with placebo (P<0.001), reported Farid Saad, PhD, of Bayer Schering in Berlin.

Although fasting plasma glucose levels did not change, insulin levels dropped significantly among participants in the active treatment group, mainly among those with abnormally high levels at baseline, Saad told attendees here at the World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension.

There were also trends toward normalized levels of certain blood lipids, serum leptin, and inflammation markers.

Many men with diabetes or metabolic syndrome show abnormally low testosterone levels, which has prompted several research groups and now the drug industry to investigate testosterone supplements as a therapy.

In March, for example, British researchers reported favorable results in diabetic and prediabetic men with a testosterone gel produced by a different company.

Bayer Schering has its own topical testosterone gel, with some results reported here as well, but the company is also interested in marketing its depot injectable version (Nebido) for this purpose. The product is currently approved outside the U.S. as a treatment for hypogonadism.

In the study Saad reported here, 184 men were randomized in a 3:2 ratio to the testosterone injection, at 1 g per dose, or placebo. Three injections were given, at weeks zero, six, and 18. Saad reported results of evaluations conducted at weeks 18 and 30.

Men receiving the hormone injections showed markedly greater decreases at week 30 in body mass index (BMI) and waist circumference as well as in body weight, according to Saad.

Mean BMI declined by 1.3 points from a baseline level of 36, compared with a 0.1-point decrease in the placebo group (P<0.001).

Similarly, waist circumference in the active treatment group shrank by 6 cm (2.5 inches) versus 1.5 cm (less than one inch) with placebo (P<0.001). Mean waist circumference at baseline was about 117 cm (46 inches).

Men in the placebo group lost about 0.3 kg compared with the 4-kg decline in the testosterone group (P<0.001).

Saad indicated that the weight loss was probably not a direct hormonal effect. Instead, he said, men on testosterone likely felt more energetic, exercising more and feeling motivated to eat a healthier diet.

Little to no change in fasting plasma glucose was noted during these first 30 weeks of treatment, Saad reported, but there was a significant decline in fasting insulin levels with the hormone treatment.

From a baseline value of about 26 mIU/L, insulin levels fell to 20. In the placebo group, mean levels increased slightly from 20.5 to 22 mIU/L (P=0.04 testosterone versus placebo).

Saad observed that the most substantial declines occurred in those patients with insulin levels above 26.4 mIU/L at baseline. The mean for those receiving the hormone dropped from 44 to 32 mIU/L (P=0.001), whereas there was almost no decline seen in patients with baseline insulin in the normal range.

The testosterone group showed nonsignificant trends toward reductions in LDL cholesterol (also seen with placebo) as well as increases in HDL levels. Mean serum leptin fell by nearly half (P<0.001) by week 30, with the 14.04-ng/mL level just above the normal range (upper limit, 13 ng/mL).

Saad also reported significant reductions in C-reactive protein and tumor necrosis factor-alpha levels in the treatment group, whereas increases or no change were seen in the control patients.

Session chair Robert Niecestro, PhD, managing director of the drug development firm Accelapharm in New York City, commented that the weight loss seen with the treatment was particularly impressive.

“I’ll be interested to see if it persists for three years,” he said.

Niecestro cautioned that these were early results from a planned three-year study. Consequently, some of the nonsignificant trends could become significant as the study progresses, or they could turn out to be temporary blips, he suggested.

The study was funded by Bayer Schering.

Saad was an employee of Bayer Schering. Niecestro was owner and managing director of Accelapharm. No other potential conflicts of interest were reported.

Primary source: World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension

Source reference:

Kalinchenko S, et al “Effects of testosterone on metabolic syndrome and inflammation in hypogonadal men: the Moscow study” CODHy 2010.


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