A new study reveals that Testosterone improves body composition in men with low testosterone!
The benefits of Testosterone Replacement Therapy (TRT) are numerous and well-known: Evaporating slabs of lard, especially around the midsection; increased strength and muscle mass: exploding surges of energy; better sleep; a long-dormant optimistic mood, better concentration, and the thrill of a roaring back to life libido!
Why does this happen? Why does the so-called “manly hormone” testosterone produce such dramatic benefits?
To answer those questions, a new study looked at the effects of testosterone on metabolism. It concluded that testosterone fine-tunes body composition, even in men with hypogonadism (low testosterone aka “Low-T”) levels.
The recent study was led by Dr. Reina Villareal, an endocrinologist at the Michael E. DeBakey VA Medical Center in Houston and a professor at the nearby Baylor College of Medicine. Along with Dr. Fnu Deepika and several researchers, the study's goal was to see if TRT could change body composition, metabolic profile, bone turnover markers, and bone mineral density (BMD). Bone mineral density is a critical metric in older people since it measures bone thickness, and bone turnover is the process of resorption followed by replacement by new bone with a minor change in shape.
To emphasize the significance of the study, Dr. Villareal stated that “This could mean that men in some ways could derive benefit from T therapy even if their T level is not as low as defined by the Endocrine Society,” whose guideline for Low-T is less than 264 nanograms per deciliter (ng/dL).
She added, “I am not advocating to treat anyone with normal T levels for those benefits because of the serious side effects associated with T therapy, such as an increase in cardiovascular issues, blood clots, and prostate enlargement. There is an ongoing randomized placebo-controlled study with over 5,000 men that is addressing the cardiovascular safety of T replacement therapy. That will likely confirm or dispute the safety concerns of T replacement therapy.”
Testosterone Replacement Therapy has been growing by leaps and bounds recently, and the controversy concerning its benefits and risks rages. Testosterone is a crucial male hormone responsible for the male libido, strengthening bones, manufacturing red blood cells, and muscle size and strength.
Around age 30, men begin to see their testosterone levels ebbing at approximately 10% per decade if the issue is not addressed. In addition to aging, a link has been established between Low-T, obesity, and type 2 diabetes have low T levels, according to the Endocrine Society.
TRT is not prescribed for obesity, but testosterone is a powerful tool in the battle against obesity due to the hormone’s ability to ramp up muscle mass and scorch body fat, leading to healthier body composition.
The idea for Villareal’s study was the conclusion from another study that testosterone levels influence (BMD) response to TRT in men with Low-T. That study found that a baseline testosterone level of less than 200 ng/dL is related to more significant increases in spine BMD. A BMD test helps clinicians uncover osteoporosis and predict the risk for bone fractures.
Villareal and her colleagues embarked on a mission to see if body composition and metabolic response vary according to baseline testosterone levels. Studies have shown that these outcomes could be uplifted with TRT, but it’s uncertain if the response would change according to testosterone levels.
The results were unexpected.
The study consisted of 105 male Veterans, ages 40 to 74, with Low-T. It covered five years from 2011 to 2016 at the Michael E. DeBakey VA and the New Mexico VA Health Care System. The authors called it the initial study to determine if the effects of TRT on body composition, metabolic profile, and bone turnover markers are regulated by testosterone levels.
The researchers examined the effects of TRT on men with Low-T, defined as lower than 300 ng/dL, by the Endocrine Society’s guideline until 2018. That year, its guideline was lowered to less than 264 ng/dL. This change is meaningful since the study was conducted and concluded before that change. Therefore, some participants would have normal testosterone levels based on the new criteria.
The TRT regimen consisted of injecting 200 milligrams every two weeks of testosterone cypionate (trade name Depo-Testosterone), an androgen and anabolic steroid used mainly to treat low T levels in men.
The dose was later adjusted to a blood level of 500 to 800 ng/dL, then 300 to 600 ng/dL after year three of the study, upon the recommendations of the FDA. Side effects from the drug were similar to previous reports.
Dr. Villareal and her team discovered that men benefited from TRT regardless of their baseline testosterone level. For example, men with levels less than 264 ng/dL showed a more significant increase at 18 months in total fat-free mass, mainly lean muscle mass, compared with those higher than 264 ng/dL.
Contrary to the study hypothesis, men with testosterone levels above 264 ng/dL appeared to enjoy more significant benefits from a metabolic standpoint, including a lowering of Hemoglobin A1c (HbA1c), a diabetes marker, along with a drop in blood glucose levels, which shoot up in people with diabetes and LDL (bad cholesterol).
A leptin drop, the so-called “satiety hormone,” which lowers appetite, was attributed mostly to a loss of fat mass, which produces leptin. But that should not be seen as an adverse effect of TRT, according to Villareal.
“We found that surprising,” she says. “Our original hypothesis was that response in these parameters will be better for those with lower testosterone levels. That did not happen, suggesting that those with normal T by the current guidelines will benefit from the drug.”
However, the researchers urged caution concerning TRT. “Although prior studies have suggested improvement in insulin sensitivity in men with low T, a recommendation to give T to improve the metabolic profile remains controversial. Our findings support the partial metabolic benefit from T among men with levels of more than 264 ng/dL who, by current guidelines, will not be treated with T. Therefore, the information presented in the manuscript could be valuable for both clinicians and patients in shared decision-making.”
Concerning the effect testosterone has on obesity, Dr. Villreal said that “We surmise that the better response in fat-free mass in those with lower T levels could be due to greater sensitivity of the muscle to testosterone replacement than those with higher levels. However, one should not forget that those with higher levels had an increase in fat-free mass, as well, only to a lesser extent compared to those with lower T levels.
“On the other hand,” she continued, “the better metabolic response among those with higher T levels is hard to explain, except that maybe the group with less than 264 ng/dL needed more time on adequate T levels to see a significant improvement in blood sugar and other metabolic factors such as cholesterol. We are working on clarifying the reason for this finding in a lab” at the Michael E. DeBakey VA.
Dr. Villareal and her team hope for a VA-funded study to examine TRT's impact on men with diabetes and Low-T. The researchers are also measuring changes in bone structure and strength.
“We hope to reach a conclusion for our findings from this cohort down the road,” she says. She and her team are also interested in other results, noting that evidence has uncovered a link between bone metabolism and glucose metabolism, or diabetes control. “Hence, any change in bone metabolism brought about by T therapy may also be accompanied by changes in glucose metabolism,” she notes.
“Since we are also assessing all the metabolic parameters in this study, broadly, we would like to explore if changes in bone parameters associated with T therapy will correlate with changes in metabolic parameters. “We’ll know more as time goes on.”
The results appeared in Frontiers in Endocrinology in July 2022.
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