Studies examine risk factors for low, high T

March 9, 2015

A handful of new studies reveal new information about risk factors for both low and high testosterone as well as the potential risks associated with each.

A handful of new studies reveal new information about risk factors for both low and high testosterone as well as the potential risks associated with each.

The research was presented at ENDO 2015, the Endocrine Society’s annual meeting, in San Diego.

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In the first study, men with borderline testosterone levels were found to have higher rates of depression and depressive symptoms than the general population. Principal author Michael S. Irwig, MD, of George Washington University in Washington, and colleagues studied 200 adult men between 20 and 77 years of age whose testosterone levels were borderline (between 200 ng/dL and 350 ng/dL). The authors collected the men’s demographic information, medical histories, medication use, and signs and symptoms of hypogonadism.

They remeasured the men’s total testosterone and assessed depression from their medical history and depressive symptoms with the validated Patient Health Questionnaire 9 (PHQ-9).

Using a score of 10 or higher on the PHQ-9, 56% of the study participants had significant depressive symptoms, known diagnosis of depression, and/or use of an antidepressant. Their rates of depressive symptoms were markedly higher than the 15% to 22% in an ethnically diverse sample of primary care patients and the 5.6% among overweight and obese U.S. adults.

The population also had a high prevalence of overweight (39%), obesity (40%), and physical inactivity; other than walking, 51% of the men did not engage in regular exercise. The most common symptoms reported were erectile dysfunction (78%), low libido (69%), and low energy (52%).

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“Over half of men referred for borderline testosterone levels have depression. This study found that men seeking management for borderline testosterone have a very high rate of depression, depressive symptoms, obesity, and physical inactivity. Clinicians need to be aware of the clinical characteristics of this sample population and manage their comorbidities such as depression and obesity,” Dr. Irwig said in an Endocrine Society press release.

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Another study explored the relationship between declining reproductive hormones and decreasing sexual function in older men.

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For the study, lead author Benjumin Hsu, MPH, of the School of Public Health and the ANZAC Research Institute of the University of Sydney in New South Wales, Australia, and colleagues assessed men 70 years of age and above in Sydney, Australia, who took part in the Concord Health and Ageing in Men Project. The authors tested the men at baseline (n=1,705) and again 2 years later (n=1,367).

At both visits, the authors asked the participants questions about their sexual functions and measured the men’s serum testosterone, dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) by liquid chromatography-tandem mass spectrometry; and they measured the men’s sex hormone-binding globulin, luteinizing hormone, and follicle-stimulating hormone by immunoassay.

Over 2 years, baseline serum testosterone, DHT, E2, and E1 did not predict decline in sexual activity, sexual desire, and erectile function. By contrast, the decline in testosterone (but not in DHT, E2, or E1) over time, though less than 10%, was strongly related to decreased sexual activity and desire, but not to erectile dysfunction.

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“We found that over 2 years, men with declining serum concentrations of testosterone were more likely to develop a significant decrease in their sexual activity and sexual desire. In older men, decreased sexual activity and desire may be a cause-not an effect-of low circulating testosterone level,” Dr. Hsu said in a press release from the Endocrine Society.

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In the third study, researchers reported findings that could shed light on how hormone levels impact heart disease in men.

The study, conducted in 400 healthy men ages 20 to 50 years, found that higher levels of testosterone led to lower levels of HDL cholesterol, but that estrogen appeared to have no effect on HDL cholesterol. In contrast, the authors found that low levels of estrogen led to higher fasting blood glucose levels, worsening insulin resistance, and more fat in muscle.

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“These observations may help explain why men have a higher risk of cardiovascular disease,” lead investigator Elaine Yu, MD, MSc, of Harvard Medical School, Boston, said in a press release from the Endocrine Society.

Dr. Yu and her co-authors were able to determine whether estrogen or testosterone regulated various cardiovascular risk factors by comparing two groups of men whose hormone levels were temporarily changed with combinations of medications.

At the start of the study, all men received goserelin (Zoladex) to suppress production of testosterone and estrogen. Then the 198 men in the first group received daily treatment for 4 months with either a placebo gel or one of four doses of testosterone gel (AndroGel), ranging from low to high (1.25 to 10 grams). This treatment set the men’s testosterone levels from very low (as in before puberty) to high-normal, Dr. Yu said.

The other group, made up of 202 men, received the same treatment as in group 1 but also received anastrozole (Arimidex) to block conversion of testosterone to estrogen. Men naturally convert some testosterone to estrogen. Blocking this process resulted in very low levels of estrogen in the second group, according to Dr. Yu.

Study participants had their weight measured and had fasting blood tests for markers of heart disease and diabetes. At the start and end of the study, they had a thigh scan with quantitative computed tomography to measure muscle fat.

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The authors found that neither testosterone nor estrogen regulated changes in LDL cholesterol, blood pressure, and body weight.

Grants from the National Institutes of Health and AbbVie supported the study. The drug makers provided the medications used in this study at no cost.

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