Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers

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BACKGROUND:

The relation between testosterone (T) plasma concentration and cardiovascular (CV) risk is unclear, with evidence supporting increased risk in men with low and high T levels. Few studies have assessed CV risk as a function of plasma T levels using objective biomarkers.

AIM:

To determine the relation between T levels and high-sensitivity CV risk biomarkers.

METHODS:

Ten thousand forty-one male patients were identified in the database of a commercial clinical laboratory performing biomarker testing. Patients were grouped by total T concentration and associations with the following biomarkers were determined: cardiac troponin I (cTnI), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-17A, N-terminal pro-B-type natriuretic peptide (NTproBNP), high-density lipoprotein (HDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), and leptin.

OUTCOMES:

Association of CV risk markers with levels of T in men.

RESULTS:

The median age of the cohort was 58 years (interquartile range = 48-68), and the median plasma T level was 420 ng/dL (interquartile range = 304-565); T levels did not vary with patient age. An inverse relation between plasma T levels and CV risk was observed for 9 of 10 CV markers: cTnI, ET-1, IL-6, TNF-α, NTproBNP, HDL cholesterol, hs-CRP, HbA1c, and leptin. Even after adjusting for age, body mass index, HbA1c, hs-CRP, and HDL cholesterol levels, the CV markers IL-6, ET-1, NTproBNP, and leptin were significantly associated with a T level lower than 250 ng/dL.

CLINICAL IMPLICATIONS:

Men with low T levels could be at increased risk for increased CV disease as seen by increased CV risk markers.

STRENGTH AND LIMITATIONS:

This study was performed in a group of 10,041 men and is the first study to examine CV risk associated with circulating T levels using a large panel of 10 objective biomarkers. This study is limited by an absence of clinical data indicating whether men had pre-existing CV disease or other CV risk factors.

CONCLUSION:

Men with low plasma T levels exhibit increases in CV risk markers, consistent with a potential increased risk of CV disease. Pastuszak AW, Kohn TP, Estis J, Lipshultz LI. Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers. J Sex Med 2017;XX:XXX-XXX.

Article Source: https://www.ncbi.nlm.nih.gov/pubmed/28757119

 

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Infertility in men could point to more serious health problems later in life

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Poor sperm quality affects about one in ten men and may lead to fertility problems. These men also have an increased risk of developing testicular cancer, which is the most common malignant disease of young males. And, even if they don’t develop testicular cancer, men with poor sperm quality tend to die younger than men who don’t have fertility problems.

Couples who can’t achieve pregnancy usually go to fertility clinics for treatment. At these clinics, emphasis is put on deciding whether the couple needs assisted reproduction or not, and, if so, to choose between different methods (such as IVF, IUI, or ICSI) for doing this. In most cases, these treatments lead to pregnancy and a live birth. So the problem seems to be solved. But if infertility is an early symptom of an underlying disease in the man, fertility clinics won’t pick it up.

Missed opportunity

Testicular cancer is easy to detect. In men seeking treatment for fertility problems, a simple ultrasound scan of the testes can reveal early cancer, so a life-threatening tumour can be prevented. If detected, 95% of all cases can be cured. But, unfortunately, testicular ultrasound scans are rarely performed at fertility clinics as the focus tends to be on sperm numbers and which method of assisted reproduction to use.

And testicular cancer is not the only threat to young infertile men’s health. Serious health problems, such as metabolic syndrome (high blood pressure, high blood sugar and obesity), type 2 diabetes and loss of bone mass are also much more common conditions among infertile men. These disorders are possible to prevent, but if left untreated often lead to premature death.

A possible culprit

At Lund University in Malmö, Sweden, we have – together with other research groups – made a number of studies focusing on the link between male fertility problems and subsequent risk of serious diseases. We cannot yet explain the causes, but testosterone deficiency is a strong candidate. My research team found that 30% of all men with impaired semen quality have low testosterone levels. And men totally lacking the hormone have early signs of diabetes and bone loss.

We recently conducted a study in which we investigated almost 4,000 men below the age of 50 and who had had their testosterone measured 25 years ago. We found that the risk of dying at a young age was doubled among those with low testosterone levels compared with men with normal levels of this hormone.

Although testosterone treatment may not necessarily be the best preventive measure, these findings makes it possible to identify men at high risk so that they can be advised about lifestyle changes, such as losing weight or quitting smoking – lifestyle changes that will help reduce the risk of developing type 2 diabetes, cardiovascular disease and osteoporosis.

A relatively high proportion of men get in touch with their doctor about infertility problems and, as they represent a high-risk group for some of the most common diseases occurring later in life, perhaps it is time to change the routines for managing them. With the knowledge we now have regarding these men’s health, the least we can demand from doctors is to identify those who are at risk of serious diseases after they have become fathers. This is cheap and only requires simple tests. It is no longer enough to just evaluate the number of sperm.

 

Written by:  Aleksander Giwercman And Yvonne Lundberg Giwercman, The Conversation

Article Source: https://medicalxpress.com/news/2017-05-infertility-men-health-problems-life.html

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Bone Density, Anemia Improve With Testosterone in Low-T Men

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Study Highlights

  • Snyder and colleagues:
    • Study participants were men at least 65 years old with 2 serum testosterone results of less than 275 ng/dL.
    • Men were randomly assigned to receive testosterone gel with titration to maintain serum testosterone levels commensurate with those of a young man, or placebo gel. The treatment period was 12 months.
    • The main study outcome was BMD. Participants underwent BMD testing with quantitative computed tomography and dual energy x-ray absorptiometry of the spine and hip at baseline and at 12 months.
    • 211 men participated in the trial. The mean age of participants was 72.3 years, and the baseline mean testosterone level was slightly more than 230 ng/dL.
    • vBMD increased in the testosterone group by a mean of 7.5%, compared with an increase of only 0.8% in the placebo group (P <.01).
    • Measurements of hip trabecular and peripheral vBMD were also superior in the testosterone group vs the placebo group.
    • Testosterone appeared more effective in increasing trabecular vs peripheral BMD, and in improving BMD in the spine vs the hip.
    • 19 fractures were reported during the treatment year and 1 year after the treatment period, with no evidence of a difference in fracture rates in comparing the testosterone group vs the placebo group.
  • Roy and colleagues:
    • The study was conducted as a double-blind, placebo-controlled trial among men 65 years or older. All participants had a serum testosterone level of less than 275 ng/dL.
    • Men were randomly assigned to receive testosterone gel with titration to maintain serum testosterone levels commensurate with those of a young man, or placebo gel. The treatment period was 12 months.
    • There were 788 men in the study, of whom 126 were anemic, as defined by a hemoglobin level of 12.7 g/dL or lower. Approximately half of men with anemia had no known cause for anemia.
    • The main study outcome was the effect of testosterone therapy on hemoglobin levels among men with anemia.
    • The mean age of participants was 74.8 years, and the mean serum testosterone level among men with anemia was 222 ng/dL at baseline.
    • 54% of men with unexplained anemia who were treated with testosterone experienced an increase in hemoglobin levels of 1.0 g/dL or more, compared with only 15% of men with similar anemia treated with placebo (adjusted OR, 31.5; 95% CI, 3.7-277.8).
    • 58.3% of men treated with testosterone experienced resolution of their anemia, compared with 22.2% of men treated with placebo.
    • Testosterone also raised hemoglobin levels vs placebo among men with a known cause of anemia.
    • Hemoglobin levels increased past 17.5 g/dL in 6 men without anemia at baseline.

Clinical Implications

  • A retrospective cohort study by Cheetham and colleagues finds that testosterone therapy among men with evidence of testosterone deficiency is associated with lower risks for cardiac disease and cerebrovascular disease, even among men older than 65 years and those with preexisting cardiovascular disease.
  • Two new studies demonstrate that testosterone treatment can correct anemia and improve BMD among men with low testosterone levels at baseline.
  • Implications for the Healthcare Team: The current studies further demonstrate potential benefits of testosterone therapy among men with testosterone deficiency. Testosterone therapy was also associated with a lower risk for cardiovascular events in one study. Nonetheless, clinicians should continue to perform shared decision making regarding testosterone therapy and apply this treatment only among men with established testosterone deficiency.

Article Source: http://www.medscape.org/viewarticle/876307

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Shift Work Throws Urologic Health Off Schedule

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Nonstandard shifts and a circadian rhythm disturbance known as shift work sleep disorder contribute to a significant increase in urinary tract symptoms and reproductive problems, according to three studies conducted at the Baylor College of Medicine in Houston.

“A 45-year-old shift worker with shift work sleep disorder might look like a 75-year-old man in terms of his lower urinary tract symptoms,” John Sigalos, a medical student and investigator on one of the studies, said here at the American Urological Association 2017 Annual Meeting.

The other studies presented demonstrate that male shift workers with shift work sleep disorder have lower testosterone levels and more hypogonadal symptoms than daytime workers, and that infertile shift workers, especially those who work rotating shifts, have significantly worse semen parameters than infertile men who work the day shift.

In the United States, approximately 15% of the labor force works late-night or rotating shifts.

Lower Urinary Tract Symptoms Study

To determine the effect of poor sleep quality and shift work on lower urinary tract symptoms, Sigalos and his colleagues retrospectively reviewed the medical records of men treated at the Baylor andrology clinic from 2014 to 2016.

All the men had completed the International Prostate Symptom Score (IPSS) to evaluate lower urinary tract symptoms, completed questionnaires about work schedules and sleep disorders, and had blood samples taken.

Of the 2487 participants, 766 (30.8%) reported working nonstandard shifts in the previous month and, of these, 36.8% were considered to be at high risk for sleep disorders.

Mean IPSS score was higher in shift workers with sleep disorders than in shift workers without, and daytime workers (7.77 vs 5.37 vs 6.84; P < .0001 between all groups).

IPSS scores were 3.1 points lower in shift workers with sleep disorders than in shift workers without, after age, comorbidities, and testosterone levels were controlled for (= .0001).

These findings suggest that poor sleep quality — rather than shift work itself — contributes to the increase in lower urinary tract symptoms. Patients at risk for shift work sleep disorder should be screened for lower urinary tract symptoms and counseled about the risk, Sigalos told Medscape Medical News.

Hypogonadism Study

The potential for hypogonadal symptoms and sexual dysfunction was examined by another group of Baylor investigators who used the same cohort of men.

On multivariable analyses that controlled for age, Charlson comorbidity score, and testosterone levels, mean scores on the quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire were 0.8 points lower in nonstandard shift workers than in daytime workers (P < .01). And mean qADAM score was 3.9 points lower in shift workers at high risk for sleep disorders than in shift workers at low risk (P < .01).

In addition, there was an independent association between high risk for shift work sleep disorder and lower testosterone levels after age, comorbidities, and history of testosterone supplementation were controlled for (P < .01).

Semen Parameters Study

The effects of shift work and sleep quality on semen parameters and reproductive hormones in men were assessed in a prospective study by Taylor Kohn, MD, and his colleagues.

The study participants — 75 infertile shift workers, 96 infertile nonshift workers, and a control group of 26 fertile men — completed questionnaires about shift work and sleep quality, and underwent semen analysis and hormone testing.

Sperm density was significantly lower in infertile shift workers than in infertile nonshift workers (P = .012), as were total motile counts (P = .019) and testosterone levels (= .026).

However, the differences in sperm motility, forward progression measures, luteinizing hormone levels, and follicle-stimulating hormone levels were not significant.

All semen parameters were significantly lower in the infertile shift workers than in the fertile control group, and luteinizing hormone and follicle-stimulating hormone levels were significantly higher. Testosterone levels were about the same in the two groups.

On linear regression that controlled for age, Charlson comorbidity index, tobacco use, and average income, there was a significant negative association between total motile count and shift work (P = .039), and a significant positive association between total motile count and previous fertility (P = .041).

In addition, total motile counts were significantly lower in men who worked rotating shifts than in those who worked fixed shifts (P < .05).

The type of job shift workers performed also made a difference. Men who performed physical labor in environments where chemical use was common (such as oil fields and refineries) had significantly lower total motile counts than physical laborers without chemical exposure, medical workers, white-collar workers, and first responders (P < .05).

Sleep satisfaction also seemed to play a role. “When assessing reported overall sleep amounts in the previous month, follicle-stimulating hormone and testosterone levels trended downward as men became more unsatisfied with the amount of sleep they were getting,” Dr Kohn reported.

Thinking Beyond the Prostate

It is important for urologists to think beyond the prostate when treating men with lower urinary tract symptoms or sexual dysfunction, said Howard Adler, MD, clinical associate professor of medicine at the Stony Brook University School of Medicine in New York.

When men present with symptoms like those reported in these studies, clinicians need to consider not only prostate-related symptoms, but also age-related changes in bladder function, renal function, and other medical conditions, such as diabetes, he told Medscape Medical News.

At Stony Brook, Dr Adler explained, he and his colleagues have begun “asking patients about sleep habits and snoring, and are sending them for sleep studies to see if they have apnea or something else, especially patients with a lot of night-time urination.”

The studies were supported by the Baylor College of Medicine. The authors and Dr Adler have disclosed no relevant financial relationships.

American Urological Association (AUA) 2017 Annual Meeting: Abstracts MP13-12 and PD13-08 presented May 12, 2017; Abstract MP91-06 presented May 16, 2017.

Written By: Neil Osterweil

Article Source: http://www.medscape.com/viewarticle/880096#vp_1

 

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Testosterone Does Not Appear to Increase The Risk For Cardiovascular Disease

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Testosterone replacement therapy does not appear to increase the risk for cardiovascular disease or thromboembolic events in middle-aged men.

In fact, the risk for a cardiovascular event was lower in men taking supplemental testosterone than in those who were not, said lead investigator Julian Hanske, MD, from Ruhr University Bochum in Herne, Germany, who collaborated on the study during a fellowship at Brigham & Women’s Hospital in Boston.

But physicians should know whether a patient suffers from obstructive sleep apnea before prescribing testosterone, Dr Hanske said here at the European Association of Urology 2017 Congress.

Cohort studies of the cardiovascular and thromboembolic consequences of supplemental testosterone have generally relied on sources such as the Surveillance, Epidemiology, and End Results Medicare database, which is limited to an older population, he told Medscape Medical News.

To get a better handle on the relative risks associated with testosterone replacement therapy in a younger population, Dr Hanske and his team searched the TRICARE American military insurance database, which covers all retired and active-duty military personnel and their dependents.

They looked for men 40 to 65 years of age treated for low levels of testosterone. Patients were excluded if they had a history of heart disease, thromboembolism, prostate cancer, or obstructive sleep apnea.

For the final cohort, 3422 men who took testosterone were matched with 3422 control subjects who did not by year of birth, then by date of first testosterone prescription, and then by race and baseline comorbidities.

The study outcomes were event-free survival and absolute risk for cardiovascular disease, thromboembolism or obstructive sleep apnea.

We have so many fears of testosterone replacement therapy.

Cardiovascular event-free survival was significantly better in the testosterone group than in the control group (P = .0085), and risk for coronary artery disease was lower in the testosterone group (P = .0082).

There was no difference in thromboembolic event-free survival between the testosterone and control groups (P = .0998).

These findings are reassuring, said session comoderator Raanan Tal, MD, head of the male infertility program at Rambam Medical Center in Haifa, Israel.

“We have so many fears of testosterone replacement therapy, and actually what they showed is that so many beliefs that we have cannot be supported,” he told Medscape Medical News.

“The fact that you don’t have an increase in cardiovascular events or thrombotic events is an important message — more important than the risk of increased obstructive sleep apnea,” he explained.

But the other comoderator said he thinks the findings would be more compelling if the investigators had used propensity-score matching or a similar statistical method to ensure a close case–control match.

“Age is a risk factor,” Andrea Salonia, MD, from the Vita-Salute San Raffaele University in Milan, pointed out. “The younger the patient, the lower the probability of having difficulties sleeping at night, and they did not adjust for that specific issue, or at least they did not find any kind of difference according to this specific variable.”

“At the same time, the number of patients they considered was amazing, and it is probably one of the most important studies in terms of the huge cohort they selected,” Dr Salonia told Medscape Medical News.

Dr Hanske, Dr Tal, and Dr Salonia have disclosed no relevant financial relationships.

European Association of Urology (EAU) 2017 Congress: Abstract 256. Presented March 25, 2017.

Article Source: http://www.medscape.com/viewarticle/877786

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Testosterone therapy improves insulin sensitivity in diabetic men

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The January 2016 issue of the journal Diabetes Care reported the outcome of a randomized trial that revealed a beneficial role for testosterone treatment in men with diabetes.

“We hypothesized that testosterone may be an anti-inflammatory and insulin sensitizing agent since it has been known for some time that testosterone reduces adiposity and increases skeletal muscle,” remarked lead researcher Paresh Dandona, MD, PhD, who is a Distinguished Professor at the State University of New York and chief of endocrinology, diabetes and metabolism in the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo. “Our previous work has shown that obesity is associated with oxidative stress and inflammation, and inflammatory mediators are known to interfere with insulin signaling.”

The trial included 94 type 2 diabetic men, among whom 44 had low testosterone levels and reduced insulin signaling genes indicative of decreased insulin sensitivity. Participants with low testosterone received a weekly testosterone injection or a placebo for 24 weeks. Body weight, body fat, markers of inflammation, insulin sensitivity and other factors were assessed before and after treatment.

At the end of the trial, men who received testosterone experienced a more than six pound average loss of body fat and an equal increase in muscle mass. They also had lower levels of the inflammatory markers C-reactive protein, interleukin-1b and tumor necrosis factor-a. “Most importantly, we saw a dramatic increase in insulin sensitivity, demonstrated by a 32 percent increase in the uptake of glucose by tissues in response to insulin,” Dr Dandona reported.

“Testosterone treatment for men, where indicated, will improve sexual function and increase skeletal muscle strength and bone density,” Dr Dandona noted. “This is the first definitive evidence that testosterone is an insulin sensitizer and hence a metabolic hormone.”

Article Source: http://www.lifeextension.com/WhatsHot/2015/11/November-Whats-Hot-Articles/Page-01#test

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Effects of taking tadalafil 5 mg once daily on erectile function and total testosterone levels in patients with metabolic syndrome.

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We aimed to evaluate the efficacy of tadalafil 5 mg once-daily treatment on testosterone levels in patients with erectile dysfunction (ED) accompanied by the metabolic syndrome. A total of 40 men with metabolic syndrome were evaluated for ED in this study. All the patients received 5 mg tadalafil once a day for 3 months. Erectile function was assessed using the five-item version of the International Index of Erectile Function (IIEF) questionnaire. Serum testosterone, follicle-stimulating hormone and luteinising hormone levels were also evaluated, and blood samples were taken between 08.00 and 10.00 in the fasting state. All participants have three or more criteria of metabolic syndrome. At the end of 3 months, mean testosterone values and IIEF scores showed an improvement from baseline values (from 3.6 ± 0.5 to 5.2 ± 0.3, from 11.3 ± 1.9 to 19 ± 0.8 respectively). After the treatment, serum LH levels were decreased (from 5.6 ± 0.6 to 4.6 ± 0.5). There was significantly difference in terms of baseline testosterone and luteinising hormone values and IIEF scores (p < .05). Based on our findings, we recommend tadalafil 5 mg once daily in those men with erectile dysfunction especially low testosterone levels accompanied by metabolic syndrome.

Article Source: https://www.ncbi.nlm.nih.gov/pubmed/28295481

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