Testosterone Treatment In Men - Risk To The Heart?

At the Endocrine Society’s recent ENDO 2015 meeting in San Diego, I managed to score a seat in a packed-to-overflowing symposium discussing some of the controversies surrounding testosterone therapy in men.

At the heart of the discussion ws the fact that testosterone prescribing in men has dramatically increased over the last several years, primarily due to an increase in prescribing of this hormone to men who do not have a medical reason for failure of testosterone production (ie a testicular or pituitary problem), but rather, are men who have a low-ish testosterone due to aging or obesity, in hopes that they may feel better with testosterone therapy.   The prescribing of testosterone in men without a true failure of testosterone production has raised a number of safety concerns – in particular, whether testosterone may increase the risk of heart attacks or stroke.

The first point that was made in the symposium by Dr Alvin Matsumoto is that men may be labelled as having low testosterone, when, in fact, they don’t.  The problem here lies with a number of concerns with the accuracy of measurement of testosterone levels in men:

• First of all, testosterone needs to be measured in the morning, as levels are highest in the morning and fall later in the day; 'normal' ranges have been developed based on the early morning measurements.  
• Second, there are a lot of problems with the accuracy of testosterone measurement - one study looked at over 1000 different labs and found that testosterone levels on the same sample varied by 6 fold (ranging from very low to well within the normal range).  
• Third, testosterone levels are not the same from day to day in one particular man - in fact, in men who have a low testosterone measured initially, about a third will have a normal level on repeat testing.  

Dr Shehzad Basaria then took us through an excellent review of the conflicting data around the effect of testosterone on cardiovascular (CV) risk.  Population studies suggest that testosterone treatment decreases the risk of CV events, but it is possible that it is men more concerned about/interested in their health that were taking the testosterone, so these results may just reflect that healthier men were tending to take testosterone in the populations studied.  Other retrospective studies, on the other hand, have suggested that testosterone treatment increases the risk of CV events – these studies suggested that it is older men, and those with pre-existing heart disease, who had the highest risk.  This is highly relevant to the discussion of whether it is safe to prescribe testosterone to men with age- or obesity-related decline in testosterone, as this is a group of men who are older and more likely to have pre existing heart disease.

We always look to randomized, controlled clinical trials for the answers to these questions if at all possible – and in fact, a recent study called the TOM study was stopped early because they saw a higher risk of CV events in the group of men receiving testosterone treatment.   The TOM study results have been criticized because they were studying muscle strength as their primary endpoint of interest and not CV events per se – but the results are what they are.

As far as how exactly testosterone treatment could increase the risk of heart attacks, we don’t know, but several possibilities have been suggested, including increase in clotting tendency/inflammation, driving testosterone levels too high with treatment, and fluid retention.

Because of the concerns that testosterone treatment may increased the risk of cardiovascular events, the FDA has now stated that testosterone treatment is only approved for men with true failure of testosterone production caused by certain medical conditions (these would include a primary problem with the testicles such as previous injury, mumps, or chromosomal issues; or the pituitary gland such as a pituitary tumor or radiation damage). They go on to state that the benefit and safety of testosterone has not been established for the treatment of low testosterone due to aging, even if a man's symptoms seem related to low testosterone.  The FDA also now mandates that the labeling for testosterone treatments includes a warning that it may increase the risk of heart attack or stroke.

Clearly, much more research is needed to answer our questions in this controversial area.

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www.drsue.ca © 2015

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Bariatric Surgery For Diabetes Prevention?

Over the last decades, many modalities to prevent type 2 diabetes have been studied.  Lifestyle changes, particularly if they result in weight loss, can be very powerful to prevent this condition.  Of all of the medications studied, only metformin has so far been recommended to decrease the risk of developing diabetes in people who have prediabetes.  Now, studies are coming out, showing that bariatric (obesity) surgery can be very powerful to prevent type 2 diabetes.

One such study, published recently in The Lancet (Diabetes & Endocrinology),  looked at over 2000 patients who had bariatric surgery, and compared them to a group of matched patients who had not had obesity surgery.  They found that, over a median of 2.8 years and a maximum of 7 years of follow up, patients who had bariatric surgery had an 80% lower risk of developing diabetes compared to people who had not had bariatric surgery.

Another recent study was a systemic review and meta-analysis that looked at the power of different interventions to prevent diabetes. In examination of studies of physical activity +/- diet, anti diabetic medications, obesity medications, and bariatric surgery, they found all of these strategies to be of benefit.  Bariatric surgery stood out as being the most effective to prevent diabetes, with a 90% reduction in risk.

So the question then becomes, should we advocate for obesity surgery for the purpose of prevention of diabetes?  Well, as for any treatment or prevention of any medical condition, it's important to balance the benefits vs risks.  Bariatric surgery is invasive, and the most successful modalities (gastric bypass and sleeve gastrectomy) are permanent procedures.  These procedures have a long list of possible complications that need to be taken into consideration.

While bariatric surgery may be the best treatment option for some patients with obesity and existing type 2 diabetes, obstructive sleep apnea, severe high blood pressure, or severe osteoarthritis, it seems that using surgery solely to prevent these conditions may be outweighed by potential risks.  That being said, a marked reduction in risk of developing type 2 diabetes is certainly an added bonus to the patient having bariatric surgery who is having bariatric surgery for other reasons.


Thanks to my friend Gord for the inspiration for this blog post!

Follow me on twitter! @drsuepedersen

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ENDO 2015: Diabetes and Bones

And....we're off!!! ENDO 2015 is off to a fabulous start.  I'm excited to share with you our learnings about diabetes and bone disease from a symposium held this morning.  You'll need a few extra minutes to read this post - it's a little longer than my usual blogs - so much to cover and share!  Grab a cuppa and get comfy. :)


We were first provided an overview of the impact of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) on the skeleton, by Dr Ann Schwartz.  We learned that diabetics are at an increased risk of fracture (broken bones) than people without diabetes. In T1DM, bone density is lower than in non diabetics, suggesting a moderately increased risk of hip fracture.  However, studies have shown that a type 1 diabetic is actually at over a 6 times higher risk of a hip fracture compared to a non diabetic (much higher than differences in bone density would suggest), suggesting that there is much more to the story than a lower bone density.

In type 2 diabetics, the situation is different.  As 90% of T2DM patients struggle with overweight or obesity, bone densities are higher, a result of the higher body weight that the skeleton supports. Despite this, T2DM patients are at 40% higher risk of hip fracture; after adjusting for body mass index (BMI), there is a 70% increased risk of hip fracture compared to non diabetics.  

While diabetics are at a higher risk of falls (see below for more thoughts on this), studies that controlled for falls still show a higher fracture risk – again suggesting that there is something going on in the bones themselves that increase fracture risk.

So why are diabetics at a higher risk of fracture for a given bone density?  Many possibilities have been suggested in terms of differences in bone structure at the microarchitectural level, but as Dr Mary Larsen Bouxsein pointed out, there is little that is currently understood about exactly what is happen at the microscopic level in terms of the damage that high blood sugars could be doing to bone.  Dr Josh Farr showed us data suggesting that cortical bone microarchitecture in women appears to be compromised in T2DM due to decreased bone formation and turnover, but these studies are limited by size and data are not available in men.

As diabetics have a higher fracture risk for a given bone density, our traditional means of evaluating fracture risk may not be appropriate.  It has been shown that bone density testing (using the T score) does predict risk of hip fracture in diabetics, but at a particular T score, the fracture risk is higher than a non diabetic with the same T score.  The FRAX score, which we often use to predict risk of fracture in our patients, underestimates the risk of fracture in T2DM.

Medications that treat type 2 diabetes may have variable effects on bone as well, as reviewed by Dr Christian Meier.  Metformin, our first line treatment for type 2 diabetes, seems to be protective of the bones.  We know that the group of medications called thiazolidinediones increase the risk of fracture in postmenopausal women and older men, and with longer duration of treatment. There is some evidence to suggest that the group of type 2 diabetes medications called incretin therapies may be protective of bone, but much further study needs to be done.  A newer class of medications called the SGLT2 inhibitors may slightly increase fracture risk, but again, much more study is needed in this area.

A few important points that I would like to highlight (from this session, as well as my own thoughts):  

• It is crucially important to avoid low blood sugars in patients with diabetes.  A low blood sugar can cause a fall that can result in a fracture.  
• Prevention of diabetic nerve damage is also crucial, as fall risk increases in those who have loss of sensation to their feet.  
• Being fit and strong is also important to prevent falls. 
• Finally, checking vitamin B12 in patients on metformin is important as well, as low vitamin B12 can cause nerve damage, and metformin can rarely cause vitamin B12 levels to be low.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015

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