Low Testosterone in Type 2 Diabetes; A Hidden Epidemic?

Evan David Rosen, M.D., Ph.D. Assistant Professor of Medicine, Harvard Medical School

Among endocrinologists, it’s well-known that patients with type 1 diabetes are at risk for other hormonal disorders, including hypothyroidism, premature ovarian failure, and Addison’s disease (glucocorticoid deficiency). Like type 1 diabetes, these are all autoimmune diseases, and people who manifest one such disorder often manifest others as well.

It is less well appreciated that type 2 diabetes, which is not an autoimmune disorder, is also associated with other endocrine diseases, in particular hypogonadism in men. In women, ovarian disorders can sometimes be classified as hypogonadism. For instance, women with the polycystic ovarian syndrome are often (but not always) overweight, and thus can have a mixed pattern of insulin resistance and abnormal reproductive hormone levels. This can lead to irregular menstrual cycles, and this is a well-known if poorly understood phenomenon. But what I’m specifically talking about here is the association between low testosterone levels in men with type 2 diabetes.

Studies linking low testosterone levels to type 2 diabetes have been around since the early 1990’s, but they haven’t received much attention. Certainly, there are reasons why the link might not be as interesting as it appears at first blush. For example, both type 2 diabetes and low testosterone levels are associated with aging, and it doesn’t take an endocrinologist to figure that some older men will randomly have BOTH diabetes and low testosterone levels. But some studies have shown that testosterone levels are lower in diabetic men vs. non-diabetic men even if one carefully studies men of the same age.

Other skeptics have pointed out that obese men (who are more likely to have type 2 diabetes) have lower levels of sex hormone binding globulin (SHBG), a protein that acts as a carrier of testosterone in the blood. If SHBG levels are low, it will appear on blood tests as if testosterone levels are low, when in fact the "free" hormone that circulates in the blood unbound to SHBG will actually be normal.

But a new study shows that free testosterone levels, measured by a special assay, are in fact lower in men with type 2 diabetes than in non-diabetic men. Furthermore, this new study adds an interesting new wrinkle. Fully one third of the 103 men studied with type 2 diabetes had low total and free testosterone levels. But what was most intriguing was that these men did not seem to have the type of hypogonadism that comes with ageing, called primary hypogonadism. In this condition, the testes wear out, and so make less testosterone, despite high levels of the appropriate stimulating hormones from the pituitary gland. (Primary hypogonadism is what happens during menopause in women, for example, when the ovaries stop making estrogen). In these diabetic men, however, levels of the pituitary hormones were much lower than expected—suggesting that the men’s pituitary glands were not functioning properly. (Alternatively, the hypothalamus, the part of the brain that tells the pituitary what to do, could be malfunctioning).

Why is all this interesting? Well, for a few reasons. First, this form of hypogonadism is not considered to be all that common, and when we identify it, we usually search for relatively rare conditions, like large pituitary tumors. These observations suggest that there is a huge pool of men out there with this condition who are not being diagnosed. What are the effects of low testosterone levels? Well, they can range from virtually nothing to fatigue, anemia, bone loss, loss of sexual drive, and erectile dysfunction.

This last point in particular is important; diabetic men are highly prone to erectile dysfunction because of nerve damage and poor circulation. These conditions are difficult to treat, and many men suffer in silence because they never bring their erectile dysfunction to their doctor’s attention in the first place, or because there are few treatment options available even when they do talk about it. But hypogonadism is relatively easy to treat with testosterone supplements (usually given as a gel or a skin patch), suggesting that many men may not be receiving effective therapy for erectile dysfunction if they never get a testosterone level checked.

These results need to be confirmed in more diabetic men, and studies need to be done to look at the effectiveness of testosterone replacement in this group of patients. Testosterone replacement is not for everyone, as it can promote the growth of prostate cancer (which could be undiagnosed) and can (in rare instances) increase the number of red blood cells to the point that blood flow becomes sluggish. Nonetheless, any man with type 2 diabetes who complains of fatigue, loss of interest in sex, or erectile dysfunction should get total and free testosterone levels measured if they and their physician decide that they would be a candidate for testosterone. Eventually, testosterone measurement is likely to become routine in the treatment of men with diabetes, in the same way that cholesterol levels and blood pressure are now followed as a matter of course. Until then, it’s up to patients to ask, and doctors should be thinking about hypogonadism in all of their male patients with type 2 diabetes.

Reference:

Sandeep Dhindsa, Sathyavani Prabhakar, Manak Sethi, Arindam Bandyopadhyay, Ajay Chaudhuri and Paresh Dandona. Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 11 5462-5468.