This was associated with SHBG concentrations in the low normal range. This study also demonstrated that these patients had inappropriately low LH and FSH concentrations. Thus, these patients had hypogonadotrophic hypogonadism (HH).

Although it has been known for two decades that males with type 2 diabetes have low testosterone concentrations and that subjects with low testosterone concentrations are likely to develop type 2 diabetes, the issue of low testosterone concentrations has been treated as a marker associated with type 2 diabetes and features of the metabolic syndrome.

These studies were based on total testosterone concentrations. The first study to attract attention towards the low testosterone concentrations as a feature of clinically relevant hypogonadism in type 2 diabetic males (age range: 28 to 80 years) was based on free testosterone concentrations.

Total and free testosterone concentrations were also inversely related to age as expected and to BMI. However, hypogonadism was not entirely dependent upon obesity since 25% of non-obese patients(31% of lean and 21% of overweight) also had HH. This observation has now been confirmed by studies from the UK, Brazil, Italy and Australia.

Clearly, therefore, HH occurs frequently in males with type 2 diabetes. Type 2 diabetic men with low testosterone have also been found to have a high prevalence of symptoms suggestive of hypogonadism. All of the above studies were based on middle aged patients.

The first study to investigate the occurrence of HH in younger patients with type 2 diabetes has recently been published. In this study, patients between the ages of 18 and 35 years were shown to have HH at a rate of 58%. However, in this study all hypogonadal patients were obese since type 2 diabetes in the young is largely dependent on the presence of obesity.

Nevertheless, the presence of HH at such a high rate is alarming because such patients with HH are in their prime reproductive years and are likely not only to suffer from features of low testosterone concentrations but also potentially from impaired spermatogenesis.

The issue of spermatogenesis and fertility needs to be investigated further. Obesity itself has also been associated with decreased spermatogenesis. It is not yet known whether the decreased sperm count in obesity is due to low FSH, low testosterone or to some other factor associated with obesity.

In contrast to the frequent occurrence of HH in type 2 diabetes, this syndrome does not occur in type 1 diabetes. This has been confirmed in studies of both middle aged and young type 1 diabetes. Indeed, these patients have high normal total testosterone concentrations partly because they have high normal SHBG concentrations. Therefore, their FT concentrations tend to be in the mid normal range.

The presence of type 2 diabetes in over 20 million in the US leads us to estimate that approximately 3.5 million patients may have HH. Among them, a sizable number are likely to be in their prime reproductive years. This is going to pose a substantial load at the public health level in terms of inadequate sexual function and potential infertility.

These issues need to be addressed appropriately in terms of the understanding of the pathogenic mechanisms and the correct strategies for treatment. Last but not the least we have think about the prevention of the massive and progressive epidemic of type 2 diabetes which in its wake now brings hypogonadism and the associated morbidity.