Testosterone and Sexual Dysfunction, Quality of Life and Mortality - INTERVIEW
We have studied men with testosterone deficiency in type 2 diabetes from a large general practice population, and we found that about 40% of men had testosterone levels below 12 nmol/L, and about 18% had levels below 8 nmol/L, which is the level that most people would agree should be treated.
We’ve found that when we treated men with type 2 diabetes and low testosterone, the earliest improvement was sexual desire, which improved within 4 to 6 weeks. There was also improvement in general well-being in terms of energy levels and mood. But improvement in sexual function measured by erectile function could take up to 6 months to improve. Therefore, any trial of testosterone therapy must be of a duration of a minimum of 6 months, particularly in patients with type 2 diabetes. We also found that men who had poorly controlled diabetes with HbA1c above 7.5 improved by about .4% in their HbA1c over the 6-month period. When we treat men with hypogonadism and type 2 diabetes with testosterone, we’ve got to realize that this is long-term treatment. And we shouldn’t consider treating patients just for two or three months to give them a quick trial, which happens too readily. What we find is that there are prompt improvements in terms of libido and in terms of general well-being and mood. But it takes much longer for sexual function in terms of erectile performance to improve. And it also takes about 6 months for glycemic control to improve, or for total cholesterol to improve. And particularly weight reduction can take up to 12 months. Our patients lost about 4 cm in waist circumference, and those with poorly controlled diabetes saw about a .4% improvement in HbA1c.
Patients notice benefits in a number of ways when they are started on testosterone therapy. The earliest symptoms of hypogonadism are sexual symptoms, and these are the most common symptoms that cause men to seek medical help. Sexual symptoms are often the ones that they want to improve most quickly, and improvement in sexual symptoms is one of the benefits of testosterone therapy with the fastest onset. So sexual desire improves and then morning erections come back, and erectile function improves. We use the Aging Male Symptom score which looks at different aspects of men’s health. And we found an improvement in the AMS score of about 7 or 8 points over the 6 months of our trial. We found that depression was slow to improve, and indeed, we found that patients who were depressed had the worst improvement at all. In fact, some of them did not respond to testosterone at all. And that was quite an important finding. But after 12 months, there were signs that the depression was beginning to improve. So, the message is, it’s long-term treatment that’s required.
We found that when we followed up patients from our studies, we first of all looked at the patients who had low testosterone, who were not treated. And when compared with those, with the normal testosterone, we confirmed the findings of other studies that men with type 2 diabetes and hypogonadism have increased risk all-cause mortality. And it’s quite important to take home that message. If you do nothing, these patients die earlier. But what we found is that in the group that we treated, and we had 175 patients who were treated for longer than a year, and we’ve had about 80 patients who were treated for 5 years – what we found was that not only was the mortality as good as those who had a normal testosterone, but it was in fact a lower mortality than those patients who had testosterone levels in the normal range at screening. You might say, “Why is this?” Well, the likelihood is that the patients who we treated with long-acting testosterone undecanoate for 1 year had testosterone levels up with the 15-20 nmol/L range, whereas men with so-called “normal” testosterone levels were very much in the low-normal range, just above 12 nmol/L. This suggests that there are benefits of having the therapeutic target set a bit higher when we treat patients.
As for why this mechanism, we know that low testosterone is associated with frailty and chronic illness. So, a lot of men with type 2 diabetes suffer from chronic illnesses and are generally weaker. And therefore, the ability to respond to intercurrent illnesses that crop up will be reduced. So, diseased men with low testosterone who get an infection during winter probably got less chance of surviving that. But also, if we look at the metabolic improvements in terms of lowering total cholesterol, improving HbA1c, treating visceral adiposity, these are parameters which have been shown in studies like UK PDS to equate to reduction in cardiovascular mortality over many years.
When we start a patient on testosterone therapy, I think it’s important to tell the patients what types of therapy there are and allow them to make the choice. I think they make the choice very quickly. There are some patients who prefer the gel. And they feel that they are in control when using the gel. But by far, the majority of patients I see, because of their low testosterone, often suffering from mild depression and cognitive impairment. They are slow and less motivated to adhere to testosterone treatment. In those patients, I think there is a tremendous advantage in giving them a long-acting treatment, because you know the treatment was given by the clinic nurse and when it was given, and that it will be in the system for up to 12 weeks. In contrast, when using a gel, you find that patients often have problems getting appointments to see their doctor, he only gives them treatment for a month or even less. He does not titrate the dose. He makes them come back for follow-up appointments, but they cannot get an appointment, so they go several weeks without treatment. They then forget to take it when they go on holiday. And when you review them, you invariably do not know whether they have been treated or not. When you see a patient who has been on long-acting testosterone undecanoate injection you know how many injections they have received, so you know that what you are seeing is the result of the testosterone therapy.
I always measure testosterone in patients presenting with erectile dysfunction. Even if you think you know what the cause of erectile dysfunction is, if they have had a radical prostatectomy for example, a lot of urologists do not measure the testosterone because it seems clear that the erectile function was related to the low testosterone. But the patient may have had an element of erectile dysfunction before, and this was just the event that finished it off altogether. If you do not measure testosterone you will not be able to make the right clinical decisions. We know that all erectile dysfunction therapies need a testosterone level of above about 10.4 nmol/L to be effective. So, you can waste a lot of time and medication giving patients therapies that were never going to work.
Another patient group in whom I would always measure testosterone is type 2 diabetes because of their high prevalence of hypogonadism and their poor response to all erectile dysfunction therapies. Low testosterone further reduces the chances of responding to erectile dysfunction treatment. So, it is absolutely vital that testosterone levels are measured. According to the recent guidelines of the American Academy of Clinical Endocrinologists (AACE), patients with bellies - that is visceral obesity - should have their testosterone measured. This means that all men with a waist circumference above 98 cm should have their testosterone levels checked, because low testosterone is a modifiable factor in the management of their obesity. I agree wholeheartedly with that.
Also, we should be measuring testosterone levels in patients who are on long-term opiates for chronic conditions or anti-convulsants. Also, patients with HIV, chronic renal disease and COPD. These are patients who are often neglected, but often have marked hypogonadism.
Prof. Dr. med. Marija Pfeifer Medical Faculty University of Ljubljana, Slovenia