I’m always grateful for the relative peace of the summer season, allowing me to catch my breath from the hectic pace of conferences, lectures, and the urgency of multiple projects and deadlines that occur during the “serious season” of the spring and fall. Yet the mental regrouping and the type of work that occurs during this time really sets the tone for the rest of the year. I’m going to enjoy this month, and I look forward to hitting the ground running again in September.
One thing that has occupied my time has been the search for a new management team for the Androgen Society (AS). I’m proud to have co-founded the AS seven years ago, and it has achieved the original goal of becoming the premier global platform for research and education regarding testosterone deficiency and its treatment. Our annual meeting this past May in Boston included many of the most prominent researchers and clinicians in the field from around the world, and many attendees said this was the best testosterone-related meeting they had ever attended. I agree! We are near finalizing an agreement with a new management team, and I am excited by what the AS can achieve in the next couple of years so that the critical educational work of the AS will reach a broader audience.
If you’re interested enough in testosterone to be reading this newsletter, I encourage you to join the AS. We have so much good stuff coming, much of which will be available only to members. You can join here.
On the research front, I’d like to comment on the remarkable recent paper published by Bu Yeap and coworkers titled “Associations of testosterone and related hormones with all-cause and cardiovascular mortality and incident cardiovascular disease in men: individual participant data meta-analysis,” and published in Annals of Internal Medicine (2024, 177:768-81). This was an analysis of data obtained from nine prospective cohort studies of community-dwelling men for which they had individual data, and a minimum of 5 years of follow-up. The goal was to investigate whether blood test results for testosterone and related hormones were associated with death from any cause, death from cardiovascular (CV) disease, or new onset CV disease. This was a high-quality study authored by several of the most experienced and respected testosterone investigators.
The study was based on 255,830 participant-years of data. To understand the term, “participant-year,” it combines the size of the population and the duration of follow-up. Imagine 100 individuals followed for 1 year. That would provide 100 participant-years of study. So, 255,830 participant-years is an impressive amount of data!
Three items were associated with increased all-cause mortality; testosterone concentrations less than 213 ng/dl (7.4 nmol/L), elevated LH concentrations greater than 10 IU/L, and estradiol concentrations less than 5.1pmol/L. There was also an association with CV mortality for men with even lower T concentrations of 153 ng/dl or less. Lower SHBG concentrations were associated with lower all-cause mortality and lower CV mortality. Low DHT concentrations were also associated with both all-cause mortality and CV mortality. The magnitude of the increased risk for most of these associations was approximately 20%.
What does all this mean? Since these are associations, one cannot say that the low levels of T caused or contributed directly to the increased mortality, but that is certainly one possibility. Another equally plausible interpretation is that low levels of T reflect poor general health status, and T levels here are merely acting as an indicator or biomarker for medical conditions that predispose to greater risk of all-cause or CV death. Nonetheless, these results provide additional confirmation that higher T levels are NOT associated with increased CV risk. And in my opinion, these results strongly argue for the value of a serum T blood test as the single best test to assess male health!
I would add that some of the results for non-T items such as estradiol, SHBG, and DHT are all easily understandable and consistent with a T-driven phenomenon. Estradiol and DHT are derived directly from T, so when T is low, both of those hormones also tend to be low. Low SHBG is also associated with higher free T, and so it makes sense that low SHBG here was associated with decreased mortality risk.
Between the reassuring results of the recent TRAVERSE study (largest-ever testosterone RCT), this new study by Yeap et al, and other RCTs and observational studies, I believe we can now say definitively that higher serum T is not associated with CV risk. More intriguingly, several studies- including this one by Yeap et al- suggest that low T may be a risk factor for mortality and other studies have reported results that T therapy in T-deficient men may reduce mortality. Step by step, the importance of having normal T for male general health is gaining awareness in the medical community.
Enjoy the rest of your summers, and I’ll be in touch again soon.
Abe Morgentaler, MD