Sunday, June 4, 2023

Testosterone Replacement for Men

Reasons why you should consider Testosterone Replacement Therapy (TRT)



What happens to testosterone [T] with age?

First: available ie ‘free’ T declines with age.

Here is data from the European Male Aging Study.[1].



The graph shows ‘free T’ ie that which is biologically available rather than bound to serum protein and distinguishes between those who have a high BMI [are fat] shown by the redline and those with a low BMI shown by the olive green line. NB Free T is much less than Total T and the units here are nmol/L [ie pmol/L/ x 103]. The data in the next picture is in pmol/L.

The key points in the diagram are:

First: Being fat lowers your free T, substantially ie those on the redline are worst off. Lots of older men are overweight so are at risk of this. You can see that for a normal-weight man [yellow line] at 75-79 the average level ie the line on the graph, is 21% below that of 40 year old. 

Second: There is great variation between individuals of the same age. This is data is from a study that corrected results from several studies to allow for differences in assay technique- ie ‘harmonisation’ and thus create a larger dataset[i]. It shows Total T ie Free+ bound T, by age group. This is a ‘box and whisker’ plot designed to show the variation effectively. More about this technique here[2].

The graph shows 3 age groups ie 50’s, 60’s and 70’s. The different colours indicate they come from different original datasets. 

The circle shows the box that is the range and position of 50% of the population and the horizontal line in the box is the median. The whiskers top and bottom show the top 25% and bottom 25%. On the left the orange dotted line shows the level of T at which symptoms appear – typically below 15 nmol/L.

Summary: what do these 2 studies show us?

  1. Free T [the active ingredient] declines with age but total T doesn’t to the same extent.
  2. This is mainly to do with the impact of individual issues eg ‘fatness’ that are more important than age alone.
  3. There are many men with good T levels even in the 70’s.
  4. Some outliers [the dots outside the top whisker] have surprisingly high T levels at older ages.
  5. However there are around 30-40% of men who have borderline or low levels and are definitely ‘at risk’ of the consequences of low T.
  6. For fatter men TRT may be a vital therapy.

Take Home: It is necessary to measure T or use a clinical index in all men over 50 to identify who is likely to develop a problem. I believe this is just as important a screening tool as blood lipids, blood sugar or the PSA.

NB. Men with low T lose their morning erection.

Why does it matter, what are low T individuals ‘at risk’ of?

The real importance of maintaining testosterone – anti-ageing effects.

Men with low T levels have several problems eg low libido, erectile dysfunction and low mood. They are of course very important to the individual concerned but aren’t public health issues.

The critical feature is that T is an essential anti-ageing hormone.

Low T levels increase the risk of:

  1. Cardiovascular disease [heart attack and stroke]
  2. Muscle wasting and loss of strength leading to injury prone frailty.
  3. Bone loss and osteoporotic fracture [hip and lumbar vertebral collapse]
  4. Dementia notably Alzheimer’s Disease [AD].

Men who present with erectile dysfunction may have low T but in addition critical small artery damage [in the penis and the heart muscle] and are at risk of a heart attack.

TRT has benefits. In the Testosterone Trials, symptomatic men 65 years or older with low testosterone level (<9.5 nmol/L), received 1 year of ΤRΤ. It  significantly improved sexual function, bone mineral density, 6-minute walking distance, depressive symptoms, and haemoglobin levels.

And AD? A review covered twelve articles on the effect of androgen deprivation therapy and seventeen on T therapy impact on AD[3]. Men with androgen deprivation showed a higher incidence of AD. TRT in hypogonadal men with AD and cognitive impairment had positive results. The majority of studies show T administration improves memory and cognition [if it is already diminished]. 

The conclusions are therefore twofold for men with low T: first TRT can benefit established AD and second it seems likely that timely TRT prevents it from developing

Summary 

The 4 items on the list severely impact Quality of Life and Longevity. Given that TRT has no significant risk [see Part 2] preventing these is both possible and desirable.

References

[Jean-Marc Kaufman and others, Aging and the Male Reproductive System, Endocrine Reviews, Volume 40, Issue 4, August 2019, Pages 906–972, https://doi.org/10.1210/er.2018-00178

[1] Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, Lapauw B, Fiers T, Matsumoto AM, Bhasin S. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe. J Clin Endocrinol Metab. 2017 Apr 1;102(4):1161-1173. doi: 10.1210/jc.2016-2935. PMID: 28324103; PMCID: PMC5460736.

[2] https://flowingdata.com/2008/02/15/how-to-read-and-use-a-box-and-whisker-plot

[3] Bianchi VE. Impact of Testosterone on Alzheimer's Disease. World J Mens Health. 2022 Apr;40(2):243-256. doi: 10.5534/wjmh.210175. Epub 2022 Jan 2. PMID: 35021306; PMCID: PMC8987133.


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