The relationship between Low Testosterone and insulin resistance remains controversial, there is a strong body of evidence indicating that SEVERE androgen deficiency (say TT below 300 ng/dl) is associated with insulin resistance such as in men undergoing androgen deprivation therapy. The question that remains unanswered is whether treating subclinical hypogonadism (subnormal testosterone) can improve insulin resistance or can improve glucose tolerance.
A study was published online earlier this year based on the issue in which 308 men aged >60 with low to subnormal testosterone (defined as 100-400 ng/dl) or low free testosterone (defined as lower than 50pg/ml) were given testosterone replacement. Insulin sensitivity was measured at 3 and 36 months after initiation of testosterone replacement therapy. The study came to the conclusion that āTestosterone administration for 36 months in older men with low or low - normal testosterone levels did not improve insulin sensitivityā however I found this study troubling and I will explain why
The treatment method in this study was androgel (androgel isnāt very effective), the aim of the study was to get the participants testosterone concentrations between 500 and 900 ng/dl, however this was not achieved. Testosterone levels increased from a baseline average of 330 ng/dl to 477 ng/dl. The fact that there was no statistically significant improvement in insulin sensitivity is not surprising given that testosterone levels were still what I would consider ālowā on treatment. I donāt know about the individuals on this website, but I donāt consider a total testosterone of only 477 ng/dl enough to reap the proper benefits TRT has to offer for male with low or subnormal testosterone levels. Free testosterone levels increased from an average of 68 pg/ml to 94 pg/mlā¦. A free testosterone of 94 pg/ml is on the low side. Based on this study I would say the testosterone replacement given wasnāt adequate āreplacementā.
I took this graph from a different study (canāt be bothered to find it), however this graph clearly shows a strong positive correlation between insulin resistance and lower testosterone levels, in fact, the few with high testosterone levels (30-50 nmol------865-1441 ng/dl) seem to all be well within healthy limits when it comes to fasted insulin tests. The majority of dots that could be categorized as individuals with insulin resistance have total testosterone levels between 7-mid 20ās in nmol (202-662 ng/dl). Low levels of SHBG have also been shown to be associated with insulin resistance, and once again from this dot plot a strong positive correlation can be noted (P value is <0.0001, typically any value above or at .05 is of clinical significance)ā¦ And I have/had low T for a while and have low SHBGā¦ I have impaired glucose tolerance and insulin sensitivity
With what I saw from the small sample of data shown above, I became curious as to whether higher concentrations of testosterone (as in upper limits of normal to mildly supraphysiological (is 1000-1400 ng/dl supraphysiological?))ā¦ has any beneficial effect on insulin sensitivity compared to men with normal or low normal testosterone levels). I couldnāt find much on the subject which isnāt surprising considering it must be incredibly hard to convince the ethics committee to greenlight a study relating to anabolic steroids in any dose other than the bare minimum for replacement, however it has been done before.
After a small search I came across two studies, both had the same doses of androgen administered, however the fatal flaw in both studies came with regards that the androgens were administered to normal, healthy men, not men with insulin insensitivity or subnormal testosterone levels. Nevertheless both studies administered Testosterone enanthate or nandrolone decanoate to normal men at doses of 100mg or 300mg/week. 100mg/week is a solid replacement dose and 300mg/week should get MOST individuals into territory that is well above what a normal male would produce testosterone wise (would probably get me to around 1300-1500 ng/dl considering 109 mg/week has me at between 600 and 350) and nandrolone decanoateā¦ well iām not really sure why they chose to include this but nevertheless the results are STILL INTERESTING. The androgens werenāt given for a long duration of time, four weeks in the one study and six weeks in the other. In the end of each study testosterone enanthate in all groups was documented to have no beneficial or adverse affect on insulin sensitivity or glucose tolerance, however the agent was only administered for a short period of time. Nandrolone decanoate was found to āimprove glucose metabolism by enhancing non insulin-mediated glucose disposalā. Other studies on high dose chronic testosterone administration (as contraceptive or just high dose testosterone) in doses of 200-600mg/week have been studied, however I donāt believe effects on glucose tolerance or insulin sensitivity have been recorded. What Iām curious about is whether high normal levels (as in top fiveish percent of men levels) would improve insulin sensitivity in a male with subnormal testosterone levels or insulin insensitivity.
Testosterone levels for male population taken from a study
Finally, Iām not saying or recommending anyone to start injecting higher doses of testosterone, prolonged exposure to testosterone levels that are higher than normal, especially in individuals who are already not in optimal health may cause unpleasant side effects such as high blood pressure, water retention, gynecomastia, prostate enlargement, male pattern baldness and long term complications could include heart enlargement, high hematocrit etc (although personally I think the side effects/ risk is way way overblown). Iām just posting a THEORY I have that suggests testosterone levels on the higher side of norma might be associated with improved insulin sensitivity and glucose tolerance, however thereās a decent chance Iām wrong, Iām not a doctor or an expert by any means, just a person who is bored and is therefore writing random papers and posting them on this website on the TRT forum. My next article will be on why reference ranges for testosterone bother me.
Studies:
https://academic.oup.com/jcem/article/103/4/1678/4822914 (testosterone not associated with improved insulin sensitivity in older men)
(couldnāt be bothered to find the study I got the one graph from)
Androgen deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth - PubMed (androgen deprivation therapy and insulin resistance)
https://academic.oup.com/jcem/article/96/8/2430/2834349 (testosterone levels in young men)
Nandrolone, a 19-nortestosterone, enhances insulin-independent glucose uptake in normal men - PubMed (nandrolone and testosterone on glucose and insulin sensitivity)
The administration of pharmacological doses of testosterone or 19-nortestosterone to normal men is not associated with increased insulin secretion or impaired glucose tolerance - PubMed (nandrolone and testosterone again on insulin and glucose)