I was actually expecting someone to raise this issue as recently I was reading up, among other things, on the relationship between low t and diabetes, and the possible implications of the available studies on the alledged link between adult type II diabetes and hypogonadism. After a lot of reading and researching, the best conclusion that I can come up with at the moment, is that hypogonadism as such does not lead to diabetes, however, hypogonadism is usually a complication (as opposed to being contributing) of diabetes in about 20% to 40% of cases. At most, obesity as a complication of hypogonadism appears to be the only indirect risk factor for accelerating the development of diabetes. Additionally, most of the evidence points toward that there is very litte to no stand-alone effect of testosterone (either external or internal) upon glucose metabolism and insulin resistance. It really looks as if neither castration nor hrt have much of effect in this regard. Closer attention should be payed, instead, to diet management, excersize and family history as the most decisive risk factors for your chances of becoming a diabetic.
Having said that, I would like to go through some of the relevant studies, and their findings, with a recent study (2004) examining the extent of hypogonadism in men with diabetes as a basis for my comments.
Here's the study involving 103 men with diabetes, with the aim of investigating the prevalence of hypogondism among diabetics:
http://www.medicalnewstoday.com/medical ... wsid=17023
http://www.cbsnews.com/stories/2004/12/ ... 8541.shtml
The researchers claim that their study is more accurate than it's predecessors, mainly because previous studies had problems with testosterone assays and had relatively small number of participants (it should be noted that the largest study so far did not enroll more than 200 men, at most, while the rest had less than 60).
Sandeep Dhindsa, M.D., UB assistant professor of medicine and first author on the study, said the findings are important because hypogonadism has not been recognized as a complication of type 2 diabetes, and the high prevalence of 30 percent was unexpected.
Thus, their results indicate that about 30% of men with diabetes show up with hypogonadism. On the other hand, of course, it also means that a significant majority of diabetic men - about 70% - do not, in fact, have hypogonadism. It is interesting to note that other studies have found that SHBG (sex hormone binding globulin) concentrations were also often lower among obese and diabetic men. Decreased SHBG implies less binding of biologically active gonadal hormones, and may in theory compensate somewhat for the overall reduction in total t by making the unbound free t and estradiol more active. In contrast, SHBG levels often increase with age in men.
http://www.nature.com/ijir/journal/v15/ ... 310005FBC7 040A3DC
Furthermore, in one study, about half of 30 men with premature balding that resembled a hormonal profile similar to women with PCOS with reduced SHBG and increased levels of free t, were found to have impaired insulin sensitivity
and glucose tolerance.
http://www.aepress.sk/_downloads/dl.php ... 04_127.pdf
The above studies suggest that being eugonadal or even hyperandrogenic in no way preclude diabetic complications, and that hyperandrogenimia in men might be an additional complication, as opposed to hypogonadism.
.. None of the men had been diagnosed previously with low testosterone levels. .. "Further studies will help us determine why type 2 diabetic patients are more prone to developing hypogonadism," he said. "While obesity may explain part of the high prevalence of hypogonadism, it is likely that other factors associated with type 2 diabetes also contribute significantly. This area is clearly ripe for further investigation."
Wich basically means that hypogonadism at this point was seen as complimentary to diabetes - i.e. as a complication - rather than contributing, or even causative. In this study, the authors noted that all of the men examined apparently developed accelerated hypogonadism after becoming diabetic. It seems, for the most part, that the resulting metabolic syndrome wich normally accompanies diabetes may have an important inhibitory/impairing effect on gonadal function. Several other studies have demonstrated that improving obesity and insulin resistance alone very often results in substantial increases in endogenous androgens (mostly total, as opposed to free levels). For example, in a study of 24 moderately obese men with a mean total t level of 400 ng/dl, a 3 week weight reduction (mean -43 pounds) increased total t to 536 ng/dl (however, free t, as well as estradiol, were reduced as a result of weight loss). The authors concluded that "increased circulating estrogens and reduced androgen binding were found in moderately obese men, which were completely corrected with weight loss.".
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
Progressive obesity was also found to be associated with decreased
LH output and reduced t levels.
http://www.ncbi.nlm.nih.gov/entrez/quer ... s=11126339
In another study (actually 2 separate studies by same authors), an experimental temporary suppression of insulin in both obese and lean men produced an acute reduction in circulating androgens. An artificial boost in insulin in obese (who had lower mean t), but not lean men, resulted in increased total endogenous androgen levels, albeit with a few important indiviual variations. The conclusion of the authors was that "These findings are consistent with the hypothesis that insulin may regulate testosterone blood levels also in male subjects. Whether these effects are primarily due to increased hormone secretion or reduced clearance needs to be investigated."
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
Taken together, these studies suggest that both insulin and obesity may have an important isolated regulatory effect on testsoterone secretion, and that metabolic complications of diabetes, therefore, may lead to significantly reduced t levels in a minority of diabetic men. This could, in turn, plausibly account for most of the correlation between hypogonadism and diabetes as observed in several studies. Alternatively, increased estrogen and decreased total testosterone (or increased estrogen alone, when applied to eunuchs in whom f. ex. gynecomastia is particularly advanced) may predispose to obesity wich may result in an indicrect relationship between sex hormones and insulin sensitivity (as obesity itself is usually associated with reduced insulin sensitivity and elevated leptin levels).
Although obesity is associated with hypogonadism and is prevalent among type 2 diabetics, only 10-15 percent of the variation in low free testosterone levels could be attributable to body mass index, Dhindsa said. More than 30 percent of lean patients also were hypogonadal.
As implied above, the remaining 15% might well be accounted for by the initial disturbances in insulin secretion.
"The data are not sufficient to recommend testosterone replacement for men with diabetes," Cunningham says. "One of the things that could be important is when you treat a man with male sex hormone, it increases lean body mass and causes some decrease in fat mass. There is some issue whether testosterone might improve diabetic men's insulin sensitivity. The studies we have are not definitive."
The authors are right on the spot in noting that the data is very sparse and insufficient when it comes to hrt for diabetics. So much so that, in fact, a careful search through medical journals reveals that there has been so far only ONE (!) relevant study and at that, involving only 11 patients. Interestingly, the study reported that 3 months of hrt had no significant impact upon diabetic metabolism.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Another study is currently underway, funded by Solvay Pharmaceuticals Inc (manufacturer of androgel), wich attempts to examine some of the effects of hrt gel on diabetics; the results of this currently on-going study are expected to arrive first in 2008.
Most other studies that considered the effects of testsoterone on insluin and glucose levels in non-diabetics found that, while there was some reduction in leptin and BMI (mostly fat mass), hrt appears to have no significant effect on the more important diabetic factors such as insulin sensitivity or fasting glucose. A general finding across several studies is that androgens are very often associated with impaired insulin sensitivty and increased risk of diabetes in women (with PCOS, although male hrt was also found to worsen insulin sensitivity in post-menopausal women), but also in bodybuilders (
http://jcem.endojournals.org/cgi/conten ... f_ipsecsha ), and male rats with diabetes (
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract ,
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum and
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum). There is some discrepancy among several studies (with some reporting beneficial
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
, most neutral,
#1 88 obese HIV infected men were randomized and subjected to 10g testosterone gel or placebo daily for 24-weeks. Despite decreases in both total and abdominal body fat in the t group, the authors concluded that "Plasma insulin, fasting glucose, and total, HDL and LDL cholesterol levels did not change significantly."
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
#2 In a Finnish study, boys with late puberty were given androgens and androgens + aromatase inhibitor with the aim of evaluating the effects of sex hormones on insulin sensitivity. The conclusion was that "The insulin concentration in the testosterone-plus-placebo-treated group did not change. In contrast, in the testosterone-plus-letrozole-treated group, the concentration decreased during letrozole treatment, indicating improved insulin sensitivity." , however "The findings indicate that androgens do not directly alter insulin sensitivity in boys during puberty. In contrast, the observations suggest tight regulation of glucose--insulin homeostasis by GH in boys at this stage."
http://eje-online.org/cgi/content/abstract/146/3/339
#3 Another study on 7 adolescents (14 to 16 yr) with delayed puberty and a mean t-level of 23 ng/dl, were given testosterone wich increased their meant t to about 422 ng/dl, accompained by a reduction in leptin and fat mass (but increased body weight). However, the conclusion was that "4 months of low-dose testosterone therapy results in the following: .... 7) no change in insulin sensitivity of glucose metabolism."
http://jcem.endojournals.org/cgi/conten ... 82/10/3213
#4 A study investigating the effects of anabolic steroids in 15 powerlifters vs. 6 obese and 10 sedentary lean men on insulin resistance concluded that "Powerlifters who ingested anabolic steroids had diminished glucose tolerance compared to the nonsteroid- using group, despite having substantially higher postglucose serum insulin concentrations. Postglucose insulin responses were also higher in steroid users than in the sedentary nonobese and sedentary obese reference groups. These results indicate that powerlifters who ingest anabolic steroids have diminished glucose tolerance, which is likely to be secondary to insulin resistance."
http://jcem.endojournals.org/cgi/conten ... f_ipsecsha
#5 A group of 11 diabetic men were given intramuscular injections of testosterone depot 100 mg/3 weeks for 12 weeks. No significant changes were observed on insulin sensitivity and glucose response.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
#6 An interesting experimental study wich examined the effects of various doses of androgens (25, 50, 125, 300, or 600 mg T enanthate) on 61 healthy eugonadal men, including chemical castration (GnRH agonist), on, among other things, insulin sensitivity and plasma lipids. The authors concluded that: "The insulin sensitivity index, glucose effectiveness, and acute insulin response to glucose, derived from the insulin-modified, frequently sampled, iv glucose tolerance test using the Bergman minimal model, did not change significantly at any dose."
The full text version of the study contains an interesting discussion and overview of references to relevant stuides examining the relationship between insulin sensitivity and androgens, and is well worth reading in it's entirety.
http://jcem.endojournals.org/cgi/conten ... /1/136#R17
and others deleterious (see above) effects on diabetic risk factors of administered androgens), and some of the studies with very small number of participants and limited abstracts may involve an addictional risk of chance and/or researcher bias.
