Testosteron-er ikke det farlig da?
I vår kultur er testosteronet myteomspunnet og dels tabubelagt. Stadig mer forskning viser nå imidlertid resultat som peker i retning av at testosteron er særdeles viktig for mer enn å bygge muskler og reprodusere. Disse funnene reiser interessante spørsmål om feks. bruk av testosteron-tilskudd for menn for å bekjempe aldersdiabetes, depresjon og hjerte-kar sykdommer.
Kanskje et emne kun for de spesielt interesserte her på forumet, men dette er ihvertfall rykende ferskt fra novemberutgaven av The Journal of Clinical Endocrinology & Metabolism, denne artikkelen er raskt blitt svært mye omtalt.
Spørsmålet man stiller seg er om behandling med testosterontilskudd både har en anti-inflammatorisk effekt, minsker kroppsfett, bedrer insulinfølsomhet, har en direkte (!) heldig effekt ifm. innsnevring av blodårer og har betydelige gunstige effekter på kognitive evner og mental helse for menn med lavt testosteron-nivå (svært høye verdier av testosteron kan ha en langt mindre gunstig effekt på samme parametre). Utgangspunktet for denne forskningen er de funn som viser at en høy andel av menn med aldersdiabetes og metabolsk syndrom har lave testosteron-nivåer (FT fritt testosteron nivå).
The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 11 5462-5468
Copyright © 2004 by The Endocrine Society
Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes
Sandeep Dhindsa, Sathyavani Prabhakar, Manak Sethi, Arindam Bandyopadhyay, Ajay Chaudhuri and Paresh Dandona
Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209
Fra discussion-delen av artikkelen
"It is believed that the low total T in obesity is caused by low SHBG concentrations. However, FT levels have also been found to be low in massively obese males, and the defect appears to be at the hypothalamic or pituitary level. Zumoff et al. (31) studied 48 healthy men (mean age, 33.2 yr) with BMI ranging from 21–95 kg/m2 and found that both FT and non-SHBG-bound T (calculated from T and SHBG) correlated inversely with BMI. Vermeulen et al. (32) found that 35 obese men (mean BMI, 41.1 kg/m2) had significantly lower FT levels than 54 lean men (0.31 vs. 0.42 nmol/liter). The FT levels correlated inversely with BMI. They also compared LH pulsatility over 12 h in eight obese and lean men and found that the mean integrated LH levels over 12 h were significantly lower in obese men. FT levels correlated positively with the sum of LH pulse amplitudes in each individual (32). It is remarkable that 57.9% of massively obese (BMI > 40) patients in our study were hypogonadal. Furthermore, LH levels in our study correlated significantly and positively with FT concentrations (r = 0.287; P < 0.05). Thus, data from the literature in humans and NIRKO mice and from our study seem to suggest that obesity/insulin resistance is associated with hypogonadism and that the hypogonadism appears to be hypogonadotropic in nature. Obesity is associated with increased plasma levels of proinflammatory cytokines such as TNF- , IL-6, C-reactive protein, and adhesion molecules (33, 34, 35). In this regard, it is interesting to note that TNF- and IL-1ß have been shown to reduce hypothalamic GnRH and LH secretion in animals and in vitro (36, 37).
In our study, both FT and BT correlated significantly with BMI (r = –0.382 and –0.317, respectively). These data are the first to show that FT (measured by ED) correlates inversely with BMI in type 2 diabetics. However, on the basis of the correlation coefficient, it can be derived that only 10–15% of variability (r2) in FT can be explained by BMI. Furthermore, a large number (31.3%) of lean subjects in our study were hypogonadal. Thus, although 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.
A diagnosis of hypogonadism commits the patient to life-long androgen replacement therapy. Experts disagree on how hypogonadism should be defined. Although in many studies (including ours), hypogonadism is defined solely on the basis of T levels, others argue that hypogonadism should be defined by the presence of a clinical syndrome in association with low total T and FT levels. A practical bioassay of T activity is not yet available. Furthermore, different androgen-dependent physiological processes appear to require a different serum level of T (38). Serum T levels in the lower range of normal are able to maintain aspects of sexual functions, but muscle strength, muscle size, and fat-free mass increase progressively in a dose-dependent fashion with increase in circulating T concentrations even within the normal range (39, 40). Because there is no clear consensus as to what the normal range for total T should be, both diagnosis of hypogonadism and monitoring of therapy after T treatment pose problems.
Even fewer data are available for normal ranges of FT. In our study, we found that if hypogonadism had been defined as a total T of less than 300 ng/dl, there would have been 12% false negatives and 36% false positives on the basis of low FT (FT or cFT). Therefore, any patient with type 2 diabetes who has a low or low normal T should have FT measured before he is labeled as hypogonadal. Because the technique for ED is cumbersome and not readily available, whereas cFT values (using T and SHBG) are reliable, cFT can also be used instead of FT in a clinical setting (41).
Hypogonadism is associated with an increase in fat mass, decreased muscle mass, accelerated bone loss, and decreased libido, and treatment with T results in improvement in these parameters (42). The high prevalence of hypogonadism in type 2 diabetes raises important issues about its possible consequences on libido, erectile dysfunction, body musculature, abdominal adiposity, bone density, mood, and cognition. It has been recently shown that T has an antiinflammatory and antiatherogenic effect in experimental animals and in humans (43). This raises the question of whether T deficiency can be proatherogenic. Thus, the question of T replacement becomes an important issue. This question needs to be addressed in prospective randomized studies (44).
In conclusion, hypogonadotropic hypogonadism is a common defect in type 2 diabetes that requires further assessment in terms of the etiology of the defect and the possible consequences, complications, and treatment".