http://www.muscleblog.es/2013/01/el-fra ... epresivos/
http://www.nejm.org/doi/full/10.1056/NE ... 2302392704The Use of Testosterone in the Treatment of Depressions
Mark D. Altschule, M.D.†, and Kenneth J. Tillotson, M.D.‡
N Engl J Med 1948; 239:1036-1038December 30, 1948DOI: 10.1056/NEJM194812302392704
This article has no abstract; the first 100 words appear below.
Sex hormones and related substances have been used in the treatment of depressions for a number of years. Although the use of estrogenic substances of various types has yielded disappointing results in deeply depressed women, the injection of testosterone has been known for a decade or more to cause remission in male patients with depressions, provided large doses are used. Danziger and Blank1 reviewed the earlier clinical literature bearing on this point; a more recent review by Danziger et al.2 is also available. The rationale for the use of testosterone in the past has been that of replacement therapy in . . .
DHT Favorece la neuroplasticidad neuronal
Reducción del miedoMild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis.
Okamoto M, Hojo Y, Inoue K, Matsui T, Kawato S, McEwen BS, Soya H.
Mild exercise activates hippocampal neurons through the glutamatergic pathway and also promotes adult hippocampal neurogenesis (AHN). We hypothesized that such exercise could enhance local androgen synthesis and cause AHN because hippocampal steroid synthesis is facilitated by activated neurons via N-methyl-D-aspartate receptors. Here we addressed this question using a mild-intense treadmill running model that has been shown to be a potent AHN stimulator. A mass-spectrometric analysis demonstrated that hippocampal dihydrotestosterone increased significantly, whereas testosterone levels did not increase significantly after 2 wk of treadmill running in both orchidectomized (ORX) and sham castrated (Sham) male rats. Furthermore, analysis of mRNA expression for the two isoforms of 5α-reductases (srd5a1, srd5a2) and for androgen receptor (AR) revealed that both increased in the hippocampus after exercise, even in ORX rats. All rats were injected twice with 5'-bromo-2'deoxyuridine (50 mg/kg body weight, i.p.) on the day before training. Mild exercise significantly increased AHN in both ORX and Sham rats. Moreover, the increase of doublecortin or 5'-bromo-2'deoxyuridine/NeuN-positive cells in ORX rats was blocked by s.c. flutamide, an AR antagonist. It was also found that application of an estrogen receptor antagonist, tamoxifen, did not suppress exercise-induced AHN. These results support the hypothesis that, in male animals, mild exercise enhances hippocampal synthesis of dihydrotestosterone and increases AHN via androgenenic mediation.
http://www.ncbi.nlm.nih.gov/pubmed/16458259A single administration of testosterone reduces fear-potentiated startle in humans.
Hermans EJ, Putman P, Baas JM, Koppeschaar HP, van Honk J.
Ample evidence from animal research indicates that the gonadal steroid hormone testosterone has fear-reducing properties. Human data on this topic, however, are scarce and far less unequivocal. The present study therefore aimed to scrutinize anxiolytic effects of a single dose of testosterone, using a direct physiological index of fear in humans.
Twenty healthy female participants were tested in a double-blind, placebo-controlled crossover design involving sublingual administration of a single dose of testosterone. Four hours after intake, we assessed effects on baseline startle and fear-potentiated startle in a verbal threat-of-shock paradigm.
In accordance with predictions, testosterone administration resulted in reduced fear-potentiated startle, without affecting baseline startle.
This study provides direct evidence that a single dose of testosterone reduces fear in humans. The relationship of this effect to previous research on anxiolytic effects of benzodiazepines, as well as possible mechanisms of action, is discussed.
Mejora de la función cortical asociada a la depresión
http://www.ncbi.nlm.nih.gov/pubmed/16179660Administration of testosterone increases functional connectivity in a cortico-cortical depression circuit.
Schutter DJ, Peper JS, Koppeschaar HP, Kahn RS, van Honk J.
Increasing evidence suggests that the steroid hormone testosterone (T) enhances libido and decreases depression. Even a single administration of T (0.5 mg sublingually) in healthy young women is sufficient to enhance physiological sexual responsiveness. Such physiological evidence is not yet available for the link between T and depression. Recent research has revealed that lowered functional connectivity in a specific cortico-cortical pathway may be a sensitive physiological index for depression. This pathway, comprised of the left prefrontal and right parietal cortex, has been named a cortical depression circuit. In the present study, a single dose of T was administered to healthy young women to investigate the effects on the functional connectivity in this cortico-cortical depression circuit. It was hypothesized that administration of T would lead to an increase of functional connectivity. In a double-blind placebo-controlled, crossover design, fourteen healthy females received (sublingually) a single dose of 0.5 mg T or placebo in a randomly assigned fashion. Three hours after drug administration the functional coupling between the left prefrontal and right parietal cortex was established by measuring the interhemispheric electroencephalogram (EEG) coherence for the different frequency bands. Compared to placebo, T administration significantly increased the functional connectivity in the sigma (1-3 Hz) frequency range between the left prefrontal and right parietal cortex. Reductions in interhemispheric coherence in the sigma frequency range have been observed in clinically depressed patients. Thus the present findings may provide a first insight into the neurobiological mechanism by which T decreases depression. The fact that only a single dose of T was able to induce the effect in healthy female subjects suggests that the mechanism is highly sensitive. A feasible application of T treatment in the struggle against depression is discussed.
Personas depresivas tienen menores niveles de Testosterona y disrupción en los ritmos de pulso de LH
http://www.psychosomaticmedicine.org/co ... 3/292.longTestosterone, Gonadotropin, and Cortisol Secretion in Male Patients With Major Depression
Ulrich Schweiger, MD,
Michael Deuschle, MD,
Bettina Weber, MD,
Andreas Körner, MD,
Claas-Hinrich Lammers, MD,
Jürgen Schmider, MD,
Ulrike Gotthardt, MD and
Isabella Heuser, MD
+ Author Affiliations
From the Max-Planck-Institute of Psychiatry, Clinical Institute, Munich, Germany.
Address reprint requests to: Ulrich Schweiger, MD, Klinik für Psychiatrie, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. Email: email@example.com-Luebeck.de
OBJECTIVE: Previous studies of sex hormone concentrations in depression yielded inconsistent results. However, the activation of the hypothalamic-pituitary-adrenal system seen in depression may negatively affect gonadal function at every level of regulation. The objective of this study was to explore whether major depressive episodes are indeed associated with an alteration of gonadal function.
METHODS: Testosterone, pulsatile LH secretion, FSH, and cortisol were assessed using frequent sampling during a 24-hour period in 15 male inpatients with major depression of moderate to high severity and in 22 healthy comparison subjects (age range 22–85 years).
RESULTS: An analysis of covariance model showed that after adjustment for age only, daytime testosterone (p < .01), nighttime testosterone (p < .05), and 24-hour mean testosterone secretion (p < .01) were significantly lower in the depressed male inpatients. There was also a trend for a decreased LH pulse frequency in the depressed patients (p < .08).
CONCLUSIONS: Gonadal function may be disturbed in men with a depressive episode of moderate to high severity.
TestoGel efectivo en hombres hipogonadales
http://www.ncbi.nlm.nih.gov/pubmed/12505808Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial.
Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI.
Testosterone supplementation may produce antidepressant effects in men, but until recently it has required cumbersome parenteral administration. In an 8-week randomized, placebo-controlled trial, the authors administered a testosterone transdermal gel to men aged 30-65 who had refractory depression and low or borderline testosterone levels.
Of 56 men screened, 24 (42.9%) displayed morning serum total testosterone levels of 350 ng/dl or less (normal range=270-1070). Of these men, 23 entered the study. One responded to an initial 1-week single-blind placebo period, and 22 were subsequently randomly assigned: 12 to 1% testosterone gel, 10 g/day, and 10 to identical-appearing placebo. Each subject continued his existing antidepressant regimen. Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial.
The groups were closely matched on baseline demographic and psychiatric measures. Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo. These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale. A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory. One subject assigned to testosterone reported increased difficulty with urination, suggesting an exacerbation of benign prostatic hyperplasia; no other subject reported adverse events apparently attributable to testosterone.
These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels.
Testosterone replacement therapy for the treatment of neurological and neuropsychiatric disorders.
Gold SM, Voskuhl RR.
There is an accumulating body of evidence in the literature suggesting that testosterone may be neuroprotective and therefore have therapeutic value in the treatment of neurodegenerative diseases. In this article, the potential mechanisms of action of testosterone on the central nervous system are discussed, as well as the current evidence supporting the effect of testosterone on neurological impairment. Lower endogenous testosterone levels appear to be associated with some neurological disabilities. Conversely, a therapeutic benefit of exogenous testosterone supplementation on some cognitive abilities has been shown in pilot trials involving healthy elderly men as well as patients with multiple sclerosis and Alzheimer's disease. Further study of the therapeutic potential of testosterone is warranted in neurological and neuropsychiatric diseases.