Low-dose Testosterone Replacement Research Articles

Low-dose testosterone replacement therapy and electrically evoked resistance training enhance muscle quality after spinal cord injury.

Low-dose testosterone replacement therapy and electrically evoked resistance training enhance muscle quality after spinal cord injury.

071 Estradiol does not Increase with Low-dose Testosterone Replacement in Women after Menopause

Testosterone is partially converted to estradiol during the metabolic process. Therefore, it may be pointed out that when testosterone is administered to women, estradiol is increased even though estradiol is not administered, which may increase the risk of uterine cancer and breast cancer. Therefore we report the estradiol level before and after the replacement of Testosterone Enanthate in patients after menopause.

Sixteen weeks of testosterone with or without evoked resistance training on protein expression, fiber hypertrophy and mitochondrial health after spinal cord injury.

We investigated the effects of testosterone replacement therapy (TRT) with and without evoked resistance training (RT) on protein expression of key metabolic and hypertrophy regulators, muscle fiber cross-sectional area (CSA), and markers of mitochondrial health after spinal cord injury (SCI). Twenty-two men with chronic motor complete SCI were randomly assigned to either TRT + RT (n = 11) or TRT (n = 11) for 16 wk. TRT + RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. TRT was administered via testosterone patches (2-6 mg/day). Muscle biopsies were obtained before and after 16 wk from the right vastus lateralis. Expression of proteins associated with oxidative muscles and mechanical loading (PGC-1α and FAK), muscle hypertrophy (total and phosphorylated Akt, total and phosphorylated mTOR), and cellular metabolism (total and phosphorylated AMPK and GLUT4) were evaluated. Immunohistochemistry analysis was performed to measure fiber CSA and succinate dehydrogenase (SDH) activity as well as mitochondrial citrate synthase (CS) activity and complex III (CIII) activities. TRT + RT demonstrated a robust 27.5% increase in average fiber CSA compared with a -9% decrease following TRT only (P = 0.01). GLUT4 protein expression was elevated in the TRT + RT group compared with TRT only (P = 0.005). Total Akt (P = 0.06) and phosphorylated Akt Ser389 (P = 0.049) were also elevated in the TRT + RT group. Mitochondrial activity of SDH (P = 0.03) and CS (P = 0.006) increased in the TRT + RT group, with no changes in the TRT-only group. Sixteen weeks of TRT with RT resulted in fiber hypertrophy and beneficial changes in markers of skeletal muscle health and function.NEW & NOTEWORTHY Fiber cross-sectional area (CSA), protein expression, mitochondrial citrate synthase (CS), and succinate dehydrogenase (SDH) were measured following 16 wk of low-dose testosterone replacement therapy (TRT) with and without electrically evoked resistance training (RT) in men with spinal cord injury (SCI). Fiber CSA and protein expression of total GLUT4, total Akt, and phosphorylated Akt increased following TRT + RT but not in the TRT-only group. Mitochondrial CS and SDH increased after TRT + RT but not in TRT-only group.

Low-Dose Testosterone and Evoked Resistance Exercise after Spinal Cord Injury on Cardio-Metabolic Risk Factors: An Open-Label Randomized Clinical Trial.

The purpose of the work is to investigate the effects of low-dose testosterone replacement therapy (TRT) and evoked resistance training (RT) on body composition and metabolic variables after spinal cord injury (SCI). Twenty-two individuals with chronic motor complete SCI (ages 18-50 years) were randomly assigned to either TRT+RT (n = 11) or TRT (n = 11) for 16 weeks following a 4 -week delayed entry period. TRT+RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. TRT was administered via testosterone patches (2-6 mg/day). Body composition was tested using anthropometrics, dual energy x-ray absorptiometry, and magnetic resonance imaging. After an overnight fast, basal metabolic rate (BMR), lipid panel, serum testosterone, adiponectin, inflammatory and anabolic biomarkers (insulin-like growth factor-1 and insulin-like growth factor-binding protein 3 [IGFBP-3]), glucose effectiveness (Sg), and insulin sensitivity (Si) were measured. Total body lean mass (LM; 2.7 kg, p < 0.0001), whole muscle (p < 0.0001), and whole muscle knee extensor cross-sectional areas (CSAs; p < 0.0001) increased in the TRT+RT group, with no changes in the TRT group. Visceral adiposity decreased (p = 0.049) in the TRT group, with a trend in the TRT+RT (p = 0.07) group. There was a trend (p = 0.050) of a 14-17% increase in BMR following TRT+RT. Sg showed a trend (p = 0.07) to improvement by 28.5-31.5% following both interventions. IGFBP-3 increased (p = 0.0001) while IL-6 decreased (p = 0.039) following both interventions, and TRT+RT suppressed adiponectin (p = 0.024). TRT+RT resulted in an increase in LM and whole thigh and knee extensor muscle CSAs, with an increase in BMR and suppressed adiponectin. Low-dose TRT may mediate modest effects on visceral adipose tissue, Sg, IGFBP-3, and IL-6, independent of changes in LM.

Effects of Testosterone Therapy on Cardiovascular Risk Markers in Androgen-Deficient Women with Hypopituitarism

Low-dose testosterone replacement therapy in women with relative androgen deficiency has been shown to have beneficial effects on body composition, bone mass, and psychosexual function. However, the safety of chronic testosterone administration on cardiovascular risk and insulin resistance is unknown. The aim of the study was to determine the effects of physiological testosterone replacement on cardiovascular risk markers and insulin resistance in women. A 12-month, randomized, placebo-controlled study was conducted. A General Clinical Research Center was the setting for the study. A total of 51 women of reproductive age with androgen deficiency due to hypopituitarism participated. Study participants were randomized to physiological testosterone administration, 300 mug daily, or placebo, by patch. We measured fasting glucose, fasting insulin, insulin-resistance homeostasis model of assessment (IRHOMA), quantitative insulin sensitivity check index (QUICKI), high-sensitivity C-reactive protein, vascular cell adhesion molecule (VCAM), leptin, lipoprotein (a), apolipoprotein A1, and homocysteine. At 12 months, fasting insulin and IRHOMA were significantly lower in the testosterone compared with the placebo group, and there was a trend toward a higher QUICKI level at 12 months in the testosterone compared with the placebo group. These differences were no longer significant after controlling for baseline levels. We observed no effect, either positive or negative, of testosterone administration on high-sensitivity C-reactive protein, VCAM leptin, lipoprotein (a), or apolipoprotein A1. Our data suggest that physiological testosterone replacement in women with hypopituitarism for 12 months does not increase, and may improve, insulin resistance. Chronic low-dose testosterone administration does not increase markers of cardiovascular disease reflecting several different mechanistic pathways. Large, randomized, placebo-controlled, long-term prospective studies are needed to determine whether low-dose testosterone replacement affects cardiovascular risk and event rates in women.

DHEA and Testosterone in the Elderly

To the Editor: In their report on the effects of dehydroepiandrosterone (DHEA) and testosterone when used as antiaging supplements, Nair et al. (Oct. 19 issue)1 conclude that low-dose testosterone replacement in elderly men has no “physiologically relevant beneficial effects on body composition, physical performance, [or] insulin sensitivity.” However, this conclusion is premature, since the testosterone replacement administered failed to achieve physiologic testosterone levels throughout the study period (Fig. 2 of the article). Moreover, despite the marginal increase in testosterone levels achieved, improvements in fat-free mass, fasting insulin levels, and bone mineral density were observed. Other studies of testosterone replacement, including those cited to support the authors’ conclusions,2 have shown a decrease in fat mass (12.5%) and an increase in lean mass (4%) when physiologic testosterone levels are achieved in elderly men. Studies of standard doses of testosterone in the treatment of testicular failure3 have shown additional positive effects on muscle strength, physical performance,4 and bone mineral density.5 Large, long-term trials are clearly needed to assess the risks and benefits of testosterone replacement in elderly men, and caution should be exercised regarding the treatment of andropause in men. However, the serum testosterone level achieved should be within the normal range to assess the effect on outcome measures adequately.

DHEA in Elderly Women and DHEA or Testosterone in Elderly Men

Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown. We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life. As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects. Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).

Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa

Abnormalities in brain metabolism have not been consistently well localized in anorexia nervosa (AN), and effects of specific therapies on these functional abnormalities have not been studied. Androgen replacement therapy improves mood, well-being and cognitive function in men with androgen deficiency. We therefore hypothesized that women with AN and relative androgen deficiency would exhibit regional brain hypometabolism compared with healthy controls, and that low-dose physiologic androgen replacement would attenuate the hypometabolism in some of these brain loci. We used FDG PET and statistical parametric mapping methods to investigate regional brain glucose metabolism in (1) 14 women with AN and 20 healthy control subjects of similar mean age and (2) women with AN after randomization to low-dose replacement testosterone therapy or placebo. Cerebral metabolism was decreased in the posterior cingulate, pregenual anterior cingulate, left middle temporal, right superior temporal, and left dorsolateral prefrontal cortex in the AN group compared with controls. In AN patients receiving testosterone, cerebral metabolism increased in the posterior cingulate, subgenual anterior cingulate, premotor cortex, right caudate and right parietal lobes. In conclusion, our data demonstrate distinct loci of regional brain hypometabolism in women with AN compared with controls. Moreover, abnormalities in one of these regions—the posterior cingulate cortex—were attenuated towards normal with low-dose testosterone replacement therapy. Further study is warranted to replicate these findings, as well as to determine their physiological and clinical significance.

Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa

Abnormalities in brain metabolism have not been consistently well localized in anorexia nervosa (AN), and effects of specific therapies on these functional abnormalities have not been studied. Androgen replacement therapy improves mood, well-being and cognitive function in men with androgen deficiency. We therefore hypothesized that women with AN and relative androgen deficiency would exhibit regional brain hypometabolism compared with healthy controls, and that low-dose physiologic androgen replacement would attenuate the hypometabolism in some of these brain loci. We used FDG PET and statistical parametric mapping methods to investigate regional brain glucose metabolism in (1) 14 women with AN and 20 healthy control subjects of similar mean age and (2) women with AN after randomization to low-dose replacement testosterone therapy or placebo. Cerebral metabolism was decreased in the posterior cingulate, pregenual anterior cingulate, left middle temporal, right superior temporal, and left dorsolateral prefrontal cortex in the AN group compared with controls. In AN patients receiving testosterone, cerebral metabolism increased in the posterior cingulate, subgenual anterior cingulate, premotor cortex, right caudate and right parietal lobes. In conclusion, our data demonstrate distinct loci of regional brain hypometabolism in women with AN compared with controls. Moreover, abnormalities in one of these regions—the posterior cingulate cortex—were attenuated towards normal with low-dose testosterone replacement therapy. Further study is warranted to replicate these findings, as well as to determine their physiological and clinical significance.

RESTORATION OF SEXUAL BEHAVIOR AND DOPAMINERGIC NEUROTRANSMISSION BY LONG TERM EXOGENOUS TESTOSTERONE REPLACEMENT IN AGED MALE RATS

Purpose We investigated the effects of long-term testosterone replacement on copulatory behaviour and dopaminergic neurotransmission in the medial preoptic area of aged male rats. Materials and Methods The rats were divided into 3 groups depending on testerone replacement. Those in the long-term replacement group were castrated at the age of 12 months and received testosterone replacement thereafter for 12 months. In the short-term replacement group, rats were castrated at the age of 22 months and high or low dose testosterone replacement was done for 2 months. The control group consisted of aged rats 24 months old and young rats 12 weeks old, neither of which had been castrated or received testosterone replacement. We observed sexual behavior in rats of these groups. After a behavioral test, we measured the tissue concentration of dopamine in the MPOA and the change rate of the extracellular dopamine level induced by infusion of N-methyl-D-aspartic acid (NMDA) in the MPOA and compared the long-term replacement and no-replacement groups. Results The rats in the long-term replacement group showed a mount rate at the same level as that of young rats at 6 weeks after starting replacement and it was maintained to 24 months of age. Their mount rate was significantly higher than that of the rats with the short-term replacement. A significantly higher change rate of dopamine release was recognized in the long-term group; however, no significant difference in the concentration of dopamine was recognized between aged rats with long-term replacement and those without replacement. Conclusions Aged rats (24 months old) with long-term testosterone replacement maintained almost the same level of mount behavior as young rats (12 weeks old). The results imply that long-term testosterone replacement may favorably alter the decline in the process of sexual activity with aging. The restoration by testosterone replacement of dopaminergic activity in the MPOA may be involved in the maintenance of sexual function in aged rats.