Testosteron enanthaat: feiten en verzinsels!

DE FEITEN OVER TEST ENANTHAAT:

Werking Testosteron enanthaat:
-T E verhoogt VetVrije Massa (VVM) en krachttoename, maar heeft geen invloed op spiermoeheid. De toename in spiermassa wordt veroorzaakt door een verhoogde netto proteine synthese en hergebruik van intracellulaire aminozuren in skeletspieren.
-De meeste studies laten een significante dosis-afhankelijke vermindering in vetweefsel zien door T E.
-Je wint wel VVM door T E wanneer je niet bulkt.
-Je wint wel VVM door T E wanneer je slechts 1,2-1,5 g/kg eiwit gebruikt.

Bijwerkingen:
-T E verandert het humeur niet en geeft geen aanleiding tot agressief gedrag. Vreemd genoeg is de door veel mensen gerapporteerdere verhoging in seksueelfunctioneren niet terug gevonden in dubbelblind uitgevoerde, gerandomiseerde, placebo gecontrolleerde onderzoeken bij doseringen t/m 600 mg T E/week.....
-T E verandert PSA (prostaat) en lever enzymen niet.
-T E verandert cholesterol, triglyceriden en LDL niet, maar is negatief gecorreleerd aan HDL.
-200 mg T E/week gedurende 15 maanden vermindert spermaconcentratie, maar heeft geen negatief effect op de werking van de overblijvende spermatozoa.
-Lange termijn effecten van T E op de prostaat en het hart zijn onbekend. Maar 1 apenstudie (33 maanden) laat een significante toename in het gewicht van beide prostaatlobben zien.
-Oudere mannen krijgen dezelfde verhoging in VVM en krachttoename, maar hebben wel meer side effects door T E. De gecombineerde supplementatie van finasteride met T E verminderd de impact van testosteron op prostaat grootte en PSA in oudere mannen.

Testosterone dose-response relationships in healthy young men
To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, coïtusual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

This was a double-blind, randomized study consisting of a 4-wk control period, a 20-wk treatment period, and a 16-wk recovery period.

The participants were healthy men, 18-35 yr of age, with prior weight-lifting experience and normal testosterone levels.

Energy and protein intakes were standardized at 36 kcal · kg-1 · day-1 and 1.2 g · kg-1 · day-1, respectively.

To determine whether the apparent changes in fat-free mass by DEXA scan and underwater weighing represented water retention, we measured total body water and compared the ratios of total body water to fat-free mass before and after treatment in each group. The ratios of total body water to fat-free mass by underwater weighing did not significantly change with treatment in any treatment group (Table 3), indicating that the apparent increase in fat-free mass measured by underwater weighing did not represent water retention in excess of that associated with protein accretion.

Body composition analysis:
http://ajpendo.physiology.org/cgi/content-nw/full/281/6/E1172/T3

Change in fat-free mass (A), fat mass (B), leg press strength (C), thigh muscle volume (D), quadriceps muscle volume (E), coïtusual function (F), insulin-like growth factor I (G), and prostate-specific antigen (H):
http://ajpendo.physiology.org/cgi/content-nw/full/281/6/E1172/F1

Total cholesterol, plasma low-density lipoprotein cholesterol, and triglyceride levels did not change significantly at any dose. Serum PSA, creatinine, bilirubin, alanine aminotransferase, and alkaline phosphatase did not change significantly in any group, but aspartate aminotransferase decreased significantly in the 25-mg group. Two men in the 25-mg group, five in the 50-mg group, three in the 125-mg group, seven in the 300-mg group, and two in the 600-mg group developed acne.
The treatment regimen was well tolerated. There were no significant changes in PSA or liver enzymes at any dose. However, long-term effects of androgen administration on the prostate, cardiovascular risk, and behavior are unknown.
There were no significant changes in overall coïtusual activity or coïtusual desire in any group, including those receiving the 25-mg dose.
We did not find significant changes in PSA at any dose, indicating that the lowest dose of testosterone maintained PSA levels. We did not measure prostate volume in this study; therefore, we do not know whether prostate volume exhibits the same relationship with testosterone dose as PSA levels.

http://ajpendo.physiology.org/cgi/content/full/281/6/E1172

The Effects of Supraphysiologic Doses of Testosterone on Muscle Size and Strength in Normal Men
We randomly assigned 43 normal men to one of four groups: placebo with no exercise, testosterone with no exercise, placebo plus exercise, and testosterone plus exercise. The men received injections of 600 mg of testosterone enanthate or placebo weekly for 10 weeks. The men in the exercise groups performed standardized weight-lifting exercises three times weekly.
Among the men in the no-exercise groups, those given testosterone had greater increases than those given placebo in muscle size in their arms (mean [±SE] change in triceps area, 424±104 vs. -81±109 mm2; P<0.05) and legs (change in quadriceps area, 607±123 vs. -131±111 mm2; P<0.05) and greater increases in strength in the bench-press (9±4 vs. -1±1 kg, P<0.05) and squatting exercises (16±4 vs. 3±1 kg, P<0.05). The men assigned to testosterone and exercise had greater increases in fat-free mass (6.1±0.6 kg) and muscle size (triceps area, 501±104 mm2; quadriceps area, 1174±91 mm2) than those assigned to either no-exercise group, and greater increases in muscle strength (bench-press strength, 22±2 kg; squatting-exercise capacity, 38±4 kg) than either no-exercise group. Neither mood nor behavior was altered in any group.

The subjects were normal men weighing 90 to 115 percent of their ideal body weights; they were 19 to 40 years of age and had experience with weight lifting.

Two weeks before day 1, the men were instructed to begin following a standardized daily diet containing 36 kcal per kilogram of body weight, 1.5 g of protein per kilogram, and 100 percent of the recommended daily allowance of vitamins, minerals, and trace elements. The dietary intake was adjusted every two weeks on the basis of changes in body weight.

Acne developed in three men receiving testosterone and one receiving placebo, and two men receiving testosterone reported breast tenderness, but no other side effects were noted. The serum liver-enzyme concentrations, hemoglobin concentrations, hematocrits, and red-cell counts did not change in any study group (Table 2). Serum creatinine concentrations did not change, except in the testosterone-plus-exercise group, in which the mean (±SE) serum creatinine concentration increased from 1.0 mg per deciliter (88 µmol per liter) to 1.1 mg per deciliter (97 µmol per liter) (P=0.02). Plasma concentrations of total and LDL cholesterol and triglycerides did not change in any study group; plasma HDL cholesterol decreased significantly in the placebo-plus-exercise group. There was no change in the serum concentration of prostate-specific antigen in any group.

The base-line serum concentrations of luteinizing hormone, follicle-stimulating hormone, and coïtus hormone-binding globulin were similar in the four groups, and the concentrations decreased significantly in the two testosterone groups:
[Link niet meer beschikbaar]

Fat-free mass did not change significantly in the group assigned to placebo but no exercise (Table 4 and Figure 1). The men treated with testosterone but no exercise had an increase of 3.2 kg in fat-free mass, and those in the placebo-plus-exercise group had an increase of 1.9 kg. The increase in the testosterone-plus-exercise group was substantially greater (averaging 6.1 kg). The percentage of body fat did not change significantly in any group (data not shown):
[Link niet meer beschikbaar]

http://content.nejm.org/cgi/content/full/335/1/1?ijkey=7bd3ad13ebc92b4f32d4393ece135057dd181c27

Effect of testosterone administration and weight training on muscle architecture.
PURPOSE: The purpose of this study was to assess muscle architecture changes in subjects who were administered supraphysiologic doses of testosterone enanthate (TE) and concurrently performed heavy resistance training. METHODS: Ten subjects were randomly selected from the 21 subjects who participated in a previously published study (12). Subjects were allocated to one of two groups as per Giorgi et al. (12) and received either a saline-based placebo (nonTE) or a 3.5-mg.kg-1 body weight dose of TE by deep intramuscular injection once a week for 12 wk. Subjects also performed heavy resistance training using exercises that targeted the triceps brachii muscle. Before and after the training period, free-weight one-repetition-maximum (1-RM) bench press strength was tested, muscle thickness and pennation of the triceps brachii lateralis were measured using ultrasound imaging, and fascicle length was estimated from ultrasound photographs. RESULTS: There were no significant between-group differences in muscle thickness changes despite a trend toward increased thickness in TE subjects (TE, 23.5%, vs nonTE, 13.8%). However, 1-RM bench press performance and muscle pennation increased significantly in TE subjects compared with nonTE subjects (P < 0.05). There was also a trend toward longer fascicle lengths in the muscles of nonTE subjects. CONCLUSION: The results of the present study suggest that the use of TE in conjunction with heavy resistance training is associated with muscle architecture changes that are commonly associated with high-force production. Since there was little difference between the groups in muscle thickness, changes in pennation and possibly fascicle length may have contributed to strength gains seen in TE subjects.

Muscular strength, body composition and health responses to the use of testosterone enanthate: a double blind study.
To determine the effect the steroid, testosterone enanthate (TE) had on upper body strength, body composition and health. Twenty one male weight training subjects were randomly assigned in a double blind method to either a 3.5 mg(-1) x kg(-1) TE (n=11) or placebo (n=10) weight training group. The subjects were monitored during a 12 week administration phase and a subsequent 12 week follow up phase. Subjects were tested on a number of strength and size measurements, whilst having their health monitored. The results from the study revealed that the testosterone/weight training group improved significantly (p<0.05) more than the placebo/weight training group during and immediately after the administration phase on a 1 repetition maximum bench press. With regards to body composition, body weight, arm girth and rectus femoris circumference all increased significantly greater in the TE group compared to the placebo. Furthermore, the abdomen skinfold showed significant decreases in the TE group compared to the placebo group at post testing, follow up mid testing and the follow up post testing occasions. With the exception of the abdomen skinfold no within or between group differences were evident following a cycling off period of 12 weeks. Changes to baseline health indicators were reported in some subjects following testosterone usage. This included an average elevation in systolic blood pressure in all TE subjects by 10 mm Hg, a mild increase in hereditary frontal alopecia, increased muscle tightness (hamstrings and pectorals), a mild increase in libido over the first two weeks with a subsequent fall to normal, mild acne, subjective changes to personality including an increase in aggression, irritability and positive mood responses. Consequently, moderate doses of TE combined with weight training can result in short term significant changes in upper body strength and body composition, with corresponding changes to baseline health in some individuals.

Testosterone injection stimulates net protein synthesis but not tissue amino acid transport.
Testosterone administration (T) increases lean body mass and muscle protein synthesis. We investigated the effects of short-term T on leg muscle protein kinetics and transport of selected amino acids by use of a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis (FSR) and breakdown (FBR) rates of skeletal muscle protein were also directly calculated. Seven healthy men were studied before and 5 days after intramuscular injection of 200 mg of testosterone enanthate. Protein synthesis increased twofold after injection (P < 0.05), whereas protein breakdown was unchanged. FSR and FBR calculations were in accordance, because FSR increased twofold (P < 0.05) without a concomitant change in FBR. Net balance between synthesis and breakdown became more positive with both methodologies (P < 0.05) and was not different from zero. T injection increased arteriovenous essential and nonessential nitrogen balance across the leg (P < 0.05) in the fasted state, without increasing amino acid transport. Thus T administration leads to an increased net protein synthesis and reutilization of intracellular amino acids in skeletal muscle.

Testosterone treatment in adolescents with delayed puberty: changes in body composition, protein, fat, and glucose metabolism.
Previously, we demonstrated decreased protein breakdown and insulin resistance in pubertal adolescents compared with prepubertal children. Puberty-related increases in coïtus steroids and/or GH could be potentially responsible. In the present study, the effects of 4 months of testosterone enanthate (50 mg in every 2 weeks) on body composition, protein, fat, and glucose metabolism and insulin sensitivity were evaluated in adolescents with delayed puberty.
After 4 months of testosterone treatment, height, weight, and fat free mass (FFM) increased and fat mass, percent body fat, plasma cholesterol, high- and low-density lipoproteins, and leptin levels decreased significantly. Whole-body proteolysis and protein oxidation were lower after testosterone treatment (proteolysis, 0.49 +/- 0.03 vs 0.54 +/- 0.04 g.h.kg FFM, P = 0.032; oxidation, 0.05 +/- 0.01 vs. 0.09 +/- 0.01 g.h.kg FFM, P = 0.015). Protein synthesis was not different, and resting energy expenditure was not different. Total body lipolysis was not affected by testosterone treatment, however, fat oxidation was higher after testosterone (pre-: 2.4 +/- 0.7 vs. post-: 3.5 +/- 0.7 mumol.kg.min, P = 0.031). During the 40 mU.m2.min hyperinsulinemia, insulin sensitivity of glucose metabolism was not affected with testosterone therapy (59.1 +/- 8.8 vs. 57.1 +/- 8.2 mumol.kg.min per muU/mL). However, metabolic clearance rate of insulin was higher posttestosterone (13.6 +/- 1.1 vs. 16.7 +/- 0.8 mL.kg.min, P = 0.004). In conclusion, after 4 months of low-dose testosterone treatment in adolescents with delayed puberty 1) FFM increases and fat mass and leptin levels decrease; 2) postabsorptive proteolysis and protein oxidation decrease; 3) fat oxidation increases; and 4) insulin sensitivity in glucose metabolism does not change, whereas insulin clearance increases. These longitudinal observations are in agreement with our previous cross-sectional studies of puberty and demonstrate sparing of protein breakdown of approximately 1.2 g.kg.day FFM, wasting of fat mass, but no change in insulin sensitivity after short periods of low-dose testosterone supplementation.

Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension.
To examine the relationship between testosterone dose and muscle performance, 61 healthy, eugonadal young men (aged 18-35 yr) were randomized to 1 of 5 groups, each receiving a long-acting GnRH agonist to suppress endogenous testosterone production plus weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate for 20 wk. These doses produced mean nadir testosterone concentrations of 253, 306, 542, 1345, and 2370 ng/dl, respectively. Maximal voluntary muscle strength and fatigability were determined by a seated leg press exercise. Leg power was measured using a validated leg power instrument. Specific tension was estimated by the ratio of one repetition maximum muscle strength to thigh muscle volume determined by magnetic resonance imaging. Testosterone administration was associated with a dose-dependent increase in leg press strength and leg power, but muscle fatigability did not change significantly during treatment. Changes in leg press strength were significantly correlated with total (r = 0.46; P = 0.0005) and free (r = 0.38; P = 0.006) testosterone as was leg power (total testosterone: r = 0.38; P = 0.007; free testosterone: r = 0.35; P = 0.015), but not muscle fatigability. Serum IGF-I concentrations were not significantly correlated with leg strength, power, or fatigability. Specific tension did not change significantly at any dose. We conclude that the effects of testosterone on muscle performance are specific; it increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. The changes in leg strength and power are dependent on testosterone dose and circulating testosterone concentrations and exhibit a log-linear relationship with serum total and free testosterone. Failure to observe a significant testosterone dose relationship with fatigability suggests that testosterone does not affect this component of muscle performance and that different components of muscle performance are regulated by different mechanisms.

Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men.
Testosterone supplementation reduces total body adipose tissue (AT), but we do not know whether the effects are uniformly distributed throughout the body or are region specific, or whether they are dose related. We determined the effects of graded doses of testosterone on regional AT distribution in 54 healthy men (18-35 yr) in a 20-wk, randomized, double-blind study of combined treatment with GnRH agonist plus one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE). Total body, appendicular, and trunk AT and lean body mass were measured by dual-energy x-ray absorptiometry, and sc, intermuscular, and intraabdominal AT of the thigh and abdomen were measured by magnetic resonance imaging. Treatment regimens resulted in serum nadir testosterone concentrations ranging from subphysiological to supraphysiological levels. Dose-dependent changes in AT mass were negatively correlated with TE dose at all sites and were equally distributed between the trunk and appendices. The lowest dose was associated with gains in sc, intermuscular, and intraabdominal AT, with the greatest percent increase occurring in the sc stores. At the three highest TE doses, thigh intermuscular AT volume was significantly reduced, with a greater percent loss in intermuscular than sc depots, whereas intraabdominal AT stores remained unchanged. In conclusion, changes in testosterone concentrations in young men are associated with dose-dependent and region-specific changes in AT and lean body mass in the appendices and trunk. Lowering testosterone concentrations below baseline increases sc and deep AT stores in the appendices and abdomen, with a greater percent increase in sc depots. Conversely, elevating testosterone concentrations above baseline induces a greater loss of AT from the smaller, deeper intermuscular stores of the thigh.

Effects of GH and/or coïtus steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men.
Aging is associated with reduced GH, IGF-I, and coïtus steroid axis activity and with increased abdominal fat. We employed a randomized, double-masked, placebo-controlled, noncross-over design to study the effects of 6 months of administration of GH alone (20 microg/kg BW), coïtus hormone alone (hormone replacement therapy in women, testosterone enanthate in men), or GH + coïtus hormone on total abdominal area, abdominal sc fat, and visceral fat in 110 healthy women (n = 46) and men (n = 64), 65-88 yr old (mean, 72 yr). GH administration increased IGF-I levels in women (P = 0.05) and men (P = 0.0001), with the increment in IGF-I levels being higher in men (P = 0.05). Sex steroid administration increased levels of estrogen and testosterone in women and men, respectively (P = 0.05). In women, neither GH, hormone replacement therapy, nor GH + hormone replacement therapy altered total abdominal area, sc fat, or visceral fat significantly. In contrast, in men, administration of GH and GH + testosterone enanthate decreased total abdominal area by 3.9% and 3.8%, respectively, within group and vs. placebo (P = 0.05). Within-group comparisons revealed that sc fat decreased by 10% (P = 0.01) after GH, and by 14% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, sc fat decreased by 14% (P = 0.05) after GH, by 7% (P = 0.05) after testosterone enanthate, and by 16% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, visceral fat did not decrease significantly after administration of GH, testosterone enanthate, or GH + testosterone enanthate. These data suggest that in healthy older individuals, GH and/or coïtus hormone administration elicits a coïtusually dimorphic response on sc abdominal fat. The generally proportionate reductions we observed in sc and visceral fat, after 6 months of GH administration in healthy aged men, contrast with the disproportionate reduction of visceral fat reported after a similar period of GH treatment of nonelderly GH deficient men and women. Whether longer term administration of GH or testosterone enanthate, alone or in combination, will reduce abdominal fat distribution-related cardiovascular risk in healthy older men remains to be elucidated.

The effects of supraphysiological doses of testosterone on angry behavior in healthy eugonadal men--a clinical research center study.
Anecdotal reports of "roid rage" and violent crimes by androgenic steroid users have brought attention to the relationship between anabolic steroid use and angry outbursts. However, testosterone effects on human aggression remain controversial. Previous studies have been criticized because of the low androgen doses, lack of placebo control or blinding, and inclusion of competitive athletes and those with preexisting psychopathology. To overcome these pitfalls, we used a double-blind, placebo-controlled design, excluded competitive athletes and those with psychiatric disorders, and used 600 mg testosterone enanthate (TE)/week. Forty-three eugonadal men, 19-40 yr, were randomized to 1 of 4 groups: Group I, placebo, no exercise; Group II, TE, no exercise; Group III, placebo, exercise; Group IV, TE plus exercise. Exercise consisted of thrice weekly strength training sessions. The Multi-Dimensional Anger Inventory (MAI), which includes 5 different dimensions of anger (inward anger, outward anger, anger arousal, hostile outlook, and anger eliciting situations), and a Mood Inventory (MI), which includes items related to mood and behavior, were administered to subjects before, during, and after the 10 week intervention. The subject's significant other (spouse, live-in partner, or parent) also answered the same questions about the subject's mood and behavior (Observer Mood Inventory, OMI). No differences were observed between exercising and nonexercising and between placebo and TE treated subjects for any of the 5 subdomains of MAI. Overall there were no significant changes in MI or OMI during the treatment period in any group. Conclusion: Supraphysiological doses of testosterone, when administered to normal men in a controlled setting, do not increase angry behavior. These data do not exclude the possibility that still higher doses of multiple steroids might provoke angry behavior in men with preexisting psychopathology.

Effect of testosterone administration on coïtusual behavior and mood in men with erectile dysfunction.
This double-blind placebo controlled, cross-over study was carried out to assess the effect of testosterone administration on coïtusual behavior mood, and psychological symptoms in healthy men with erectile dysfunction. Biweekly injections of 200 mg of testosterone enanthate were given over a period of 6 weeks separated by a washout period of 4 weeks. Blood samples for hormonal assessment, behavioral and psychological ratings were obtained prior to each injection. Luteinizing hormone remained significantly depressed but circulating testosterone had returned to baseline levels by 2 weeks following each hormonal injection. The ejaculatory frequency during the testosterone phase was statistically higher than during the placebo phase. There were marked, although statistically nonsignificant, increases in median frequency of reported coïtusual desire, masturbation, coïtusual experiences with partner, and sleep erections during the testosterone period. Testosterone did not have demonstrable effects on ratings of penile rigidity and coïtusual satisfaction. Mood variables and psychological symptoms did not change following hormonal administration. Results suggest that androgen administration to eugonadal men with erectile dysfunction may activate their coïtusual behavior without enhancing erectile capacity and without effects on mood and psychological symptoms.

Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial.
METHOD: A 6-week double-blind, placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: Thirty patients were randomly assigned to an intervention; 13 received testosterone, and 17 received placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/-50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received testosterone achieved normalization of their testosterone levels. The HAM-D scores decreased in both testosterone and placebo groups, and there were no significant between-group differences: reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo. Response rate, defined as a 50% or greater reduction in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in coïtusual function (p = .02). CONCLUSION: In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.

Testosterone supplementation: what and how to give.
Several epidemiological studies have demonstrated a gradual decrease of serum testosterone with aging in men. A considerable number of men will experience hypogonadal androgen levels, defined by the normal range for young men. Thus, in addition to the long-standing use of androgen replacement therapy in the classical forms of primary and secondary hypogonadism, age-associated testosterone deficiency has led to considerable developments in application modes for testosterone. Since oral preparations of testosterone are ineffective, due to the first-pass effect of the liver, or, in case of 17 alpha-alkylation, cause hepatotoxicity, intramuscular injection of long-acting esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. However, the large fluctuations of serum testosterone levels cause unsatisfactory shifts of mood and coïtusual function in some men; combined with the frequent injections, this delivery mode is thus far from being ideal. In contrast, the transdermal testosterone patches are characterized by favorable pharmacokinetic behavior and have proven to be an effective mode of delivery. Safety data over 10 years indicate no negative effect on the prostate. Nevertheless, the scrotal testosterone patch system is hampered by the application site, which is not easily accepted by many subjects; the non-scrotal patch has a high rate of skin irritations. In view of the drawbacks of the currently available preparations, the most recent developments in testosterone supplementation appear to be highly promising agents. Androgen, which has been available in the United States since mid-2000, will be introduced this year in most European markets as Testogel, a hydroalcoholic gel containing 1% testosterone. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and to correct the signs and symptoms of hypogonadism. The gel has shown to be very effective and successful in American patients, who have benefited from its availability for almost 3 years. Furthermore, in phase II and III clinical studies, the intramuscular injection of 1000 mg testosterone undecanoate every 12-15 weeks has led to extremely stable serum testosterone levels for a prolonged period of time and has resulted in excellent efficacy. It is very likely in the future that these products will be the mainstay of testosterone supplementation. Whereas the indication for testosterone substitution for men with classical forms of hypogonadism is unequivocal, the use of testosterone in men with age-associated hypogonadism is less uniformly accepted. Yet, the few studies addressing this question indicate that men with testosterone serum levels below the lower normal limit for young adult men and with lack of energy, libido, depressed mood and osteoporosis may benefit from testosterone supplementation. However, it should be kept in mind that the experience documented in studies is limited. Nevertheless, serious side-effects, especially in regard to the prostate, did not occur, with the longest study extending over 3 years.

The effect of supraphysiologic doses of testosterone on fasting total homocysteine levels in normal men.
Elevated total homocysteine (tHcy) levels are associated with increased risk for atherosclerotic cardiovascular disease. tHcy levels are higher in men than in women, and estrogen replacement therapy may reduce tHcy levels in postmenopausal women. The effect of androgenic hormones on tHcy levels in men has not been examined. The present study determined the effect of supraphysiologic doses of testosterone, with or without its aromatization to estradiol, on fasting tHcy levels in 14 normal male weightlifters aged 19-42 years. Subjects received testosterone-enanthate (200 mg/week intramuscularly), the aromatase inhibitor, testolactone (1 g/day orally), or both drugs together in a crossover design. Each treatment lasted 3 weeks and each treatment was separated by a 4-week washout. Both testosterone regimens increased serum testosterone levels, whereas estradiol increased only during testosterone alone. Mean tHcy levels were not significantly altered when testosterone was given alone or together with testolactone. Testolactone did not significantly influence tHcy levels. We conclude that short-term, high-dose testosterone administration does not affect fasting tHcy levels in normal men.

Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men.
We investigated whether the androgen type or application mode or testosterone (T) serum levels influence serum lipids and lipoprotein levels differentially in 55 hypogonadal men randomly assigned to the following treatment groups: mesterolone 100 mg orally daily ([MES] n = 12), testosterone undecanoate 160 mg orally daily ([TU] n = 13), testosterone enanthate 250 mg intramuscularly every 21 days ([TE] n = 15), or a single subcutaneous implantation of crystalline T 1,200 mg ([TPEL] n = 15). The dosages were based on standard treatment regimens. Previous androgen substitution was suspended for at least 3 months. Only metabolically healthy men with serum T less than 3.6 nmol/L and total cholesterol (TC) and triglyceride (TG) less than 200 mg/dL were included. After a screening period of 2 weeks, the study medication was taken from days 0 to 189, with follow-up visits on days 246 and 300. Before substitution, all men were clearly hypogonadal, with mean serum T less than 3 nmol/L in all groups. Androgen substitution led to no significant increase of serum T in the MES group, subnormal T in the TU group (5.7 +/- 0.3 nmol/L), normal T in the TE group (13.5 +/- 0.7 nmol/L), and high-normal T in the TPEL group (23.2 +/- 1.1 nmol/L). 5 alpha-Dihydrotestosterone significantly increased in all treatment groups compared with baseline. Compared with presubstitution levels, a significant increase of TC was observed in all treatment groups (TU, 14.4% +/- 3.0%; MES, 18.8% +/- 2.5%; TE, 20.4% +/- 3.0%; TPEL, 20.2% +/- 2.6%). Low-density lipoprotein cholesterol (LDL-C) also increased significantly by 34.3% +/- 5.5% (TU), 46.4% +/- 4.1% (MES), 65.2% +/- 5.7% (TE), and 47.5% +/- 4.3% (TPEL). High-density lipoprotein cholesterol (HDL-C) showed a significant decrease by -30.9% +/- 2.8% (TU), -34.9% +/- 2.5% (MES), -35.7% +/- 2.6% (TE), and -32.5% +/- 3.5% (TPEL). Serum TG significantly increased by 37.3% +/- 11.3% (TU), 46.4% +/- 10.3% (MES), 29.4% +/- 6.5% (TE), and 22.9% +/- 6.7% (TPEL). TU caused a smaller increase of TC than TE and TPEL, whereas the parenteral treatment modes showed a lower increase of TG. There was no correlation between serum T and lipid concentrations. Despite the return of serum T to pretreatment levels, serum lipid and lipoprotein levels did not return to baseline during follow-up evaluation. In summary, androgen substitution in hypogonadal men increases TC, LDL-C, and TG and decreases HDL-C independently of the androgen type and application made and the serum androgen levels achieved. Due to the extended washout period for previous androgen medication and the exclusion of men with preexisting hyperlipidemia, this investigation demonstrates more clearly than previous studies the impact of androgen effects on serum lipids and lipoproteins. It is concluded that preexisting low serum androgens induce a "male-type" serum lipid profile, and increasing serum androgens further within the male normal range does not exert any additional effects. The threshold appears to be above the normal female androgen serum levels and far below the lower limit of normal serum T levels in adult men. These findings may have considerable implications for the use of androgens as a male contraceptive and for androgen therapy in elderly men.

Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I containing lipoproteins.
Eleven Chinese hypogonadal men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly intervals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of treatment. Plasma cholesteryl ester transfer protein (CETP) activity and lipolytic enzymes activities in post-heparin plasma were measured to determine the mechanisms underlying testosterone-induced changes in HDL. RESULTS: The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No changes were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after 12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in plasma CETP and lipoprotein lipase activities after testosterone replacement but there was a transient increase in hepatic lipase (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase in HL activity (r = 0.62, P < 0.05). CONCLUSIONS: Testosterone replacement in the form of parenteral testosterone ester given 4-weekly, although unphysiological, was not associated with unfavourable changes in lipid profiles. The reduction in HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti-atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.

Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis.
To determine the complications, toxicities, and compliance of long term testosterone replacement in hypogonadal males, we retrospectively assessed 45 elderly hypogonadal men receiving testosterone replacement therapy and 27 hypogonadal men taking testosterone. Hypogonadism was defined as a bioavailable testosterone serum concentration of 72 ng/dL or less. Both groups received baseline physical examinations and blood tests. The testosterone-treated group received 200 mg testosterone enanthate or cypionate im every 2 weeks, and follow-up examinations and blood samplings were performed every 3 months. The control group had a single follow-up blood test and physical examination. There was no significant difference in the initial blood tests in the two groups. At 2 yr follow-up, only the hematocrit showed a statistically significant increase in the testosterone-treated group compared to the control group (P < 0.001). A decrease in the urea nitrogen to creatinine ratio and an increase in the prostate-specific antigen concentration was not statistically significant. Eleven (24%) of the testosterone-treated subjects developed polycythemia sufficient to require phlebotomy or the temporary withholding of testosterone, one third of which occurred less than 1 yr after starting testosterone treatment. There was no significant difference in the incidence of new illness in the two groups during the 2-yr follow-up. Although self-assessment of libido was dramatically improved in the testosterone-treated group (P < 0.0001), approximately one third of the subjects discontinued therapy. In conclusion, testosterone replacement therapy appears to be well tolerated by over 84% of the subjects. Long term testosterone replacement to date appears to be a safe and effective means of treating hypogonadal elderly males, provided that frequent follow-up blood tests and examinations are performed.

Oligozoospermia induced by exogenous testosterone is associated with normal functioning residual spermatozoa.
PATIENT(S): Twelve healthy men were studied while participating in a multicenter T enanthate contraceptive efficacy study. Data were analyzed from only eight subjects, whose sperm concentrations were between 1.3 and 10 x 10(6)/mL at the suppression phase. INTERVENTION(S): Testosterone enanthate (200 mg) was administered IM weekly during the suppression and treatment (efficacy) phases (total 15 months). MAIN OUTCOME MEASURE(S): Sperm function tests (stimulated acrosome reaction, sperm hyperactivation [HA], and zona-free hamster oocyte penetration tests) were performed during the pretreatment, suppression (usually after 6 to 10 weeks of treatment, when sperm concentration was anticipated to decrease to < 10 x 10(6)/mL), and recovery phases. Studies were not done during the contraceptive efficacy phase because only one of the subjects was not azoospermic. RESULT(S): Mean sperm concentration was reduced but sperm motility, motility characteristics, and morphology were not affected by T enanthate treatment. The residual spermatozoa in the ejaculate could acrosome react, exhibited normal HA, and maintained the capacity to penetrate and fuse with the oocyte. CONCLUSION(S): Suppression of spermatogenesis to moderate oligozoospermia (< 10 x 10(6)/mL) with exogenous T enanthate administration was not associated with impaired sperm function of the residual spermatozoa. The study did not exclude the possibility that disorders of sperm function might occur when spermatogenesis is suppressed further to very severe oligozoospermia (< 1 x 10(6)/mL), commonly observed in hormonal male contraceptive clinical trials.

Changes in structure and functions of prostate by long-term administration of an androgen, testosterone enanthate, in rhesus monkey (Macaca mulatta).
The present study is the first report that critically evaluates the effects of long-term use of TE on prostate structure and functions. Adult male rhesus monkeys received intramuscular injections of 50 mg of TE once in 14 days for 33 months. The cranial and caudal lobes of the prostate, which were removed under ketamine anesthesia, were processed for the preparation of semithin sections to evaluate histological changes. The DNA distribution in the cells was studied in single cell suspensions of cranial and caudal lobes of the prostate by using flow cytometry. Changes in the levels of testosterone, estradiol, prostate-specific acid phosphatase (PAP), and prostate-specific antigen (PSA) in samples collected during the pretreatment period and at the time of removal of the prostate were estimated by using conventional procedures. Control samples were processed simultaneously. The administration of TE for 33 months caused the following changes: 1) significant increase in the weight of both lobes of the prostate, 2) cellular hypertrophy and increase in secretory material in the cells and in the lumen of the acini in the central and peripheral zones of the two lobes of the prostate, 3) cellular hyperplasia indicated by flow cytometric analysis of DNA content, 4) significant increase in the secretion of PAP and levels of estradiol, and 5) a marked increase in fibromuscular stroma in the central and peripheral zones of both the lobes of the prostate. The present study is the first report to provide evidence that long-term androgen treatment has caused hypertrophy of the prostatic epithelial cells, which showed increased secretory activity. The hyperplastic changes indicate a need for the development of new androgens with a better pharmacokinetic profile for use in male contraceptive regimens.

Langur prostate and its hormonal modulation.
Various prostatic parameters in normal and under altered hormonal conditions suggest that the langur prostate is similar to the human and therefore could be used as surrogate for the human prostate.

Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle.
The participants in this randomized, double-blind trial were 60 ambulatory, healthy, older men, 60-75 yr of age, who had normal serum testosterone levels. Their responses to graded doses of testosterone were compared with previous data in 61 men, 19-35 yr old. The participants received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate weekly for 20 wk. Fat-free mass, fat mass, muscle strength, coïtusual function, mood, visuospatial cognition, hormone levels, and safety measures were evaluated before, during, and after treatment. Of 60 older men who were randomized, 52 completed the study. After adjusting for testosterone dose, changes in serum total testosterone (change, -6.8, -1.9, +16.1, +49.5, and +101.9 nmol/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) and hemoglobin (change, -3.6, +9.9, +20.9, +12.6, and +29.4 g/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) levels were dose-related in older men and significantly greater in older men than young men (each P < 0.0001). The changes in FFM (-0.3, +1.7, +4.2, +5.6, and +7.3 kg, respectively, in five ascending dose groups) and muscle strength in older men were correlated with testosterone dose and concentrations and were not significantly different in young and older men. Changes in fat mass correlated inversely with testosterone dose (r = -0.54; P < 0.001) and were significantly different in young vs. older men (P < 0.0001); young men receiving 25- and 50-mg doses gained more fat mass than older men (P < 0.0001). Mood and visuospatial cognition did not change significantly in either group. Frequency of hematocrit greater than 54%, leg edema, and prostate events were numerically higher in older men than in young men. Older men are as responsive as young men to testosterone's anabolic effects; however, older men have lower testosterone clearance rates, higher increments in hemoglobin, and a higher frequency of adverse effects. Although substantial gains in muscle mass and strength can be realized in older men with supraphysiological testosterone doses, these high doses are associated with a high frequency of adverse effects. The best trade-off was achieved with a testosterone dose (125 mg) that was associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength.

Effects of muscle strength training and testosterone in frail elderly males.
PURPOSE: Determine the independent and combined effects of progressive resistance muscle strength training (PRMST) and testosterone on strength, muscle mass, and function in hypogonadal elderly male recuperative care patients. METHODS: Between 1999 and 2004, 71 subjects (mean age 78.2 +/- 6.4 yr, 86% white) were enrolled. After baseline one-repetition maximum (1RM) strength testing and then randomization to one of four treatment groups (low-resistance (20% of the 1RM) exercises and weekly injections of either 100 mg of testosterone enanthate or placebo or high-intensity PRMST (> or =80% 1RM) and weekly injections), each subject received training and injections for 12 wk. RESULTS: Ten subjects withdrew from the study before its completion. Based on intent-to-treat analyses, strength improved in all groups, but was greater with high-intensity PRMST compared with low-resistance exercise (e.g., leg press, (mean +/- SE), 28 +/- 4 vs 13 +/- 4%, P = 0.009). Although testosterone led to significantly greater increases in midthigh cross-sectional muscle area compared with placebo (7.9 +/- 1.3 vs 2.4 +/- 1.4%, P = 0.005), it produced only a nonsignificant trend toward greater strength gains (e.g., leg press 25 +/- 4 vs 16 +/- 4%, P = 0.144). Change in aggregate functional performance score (the sum of 4 functional performance test scores) did not differ between the four intervention groups nor with high-intensity PRMST compared with low-resistance exercise (7 +/- 5 vs 15 +/- 5%, P = 0.263). There was not a significant interaction between exercise and testosterone for any outcome. CONCLUSION: High-intensity PRMST is as safe and well tolerated as a similarly structured low-resistance exercise regimen for very frail elderly patients, but produces greater muscle strength improvements. The addition of testosterone leads to greater muscle size and a trend toward greater strength but did not produce a synergistic interaction with exercise. Neither intervention had a significant effect on functional performance.

Testosterone improves rehabilitation outcomes in ill older men.
OBJECTIVES: To determine whether testosterone supplementation improves rehabilitation outcomes in ill older men. DESIGN: A randomized, placebo-controlled, double-blind study. SETTING: A Geriatric Evaluation and Management (GEM) unit based at a university- affiliated Veterans Affairs Medical Center. PARTICIPANTS: Fifteen men aged 65 to 90 years admitted to the GEM for rehabilitation. INTERVENTION: Subjects were randomized to receive weekly intramuscular injections with testosterone enanthate 100 mg or placebo. MEASUREMENTS: Task-specific performance using the Functional Independence Measure (FIM) and grip strength was measured at the onset of the study and at the time of discharge from the GEM. RESULTS: At baseline, FIM scores were similar between the placebo and the testosterone group (73.7 vs 70.7, P = .637), as was grip strength (49.7 vs 55.3 pounds, P = .555). At discharge from the GEM, testosterone-treated patients had improved FIM scores compared with baseline (93.6 vs 70.7; P = .012) and grip strength (68.7 vs 55.3 pounds; P = .033). In the placebo group there was no significant improvement of FIM scores compared with baseline (78.0 versus 73.7; P = .686) or of grip strength (48.9 vs 49.7 pounds; P = .686). CONCLUSIONS: Testosterone supplementation may improve rehabilitation outcomes in ill older men.

[The influence of testosterone replacement therapy on well-being, bone mineral density and lipids in elderly men]
We investigated thirty men (mean +/- SD; age 61.1 +/- 5.6 yr) with testosterone concentrations (mean +/- SEM) 2.1 +/- 0.2 ng/ml. Testosterone deficiency was replacement by intramuscular injections of testosterone enanthate 200 mg every second week from 1.5 to 6 yr. (mean +/- SD; 3.35 +/- 1.6 yr.). During the treatment serum testosterone increased reaching normal levels (mean +/- SEM; 6.6 +/- 0.2 ng/ml). This was associated with significant increase in positive mood parameters and a decrease in negative mood parameters. Also self assessment of libido, potence and dream were improved. Bone mineral density (BMD) of lumbar spine increased. We noticed significant decrease in total cholesterol, and LDL-cholesterol. Hematocrit was increase Prostate-specific antigen concentration statistically increased from 0.65 +/- 0.1 to 1.35 +/- 0.1 ng/ml (mean +/- SEM), but in the cases of its levels were in normal range. Patients with coronary heart disease demonstrated decreasing ing symptoms of angina pectoris and nitrate requirement. In summary, long-term testosterone replacement therapy in elderly men may have beneficial effects on well-being, libido, potence, dream, bone mineral density, lipids, blood cell count and body mass (BMI). This therapy appears to be safe and there is no adverse effection on prostate.

Dose-dependent effects of testosterone on coïtusual function, mood, and visuospatial cognition in older men.
To elucidate testosterone dose-response relationships in older men, we examined the effects of graded testosterone doses on coïtusual function, mood, and visuospatial cognition in healthy, older men (age, 60-75 yr). SETTING: This study was performed at the General Clinical Research Center. INTERVENTION/METHODS: Subjects each received a long-acting GnRH agonist to suppress endogenous testosterone production and were randomized to receive one of five doses (25, 50, 125, 300, and 600 mg) of testosterone enanthate weekly for 20 wk. Questionnaires were used to evaluate coïtusual function. Scores for overall coïtusual function as well as subcomponents of coïtusual function (libido, coïtusual activity, and erectile function) were calculated. RESULTS: Changes in overall coïtusual function (P = 0.003) and waking erections (P = 0.024) differed by dose. An interaction between libido and being coïtusually active was observed, such that libido changed by testosterone dose only among men who reported being coïtusually active at the beginning of the study (P = 0.009). Men's log-transformed free testosterone levels during treatment were positively correlated with overall coïtusual function (P = 0.001), waking erections (P = 0.040), spontaneous erections (P = 0.047), and libido (P = 0.027), but not with intercourse frequency (P = 0.428 ) or masturbation frequency (P = 0.814). No effects of testosterone dose were observed on two measures of mood: Hamilton's Depression Inventory (P = 0.359) and Young's Mania Scale (P = 0.851). The number of trials completed on a computer-based test of visuospatial cognition differed by dose (P = 0.042), but the number of squares correctly completed on this task did not differ by dose (P = 0.159). CONCLUSIONS: Different aspects of male behavior respond differently to testosterone. When considered together with previous data from young men, these data indicate that testosterone dose-response relationships for coïtusual function and visuospatial cognition differ in older and young men.

Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone.
Older men, particularly those with low serum testosterone (T) levels, might benefit from T therapy to improve bone mineral density (BMD) and reduce fracture risk. Concerns exist, however, about the impact of T therapy on the prostate in older men. We hypothesized that the combination of T and finasteride (F), a 5 alpha-reductase inhibitor, might increase BMD in older men without adverse effects on the prostate. Seventy men aged 65 yr or older, with a serum T less than 12.1 nmol/liter on two occasions, were randomly assigned to receive one of three regimens for 36 months: T enanthate, 200 mg im every 2 wk with placebo pills daily (T-only); T enanthate, 200 mg every 2 wk with 5 mg F daily (T+F); or placebo injections and pills (placebo). Low BMD was not an inclusion criterion. We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry. Prostate-specific antigen (PSA) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate. Fifty men completed the 36-month protocol. By an intent-to-treat analysis including all men for as long as they contributed data, T therapy for 36 months increased BMD in these men at the lumbar spine [10.2 +/- 1.4% (mean percentage increase from baseline +/- SEM; T-only) and 9.3 +/- 1.4% (T+F) vs. 1.3 +/- 1.4% for placebo (P < 0.001)] and in the hip [2.7 +/- 0.7% (T-only) and 2.2 +/- 0.7% (T+F) vs. -0.2 +/- 0.7% for placebo, (P < or = 0.02)]. Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip. After 6 months of therapy, urinary deoxypyridinoline (a bone-resorption marker) decreased significantly compared with baseline in both the T-only and T+F groups (P < 0.001) but was not significantly reduced compared with the placebo group. Over 36 months, PSA increased significantly from baseline in the T-only group (P < 0.001). Prostate volume increased in all groups during the 36-month treatment period, but this increase was significantly less in the T+F group compared with both the T-only and placebo groups (P = 0.02). These results demonstrate that T therapy in older men with low serum T increases vertebral and hip BMD over 36 months, both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men. In addition, the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy. These findings have important implications for the prevention and treatment of osteoporosis in older men with low T levels.

 

[heavy fly way]

dit vind ik een zeer goede post
ik ben momenteel zelf nu ook 2 weken aan de test.
en ik zelf word er wel veel geiler van.
wat mij zelf wel op valt moment dat hij goed door trekt even in de spier dat ik voor een tijdje wazig ben in mijn hoofd. hoort dit?

 

[krieltje]

Ik vind het ook een wereld post,ook al issie al 4 jaar oud.
Bedankt voor de bump.