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Testosterone Improves Erectile Function in Hypogonadal Patients with Venous Leakage.
J Androl. 2008 Jul 3;
Kurbatov D, Kuznetsky J, Traish AM
The goal of this study was to assess the therapeutic benefits of long-acting testosterone therapy in hypogonadal patients with erectile dysfunction (ED). We recruited 29 patients with ED ranging in age from 32 - 65 years (47 +/- 9.7) with low plasma testosterone, who did not respond to phosphodiesterase type 5 (PDE-5) inhibitors therapy. To evaluate penile arterial and venous blood flow, we employed Duplex Doppler Ultrasonography (DDU). For confirmation of diagnosis of venous leakage, pharmaco-cavernosography (PCG) was carried out in 9 patients and Magnetic Resonance Imaging (MRI) with intracavernous contrast enhancement was carried out in 8 patients. All patients were treated with 1000 mg injectable testosterone undecanoate on day one, followed by another injection after six weeks and every three months thereafter, in accordance with Nebido therapy protocol. Plasma testosterone levels were determined in all patients at baseline and after 12 and 30 weeks of testosterone treatment. The International Index of Erectile Function (IIEF-5) was administered at base line, and after 12 and 30 weeks of testosterone treatment. At base line total testosterone ranged from 7-11.8 nmol/l (200-345 ng/dl) in all patients. Twelve and 30 weeks after testosterone treatment, the mean testosterone plasma levels were 18 and 21.5 nmol/l (520 and 625 ng/dl), respectively. After twelve and 30 weeks of testosterone treatment, 20 out of the 29 patients demonstrated marked improvement in erectile function domain, as assessed by IIEF-5. This was also associated with diminution of venous leakage. We suggest that, in hypogonadal men with ED, testosterone therapy improves erectile function in patients with ED and venous leakage.
Aging Male. 2008 Jun; 11(2): 57-61
Kalinchenko S, Vishnevskiy EL, Koval AN, Mskhalaya GJ, Saad F
INTRODUCTION: Elderly men are bothered by lower urinary tract complaints designated as lower urinary tract symptoms (LUTS). In epidemiological studies LUTS appears strongly associated with erectile dysfunction, and also with metabolic syndrome. LUTS occurs at an age at which plasma testosterone levels decline, in some men to hypogonadal values. Objectives. This pilot study tested whether testosterone administration to elderly men complaining of LUTS and whose plasma testosterone levels are below normal, might alleviate LUTS. METHODS: Group 1 (n = 10) received treatment with testosterone gel (50 mg) daily for three months; group 2 (n = 20) received treatment with injections of testosterone undecanoate 1000 mg for 26 weeks. RESULTS: Upon these interventions, plasma testosterone increased to the normal range. Symptoms of LUTS, measured by the International Prostate Symptoms Score, improved significantly, and also scores of the Aging Males' Symptoms scale and international index of erectile function improved. There were no untoward effects on the prostate over this period of time of the study. CONCLUSION: Testosterone administration improved symptoms of LUTS in men with late-onset hypogonadism. The mechanism of action is as yet not understood, but it may be connected with or parallel with the effects of testosterone on penile tissues in hypogonadal men, such as on nitric oxide and phosphodiesterase.
Vascul Pharmacol. 2008 Apr 3;
Li S, Li X, Li Y
BACKGROUND: Platelets play crucial roles in the development of arterial thrombosis and other pathophysiologies leading to clinical ischemic events. Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis. The purposes of the study are to determine whether atherosclerotic plaque growth or stability is regulated by physiological doses of testosterone via its receptor, and to further investigate the possible mechanisms of inflammatory reaction. METHODS AND RESULTS: We prepared models of castrated male rabbits. Pathological sections of aorta were performed hematoxylin-eosin (HE) staining and Masson's trichrome staining. Total plasma testosterone was measured using ADVIA Centaur(R) Immunoassay System (Bayer, Germany). Serum TNF(alpha) and IL(6) were assayed using radio-immunoassay kit and serum sICAM-1 and MMP(2) were measured using ELISA kit. Our results showed that castration significantly lowered plasma testosterone levels, whereas testosterone replacement at a dose of 6 mg/kg/two-week restored circulating testosterone to physiological levels, without being altered by treatment with flutamide (a testosterone receptor inhibitor). Testosterone undecanoate replacement reduced the plaque area and the aortic intimal thickness, whereas the fibrous cap thickness and collagen contents increased in castrated rabbits. However, the presence of flutamide increased the plaque area and the aortic intimal thickness, whereas the fibrous cap thickness and collagen contents decreased in castrated rabbits again. Moreover, the levels of serum TNF(alpha), IL(6), sICAM and MMP(2) increased in cholesterol-rich diet rabbits as compared with standard diet rabbits. Castration caused increases in the levels of serum TNF(alpha), IL(6), sICAM and MMP(2) in castrated rabbits as compared with sham-operated rabbits. Treatment of testosterone undecanoate reduced the levels of serum TNF(alpha), IL(6), sICAM and MMP(2) in castrated rabbits, while the presence of flutamide increased the levels of serum TNF(alpha), IL(6), sICAM and MMP(2) again. CONCLUSION: Replacement of physiological testosterone regulates atherosclerotic plaque growth and stability via its receptor in castrated rabbits, which is probably related to their influence on inflammatory reaction.
Testosterone treatment of hypogonadal men participating in competitive sports.
Andrologia. 2008 Jun; 40(3): 195-9
Gooren LJ, Behre HM
Testosterone has a steeply dose-dependent effect on muscle mass and strength irrespective of gonadal status. So, for reasons of fairness, people who engage in competitive sports should not administer exogenous testosterone raising their blood testosterone levels beyond the range of normal. There is a ban on exogenous androgens for men and women in sports, but an exception has been made for men with androgen deficiency due to pituitary or testicular disease. Men who receive testosterone administration for the indication hypogonadism have an interest in the use of testosterone preparations generating blood testosterone levels within the normal range of healthy, eugonadal men. On the grounds of a positive correlation between blood testosterone concentrations muscle and volume/strength, they are best served with a parenteral testosterone preparation, rather than transdermal testosterone, but they should not run the risk of being excluded from competition because of supraphysiological testosterone levels. The latter is a realistic risk with the traditional parenteral testosterone esters. The new parenteral testosterone undecanoate preparation offers much better perspectives. Its pharmacokinetics have been investigated in detail and there is a fair degree of predictability of resulting blood testosterone levels with use of this preparation.
Progress and prospects in male hormonal contraception.
Curr Opin Endocrinol Diabetes Obes. 2008 Jun; 15(3): 255-60
Amory JK
PURPOSE OF REVIEW: Testosterone functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary. Low concentrations of these hormones deprive the testes of the signals required for spermatogenesis and results in markedly decreased sperm concentrations and effective contraception in a majority of men. Male hormonal contraception is well tolerated and acceptable to most men. Unfortunately, testosterone-alone regimens fail to completely suppress spermatogenesis in all men, meaning that in some the potential for fertility remains. RECENT FINDINGS: Because of this, novel combinations of testosterone and progestins, which synergistically suppress gonadotropins, have been studied. Two recently published testosterone/progestin trials are particularly noteworthy. In the first, a long-acting injectable testosterone ester, testosterone decanoate, was combined with etonogestrel implants and resulted in 80-90% of subjects achieving a fewer than 1 million sperm per milliliter. In the second, a daily testosterone gel was combined with 3-monthly injections of depot medroxyprogesterone acetate producing similar results. SUMMARY: Testosterone-based hormone combinations are able to reversibly suppress human spermatogenesis; however, a uniformly effective regimen has remained elusive. Nevertheless, improvements, such as the use of injectable testosterone undecanoate, may lead to a safe, reversible and effective male contraceptive.
J Bone Miner Res. 2008 May; 23(5): 694-704
Reim NS, Breig B, Stahr K, Eberle J, Hoeflich A, Wolf E, Erben RG
INTRODUCTION: Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. Here, we sequentially studied the effects of androgen deficiency on cortical bone in aged orchiectomy (ORX) rats. MATERIALS AND METHODS: One hundred seventy 13-mo-old male Fischer-344 rats were either ORX or sham-operated. After in vivo fluorochrome labeling, groups of 8-15 SHAM and ORX rats each were killed at 2 wk and 1, 2, 3, 4, 6, and 9 mo after surgery. To examine the effects of testosterone replacement therapy, 9-mo-old ORX rats were supplemented with testosterone undecanoate at a weekly dose of 6 mg/kg for 4 mo. Cortical bone changes in the tibial shaft were monitored by pQCT analysis and by bone histomorphometry. RESULTS: SHAM rats did not show age-related bone loss at the tibial diaphysis. pQCT analysis and bone histomorphometry showed cortical bone osteopenia in ORX rats, beginning from 2 mo after surgery until the end of the study. Androgen deficiency induced a sustained decrease in periosteal bone formation during the first 4 mo after ORX. However, although periosteal expansion of the tibial shaft tended to be slower in ORX rats compared with SHAM controls, the reduction in total cross-sectional area in ORX animals reached statistical significance only at 4 mo after surgery. The major mechanism for cortical bone loss in aged ORX rats was a progressive expansion of the marrow cavity, which was associated with an initial increase in endocortical eroded perimeter at 1 and 2 mo after surgery, followed by a sustained increase in endocortical bone formation until the end of the study. All these changes were prevented in aged ORX rats receiving testosterone supplementation in an insulin-like growth factor system-independent fashion. CONCLUSIONS: We conclude that androgen deficiency-induced cortical bone loss in aged, nongrowing rats is mainly caused by augmented endocortical bone remodeling.
Effects of testosterone therapy in older men.
JAMA. 2008 Apr 23; 299(16): 1900; author reply 1900-1
Page S, Matsumoto AM
Male hormonal contraception: a double-blind placebo-controlled study.
J Clin Endocrinol Metab. 2008 Apr 15;
Mommers E, Kersemaekers WM, Elliesen J, Kepers M, Apter D, Behre HM, Beynon J, Bouloux PM, Costantino A, Gerbershagen HP, Grønlund L, Heger-Mahn D, Huhtaniemi I, Koldewijn EL, Lange C, Lindenberg S, Meriggiola MC, Meuleman E, Mulders PF, Nieschlag E, Perheentupa A, Solomon A, Väisälä L, Wu FC, Zitzmann M
Background: This study was performed to assess spermatogenesis suppression and safety of a new combination of an etonogestrel (ENG) implant combined with testosterone undecanoate (TU) injections for male contraception. This is the first large placebo-controlled study for male hormonal contraception. Design and Study Subjects: In this double-blind, multicenter study, we randomly assigned 354 healthy men to receive either a low or high release ENG implant subcutaneously combined with intramuscular TU injections (750 mg every 10 or 12 weeks, or 1000 mg every 12 weeks), or placebo implant and injections. Treatment duration was 42 or 44 weeks and post-treatment follow up at least 24 weeks. Results: Overall, spermatogenesis was suppressed to 1 million/ml or less at week 16 in 89% of men, with approximately 94% in two high release ENG groups. Suppression was maintained up to the end of the treatment period in 91% of men. For all men who completed the treatment period, 3% never achieved
Clin Endocrinol (Oxf). 2008 Apr 3;
Moisey R, Swinburne J, Orme S
Objective: To investigate the loading regimen for intramuscular (IM) testosterone undecanoate (Nebido(R)) to determine whether testosterone and bioavailable testosterone levels achieved correlate with age or body size of subjects studied. Design: Retrospective observational study of testosterone naïve patients and patients previously treated with an alternative testosterone therapy. Patients: 51 hypogonadal men (35, 68.6% secondary hypogonadism). 8 (16%) had not previously received testosterone therapy. Measurements: Patients received an IM injection of Nebido (1000mg) at baseline and a second injection after 6 weeks. Serum was assayed at baseline and 18 weeks after commencing Nebido for total testosterone (TT) and SHBG. Bioavailable testosterone was calculated (cBioT) using TT and SHBG. Measurements were taken for weight, body mass index (BMI) and body surface area (BSA). Results: Baseline TT (mean 11.5nmol/L, range 0.3-54.8) increased by 50% after commencing Nebido (17.2nmol/L (5.4-32.8), P=0.0001). 75% of subjects had a TT within the reference range (8.0 - 25.0nmol/L). Subjects with primary hypogonadism had a higher 18 week TT (20.9nmol/L (9.8-32.8) vs. 15.5 (5.4-32.6), P=0.02) and SHBG (39.2nmol/L (11-82) vs. 25.7 (9.0-60.0), P=0.003) although the cBioT was not significantly different (4.9nmol/L (2.9-7.3) vs. 4.2 (2.0-7.9), P=0.12). The 18 week TT positively correlated with age (R=0.36, P=0.01) and negatively correlated with weight (R=-0.38, P=0.006), BMI (R=-0.42, P=0.002) and BSA (R=-0.38, P=0.007). Similarly cBioT correlated with age (R=0.28, P=0.04), weight (R=-0.29, P=0.03), BMI (R=-0.30, P=0.03) and BSA (R=-0.27, P=0.05). Age (t=2.04, P=0.05) and baseline testosterone (t=-9.26, P
[Effect of (CAG) n polymorphism of androgen receptor gene on hormonal male contraception]
Zhonghua Nan Ke Xue. 2008 Feb; 14(2): 126-30
Li JW, Yuan D, Li H, Liang XW, Lu WH, Gu YQ
OBJECTIVE: To study (CAG) n polymorphism of the androgen receptor (AR) gene in responders and non-responders of male volunteers who received testosterone undecanoate intramuscular injection for contraception and to explore the effect of the polymorphism on hormonal male contraception. METHODS: Twenty-nine non-responders and 34 responders were enrolled in this study as a test and a control group respectively. The numbers of CAG sequence repeats were determined by PCR and DNA sequencing, and the effect of (CAG) n polymorphism on hormonal male contraception was analyzed. RESULTS: The means of CAG repeats of the test and the control group were 23.62 and 22.97, with no significant difference in between (P > 0.05). The short CAG repeats (n < or = 22) constituted 51.7% in the test group and 50% in the control, while the long ones (n > 22) accounted for 48.3% and 50% , respectively. The short and the long group had a similar distribution. No association was found between CAG repeats and sperm concentration. With FSH > 0.2 IU/L, the probability of azoospermia in the long CAG repeat group was 1.5 times that of the short one. CONCLUSION: CAG repeats in the AR gene presented polymorphism in the subjects, with no significant difference between the responders and non-responders. Further investigation has yet to be performed into the relationship of hormonal male contraception with CAG repeats or other factors.