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Background: Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain., Methods: One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men., Results: As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men., Conclusions: Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton., Trial Registration: ClinicalTrials.gov, NCT00114114., Funding: AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.

Background: Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes., Methods: A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed., Results: Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH)., Conclusions: Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes.

Introduction: The relationship between Testosterone Replacement Therapy (TRT) and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA) but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE). Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy., Materials and Methods: Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns., Results: 96 men were identified. Mean age at biopsy was 63 (range 40-85) and median PSA was 3.78ng/dL (0.5-662). Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662) and mean total testosterone 254 (191-341). There were 29 (47.5%) prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9). Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7). The %PSA increase ranged from 2 to 251% (mean 93.5%). Mean total testosterone was 383 (146-792). Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7)., Conclusions: Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.

Context: Low T levels have been associated with ejaculatory dysfunction (EjD) in cross-sectional studies; however, the efficacy of T replacement in improving EjD has not been studied in a randomized controlled trial., Objective: To evaluate the efficacy of T replacement in androgen-deficient men with EjD., Design: A multicenter, double-blind, randomized, placebo-controlled, 16-week trial with T solution 2% versus placebo., Setting: Medical centers in the United States, Canada, and Mexico., Patients or Other Participants: Seventy-six men with one or more EjD symptoms, including delayed ejaculation, anejaculation, reduced ejaculate volume, and/or reduced force of ejaculation, and two total T levels <300 ng/dL (<10.41 nmol/L) measured with liquid chromatography tandem mass spectrometry., Interventions: Sixty milligrams of T solution 2% or placebo applied to the axillae for 16 weeks., Main Outcome Measures: The primary outcome was a change in the score of the three-item Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF); secondary outcomes included measured ejaculate volume, scores of the bother/satisfaction item of the MSHQ-EjD-SF, the orgasmic function domain of the International Index of Erectile Function Questionnaire, and the sexual activity log., Results: Seventy-six participants were randomized; 66 completed the study. Baseline demographic and clinical characteristics were comparable between the treatment arms. T replacement improved the MSHQ-EjD-SF score (mean score change, +3.1); however, this effect was not statistically different from placebo (mean score change, +2.5; P = .596). No differences were seen in any of the secondary outcomes or frequency of adverse events., Conclusion: T replacement was not associated with significant improvement in EjD in androgen-deficient men.

Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was to investigate whether testosterone levels are associated with serum vitamin D levels and whether seasonal variation exists. This cross-sectional study analyzed serum 25-hydroxyvitamin D [25(OH)D], total testosterone (TT), and free testosterone (FT) in 652 Korean men over 40 years of age who had undergone a comprehensive medical examination. The average age of the subjects was 56.7 ± 7.9 years, and the mean serum 25(OH)D, TT and FT levels were 21.23 ± 7.9 ng ml-1 , 4.70 ± 1.6 ng ml-1 , and 8.12 ± 3.3 pg ml-1 , respectively. In the multiple linear regression model, 25(OH)D showed positive association with TT (β =0.137, P< 0.001) and FT (β =0.103, P= 0.008). 25(OH)D and FT showed similar seasonal or monthly variation after adjustment for age. A vitamin D deficiency [25(OH)D < 20 ng ml-1 ] was associated with an increased risk of deficiencies of TT (<2.30 ng ml-1 ) (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.21-5.78, P= 0.014) and FT (<6.50 pg ml-1 ) (OR: 1.44; 95% CI: 1.01-2.06 P= 0.048) after adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use. In conclusion, we demonstrated a positive correlation between 25(OH)D and testosterone, which showed similar seasonal variation in Korean men.

Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer.After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P < 0.001). The difference in means of PSA levels were significant higher for patients that received testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117-0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48-2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls.Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration is minimal.

Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. The aim of this study was to evaluate a new immunophenotype of EPCs and EMPs in patients with arterial erectile dysfunction (ED) and late-onset hypogonadism (LOH). Fifty patients (58.2 ± 0.7 years) with ED and LOH were enrolled in this study. Their EPC and EMP concentrations were compared with those of 20 patients with arterial ED alone (61.2 ± 1.2 years) and of 20 healthy men (controls; 61.4 ± 1.2 years). EPC (CD45(neg)/CD34(pos)/CD144(pos)) and EMP (CD45(neg)/CD144(pos)/annexin V(pos)) blood concentrations were evaluated by flow cytometry. Patients with ED and LOH or ED alone had significantly higher blood pressure, triglycerides, homeostasis model assessment index of insulin resistance, cavernous artery acceleration time, and intima-media thickness than controls, whereas International Index of Erectile Function score, high-density lipoprotein cholesterol, and cavernous artery peak systolic velocity and resistance index were lower than those of controls. Both EPCs and EMPs were significantly higher in patients with ED and LOH compared with patients with ED alone or controls. Patients with ED alone had EPCs and EMPs significantly higher than controls. In conclusion, patients with ED and LOH showed worse metabolic parameters and cavernous artery parameters, measured by dynamic penile echo color Doppler, and higher EPCs and EMPs compared with patients with ED alone. This suggests that LOH is an additional vascular risk factor and that EPCs and EMPs may be considered predictors of endothelial dysfunction in patients with ED and LOH.

The aetiology of congenital bilateral anorchia is unknown. For many years there was speculation of an association between genetic factors and anorchia. We performed different tests in an anorchid boy, 2.5 years old, presented to us with micropenis and absence of both testes, in order to determine any possible factors contributing to the anorchia. Physical examination and hormonal, imaging, chromosomal, and molecular analyses of this case were performed. The basal FSH and LH levels were increased, and their increase in response to gonadotrophin-releasing hormone test was prolonged, while testosterone levels failed to increase after hCG administration. Ultrasonography of the pelvis and magnetic resonance of the abdomen were performed and failed to show any testicular tissue. Lastly, surgical exploration confirmed the absence of testicular structure. Chromosomal analysis revealed a normal male karyotype and molecular analysis did not reveal mutations or polymorphisms in the open reading frame of the SRY gene. Diagnostically, the lack of testosterone response to hCG stimulation is the hormonal hallmark of bilateral congenital anorchia. In addition, according to our case and previous studies, there is lack of association between genetic factors necessary for correct testicular descent and anorchia.

We describe an unusual patient with hypopituitarism who attained tall stature even without growth hormone (GH). A 37-year-old man was devoid of secondary sexual characteristics, but manifested tall stature with a eunuchoidal feature. Serum levels of GH, insulin-like growth factor-I, gonadotropins and testosterone were all below normal. GH secretion was not enhanced by any provocative stimulus. Adrenocorticotropic hormone increased after administration of corticotropin releasing hormone, but not after insulin-induced hypoglycemia. Thyrotropin increased in response to thyrotropin releasing hormone, but both free T3 and T4 did not rise. Magnetic resonance imaging disclosed a transected pituitary stalk. The present patient had hypopituitarism due to perinatal problems but had grown with the aid of non-GH growth-promoting factors, which suggests that man may be able to achieve statural growth even without GH.

Objective: The response to subcutaneous (SC) gonadotropin replacement therapy, using human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or hCG alone, was evaluated in male hypothalamic hypogonadism., Design: Sixteen patients with hypothalamic hypogonadism were treated with gonadotropins for induction of puberty and normalization of spermatogenesis. The results were analyzed retrospectively., Setting: The study was carried out in a clinical endocrinology department providing tertiary care and in private practices of endocrinology., Patients: Eight patients with idiopathic hypogonadotropic hypogonadism and eight patients with Kallmann's syndrome in prepubertal or early pubertal stages., Interventions: Human chorionic gonadotropin and hMG were administered SC in individual dosages., Main Outcome Measures: Increase of serum testosterone (T), testicular volume, semen volume, and sperm count were evaluated., Results: Normalization of serum T and complete sexual maturation was achieved in all patients. Spermatogenesis was induced in all but two patients. Seven patients showed normal findings in semen volume and sperm count, and two patients had semen quality close to normal. In five patients sperm count remained less than 10 x 10(6)/mL., Conclusions: The results obtained by SC gonadotropin replacement prove this mode of administration to be effective in stimulating steroidogenesis and spermatogenesis in hypogonadotropic males.

The response to low-dose pulsatile gonadotropin-releasing hormone (GnRH) therapy was tested in three hypogonadotropic hypogonadal male patients and a boy with delayed puberty showing different luteinizing hormone responses (delta LH) to test doses of 25 micrograms GnRH intravenously before treatment. Four male patients, 16 to 20 years of age, three with Kallmann's syndrome and one with idiopathic delay of puberty, received 2 micrograms GnRH subcutaneously every 2 1/2 hours for 3 months by the use of the Zyklomat pump (Ferring GmbH, Kiel, FRG). In two patients with Kallmann's syndrome and decreased delta LH, serum testosterone did not increase during treatment, even after increasing the dosage and changing the route of administration (4 micrograms subcutaneously or 8 micrograms intravenously every 2 1/2 hours for 4 weeks with every dosage). The third patient with Kallmann's syndrome and the boy with delayed puberty, both with normal delta LH, presented normal serum testosterone after 3 months of subcutaneous low-dose treatment. The different responses to a GnRH test dose corresponding to the response to pulsatile GnRH therapy probably reflect different degrees of maturation of the pituitary gonadotrophs.