Why Do We Need New Markers for Male Hypogonadism and How Seminal Proteomics Might Solve the Problem?

2020 ◽  
Vol 27 (12) ◽  
pp. 1186-1191
Author(s):  
Giuseppe Grande ◽  
Domenico Milardi ◽  
Silvia Baroni ◽  
Andrea Urbani ◽  
Alfredo Pontecorvi
Keyword(s):  
Serum Testosterone ◽  
Clinical Syndrome ◽  
Testosterone Replacement ◽  
Total Testosterone ◽  
Male Hypogonadism ◽  
Grey Zone ◽  
Testosterone Levels ◽  
Normal Number ◽  
Replacement Treatment

Male hypogonadism is “a clinical syndrome that results from failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic– pituitary–testicular axis”. The diagnostic protocol of male hypogonadism includes accurate medical history, physical exam, as well as hormone assays and instrumental evaluation. Basal hormonal evaluation of serum testosterone, LH, and FSH is important in the evaluation of diseases of the hypothalamus-pituitary-testis axis. Total testosterone levels < 8 nmol/l profoundly suggest the diagnosis of hypogonadism. An inadequate androgen status is moreover possible if the total testosterone levels are 8-12 nmol/L. In this “grey zone” the diagnosis of hypogonadism is debated and the appropriateness for treating these patients with testosterone should be fostered by symptoms, although often non-specific. Up to now, no markers of androgen tissue action can be used in clinical practice. The identification of markers of androgens action might be useful in supporting diagnosis, Testosterone Replacement Treatment (TRT) and clinical follow-up. The aim of this review is to analyze the main findings of recent studies in the field of discovering putative diagnostic markers of male hypogonadism in seminal plasma by proteomic techniques. The identified proteins might represent a “molecular androtest” useful as a seminal fingerprint of male hypogonadism, for the diagnosis of patients with moderate grades of testosterone reduction and in the follow-up of testosterone replacement treatment.

scholarly journals The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes

2007 ◽  
Vol 156 (5) ◽  
pp. 595-602 ◽  
Author(s):  
D Kapoor ◽  
S Clarke ◽  
R Stanworth ◽  
K S Channer ◽  
T H Jones
Keyword(s):  
Waist Circumference ◽  
Treatment Phase ◽  
Testosterone Replacement ◽  
Total Testosterone ◽  
Testosterone Replacement Therapy ◽  
Testosterone Levels ◽  
Reactive Protein ◽  
Replacement Treatment ◽  
Type 2 Diabetic

Objective: Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein (CRP) in type 2 diabetic men. Design: Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men. Patients were treated with testosterone (sustanon 200 mg) or placebo intramuscularly every 2 weeks for 3 months in random order followed by a washout period of 1 month before the alternate treatment phase. Methods: Leptin, adiponectin, resistin, tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and CRP levels were measured before and after each treatment phase. Body mass index (BMI) and waist circumference were also recorded. Results: At baseline, leptin levels significantly correlated with BMI and waist circumference. There was a significant inverse correlation between baseline IL-6 and total testosterone (r=−0.68; P=0.002) and bioavailable testosterone levels (r=−0.73; P=0.007). CRP levels also correlated significantly with total testosterone levels (r=−0.59; P=0.01). Testosterone treatment reduced leptin (−7141.9 ± 1461.8 pg/ml; P=0.0001) and adiponectin levels (−2075.8 ± 852.3 ng/ml; P=0.02). There was a significant reduction in waist circumference. No significant effects of testosterone therapy on resistin, TNF-α, IL-6 or CRP levels were observed. Conclusion: Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men. Moreover, low levels of testosterone in men are associated with pro-inflammatory profile, though testosterone treatment over 3 months had no effect on inflammatory markers.

scholarly journals Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes

2013 ◽  
Vol 169 (6) ◽  
pp. 725-733 ◽  
Author(s):  
Vakkat Muraleedharan ◽  
Hazel Marsh ◽  
Dheeraj Kapoor ◽  
Kevin S Channer ◽  
T Hugh Jones
Keyword(s):  
Type 2 Diabetes ◽  
Untreated Group ◽  
Testosterone Replacement ◽  
Testosterone Deficiency ◽  
Testosterone Levels ◽  
All Cause Mortality ◽  
Low Testosterone

ObjectiveMen with type 2 diabetes are known to have a high prevalence of testosterone deficiency. No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy (TRT). We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone.Research design and methodsA total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.8±1.3 s.d. years. Mortality rates were compared between total testosterone >10.4 nmol/l (300 ng/dl; n=343) and testosterone ≤10.4 nmol/l (n=238). The effect of TRT (as per normal clinical practise: 85.9% testosterone gel and 14.1% intramuscular testosterone undecanoate) was assessed retrospectively within the low testosterone group.ResultsMortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%; P=0.003) when controlled for covariates. In the Cox regression model, multivariate-adjusted hazard ratio (HR) for decreased survival was 2.02 (P=0.009, 95% CI 1.2–3.4). TRT (mean duration 41.6±20.7 months; n=64) was associated with a reduced mortality of 8.4% compared with 19.2% (P=0.002) in the untreated group (n=174). The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 (95% CI 1.3–3.9, P=0.004).ConclusionsLow testosterone levels predict an increase in all-cause mortality during long-term follow-up. Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes.

Correction of Androgen Deficiency in Men with Type 2 Diabetes

2021 ◽  
Vol 16 ◽  
Author(s):  
Volodymyr Pankiv ◽  
Tetyana Yuzvenko ◽  
Nazarii Kobyliak ◽  
Ivan Pankiv
Keyword(s):  
Type 2 Diabetes ◽  
Replacement Therapy ◽  
Testosterone Replacement ◽  
Control Group ◽  
Total Testosterone ◽  
Testosterone Replacement Therapy ◽  
Androgen Deficiency ◽  
Testosterone Undecanoate ◽  
Testosterone Levels

Background: In men with low levels of testosterone in the blood, it is believed that the symptoms can be regarded as an association between testosterone deficiency syndrome and related comorbidities. Aim: to investigate the effectiveness of testosterone therapy in patients with type 2 diabetes (T2D) and androgen deficiency. Materials and methods: Testosterone replacement therapy was carried out in 26 men with T2D and clinically or laboratory-confirmed androgen deficiency. The age of the subjects ranged from 35 to 69 years old. Laboratory studies included determinations of the concentration of the hormones estradiol, luteinizing hormone (LH), and prostate-specific antigen (PSA). The observation period was 9 months. Results: The average level of total blood testosterone in the subjects before treatment was 9.4 mol/l and was likely lower than that of the control group (19.3 ± 1.6 nmol/l). The levels of total testosterone in the subjects ranged from 3.9 nmol/l to 10.7 nmol/l, and hormone levels measuring less than 8.0 nmol/l were observed in only 11 patients. After a course of testosterone replacement therapy, a stabilization in total testosterone levels at the level of reference values (as compared to the start of treatment) was observed in the blood of men with T2D after 9 months of observation and the administration of the fourth injection (16.83 ± 0.75 nmol/l). Conclusion: The use of long-acting injectable testosterone undecanoate leads to normalization of total testosterone levels in the blood of men with T2D and androgen deficiency, and LH levels in these patients are unlikely to change.

Decrease in serum testosterone levels after short-term occupational exposure to diisononyl phthalate in male workers

2020 ◽  
Vol 77 (4) ◽  
pp. 214-222 ◽  
Author(s):  
Jean-Bernard Henrotin ◽  
Eva Feigerlova ◽  
Alain Robert ◽  
Mathieu Dziurla ◽  
Manuela Burgart ◽  
...  
Keyword(s):  
Occupational Exposure ◽  
Serum Testosterone ◽  
Total Serum ◽  
Total Testosterone ◽  
Type I ◽  
Short Term ◽  
Testosterone Levels ◽  
Short Term Exposure ◽  
Diisononyl Phthalate ◽  
Male Workers

ObjectiveThe objective of the study was to examine the effects of occupational exposure to diisononyl phthalate (DINP) on serum testosterone levels in male workers.MethodsFrom 2015 to 2018, 97 male workers were recruited from six French factories in the plastics industry. In a short longitudinal study, changes over 3 days in the level of total or free serum testosterone and DINP exposure were measured. DINP exposure was measured by urinary biomonitoring: mono-4-methyl-7-oxo-octyl phthalate (OXO-MINP), mono-4-methyl-7-hydroxy-octyl phthalate (OH-MINP) and mono-4-methyl-7-carboxyheptylphthalate (CX-MINP). We further analysed changes in follicle-stimulating hormone, luteinising hormone, total testosterone to oestradiol ratio and two bone turnover markers (procollagen-type-I-N propeptide, C terminal cross-linking telopeptide of type I collagen), and erectile dysfunction via standardised questionnaires (International Index of Erectile Function, Androgen Deficiency in Aging Males). Linear mixed models were used with the variables ‘age’ and ‘abdominal diameter’ included as confounder.ResultsIncreased urinary OXO-MINP was associated with a significant decrease in total serum testosterone concentrations, but only for workers who exhibited the smallest variations and lowest exposures (p=0.002). The same pattern was observed for CX-MINP but was not significant; no association with OH-MINP was detectable. More self-reported erectile problems were found in workers exposed directly to DINP at the workstation (p=0.01). No changes were observed for the other biological parameters.ConclusionsShort-term exposure to DINP is associated with a decrease in total serum testosterone levels in male workers. Our results suggest that DINP could present weak antiandrogenic properties in humans, but these need to be confirmed by other studies.

The Majority of Myeloma Patients Are Hypogonadal but This Is Not Associated with High Risk Cytogenetics

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5329-5329
Author(s):  
Beau Snoad ◽  
Samantha Hudzik ◽  
Douglas W Sborov ◽  
Nita Williams ◽  
Desiree Jones ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Serum Testosterone ◽  
Clinic Visit ◽  
Total Testosterone ◽  
Testosterone Levels ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Introduction: Hypogonadism, i.e. low total testosterone, is present in approximately a quarter of men older than 70 years (Harman SM et al, J. Clin Endo & Met, 2001, PMID 11158037 and Wu FCW et al, J Clin Endo & M et, 2008, PMID 18270261). Myeloma patients are known to suffer from fatigue and decreased functional performance, mood disturbances, and anemia; similar trends have been found in people with hypogonadism. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558). We hypothesized that total testosterone levels will be associated with overall survival from the time of diagnosis, presence of 1q21 amplification by CD138-selected FISH, anemia, and anti-depressant use. Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total testosterone was measured at the time of the initial clinic visit to the myeloma group at Ohio State. Less than 325 ng/dL was defined as the hypogonadal range, and testosterone was divided into <100 (group 1), 100-240 (group 2), 240-325 (group 3), and greater than 325 ng/dL (group 4), although normal testosterone decreases with age. Female patient testosterone levels were also analyzed and divided into <10 (group 1), 10-60 ng/dL (group 2), and >60 ng/dL (group 3). A retrospective chart review was initiated to review all myeloma patients with a serum testosterone drawn at the time of their initial clinic visit to OSU. Results: Among 418 male MM patients, median age was 65 y.o. (range 24-95), 86% were Caucasian and 14% African-American, and the distribution of ISS stage was 32% stage 1, 22% stage 2, and 19% stage 3 with 28% missing staging data. Cytogenetic data was missing from 28% of patients. Out of 418 male MM patients, 29 (7%) had serum testosterone <100, 202 (48%) with testosterone 100-240, 79 (19%) with testosterone 241-325, and 108 (26%) > 325 ng/dL. Out of 172 female MM patients, 44 (26%) had an undetectable serum testosterone, 120 (70%) with testosterone 10-60, and 8 (5%) with testosterone > 60. Among male MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum testosterone including all 4 groups demonstrated no significant differences (p=0.917) with only 80 events. Among 275 male MM patients with cytogenetic information available, there was no correlation between presence of 1q21 trisomies or tetrasomies and overall survival (r=0.0714, p=0.238). There was a strong and expected correlation between testosterone and BMI (r=0.14, p=0.00468). Among 161 total female MM patients, log-rank analysis with serum testosterone including all 3 groups also demonstrated no differences (p=0.416) with only 29 events in total. Among 101 females with cytogenetic information, there was also no correlation with 1q21 amplification (r=0.0895, p=0.373). Conclusion: The majority of male MM patients (74%) have secondary hypogonadism and approximately half have total testosterone levels <240 ng/dL. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with anemia and medication use (specifically opiates and anti-depressants) will also be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

scholarly journals Serum testosterone levels in male hypogonadism: Why and when to check-A review

2017 ◽  
Vol 71 (11) ◽  
pp. e12995 ◽  
Author(s):  
Mark Livingston ◽  
Anura Kalansooriya ◽  
Andrew J. Hartland ◽  
Sudarshan Ramachandran ◽  
Adrian Heald
Keyword(s):  
Serum Testosterone ◽  
Male Hypogonadism ◽  
Testosterone Levels

Substitution therapy of hypogonadal men with transdermal testosterone over one year

1988 ◽  
Vol 118 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Monika Bals-Pratsch ◽  
Klaus Langer ◽  
Virgil A. Place ◽  
Eberhard Nieschlag
Keyword(s):  
Clinical Chemistry ◽  
Day Treatment ◽  
Treatment Phase ◽  
Serum Testosterone ◽  
Male Hypogonadism ◽  
Substitution Therapy ◽  
Entire Treatment Period ◽  
Testosterone Levels ◽  
Physiological Range ◽  
Testosterone Substitution

Abstract. Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range. Recently, a transdermal therapeutic system (TTS) for the delivery of testosterone was developed which, when applied to the scrotum, provides smooth serum testosterone levels. Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day. In all patients serum testosterone and dihydrotestosterone (DHT) determined 3–5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period. The DHT/testosterone ratio remained constant. In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals. In these patients serum testosterone levels in the physiological range were seen during the entire observation period, whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase. All patients in the 14-month treatment study were clinically well substituted and responded with good compliance. Clinical chemistry showed no abnormalities during treatment. Thus, the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism.

scholarly journals Endogenous testosterone to prostate-specific antigen relationship in men without prostatic diseases: a 10-year retrospective study

2018 ◽  
Vol 5 (4) ◽  
pp. 1186
Author(s):  
Promise N. Wichendu ◽  
Ehimen P. Odum ◽  
Collins Amadi ◽  
Benjamin M. Aleme
Keyword(s):  
Retrospective Study ◽  
Specific Antigen ◽  
Serum Testosterone ◽  
Tertiary Hospital ◽  
Total Testosterone ◽  
Hospital Data ◽  
Testosterone Levels ◽  
Prostatic Diseases ◽  
Total Psa ◽  
Prostate Diseases

Background: The relationship between endogenous testosterone and PSA in men without prostatic diseases is controversial. Hence, this study was designed to investigate this relationship among healthy Nigerian men.Methods: A retrospective study of serum total testosterone (TT) and total PSA records of 1066 prostate disease-free men was undertaken in a Nigerian tertiary Hospital. Data on age, serum testosterone, and PSA from 1st January 2007 to December 2016 was abstracted and analysed.Results: The mean age, serum PSA, and serum total testosterone levels among study cohorts are 58.40±12.24 years, 3.0±2.24 µg/l, and 15.5±0.53 nmol/l respectively. There was an inverse relationship between serum PSA and testosterone levels with age. Subjects with high-risk PSA level (PSA>4.0 µg/l) had statistically significant higher PSA (p<0.001) and TT (p<0.001) values compared to the low-risk PSA level group. Subjects in the eugonadism group had higher PSA levels than those in the hypogonadism group (eugonadism 3.90µg/l±2.22 versus hypogonadism 2.18µg/l±2.30; p=0.012). Age correlated positively with PSA (p<0.001), but negatively with TT (p<0.001) while PSA correlated positively with TT (p<0.001).Conclusions: The findings of this study suggest an association between endogenous TT and PSA among healthy men without prostatic diseases and augment the evidence that serum TT maybe linked to prostate diseases. Clinical decisions regarding PSA should factor the levels of endogenous TT to enhance clinical judgments.

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