Low Testosterone Concentrations Research Articles

A Review of Sleep Disturbance and Sexual Function: the Effect of Sleep Apnea on Erectile Function

We sought to produce a review of studies that examine how lack of sleep can modulate male sexual function, with a particular focus on recent findings about sleep apnea and erectile dysfunction (ED) and to examine novel therapeutic approaches proposed in the literature to provide literature on novel therapeutic approaches. Studies have shown that continuous positive airway pressure (CPAP), ??? used as standard therapy for obstructive sleep apnea (OSA) ??? is associated with a clinically significant improvement in the following sexual issues: erectile function, total erectile events, night penis stiffness, overall sexual satisfaction. Recent research has indicated that insufficient sleep, interrupted sleep, and sleep disorders affect sexual function. Sleep is fundamental for quality of life, but with the increasing pressures exerted by modern life there is a tendency for a reduction in sleep time. The resulting sleep debt can have a significant impact on health, including on sexual health. Penile erection is essential for reproductive success and depends on the integration of psychological, vascular, endocrine, neurological, and myogenic mechanisms, triggered by a reflexive response or by psychogenic stimuli of central origin. During sleep, erections can occur through impulses sent through the descending pathway, via spinal medulla that activate the penile system reflex in healthy males from birth until old age, independent of the dream content. OSA is associated with an increased risk of ED and/or other urological disorders. Patients with severe OSA have low testosterone concentrations and a higher prevalence of ED.

Male Equivalent Polycystic Ovarian Syndrome: Hormonal, Metabolic, and Clinical Aspects.

Recent studies identified the presence of a male polycystic ovarian syndrome (PCOS), which mainly affects men whose female relatives are afflicted with PCOS, caused by genes responsible for the susceptibility of this syndrome in women. Similar hormonal, metabolic, and clinical alterations occurring in PCOS women have also been reported in their male relatives, suggesting a association between the male and female forms of the syndrome. Although the remarkable clinical manifestation of the male equivalent PCOS is diagnosed by the early-onset androgenetic alopecia, characterized by hair recession, pronounced hypertrichosis, insulin resistance, biochemical and hormonal abnormalities, the hormonal/metabolic profile is still controversial. Men affected by early-onset androgenetic alopecia (AGA) are at risk of developing hyperinsulinemia, insulin-resistance, dyslipidaemia, and cardiovascular diseases. However, there is no consensus on the association of male equivalent PCOS with hypertension and obesity. Moreover, reduced levels of sex hormone-binding globulin have been detected in these male patients, accompanied by increased free androgens. Conversely, literature reported lower concentrations of testosterone in male equivalent PCOS when compared with the normal range, indicating a crucial role for the conversion of cortical androgens. Finally, further studies are warranted to investigate a possible link among AGA, metabolic/hormonal alterations, and acne. Our study assessed the hormo- nal, metabolic and clinical aspects of male equivalent PCOS syndrome reported in the literature to evaluate similar and divergent elements involved in the female version of the syndrome.

Low dose prenatal testosterone exposure decreases the corticosterone response to stress in adult male, but not female, mice

Gonadal steroid hormones affect the organization of the brain during sensitive periods of development, resulting in sex differences in the neuroendocrine function and behaviour of the offspring. Although alterations in developmental testosterone exposure have been hypothesized to play a role in male-biased neurodevelopmental disorders, the underlying mechanisms remain unknown. The present study investigated the hypothesis that early prenatal exposure to low concentrations of testosterone might affect the control of stress responses in later life. Pregnant CD1 mice were treated with 10 μg of testosterone propionate or sesame oil control on embryonic days 12, 14, and 16. Effects on development were assessed by measuring litter size, composition and weight, first appearance of hair, eye and ear opening, and adult body weight. Reproductive development was assessed by measuring testosterone levels in neonatal and adult males, gonad weights in both sexes and reproductive cyclicity in females. The function of the hypothalamic-pituitary-adrenal axis was determined by measuring corticosterone in hair samples from juvenile animals, as well as in plasma following restraint stress in adulthood. Prenatal testosterone treatment had no significant effects on any of the overall developmental or reproductive endpoints assessed. However, in adulthood, corticosterone responses to restraint stress were reduced in the male but not the female offspring, with no significant effect on basal corticosterone levels in either sex. Thus, a small prenatal increase in maternal testosterone may be sufficient to produce a lasting sex-specific alteration in the sensitivity of the male HPA axis to stress.

Hormone-related diseases and prostate cancer: An English national record linkage study.

Insulin‐like growth factor‐I (IGF‐I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF‐I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow‐up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadal‐associated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09–1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92–2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37–0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35–0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF‐I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.

Is testosterone replacement an effective treatment of secondary premature ejaculation?

There are very few studies that have evaluated premature ejaculation characteristics in regard to subtypes. Additionally, to our knowledge, there are no studies which have explored testosterone replacement therapy in secondary premature ejaculation patients with testosterone deficiency. Therefore, our aims were as follows: (a) to determine the characteristics of patients with premature ejaculation in regard to the four subtypes of premature ejaculation and (b) to determine the efficacy of testosterone replacement therapy in the treatment of testosterone-deficient patients with secondary premature ejaculation. Patients who applied to our clinic from May 2010 to August 2018 with premature ejaculation were included in this study. The mean age of the study group was 36.42 (min-max: 24-52) years. Those with secondary premature ejaculation were found to have significantly lower testosterone concentration compared to the other groups. Shortest mean intravaginal ejaculation latency time and lowest International Index of Erectile Function-5 score were found among those with secondary PE. In regard to treatment results, recipients of testosterone replacement demonstrated a 4.8-fold increase in mean intravaginal ejaculation latency time, while dapoxetine recipients had a 1.8-fold increase. Our findings demonstrate that testosterone replacement may be a promising treatment for those with secondary PE in the presence of testosterone deficiency.

In Adult Rats With Polycystic Ovarian Syndrome, Unilateral or Bilateral Vagotomy Modifies the Noradrenergic Concentration in the Ovaries and the Celiac Superior Mesenteric Ganglia in Different Ways.

In rats with polycystic ovarian syndrome (PCOS) induced by estradiol valerate (EV) injection, sectioning of the vagus nerve in the juvenile stage restores ovulatory function, suggesting that the vagus nerve stimulates the onset and development of PCOS. We analyzed whether in adult rats, the role played by the vagus nerve in PCOS development is associated with the nerve’s regulation of noradrenergic activity in the celiac superior mesenteric ganglion (CSMG). Ten-day-old rats were injected with corn oil [vehicle (Vh)] or EV (2 mg). At 76 days of age, rats injected with Vh or EV were subjected to sham surgery or the sectioning of one or both vagus nerves (vagotomy). The animals were sacrificed at 80–82 days of age at vaginal estrus smear. Compared to Vh-treated animals, EV-induced PCOS rats showed a lack of ovulation, the presence of follicular cysts, and a high concentration of testosterone, without changes in noradrenaline concentrations in the CSMG or ovaries. In PCOS rats, sham surgery lowered serum testosterone and noradrenaline concentrations in the CSMG but did not restore ovulation. In animals with PCOS, vagotomy lowered testosterone concentrations to a larger degree than in sham-surgery animals. The ovaries of rats with PCOS and vagotomy showed fresh corpora lutea, indicating ovulation. In EV-treated rats with unilateral vagotomy, the concentration of noradrenaline in the CSMG was similar to that in rats with PCOS and sham surgery, which did not ovulate, while in the ovaries of PCOS rats with left or bilateral vagotomy, the noradrenaline concentration was lower than that in sham-surgery-treated animals. Our results suggest that the vagus nerve regulates PCOS development through a different mechanism than the increase in the noradrenergic activity in the CSMG; however, in ovaries, the restoration of ovulation is associated with a decrease in ovarian noradrenaline.

Testosterone Treatment in Infants With 47,XXY: Effects on Body Composition.

ContextBoys with XXY have greater adiposity and a higher risk of cardiovascular disease. Infants with XXY have lower testosterone concentrations than typical boys, but no studies have evaluated adiposity in infants with XXY or the physiologic effects of giving testosterone replacement.ObjectiveTo determine the effect of testosterone on body composition in infants with XXY.DesignProspective, randomized trial.SettingTertiary care pediatric referral center.Participants20 infants 6 to 15 weeks of age with 47,XXY.InterventionTestosterone cypionate 25 mg intramuscularly monthly for three doses vs no treatment.Main Outcome MeasuresDifference in change in adiposity (percent fat mass z scores); other body composition measures, penile length, and safety outcomes between treated and untreated infants; and comparison with typical infants.ResultsThe increase in percent fat mass (%FM) z scores was greater in the untreated group than in the treated group (+0.92 ± 0.62 vs −0.12 ± 0.65, P = 0.004). Increases in secondary outcomes were greater in the testosterone-treated group for total mass, fat-free mass, length z score, stretched penile length, and growth velocity (P < 0.002 for all). At 5 months of age, adiposity in untreated infants with XXY was 26.7% compared with 23.2% in healthy male infants of the same age (P = 0.0037); there was no difference in %FM between the treated XXY boys and controls. Reported side effects were minimal and self-limited; no serious adverse events occurred.ConclusionsAdiposity of untreated infants was 15% greater than that of male controls by 5 months of age. Testosterone treatment for infants with XXY resulted in positive changes in body composition.

Clinical characterization of men with long QT syndrome and torsades de pointes associated with hypogonadism: A review and pharmacovigilance study

Long QT syndrome (LQTS) can cause the potentially fatal ventricular tachycardia torsades de pointes (TdP). QT interval corrected for heart rate (QTc) is shorter in men than in women, with testosterone contributing to shorten QTc. We recently described male hypogonadism as a reversible risk factor for acquired LQTS and TdP, but the clinical characteristics of such patients have not been characterized. To describe the clinical characteristics of men with acquired LQTS or TdP associated with hypogonadism caused by endocrine conditions or androgen deprivation therapy (ADT), and to evaluate the relationship between testosterone concentrations and electrocardiographic changes. We searched MEDLINE (to 04 January 2019) and the French pharmacovigilance database (to 09 August 2018) to identify male cases of acquired LQTS and TdP associated with endocrine hypogonadism or ADT; their narratives were gathered from reporting collaborators. We identified seven cases of TdP (one fatal) with endocrine hypogonadism, abnormally long QTc and morphologically abnormal T-wave notches. After reversion of low testosterone concentrations in the surviving patients (N=6), QTc shortened, T-wave morphology normalized and there was no TdP recurrence. Among these cases, none had mutation in the LQTS genes, three men required testosterone and three had reversible hypogonadism after resolution of a concurrent acute severe illness. We found an additional 27 reports of men with LQTS (N=6), TdP (N=9; 2/9 fatal) or sudden death (N=12; 10/12 fatal) suspected to be induced or favoured by ADT (24/27 for prostate cancer). Generally, after ADT withdrawal, QTc shortened and no TdP recurred. We propose seeking for hypogonadism caused by endocrine conditions or ADT in men presenting with TdP. Caution is warranted when ADT is used in situations at risk of TdP. Testosterone may be useful to treat or prevent TdP.

37-Year-Old Man With Fatigue and Erectile Dysfunction

37-Year-Old Man With Fatigue and Erectile Dysfunction

Predictive value of low testosterone concentrations regarding coronary heart disease and mortality in men and women - evidence from the FINRISK97 study.

IntroductionThe relevance of low testosterone concentrations for incident coronary heart disease (CHD) and mortality has been discussed in various studies. Here, we evaluate the predictive value of low baseline testosterone levels in a large population‐based cohort.MethodsWe measured the serum levels of testosterone in 7671 subjects (3710 male, 3961 female) of the population‐based FINRISK97 study.ResultsThe median follow‐up (FU) was 13.8 years. During the FU, a total of 779 deaths from any cause, and 395 incident CHD events were recorded. The age‐adjusted baseline testosterone levels were similar in subjects suffering incident events during FU and those without incident events during FU (men: 15.80 vs. 17.01 nmol L−1; P = 0.69, women: 1.14 vs. 1.15 nmol L−1; P = 0.92). Weak correlations of testosterone levels were found with smoking (R = 0.09; P < 0.001), HDL cholesterol levels (R = 0.22, P < 0.001), systolic blood pressure (R = −0.05; P = 0.011), BMI (R = −0.23; P < 0.001) and waist‐hip‐ratio (R = −0.21; P < 0.001) in men, and with eGFR (R = −0.05; P = 0.009) in women. Kaplan–Meier analyses did not reveal a positive association of testosterone levels with incident CHD or mortality. Accordingly, also in Cox regression analyses, testosterone levels were not predictive for incident CHD or mortality – neither in men (HR 1.02 [95%CI: 0.70–1.51]; P = 0.79 for lowest versus highest quarter regarding CHD and HR 1.06 [95%CI: 0.80–1.39]; P = 0.67 regarding mortality), nor in women (HR 1.13 [95%CI: 0.69–1.85]; P = 0.56 for lowest versus highest quarter regarding CHD and HR 0.99 [95%CI: 0.71–1.39]; P = 0.80 regarding mortality).ConclusionsLow levels of testosterone are not predictive regarding future CHD or mortality – neither in men, nor in women.

Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy.

BackgroundOestradiol with or without an anti-androgen (cyproterone acetate or spironolactone) is commonly prescribed in transfeminine individuals who have not had orchidectomy; however, there is no evidence to guide optimal treatment choice.ObjectiveWe aimed to compare add-on cyproterone acetate versus spironolactone in lowering endogenous testosterone concentrations in transfeminine individuals.DesignRetrospective cross-sectional study.MethodsWe analysed 114 transfeminine individuals who had been on oestradiol therapy for >6 months in two gender clinics in Melbourne, Australia. Total testosterone concentrations were compared between three groups; oestradiol alone (n = 21), oestradiol plus cyproterone acetate (n = 21) and oestradiol plus spironolactone (n = 38). Secondary outcomes included serum oestradiol concentration, oestradiol valerate dose, blood pressure, serum potassium, urea and creatinine.ResultsMedian age was 27.0 years (22.5–45.1) and median duration of hormone therapy was 1.5 years (0.9–2.6), which was not different between groups. On univariate analysis, the cyproterone group had significantly lower total testosterone concentrations (0.8 nmol/L (0.6–1.20)) compared with the spironolactone group (2.0 nmol/L (0.9–9.4), P = 0.037) and oestradiol alone group (10.5 nmol/L (4.9–17.2), P < 0.001), which remained significant (P = 0.005) after adjustments for oestradiol concentration, dose and age. Serum urea was higher in the spironolactone group compared with the cyproterone group. No differences were observed in total daily oestradiol dose, blood pressure, serum oestradiol, potassium or creatinine.ConclusionsThe cyproterone group achieved serum total testosterone concentrations in the female reference range. As spironolactone may cause feminisation without inhibition of steroidogenesis, it is unclear which anti-androgen is more effective at feminisation. Further prospective studies are required.

A robust LC-MS/MS assay with online cleanup for measurement of serum testosterone.

Accurate measurement of low levels of testosterone is critical for diagnosis and treatment of androgen disorders. The very low concentrations of testosterone in children, females, and males with androgen suppression therapies necessitate the use of mass spectrometry-based methods. We aimed to develop a liquid chromatography with tandem mass spectrometry method with simplified sample preparation and online solid-phase extraction cleanup to achieve enhanced precision, accuracy, robustness, and cost-effectiveness. The assay was linear from 10 to 20 000pg/mL with an analytical recovery of 93-104%. The total coefficient of variation was 2.5, 1.9, and 1.7% at concentration levels of 348, 5432, and 10 848pg/mL, respectively. No significant carryover was observed from samples with concentrations up to 20 000pg/mL. No significant interference was observed from androstenedione, dehydroepiandrosterone, epi-testosterone, and estriol. Comparison with CDC Hormone Standardization program (HoSt) reference samples with defined values (n=40) showed a Deming regression slope of 0.963, intercept of 28.06pg/mL, standard error of estimate was 66.9, a correlation coefficient of 0.9996, and a mean bias of -0.6%. The method met the accuracy criteria by the CDC HoSt program. In addition, we achieved >12 000 injections on a single analytical column without significant performance deterioration due to the specific online solid-phase extraction settings.

Effects of long-term release GnRH agonist “deslorelin” on testicular HSP expression, accessory sex glands and testicular functions in adult male rats

The objective of the present was to determine the effect of long-term release GnRH agonists “deslorelin” on suppression and restoration of testicular and accessory sex glands functions, and expression of HSP in testes of adult male rats. A group of twenty-eight male rats and fifty-six female rats were kept for eleven months. The male rats were subdivided into treatment (n = 18; deslorelin, an analogue of GnRH, 4.7 mg, S.C; six months) and control (n = 10; untreated), and the adult female rats were introduced with either treatment or control male rats at the 2nd, 6th and 11th months post implant insertion. At 6th month of deslorelin implants insertion, six male rats from treatment and five rats from control group were sacrificed. The remaining (twelve treatment and five control) male rats were sacrificed at 11 months. The testicular dimension were measured monthly in both treatment and control rats. The blood samples were collected for testosterone and HSP70 antibody, whereas, the testes and accessory glands were isolated for histological examination at each sacrificial time. The results showed that testicular dimension were significantly lesser in treatment group until 9 months post treatment. HSP70 protein expression was negligible at 6 months in treatment group but its intensity increased in spermatids 11 months of treatment similar to control group. Significantly lower testosterone concentrations with poor semen quality, and smaller litter size were observed in treatment group. The histological picture of accessory sex glands and seminiferous tubules shown a variable integrity in treatment group than control at 6 months implant insertion. In conclusion, the subcutaneous application of 4.7 mg of the GnRH-analogue deslorelin represents a practicable, like in the female rats, method to suppress testicular, accessory sex glands functions, testicular HSP expression and fertility in male rats. Moreover, the suppressive effects of deslorelin, continued until 11th months after removal of the implant.

The association between serum total testosterone and progression of hyperglycemia: a 15-year prospective cohort study.

The association between low testosterone concentration and increased risk of hyperglycemia in men has been demonstrated in observational and interventional studies. However, considering a variety of confounding factors, limited population-based studies have so far been conducted. Also, no information is available regarding the effect of testosterone on progressive development of dysglycemia. To examine the effect of total testosterone on development of pre-diabetes/diabetes in normoglycemic middle-aged and older men. Data were obtained from the Tehran Lipid and Glucose Study, a community-based prospective cohort of an Iranian population. Analyses were conducted on 903 normoglycemic eligible men aged 30-70years. An illness-death model was applied to estimate the probabilities of three transitional phases of normoglycemia→diabetes, normoglycemia→pre-diabetes, and pre-diabetes→diabetes. Over a median follow-up of 12years, 0.9% individuals developed diabetes. Per unit increase (ng/mL) in testosterone concentration, the transition rate from normoglycemia to pre-diabetes decreased by 6% [hazard ratios (HRs): 0.94 (95% confidence interval (CI): 0.90, 0.99)]. However, no effect for testosterone on the progression of diabetes from normoglycemia or pre-diabetes was observed [HRs: 0.79 (95% CI: 0.44, 1.41) and 0.98 (95% CI: 0.84, 1.16), respectively]. High body mass index was a strong predictor of hyperglycemia within all transitions. Independent of major confounding factors, low testosterone was associated with normoglycemia progression to pre-diabetes, but not with pre-diabetes to diabetes, which might indirectly highlight the stronger impact of other risk factors after occurrence of pre-diabetes. Low testosterone concentrations in men are associated with progression from normoglycemia to pre-diabetes, but not from pre-diabetes to diabetes.

Clinical Significance of Low Blood Testosterone Concentration in Men as a Cardiovascular Risk Factor From the Perspective of Blood Rheology.

BackgroundRecent clinical studies have indicated the importance of low blood testosterone concentration or whole blood passage time (WBPT) which reflects blood rheology as a cardiovascular risk factor. On the contrary, there are no reports regarding the association of blood testosterone concentrations and WBPT. This cross-sectional study aimed to elucidate the clinical significance of low blood testosterone concentration in men as a cardiovascular risk factor from the perspective of blood rheology using WBPT.MethodsIn total, 382 male patients with traditional cardiovascular risk factor and no history of cardiovascular disease (age (mean ± standard deviation (SD)), 64 ± 10 years) were enrolled. Serum total testosterone concentration (T-T) was measured as a marker of testosterone level in vivo, and WBPT was also measured using microchannel array flow analyzer as a commercial device. The relationship between T-T and WBPT was evaluated.ResultsThere was a significantly negative correlation between T-T and WBPT (r = -0.45; P < 0.001). Furthermore, multiple regression analysis revealed that T-T (β = -0.25; P < 0.001) could be selected as an independent variable when WBPT was used as a subordinate factor. According to receiver operating characteristic curve analysis and the result of the previous report that determined WBPT of > 72.4 s as a risk for incidence of primary cardiovascular disease, T-T of < 551.4 ng/dL is the optimal cut-off point for discriminating high WBPT.ConclusionsThe study results showed that T-T is independently and inversely associated with WBPT in male patients with traditional cardiovascular risk factor and no history of cardiovascular disease. In addition, this study suggests that the incidence of primary cardiovascular events can be prevented by maintaining T-T at approximately ≥ 550 ng/dL from the perspective of blood rheology.

Spojenie akromegálie a Klinefelterovho syndrómu u jedného pacienta

Acromegaly is a rare disorder usually caused by a benign tumour of the pituitary gland. Long-term presence of elevated growth hormone (GH) and insulin like growth factor 1 (IGF1) levels accompanying this disease is associated with complications such as cardiomyopathy, diabetes mellitus, sleep apnoea and arthropathy. Incidence of acromegaly is 3-4 patients per million per year. Klinefelter syndrome (KS) is the most common sex chromosome disorder occuring in about 1/500 live male births. Common physical features include particularly small testes, among other symptoms are tall stature, reduced muscle tone, delayed pubertal development, lack of secondary male sex characteristics and gynecomastia. We present a 32-year-old man suffering from both acromegaly and 47, XXY Klinefelter syndrome. The patient with typical acromegalic features. Laboratory tests revealed high level of GH which was not suppressed after glucose administration, high level of IGF1, low testosterone concentration with high concentation of luteinizing hormone and follicle stimulating hormone. A magnetic resonance imaging scan revealed a 25 × 18 × 18 mm macroadenoma involving the pituitary gland. A diagnosis of acromegaly was established. After this examination trans-sphenoidal resection was performed. Histopathologic and immunohistochemical findings revealed growth hormoneproducing pituitary adenoma. The presence of infertility with clinical features such as small testes, lack of secondary male sex characteristics and laboratory findings revealed hypergonadotropic hypogonadism that could not be explained by the diagnosis of acromegaly. A chromosomal karyotyping revealed a 47, XXY, confirming the diagnosis of KS. Testosterone replacement therapy wasn´t begun because of patient disagreement Postoperatively elevated plasma concentration of GH and IGF1 levels persist. Treatment by somatostatin analogues (lanreotid) was initiated at dose 120 mg every 28 days. Control magnetic resonance imaging of the sella demonstrated a residue of pituary adenoma size 14 × 14 × 7 mm. The patient is currently undergoing endoscopic revision of the residue. acromegaly - growth hormone - IGF1 - Klinefelter syndrome - testosterone.

Is it Time to Test the Effect of Weight Loss on Testosterone?

Testosterone is a sex-steroid hormone, synthesized in the testes, with biologic effects on numerous tissues. Low circulating concentrations, seen with testicular or hypothalamic–pituitary defects, are often associated with decreased sexual function, muscle mass, and poor quality of life, along with a risk of osteoporosis. Primary testicular failure can be due to testicular trauma, chemotherapy, radiation therapy, or chromosomal abnormalities, although secondary causes, also termed centrally mediated hypogonadism, are associated with pituitary tumors or hypothalamic disease. In addition to these well-known etiologies, there is an increasing appreciation that hypogonadism can be the result of aging, medications, and chronic diseases. A physiological decrease in testosterone concentrations has been well documented after the fourth or fifth decade of life and has been postulated to result from a decline in both testicular and hypothalamic–pituitary function. In scenarios in which the patient has a clear pathophysiologic mechanism for the hypogonadism, treatment with testosterone is nearly always recommended to alleviate symptoms of hypogonadism and maintain secondary sexual characteristics (1). Men on replacement therapy should be monitored for polycythemia, falls in serum high-density lipoprotein, worsening of sleep apnea, and increase in prostate-specific antigen concentrations (2, 3). Because long-term evidence of safety with supplementation is yet to be established, testosterone therapy is not routinely recommended in older men or in men with an unclear underlying etiology for their low testosterone concentrations. Because low serum testosterone is commonly observed in chronic illness, there may be less invasive ways to naturally increase serum concentrations. This circumstance creates an opportunity to explore other intervention options that could favorably increase the endogenous testosterone production in the absence of potential side effects. The interpretation of laboratory tests can be confusing in men as they age and become more obese because both factors modulate sex by hormone-binding globulin (SHBG)3 concentrations. Obese …

Clinical Impact of Blood Testosterone Concentration on Cardio-Ankle Vascular Index in Female Patients With Type 2 Diabetes Mellitus.

BackgroundInformation regarding testosterone as a significant risk factor of cardiovascular disease (CVD) in female patients with type 2 diabetes mellitus (DM) is limited. However, some clinical studies reported the importance of cardio-ankle vascular index (CAVI) as a novel physiological marker of arterial function in type 2 DM. This cross-sectional study aimed to elucidate the clinical effects of blood testosterone concentration on CAVI in female patients with type 2 DM.MethodsA total of 238 postmenopausal patients including 97 with a history of CVD with type 2 DM (age (mean ± standard deviation (SD)), 73 ± 9 years) were enrolled. CAVI was measured according to the standard technique, and serum total testosterone concentration (T-T) was also measured as a testosterone level marker in vivo. The relationship between CAVI and T-T was evaluated.ResultsCAVI is significantly higher (CVD vs. non-CVD: 10.2 ± 1.2 vs. 9.2 ± 1.0, P < 0.001), and log-T-T significantly lower (CVD vs. non-CVD: 1.2 ± 0.2 ng/dL vs. 1.5 ± 0.2 ng/dL, P < 0.001) in patients with CVD than those without CVD. CAVI was significantly negatively correlated with log-T-T (r = -0.41; P < 0.001). Furthermore, multiple regression analysis indicated that CVD (β = 0.23; P < 0.001) and log-T-T (β = -0.18; P < 0.01) were selected as independent subordinate variables for CAVI.ConclusionsThis study showed that T-T was independently inversely associated with CAVI, indicating that low testosterone concentration is a considerable risk factor for the progression of arterial dysfunction in female patients with type 2 DM.

Different functions of biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (Ap3b1) genes on spermatogenesis and male fertility.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. Pale ear (ep) and pearl (pe) mice, bearing mutations in the biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (Ap3b1) genes respectively, are mouse models of human HPS Type 1 (HPS1) and Type 2 (HPS2) respectively. In the present study we investigated and compared the reduced fertilities of ep and pe male mice. Both ep and pe males exhibited lower abilities to impregnate C57BL/6J (B6) females, and B6 females mated with ep males produced smaller litters than those mated with pe males. Delayed testis development, reduced sperm count and lower testosterone concentrations were observed in the pe but not ep male mice. However, the reduction in sperm motility was greater in ep than pe males, likely due to the mitochondrial and fibrous sheath abnormalities observed by electron microscopy in the sperm tails of ep males. Together, the results indicate that the Hps1 and Ap3b1 genes play distinct roles in male reproductive system development and spermatogenesis in mice, even though ep and pe males share common phenotypes, including reduced lysosomes in Sertoli cells and dislocated Zn2+ in sperm heads.

Extending the interval between second vaccination and slaughter: II. Changes in the reproductive capacity of immunocastrated ram lambs

Immunocastration improves the welfare of castrated commercial slaughter lambs; however, the time-point at which this technique influences semen quality and sperm production has not yet been established for various vaccination schedules. Furthermore, the effect of extended intervals between second vaccination and slaughter needs to be investigated regarding continued testosterone suppression in immunocastrated lambs. The effect of extending the interval between second immunocastration vaccination and slaughter from four to six weeks on the reproductive capacity of Dohne Merino lambs was examined. A total of 40 Dohne Merino lambs were stratified according to initial weight (45.4±3.68 kg) and randomly assigned to four treatments that included intact control rams (R), Burdizzo-castrated lambs (B) and lambs immunocastrated with either four (ICS4) or six (ICS6) weeks between second vaccination and slaughter. Blood and semen samples were collected throughout the study period to determine serum testosterone concentrations, evaluate semen quality and assess sperm viability. Semen samples from R showed improvement over the trial. Throughout the collection period, B lambs had low serum testosterone concentrations, poor sperm motility and sperm viability, as expected. However, a slight increase in the percentage of live sperm in semen samples from B lambs towards the end of the collection period indicated poor success rates of the technique in some lambs. Burdizzo-castration also caused testes tissue necrosis and abscessing, indicating physiological stress. Semen appearance scores varied for both immunocastrated treatments, but the mass motility scores decreased over time. The ICS6 lambs showed a consistent and continuous decline in serum testosterone concentrations and sperm viability, with an increased percentage of dead abnormal sperm in the semen samples at the end of the study. The ICS4 treatment was successful in interrupting serum testosterone production and reducing semen quality; however, not as consistently as the ICS6 treatment. Primary immunocastration vaccination influenced serum testosterone concentrations but consistently low levels were only realised for both treatments after secondary vaccination. Although all castration treatments influenced testes size and colour, the six-week vaccination-to-slaughter interval caused a greater decrease in testes cut surface L* (lightness) colour values and in seminiferous tubule circumference. Extending the interval between second immunocastration vaccination and slaughter resulted in a more consistent and reliable influence on reproductive capacity of immunocastrated lambs. Thus, immunocastration is a suitable alternative to Burdizzo-castration regarding the interruption of testosterone production and testis functioning.