Rate and Extent of Recovery from Reproductive and Cardiac Dysfunction Due to Androgen Abuse in Men

2020 ◽  
Vol 105 (6) ◽  
pp. 1827-1839 ◽  
Author(s):  
Nandini Shankara-Narayana ◽  
Christopher Yu ◽  
Sasha Savkovic ◽  
Reena Desai ◽  
Carolyn Fennell ◽  
...  

Abstract Context Androgen abuse impairs male reproductive and cardiac function, but the rate, extent, and determinants of recovery are not understood. Objective To investigate recovery of male reproductive and cardiac function after ceasing androgen intake in current and past androgen abusers compared with healthy non-users. Methods Cross-sectional, observational study recruited via social media 41 current and 31 past users (≥3 months since last use, median 300 days since last use) with 21 healthy, eugonadal non-users. Each provided a history, examination, and serum and semen sample and underwent testicular ultrasound, body composition analysis, and cardiac function evaluation. Results Current abusers had suppressed reproductive function and impaired cardiac systolic function and lipoprotein parameters compared with non- or past users. Past users did not differ from non-users, suggesting full recovery of suppressed reproductive and cardiac functions after ceasing androgen abuse, other than residual reduced testicular volume. Mean time to recovery was faster for reproductive hormones (anti-Mullerian hormone [AMH], 7.3 months; luteinizing hormone [LH], 10.7 months) than for sperm variables (output, 14.1 months) whereas spermatogenesis (serum follicle-stimulating hormone [FSH], inhibin B, inhibin) took longer. The duration of androgen abuse was the only other variable associated with slower recovery of sperm output (but not hormones). Conclusion Suppressed testicular and cardiac function due to androgen abuse is effectively fully reversible (apart from testis volume and serum sex hormone binding globulin) with recovery taking between 6 to 18 months after ceasing androgen intake with possible cumulative effects on spermatogenesis. Suppressed serum AMH, LH, and FSH represent convenient, useful, and underutilized markers of recovery from androgen abuse.

2008 ◽  
Vol 158 (6) ◽  
pp. 803-810 ◽  
Author(s):  
Lise Aksglaede ◽  
Rikke Beck Jensen ◽  
Elisabeth Carlsen ◽  
Petra Kok ◽  
Daniel M Keenan ◽  
...  

ObjectiveThe regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary–gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes.DesignCross-sectional study.MethodsIn this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined.ResultsBasal LH and FSH secretion was elevated 6.3- and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibullλanalysis. There was no difference between approximate entropy ratios or Weibullγanalyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution.ConclusionIn this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic–pituitary–gonadal axis has undergone functional changes.


2014 ◽  
Vol 170 (4) ◽  
pp. 555-563 ◽  
Author(s):  
M Andreassen ◽  
R B Jensen ◽  
N Jørgensen ◽  
A Juul

IntroductionGH activity may be involved in male reproductive function. A common genetic polymorphism in the gene encoding the GH receptor (GHR) results in deletion of the entire exon 3 sequence (GHRd3 isoform). The short GHRd3/d3 isoform seems more sensitive compared with full-length receptors (GHRfl/fl).AimTo investigate the associations between GH activity, evaluated by exon 3 GHR polymorphism, and serum IGF1 vs reproductive hormones, semen quality, and pre- and postnatal growth in healthy young males (n=838, mean age: 19.4 years).ResultsCompared with GHRfl/fl homozygous individuals (n=467) GHRd3/d3 homozygous individuals (n=69) tended to have larger semen volume (3.2 (2.4–4.3) vs 3.6 (2.6–4.7) ml, P=0.053) and higher serum inhibin-B levels (208 pg/ml (158–257) vs 227 pg/ml (185–264), P=0.050). Semen quality, levels of gonadotropins, testosterone, estradiol, sex hormone-binding globulin, and IGF1 were not associated with GHRd3 genotype.A twofold increase in serum IGF1 was associated with a 13% (4–23) increase in calculated free testosterone (P=0.004). By contrast IGF1 was inversely associated with serum inhibin-B (P=0.027), but showed no associations to semen quality. GHR genotype and serum IGF1 were not associated with size at birth or final height.ConclusionsGHRd3 polymorphism seemed only to have a weak influence on male reproductive function of borderline significance. The sensitive GHRd3/d3 genotype may slightly increase testicular function, as evaluated by semen volume and levels of inhibin-B, but does not seem to influence Leydig cell steroidogenesis. GHR genotype did not influence pre- and postnatal growth.


2005 ◽  
Vol 289 (6) ◽  
pp. H2616-H2623 ◽  
Author(s):  
Yun-He Liu ◽  
Oscar A. Carretero ◽  
Oscar H. Cingolani ◽  
Tang-Dong Liao ◽  
Ying Sun ◽  
...  

Using inducible nitric oxide (NO) synthase (iNOS) knockout mice (iNOS−/−), we tested the hypotheses that 1) lack of iNOS attenuates cardiac remodeling and dysfunction and improves cardiac reserve postmyocardial infarction (MI), an effect that is partially mediated by reduction of oxidative stress due to reduced interaction between NO and reactive oxygen species (ROS); and 2) the cardioprotection afforded by iNOS deletion is eliminated by Nω-nitro-l-arginine methyl ester (l-NAME) due to inhibition of endothelial NOS (eNOS) and neuronal NOS (nNOS). MI was induced by ligating the left anterior descending coronary artery. Male iNOS−/− mice and wild-type controls (WT, C57BL/6J) were divided into sham MI, MI+vehicle, and MI+l-NAME (100 mg·kg−1·day−1 in drinking water for 8 wk). Cardiac function was evaluated by echocardiography. Left ventricular (LV) maximum rate of rise of ventricular pressure divided by pressure at the moment such maximum occurs (dP/d t/instant pressure) in response to isoproterenol (100 ng·kg−1·min−1 iv) was measured with a Millar catheter. Collagen deposition, myocyte cross-sectional area, and expression of nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE), markers for ROS, were determined by histopathological and immunohistochemical staining. We found that the MI-induced increase in LV chamber dimension and the decrease in ejection fraction, an index of systolic function, were less severe in iNOS−/− compared with WT mice. l-NAME worsened LV remodeling and dysfunction further, and these detrimental effects were also attenuated in iNOS−/− mice, associated with better preservation of cardiac function. Lack of iNOS also reduced nitrotyrosine and 4-HNE expression after MI, indicating reduced oxidative stress. We conclude that iNOS does not seem to be a pathological mediator of heart failure; however, the lack of iNOS improves cardiac reserve post-MI, particularly when constitutive NOS isoforms are blocked. Decreased oxidative stress and other adaptive mechanisms independent of NOS may be partially responsible for such an effect, which needs to be studied further.


2018 ◽  
Author(s):  
Natalie Nokoff ◽  
Jessica Thurston ◽  
Allison Hilkin ◽  
Laura Pyle ◽  
Philip E Zeitler ◽  
...  

Context: Obesity is known to impact reproductive function in adults, but little is known about its effects on reproductive hormones during puberty or sex differences in these effects. Objective: To assess sex differences in effects of obesity on reproductive hormones and their relationship to insulin sensitivity and secretion. Design: Cross-sectional study including anthropometrics, serum and urine reproductive hormone concentrations, and intravenous glucose tolerance testing (IVGTT) to assess acute insulin response to glucose (AIRg) and insulin sensitivity (Si). Setting: Outpatient academic clinical research center. Patients: Fifty-one normal weight (NW, BMI-Z=-0.11 +/- 0.77, age=11.5 +/- 1.7 years) and 53 obese (BMI-Z=2.22 +/- 0.33, age=10.9 +/- 1.5 years) girls (n=54) and boys (n=50), Tanner stage 2-3. Results: Obese boys had lower total testosterone (p<0.0001) and higher concentrations of the urinary estradiol metabolite, E1c, (p=0.046) than NW boys. Obese girls had higher free androgen index (FAI, p=0.03) than NW girls. Both obese boys and girls had lower sex hormone-binding globulin (SHBG, p<0.0001) than NW. AIRg was inversely related to SHBG in boys (R2= 0.36, p<0.0001) and girls (R2=0.29, p=0.0001). Insulin resistance correlated with lower SHBG in boys (R2=0.45, p<0.0001) and girls (R2=0.24, p=0.0003), lower total testosterone for boys (R2=0.15, p=0.01), and higher FAI for girls (R2=0.08, p=0.04). Conclusion: Obese youth have lower SHBG than NW youth, but obesity has differential effects on reproductive hormones in girls vs. boys, which are apparent early in puberty. Ongoing longitudinal studies will evaluate the impact of obesity on reproductive hormones in girls and boys as puberty progresses.


Author(s):  
Fateheya M. Metwally ◽  
Asmaa M. Elfiky ◽  
Neven E. Sharaf ◽  
Hend Rashad

Abstract Objectives Di-2-ethylhexyl phthalate (DEHP) is ubiquitous, known as an endocrine disruptor. DEHP is a widespread prevalence in general and occupational populations which raised great public concerns due to its potentially harmful health effects on the male reproductive system. We aimed to assess occupational levels of DEHP on gonadotropin and gonadal hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) and evaluate its potential effects on Asp327Asn polymorphisms SHBG gene. Methods We measured the levels of DEHP of 90 male workers in one of polyvinyl chloride (PVC) industry plant using enzyme-linked immunosorbent assay. Sex hormones were examined and Asp327Asn polymorphisms SHBG gene were detected by PCR-RFLP in all participants. Results The workers were divided into low- and high- DEHP exposed groups based on the geometric mean (GM) levels (183.86 U/L) in serum. TT and TT: LH ratio were negatively correlated to DEHP levels (r=−0.213, p=0.038), (r=−0.225, p=0.027), respectively. The linear regression analysis revealed that a 10-fold increase of serum DEHP was found to be associated with 2.07 fold decreased in TT and a 2.26 fold decreased in TT/LH ratio. Conclusions Serum testosterone is negatively associated with DEHP exposure in occupational workers.


2019 ◽  
Vol 8 (2) ◽  
pp. 141-149 ◽  
Author(s):  
Morten Ruge ◽  
Tea Skaaby ◽  
Anna-Maria Andersson ◽  
Allan Linneberg

Background Reduced total hours of sleep and low quality of sleep have been suggested to be associated with low levels of male hormones. Few studies have examined the association between excessive sleep and male reproductive hormones. Objective To investigate the association of total hours of sleep and quality of sleep with serum levels of total, bioavailable and free testosterone (tT, bT and fT), sex hormone-binding globulin (SHBG) and dehydroepiandrosteron-sulfate (DHEAS). Methods Serum levels of tT, SHBG and DHEAS were measured with immunoassays in a cross-sectional population-based study of 2095 males. bT and fT were calculated in accordance with Vermeulens method. Information on total hours of sleep and sleep quality was obtained by questionnaire. Linear regression was used to calculate hormones according to total hours of sleep and the results were expressed as β-estimates and 95% confidence intervals (CI). The adjustment in the multivariable models was constructed taking age, BMI, smoking, alcohol intake and physical activity into account. Results Excessive sleep (>9 h) compared to 7–9 h of sleep was significantly associated with lower tT, bT and fT, but not with SHBG or DHEAS, after multivariable adjustment. These significant associations were also found in our analyses with hormones as continuous variables but no associations were found in our general additive model analyses. Conclusions In this cross-sectional study in men, excessive sleep associated with lower levels of male reproductive hormones. Longitudinal studies are needed to determine the causal direction of the observed association between excessive sleep and lower male reproductive hormones levels.


Author(s):  
E. Quiros-Roldan ◽  
T. Porcelli ◽  
L. C. Pezzaioli ◽  
M. Degli Antoni ◽  
S. Paghera ◽  
...  

Abstract Purpose Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. Methods We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Results Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. Conclusion Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.


2001 ◽  
Vol 281 (5) ◽  
pp. H1938-H1945 ◽  
Author(s):  
Chari Y. T. Hart ◽  
John C. Burnett ◽  
Margaret M. Redfield

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (τ), and the first derivatives of LV pressure rise and fall (dP/d t max and dP/d t min, respectively). During echocardiography, HR was lower in XK than AV mice (250 ± 14 beats/min in XK vs. 453 ± 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 ± 0.08 mm in XK vs. 3.8 ± 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 ± 1.2% in XK vs. 40 ± 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 ± 24 beats/min) and XK (342 ± 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 ± 5 vs. 6.2 ± 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/d t max: 4,402 ± 798 vs. 8,250 ± 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (τ: 23 ± 2 vs. 14 ± 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.


2013 ◽  
Vol 98 (11) ◽  
pp. 4464-4474 ◽  
Author(s):  
C. N. Jayasena ◽  
A. N. Comninos ◽  
G. M. K. Nijher ◽  
A. Abbara ◽  
A. De Silva ◽  
...  

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim: Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P &lt; .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P &lt; .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P &lt; .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.


2007 ◽  
Vol 293 (1) ◽  
pp. E270-E276 ◽  
Author(s):  
Nancy I. Williams ◽  
Sarah L. Berga ◽  
Judy L. Cameron

The role of energy imbalance versus psychosocial stress in the pathogenesis of female reproductive dysfunction characterized by anovulation and amenorrhea remains controversial. In women, functional hypothalamic amenorrhea can develop in the absence of significant weight loss, excessive exercise, or profound psychosocial disruption. We posited, therefore, that commonplace, seemingly minor stressors that alone would have minimal impact upon reproductive function might interact synergistically such that combinations of stressors would cause a greater impairment of the reproductive axis than any single stressor alone. We then developed a monkey model to test this hypothesis. Adult female cynomolgus monkeys with normal menstrual cycles were randomized into three experimental groups and studied over four menstrual cycles. The groups were: low-level psychosocial stress (i.e., moving to a new housing environment; Move, n = 8), moderate energy imbalance (Exercise + Diet, n = 9); and all stressors in combination (Move + Exercise + Diet, n = 10). Food intake, body weight, menstrual cyclicity, and reproductive hormones were assessed for two control menstrual cycles followed by two experimental cycles during which the monkeys experienced the stressors. Abnormal cycles were considered to be abnormally long or anovulatory cycles. Few abnormal cycles occurred in the Move group (1 of 8 monkeys) and in the Exercise + Diet group (1 of 9 monkeys). In contrast, 7 of 10 monkeys in the Move + Exercise + Diet group displayed at least one abnormal cycle (χ2 = 9.61, P = 0.008). These findings suggest that infertility due to hypothalamic hypogonadism can result from the combination of commonplace, seemingly minor stressors that often escape clinical attention.


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