Total Testosterone Concentrations Research Articles

Serum Testosterone and Cortisol Concentrations After Single-Dose Administration of 100-Mg Transdermal Testosterone in Healthy Men.

The growing interest in testosterone's effects on men's social behaviors, in particular aggressive, risk-taking, or status maintenance behaviors, is accompanied by a paucity of dose-dependent pharmacokinetic data. Examining the neurophysiological effects of transdermal testosterone typically includes a 4h delay before further brain-behavior measurements. Nevertheless, high heterogeneity regarding the timing of follow-up measurements and dosage remains. In a double-blind placebo-controlled design, we examined the short-term pharmacokinetic profile of 100-mg transdermal testosterone (Testotop®) to determine the optimal time for detecting testosterone-mediated effects. Across two studies, 35 healthy men received a single dose of testosterone and placebo in two separate sessions. In study one (n = 16), serum testosterone and cortisol were assessed serially every 30 min up to 2 h posttreatment. In study two (n = 19), we assessed serum testosterone and cortisol at baseline, 2 h, and 4.15 h (255 min) posttreatment. Relative to baseline and placebo, transdermal testosterone significantly increased total serum testosterone concentrations 90 min posttreatment, reaching maximum concentration between 2 h and 3 h posttreatment. Albeit elevated, serum testosterone levels gradually decreased between 2 h and 4 h following treatment. Transdermal testosterone did not suppress cortisol release. Instead, cortisol concentrations decreased according to cortisol's known circadian rhythm. Unlike previous findings showing significant testosterone concentration increases as soon as 60 min and as late as 3 h post 150-mg testosterone treatment, our 100-mg testosterone manipulation significantly increased testosterone concentrations 90 min following treatment. These pharmacokinetic data are important in facilitating the optimization of timing parameters for future testosterone challenge studies.

Sexual Activity of Patients Undergoing Testicular Sperm Extraction.

IntroductionFor couples who wish for a baby, sexual activity (through intercourse) is the only way to conceive naturally. However, the sexual activity of men undergoing testicular sperm extraction (TESE) and factors that influence it among affected couples are not clearly understood.AimTo examine sexual activity among infertile men undergoing TESE and to identify factors that influenced it.MethodsMarried Japanese male patients undergoing TESE were included. Sexual activity during the previous month was surveyed using a questionnaire, and potential predictive factors influencing sexual activity were examined.Main Outcome MeasuresTwo hundred twenty-six married men who answered a questionnaire regarding sexual frequency were reviewed retrospectively.ResultsThe patient mean age was 35.8 ± 7.5 years (range 23–67) and the mean age of their partners was 32.9 ± 4.5 years (range 23–44). Most couples (n = 193) were in their first marriage, and 33 were remarried. The mean marriage duration was 52.6 ± 42.2 months (range 1–192). Microdissection TESE and conventional TESE were performed for 152 and 74 patients, respectively. Overall, the mean sexual activity during the last month was 3.6 ± 2.6 times (range 0–15). Marriage duration was negatively correlated with the frequency of sexual activity (r = −0.23; P < .01). There were no correlations between sexual activity and patient age, partner age, marriage type (first marriage or remarried), testicular volume, or serum total testosterone concentration. Regression analysis showed that marriage duration (odds ratio = 1.01; 95% CI, 1.003–1.019; P = .009) and testicular volume (odds ratio = 0.94; 95% CI, 0.88–0.99; P = .033) were significant predictors of low sexual activity (0–1 times/month).ConclusionThe sexual activity of patients undergoing TESE was almost the same as reported previously. Patient age, partner age, testicular volume, and serum total testosterone concentration had no correlation with the reported frequency of sexual activity.Taniguchi H, Matsuda T, Nakaoka Y, et al. Sexual Activity of Patients Undergoing Testicular Sperm Extraction. Sex Med 2019;8:30–35.

Choice of informative laboratory biomarkers for the early identification of changes in neurohumoral regulation and carbohydrate exchange in workers of the mining and mechanical engineering industry

The diagnostic significance of hormones and integral indices of pituitary-adrenal, pituitary-thyroid and pituitary-gonadal system and carbohydrate metabolism (ACTH (corticotropin), aldosterone, cortisol, TSH (thyroid-stimulating hormone), free triiodothyronine (fT3), free thyroxine (fT4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total and free testosterone, insulin, integral pituitary-adrenal index (IPAI), the pituitary-thyroid index (PTI), indices of carbohydrate metabolism (Caro and HOMA-IR) was studied for the early diagnostics of disorders of neurohumoral regulation in workers of mining and mechanical engineering industries. The most informative indices, permitting to identify disorders of carbohydrate metabolism are established to be indices of insulin resistance (index Caro and index NOMA-IR) and the determination of insulin in serum. For the identification of changes in pituitary adrenal, pituitary-thyroid and pituitary-gonadal system in patients with vibration disease, sensory-neural hearing loss, comorbidity indexes IGNI, ITI, concentrations of LH and total testosterone are of the most diagnostically significance.

Weak correlations between serum and cerebrospinal fluid levels of estradiol, progesterone and testosterone in males

BackgroundNeuroactive steroids seem to be implicated in a variety of neurophysiological and behavioral processes, such as sleep, learning, memory, stress, feeding and aging. Numerous studies have also addressed this implication in various cerebral disorders and diseases. Yet, the correlation and association between steroids in the periphery, e.g. blood, and the central compartments, e.g. cerebrospinal fluid (CSF), have not yet been comprehensively assessed. As the brain is not directly accessible, and the collection of human CSF usually requires invasive procedures, easier accessible compartments, such as blood, have always attracted attention. However, studies in humans are scarce. In the present study we determined estradiol, progesterone and testosterone levels in CSF and serum of 22 males without cerebral disorders or diseases.ResultsSamples were taken under conditions corresponding closest to basal conditions with patients expecting only spinal anesthesia and minor surgery. All samples per patient were collected concomitantly. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. Correlation analysis revealed merely weak to very weak correlations for estradiol, progesterone and testosterone respectively between the CSF and serum compartments.ConclusionsTotal steroid levels of estradiol, progesterone and testosterone in CSF and serum of males without neurological disorders were determined. Weak to very weak correlations between CSF and serum were found thus suggesting that concentrations in the periphery do not parallel concentrations in the central compartments. Further research is needed to clarify to what extent and under which conditions serum levels of estradiol, progesterone and testosterone may possibly serve as a biomarker reflecting the respective concentrations in the CSF or in the brain.

P6136Intense daily cigarette smoking accelerates vascular damage of smokers with a moderate cumulative tobacco smoke exposure

Abstract Purpose Coronary artery disease death has been associated with increased cigarette smoking intensity. Aim of the study is to investigate the impact of cigarette smoking intensity on vascular function and structure changes among male smokers with similar age at starting smoking and moderate cumulative tobacco smoke exposure. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), brachial flow-mediated dilation (bFMD), carotid intima media thickness (cIMT) and microvascular damage (penile vasculature) were measured in 118 smokers consuming up to 1 pack (20 cigarettes)/day and 58 patients smoking &gt;1 pack (20 cigarettes)/day. The two groups had a similar mean cigarette smoking exposure (32 pack/years). Microvascular damage was examined by measuring penile peak systolic velocity (PSV) with a dynamic penile color Doppler ultrasonography after intracavernous injection of prostanglandin E1. Lower PSV values indicate severe penile vascular disease. Results The individuals smoking more than 1 pack/day were 10 years younger than smokers consuming up to 1 pack/day, however systolic, diastolic blood pressure, body-mass index, fasting blood glucose levels, lipid profile, C-reactive protein and total testosterone concentration were similar between the two groups. Figure shows mean bFMD, penile PSV, PWV and cIMT of the two groups. Interestingly, despite the similar cumulative smoking exposure between the two groups, the younger in age individuals with the intense cigarette smoking history had significantly lower mean bFMD and penile PSV (all P&lt;0.05) and similar PWV and cIMT compared to the mean values of older subjects smoking up to 1 pack/day. Smoking intensity and vascular changes Conclusions Intense daily smoking accelerates damage of large arteries and significantly impairs microvascular and systemic endothelial function. Considering the predictive value of vascular biomarkers, the findings of this study imply the possibility that baseline daily smoking intensity could be a better summary measure of smoking-related cardiovascular risk among young heavy smokers, relative to total pack-years of smoking.

Ultrasonographic and hormonal characterization of reproductive health and disease in wild, semiwild, and aquarium-housed southern stingrays (Hypanus americanus).

To characterize physical examination, plasma biochemical, and ultrasonographic findings in aquarium-housed, managed semiwild, and wild southern stingrays (Hypanus americanus) with and without reproductive disease. Southern stingrays from aquarium (n = 48), lagoon (managed semiwild; 34), and wild (12) habitats. Limited, opportunistic prosections were performed of presumed anatomically normal wild southern stingrays and compared with findings for aquarium-housed stingrays with reproductive disease. Ultrasonographic video data from both groups were used to assign a score (1 to 5) indicating increasing severity of ovarian and uterine reproductive disease. Plasma total 17β-estradiol, estrone, progesterone, and testosterone concentrations were measured with enzyme immunoassays validated for use in southern stingrays. Ultrasonographic ovarian scores were significantly correlated with uterine scores. No reproductive disease was detected in semiwild or wild stingrays, but 65% (31/48) of aquarium-housed stingrays had developing or advanced reproductive disease (ie, ultrasonographic ovarian or uterine score of 4 or 5). Significant correlations were identified between ovarian and uterine disease status and plasma concentrations of all steroid hormones except testosterone. Findings suggested that ultrasonography and plasma hormone concentrations may be useful in the identification of reproductive disease and determination of disease severity in southern stingrays.

P6259Unfavourable vascular risk profile of smokers with testosterone deficiency

Abstract Purpose Testosterone deficiency and cigarette smoking are both associated with increased cardiovascular (CV) mortality risk. We examined whether vascular function and structure parameters are significantly impaired in smokers with low testosterone levels. Methods Carotid intima media thickness (cIMT) and aortic pulse wave velocity (aPWV) were measured in a total of 690 patients (mean 58±7 yrs) without manifest CV/atherosclerotic disease. All patients underwent exercise stress test (and coronary angiography) to reveal coronary artery disease (CAD). Plasma total testosterone (TT) levels were measured in all patients. Results Participants were divided into four subgroups according to smoking (yes/no) and measured low or normal TT levels (low TT&lt;3.5 ng/ml). The subgroups had similar prevalence of hypertension and smoking and comparable LDL-C levels. The mean age of patients with low TT was greater than that of subjects with normal TT (P&lt;0.05). Aortic PWV was significantly higher in smokers with low TT compared to smokers with normal TT (P=0.01) and non-smokers with either low TT (P=0.005) or normal TT (P&lt;0.001) (left plot). Similarly, cIMT was significantly higher in smokers with low TT compared to smokers with normal TT (P=0.01) and non-smokers with either low TT (P=0.005) or normal TT (P&lt;0.001) (right plot). All associations remained statistically significant after adjustment for age. Among smokers with low TT both aPWV and cIMT significantly increased with increasing cigarette smoking intensity (all P&lt;0.05), whereas the associations between smoking intensity and either aPWV or cIMT were not significant among smokers with normal TT concentration (all P=NS). Interestingly, the prevalence of angiographically documented CAD was significantly higher among smokers with low TT (18%) compared to the CAD prevalence of the three other subgroups (overall P&lt;0.001). TT level, smoking and vascular profile Conclusions Carotid IMT and aortic PWV are significantly increased and the prevalence of angiographically documented CAD is greater in smokers with testosterone deficiency. Further studies should be conducted to evaluate how much of the unfavorable effect of both cigarette smoking and testosterone deficiency on coronary atherosclerotic burden is mediated by their associations with function and structure changes in the vascular wall.

The impact of diurnal variation of PSA on timing of measurement in prostate biopsy.

Prostate-specific antigen (PSA) synthesis is related to testosterone, which has a diurnal rhythm. PSA might have a diurnal variation and the timing of measurement could change the clinical practice for prostate biopsy. Male patients complaining of lower urinary tract symptoms (group 1) and diagnosed with prostate cancer (group 2) were recruited into the study. Morning fasting blood samples were withdrawn between 9.00 and 11.00 am for the determination of biochemical parameters, PSA (PSA1), total testosterone (T1), and estradiol (E1) levels. In the afternoon, between 15.00 and 15.30 pm, blood samples were again obtained from the same participants at the same day and the serum concentration of PSA (PSA2), total testosterone (T2), and estradiol (E2) were measured. A total of 160 and 30 patients were enrolled in groups 1 and 2, respectively. One hundred forty (87.5%) and 26 (86.6%) patients had a decrease in the PSA levels when measured in the afternoon. The Wilcoxon signed-rank test determined a statistically significant difference between the PSA levels measured in the morning and in the afternoon in each group. An analysis of covariance test revealed no statistically significant difference in PSA concentration between the groups after adjustment for baseline concentration (F(1.187) = 0.203, P = .653). There was a weak positive correlation between PSA1/PSA2 and T1/T2, rs (160) = 0.163, P = .034. An extra unit increase in PSA1 concentration leads to a 0.805 (95% confidence interval [CI], 0.781-0.830) and 0.828 (95% CI, 0.807-0.849) ng/mL increase in PSA2 concentration in groups 1 and 2, respectively, that is, patients with and without prostate cancer had a similar decrease in the PSA levels. When measured in the afternoon, 66.6% and 50% patients with a morning PSA level over 3 or 4 ng/mL had a PSA drop below these levels, respectively. PSA has a diurnal variation and the timing of measurement may alter the decision of the clinician for transrectal ultrasound prostate biopsy.

PRODUCTIVE PERFORMANCE, CARCASS TRAITS, LIPID PROFILE, ANTIOXIDANTS AND IMMUNITY OF GROWING RABBITS TREATED WITH GUM ARABIC UNDER EGYPTIAN SUMMER CONDITION

Effect of Gum Arabic (GA), as natural antioxidant in the diet, on growth, carcass, digestibility, liver and kidney functions, antioxidant capacity, immunity, thyroid and testosterone hormones of growing rabbits was studied under Egyptian hot condition. Male APRI line rabbits (n=90) were assigned into 3 groups fed basal diet with 0 (T1), 1 (T2) and 2 (T3) kg GA/ton. Growth performance parameters and viability rate were recorded at age intervals from 5 to 11 wk. Digestibility coefficients, carcass traits, serum biochemicals, antioxidant, immunity, and thyroid and testosterone hormones were determined at 11 wk of age. Results revealed that GA addition increased (P<0.05) growth performance, carcass traits (hind parts and dressing), serum total proteins, albumin, globulin, high-density lipoproteins, glucose, total antioxidant capacity, immunoglobulins, triiodothyronine, tetraiodothyronine and testosterone concentrations. Relative weight of carcass foreparts, weight of full digestive tract, cholesterol, triglycerides and low-density lipoproteins, hepato and renal somatic indexes, urea and malondialdehyde decreased (P<0.05) as affected by GA. In conclusion, dietary supplementation with both levels of GA can enhance productive performance, lipid profile, immune response and antioxidant defense system of growing rabbits under Egyptian summer conditions. The best results were obtained with adding 2 kg GA/ton diet.

The effect of vitamin D supplementation on the androgenic profile in men: A systematic review and meta-analysis of clinical trials.

The aim of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation on total testosterone (TT) and sex hormone-binding globulin (SHBG) in men. We searched PubMed, Scopus and Web of Science for randomized, controlled trials of vitamin D supplementation in men ≥18years old up to September 2018, without language restrictions. Meta-analysis was based on a random effects model. The systematic review was registered as CRD42018094498. We identified 3,402 articles, of which eight studies with 10 effect sizes met the inclusion criteria. Vitamin D daily dose equivalents ranged from 600 to 4,000 per day to 60,000IU per week; duration was 6weeks to 36months. In general, vitamin D supplementation had no significant effect on TT (MD=0.20, 95% CI: -0.20, 0.60, p=0.336) and SHBG (MD=1.56, 95% CI: -0.85, 3.97, p=0.204). Subgroup analysis conducted with duration of prescription, type (daily or weekly), dosing frequency and baseline vitamin D and TT concentration showed that vitamin D did not significantly affect TT. The present study did not find any evidence to support beneficial effect of vitamin D supplementation on TT and SHBG in men. Thus, further large-scale randomised controlled trials are required to evaluate the effects of vitamin D supplementation on androgen in men.

Cross-sectional associations between healthy eating index and sex steroid hormones in men-National Health and Nutrition Examination Survey 1999-2002.

Diet plays an important role in health and is a modifiable risk factor for chronic diseases. In men, sex steroid hormones influence, and are influenced by, a number of health states. Specific dietary patterns have been found to alter sex steroid hormone levels in observational and intervention studies. Thus, we hypothesized that dietary patterns captured by the Healthy Eating Index (HEI) are associated with serum concentrations of sex steroid hormones and sex hormone-binding globulin (SHBG). The objective is investigating the association between HEI and sex steroid hormones and SHBG in a general US population of men. We used data on serum sex steroid hormones and SHBG levels, HEI, and other variables collected in the National Health and Nutrition Examination Survey (NHANES), 1999-2002. A total of 550 men >20years old were included in the analysis. The cross-sectional associations between HEI (from 0 to 100 points, higher score equates to a healthier diet) with natural logarithm transformed concentrations of total and free testosterone, total and free estradiol, and SHBG were evaluated with multivariable linear regression models and adjusted for potential confounders. We also stratified by the body mass index (BMI) and race/ethnicity and tested for interactions. HEI showed a significant inverse association with free estradiol (p=0.03), but was not associated with total or free testosterone, total estradiol, or SHBG concentrations. Neither BMI nor race/ethnicity statistically significantly modified the association between HEI and sex steroid hormone levels. The present cross-sectional analysis in a representative sample of US men showed no consistent association between eating habits, sex steroid hormones, and SHBG. Longitudinal studies are needed to further investigate potential associations.

Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels.

ObjectivePharmacokinetic and efficacy data from a phase 3 testosterone nasal gel (TNG) study were stratified by baseline endogenous testosterone level in patients with testosterone deficiency. Total testosterone (TT), LH, and FSH levels, as well as erectile function, mood, and lean body mass for each group were compared. In a subset of patients with very low baseline endogenous testosterone levels (<100 ng/dL), we investigated whether TNG is a suitable treatment option.Materials and MethodsPatients with testosterone deficiency (serum TT <300 ng/dL) were treated with TNG for 3 months, followed by safety extension periods of 90 and/or 180 days. Pharmacokinetic parameters were calculated from serum hormone levels on days 30 and 90, along with efficacy measurements, which were analyzed by comparison with baseline values. Baseline and/or predose TT values were used for patient stratification.ResultsPrestudy and predose endogenous testosterone concentrations correlated. The maximal concentration of TT was nearly identical across all cohorts at days 30 and 90, whereas the average concentration over 24 hours had a slight positive dependence relative to predose levels. LH levels remained in the normal range but were decreased more in patients with higher starting baseline levels. These findings indicate that TNG works with an active hypothalamic-pituitary-gonadal axis that responds to each dose of TNG throughout the treatment period. Patients with the lowest endogenous testosterone levels received maximum exposure impact from each TNG dose. Patients with severe testosterone deficiency had similar efficacy improvements as the remainder of the study population.ConclusionAll testosterone-deficient cohorts were successfully treated with TNG.

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.

Circulating Biomarkers of Testosterone's Anabolic Effects on Fat-Free Mass.

Biomarkers that predict response to anabolic therapies could expedite the development of function-promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM). Serum samples were obtained from the 5α-Reductase Trial, a randomized trial that compared the effects of graded doses of testosterone enanthate for 20 weeks in healthy men randomized with placebo or dutasteride (dual SRD5A inhibitor). Testosterone's effects on FFM or strength measures did not differ between placebo vs dutasteride groups. Accordingly, 54 subjects treated with testosterone plus placebo were included in the discovery cohort, and 48 subjects randomized to dutasteride were included in the validation cohort. A total of 1162 biomarkers were evaluated using prespecified criteria. In the discovery cohort, testosterone administration increased propeptide of type III collagen (PRO-C3) and propeptide of type VI collagen (PRO-C6) levels in a dose- and concentration-dependent manner; increases in these biomarkers from baseline to week 12 were associated with changes in FFM from baseline to week 20 (PRO-C3: r2 = 0.437, P < 0.001; PRO-C6: r2 = 0.434, P < 0.001). Changes in PRO-C3 and PRO-C6 levels were significantly associated with changes in chest press strength (PRO-C3: r2 = 0.394, P < 0.001; PRO-C6: r2 = 0.530, P < 0.001). In the SOMAscan, changes in IGF binding protein-6 (IGFBP6) and glypican 3 (GPC3) were associated with changes in total and free testosterone levels and FFM. These findings were replicated in the Validation cohort. PRO-C3, PRO-C6, IGFBP6, and GPC3 fulfilled the prespecified criteria for biomarkers of testosterone-induced muscle anabolism. Changes in these biomarkers were associated with changes in total and free testosterone concentrations and with testosterone-induced gains in FFM.

MON-197 Peri-operative Outcomes of Vaginoplasty Using an Individualized Approach to Hormone Management in Transgender Women

For transgender and gender diverse individuals, gender identity is not congruent with the sex assigned at birth. Cross sex hormone therapy (HT) and gender affirming surgery can relieve significant dysphoria associated with gender incongruence and improve health outcomes. With changes in private insurance, state and federal regulations to cover gender-affirming treatments and procedures, there has been an increasing need and demand for trained providers and centers to provide gender-affirming health care. However, there is little data to guide management of peri-operative HT with regards to limiting risks. Most surgeons follow a protocol to stop feminizing HT 2 weeks before vaginoplasty with little data that this is effective and necessary or whether this might provoke significant dysphoria peri-operatively. We sought to determine if an age-specific and route-specific peri-operative protocol for feminizing HT was associated with increased risk for complications, changes in hormone concentrations or cardiometabolic profile. At our tertiary care academic center, transgender women over the age of 50 discontinued oral estradiol 6 weeks prior to surgery to allow enough time for clotting factors to normalize but could choose to switch to transdermal estradiol until 2 weeks prior to surgery. Younger women continued estradiol until surgery. All women restarted estradiol upon discharge from the hospital. We performed a retrospective review of pre and postoperative body mass index (BMI), blood pressure (BP), estradiol (E2) and total testosterone (TT) concentrations, fasting glucose and lipids 6 months before and after vaginoplasty. Results: A total of 59 transgender women underwent vaginoplasty over 20 months. Ten women age ≥ 50 (O) had a median age of 58 [Interquartile range (IQR) 56-62]. 49 women < age 50 (Y) had a median age of 31 [IQR 27-37]. O had significantly higher BMI than Y [29.7(IQR 28.3-34.2) vs 24.6 (21.6-28.4), p<0.01 and significantly higher BP, triglycerides, and LDL. More Y women were taking oral estradiol (53% vs 20%). There was no difference in baseline or post-surgical E2 or TT concentrations or fasting glucose. There were no complications of deep venous thrombosis, cardiovascular events or significant changes in BMI, BP, fasting glucose or lipids. In both age groups, only about half were able to decrease their estrogen dose post operatively (Y 57% vs O 44%, p=0.5). Conclusions: Continuing feminizing hormone therapy before vaginoplasty is not associated with an increased risk for complications in women under the age of 50. An individualized approach could be considered to limit the risk of worsening dysphoria post-operatively while avoiding increased risks in older women. Why estrogen doses could not be reduced more frequently after orchiectomy requires further investigation.

SUN-363 Severe Hyperandrogenism in Pre-menopausal Women

Background: Severe hyperandrogenism in pre-menopausal women is often due to ovarian and adrenal tumors. Clinical and biochemical picture on initial presentation may inform management. Objective: To describe the presentation, etiology and management of pre-menopausal women with severe hyperandrogenism. Methods: This is a retrospective study of premenopausal patients (XX genotype) age 18 to 55 with total testosterone concentrations > 150 ng/dL (normal 8-60) evaluated between 1996 and 2018. Testosterone was measured by mass spectrometry. Patients on exogenous testosterone, polycystic ovarian syndrome, or unconfirmed diagnosis were excluded. Results: Of 318 patients with testosterone >150 ng/dL, 38 (8.4%) met the inclusion criteria. Patients presented with hyperandrogenism at a median age of 32 (range 18-54) and were diagnosed with ovarian hyperandrogenism (ovarian tumors (n=9), and ovarian hyperthecosis (n=1)), congenital adrenal hyperplasia (n=12), adrenal cortical carcinoma (n=8), adrenal cortical adenoma (n=4), and Cushing disease (n=4). Median testosterone on presentation was 261 ng/dL (range 159-1366), without a significant difference between the median total testosterone in ovarian or adrenal tumors (372 [range 181-1366] vs. 290 [range 159-768], p=NS). Patients complaining of severe hirsutism demonstrated higher median testosterone compared to patients with mild hirsutism (477 ng/dL [range 173-1366] vs. 234 [162-800], p=0.04). Women with ovarian tumors and adrenal tumors presented with a median age of 36.5 years (25-54). The median duration of symptoms was not different between adrenal neoplasms and ovarian neoplasms (1 year [range 0.2-35] vs. 1.5 [range 0.25-8], p=NS). Median adrenal tumor size was 9.7 cm (3.3-19.5) and ovarian tumor size of 4.9 cm (1.1-15.5). Work-up included abdominal CT (n=16), pelvic ultrasound (n=15), and abdominal MRI (n=3). In 2 patients with ovarian tumors, ovarian imaging was inconclusive, and adrenal/ovarian vein sampling was performed. Adrenalectomy was performed in all but 1 patient (with metastatic disease) with adrenal tumors. Of 10 patients with ovarian hyperandrogenism, 1 was treated with bilateral adrenalectomy (ovarian hyperthecosis) and 9 were treated with unilateral oophorectomy. Following the surgery, all patients had improvement in their testosterone levels with a 73-98% decrease. Conclusion: Severe endogenous hyperandrogenism due either adrenal or ovarian tumors was demonstrated in 58% of pre-menopausal women. Age, total testosterone concentrations, and duration of symptoms were similar in patients with ovarian and adrenal tumors. Most patients required both adrenal and ovarian imaging to elucidate the etiology. As ovarian tumor may not be identified on imaging, adrenal/ovarian vein sampling could be considered to avoid bilateral oophorectomy.

Sex Differences in Effects of Obesity on Reproductive Hormones and Glucose Metabolism in Early Puberty.

Obesity is known to impact reproductive function in adults, but little is known about its effects on reproductive hormones during puberty. To assess sex differences in effects of obesity on reproductive hormones and their relation to insulin sensitivity and secretion. 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). Outpatient academic clinical research center. Girls (52%) and boys (48%) who were normal weight (NW; n = 51, BMI-Z score = -0.11 ± 0.77, age = 11.5 ± 1.7 years) and obese (n = 53, BMI-Z score = 2.22 ± 0.33, age = 10.9 ± 1.5 years), Tanner stage 2 to 3. Boys with obesity had lower total testosterone (P < 0.0001) and higher concentrations of the urinary estradiol metabolite, E1c, (P = 0.046) than boys with NW. Girls with obesity had higher free androgen index (FAI; P = 0.03) than NW girls. Both boys and girls with obesity had lower sex hormone-binding globulin (SHBG; P < 0.0001) than NW. AIRg was inversely related to SHBG in boys (R = 0.6, P < 0.0001) and girls (R = 0.53, P = 0.0001). Si correlated with higher SHBG in boys (R2 = 0.67, P < 0.0001) and girls (R = 0.5, P = 0.0003), higher total testosterone for boys (R = 0.39, P = 0.01), and lower FAI for girls (R = -0.2, P = 0.04). Youth with obesity have lower SHBG than youth with NW, but obesity has differential effects on reproductive hormones in girls versus 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.

FSH therapy for idiopathic male infertility: four schemes are better than one

Objective The aim of this article is to propose an algorithm that aids the clinician to choose the best therapeutic scheme of follicle-stimulating hormone (FSH) in the treatment of men with idiopathic infertility, based on testicular volume (TV) and serum total testosterone concentrations; highlighting the potential role of additional therapy with hCG in a sequential temporal scheme. Materials and methods We subdivided patients in four clinical groups: patients with normal TV and serum testosterone concentrations (A); patients with normal TV and reduced serum testosterone concentrations (B); patients with reduced TV and serum testosterone concentration (C); patient with low TV e normal serum testosterone concentrations (D). Then, we administered to each group a specific therapeutic scheme. Group A: treated with FSH alone for at least 3 months; group B: treated with hCG alone twice a week for 3 months and addition of FSH for poor responders (unmodified sperm parameters); group C: treated ab initio with FSH and hCG until the pregnancy was reached; group D: treated with FSH alone for 3 months and addition of hCG for moderate poor responders (increased TV but unmodified sperm parameters) or second cycle of FSH for 3 months for severe poor responders (unmodified TV and sperm parameters). After 6 months we evaluated the therapeutic response in term of sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate. Results 40% of patients became normozoospermic after treatment, while 30% achieved spontaneous pregnancy. B was the group that best responded to treatment in terms of normalization of seminal parameters; while the highest spontaneous pregnancy rate was obtained from the D group. B group also obtained the highest sperm DNA fragmentation normalization rate. Conclusions To date, no reliable predictors of response to treatment with FSH exist, but TV and serum testosterone concentrations can help the clinician to choose the best therapeutic scheme for men with idiopathic infertility. The groups treated with a sequential temporal scheme (B and D groups) showed better clinical results compared with two groups treated with conventional schemes (A and C groups).

Plasma total testosterone and risk of incident atrial fibrillation: The Atherosclerosis Risk in Communities (ARIC) study

ObjectiveWhether endogenous testosterone concentrations are associated with atrial fibrillation (AF) development is not well established. We assessed the association between plasma total testosterone concentrations and incident AF in a population-based longitudinal study. Study designUsing data from the prospective Atherosclerosis Risk in Communities (ARIC) study, we identified incident AF among 9282 participants who had plasma total testosterone measured by liquid chromatography tandem mass spectrometry at Visit 4 (1996–1998). Main outcome measuresAF cases were identified by electrocardiograms performed during study visits, hospital records/discharge codes, and death certificates through 2013. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident AF across quartiles of plasma total testosterone, stratified by sex, with multivariable Cox models. ResultsThe mean age of the participant sample at ARIC Visit 4 was 63 years (range 52–75); 54.5% were women. Mean (SD) plasma total testosterone levels were 537 ng/dL (213) for men and 27.6 ng/dL (34.7) for women. Over a mean of 13.7 years of follow-up, 1664 incident cases of AF were identified. Comparing those in the highest quartile of plasma total testosterone concentration to those in the lowest quartile and after adjustment for potential confounding variables, there was a positive association between plasma total testosterone and incident AF in men (HR 1.33, 95% CI 1.07, 1.66), but no such association in women (HR 0.99, 95% CI 0.80, 1.22).Conclusion A higher plasma total testosterone concentration was associated with a modestly greater incidence rate of AF in men.

Influence of metabolic syndrome on the relationship between fatty acids and the selected parameters in men with benign prostatic hyperplasia.

The purpose of our investigation was to analyze the relationship between the serum levels of fatty acids and their metabolites and the levels of the selected metabolic and hormonal parameters in patients with benign prostatic hyperplasia (BPH) with regard to concomitant metabolic syndrome (MetS). We determined serum concentrations of total (TT) and free testosterone (FT), insulin (I), dehydroepiandrosterone sulphate (DHEAS), luteinizing hormone and insulin-like growth factor 1 (IGF-1) and sex hormone-binding globulin (SHBG). Gas chromatography was performed. The patients differed in terms of hormone levels, but only the differences in SHBG and IGF-1 levels were statistically significant. Analysis of the levels of polysaturated fatty acids in BPH patients showed that MetS contributed to changes in the levels of these acids. We also analyzed the relationship between the levels of fatty acids and diagnostic parameters for MetS. Particular abnormalities were associated with single changes in the levels of fatty acids. In the diabetic patients, changes in the levels of pentadecanoic acid, heptadecanoic acid and cis-11-eicosenoic acid were demonstrated. Our findings indicate the necessity for further investigation concerning the levels of fatty acids and their impact on the development of MetS, as well as the course and clinical picture of BPH.