Serum Total Testosterone Concentrations Research Articles

Association of Exposure to Phthalate Metabolites With Sex Hormones, Obesity, and Metabolic Syndrome in US Women

Obesity and metabolic syndrome are highly prevalent among the US population and are associated with the dysregulation of sex hormones. An increase in obesity and metabolic syndrome may also be associated with exposure to phthalates. The association of exposure to phthalate metabolites with sex hormones and metabolic health has been understudied in the female population. To evaluate the association between exposure to common phthalate metabolites with total testosterone (TT) levels, sex hormone-binding globulin (SHBG) levels, obesity, and metabolic syndrome among women. This cross-sectional study used data collected from the National Health and Nutrition Examination Survey during 2013 to 2016. Female participants aged 15 years or older with urinary profiles containing common phthalate metabolites were included in this study. Statistical analyses were performed from March 15, 2021, to April 30, 2022. Urinary concentrations of phthalate metabolites were classified into tertiles, and the lowest tertile was used as a reference category. The concentrations of phthalate metabolites and their composite scores based on clustering were also used in the analysis. Serum concentrations of TT and SHBG were dichotomized into high TT levels (>46 ng/dL [to convert to nanomoles per liter, multiply by 0.0347] for age <50 years and >32 ng/dL for age ≥50 years) and low SHBG levels (<2.85 μg/mL [to convert to nanomoles per liter, multiply by 10.53]) as established for the female population. Obesity was defined as a body mass index of 30 or more (calculated as weight in kilograms divided by height in meters squared), and metabolic syndrome was defined using the National Cholesterol Education Program criteria. The serum concentrations of TT and SHBG were also included in the validation analyses. Modified Poisson models were used to estimate the adjusted relative risk (RR) with 95% CIs for the associations. Among the 2004 women included in this study, the mean (SD) age was 46.6 (18.5) years (14.7% Hispanic participants, 62.7% non-Hispanic White participants, and 13.2% non-Hispanic Black participants; 17.4% of participants were born outside the US [weighted percentages]; 230 (11.8%) had high TT levels, 210 (10.4%) had low SHBG levels, 825 (39.8%) had obesity, and 965 (45.5%) had metabolic syndrome (weighted percentages). Of the 13 phthalate metabolites, 8 had the highest tertile level greater than 6.2 ng/mL (range, 0.5-75.2 ng/mL). High levels of exposure to mono(2-ethyl-5-carboxypentyl) phthalate (RR, 1.84 [95% CI, 1.33-2.54]), mono(2-ethyl-5-oxohexyl) phthalate (RR, 1.77 [95% CI, 1.21-2.59]), mono(2-ethyl-5-hydroxyhexyl) phthalate (RR, 1.94 [95% CI, 1.34-2.81]), and monobenzyl phthalate (RR, 1.75 [95% CI, 1.21-2.54]) were associated with low SHBG levels but not with high TT levels. High levels of exposure to some of these metabolites were also associated with obesity and metabolic syndrome. Most associations were specific to premenopausal or postmenopausal women. In this cross-sectional study, exposure to certain phthalate metabolites could be associated with low SHBG levels, obesity, and metabolic syndrome depending on menopausal status.

Impact of extracorporeal shockwave therapy for erectile dysfunction and Peyronie's disease on reproductive and hormonal testicular function.

IntroductionExtracorporeal shock wave therapy is an established treatment for erectile dysfunction and Peyronie's disease. Concerns regarding the safety of extracorporeal shock wave therapy for andrological purposes on testicular function were raised by animal studies.AimTo evaluate the impact of extracorporeal shock wave therapy for erectile dysfunction or Peyronie's disease on reproductive and hormonal testicular function.MethodsWe designed a prospective controlled study in which consecutive patients were enrolled. Males aged between 18 and 40 years with mild vasculogenic erectile dysfunction or acute inflammatory Peyronie's disease and normozoospermia were included. All enrolled patients were offered extracorporeal shock wave therapy, and subjects who refused extracorporeal shock wave therapy for any reason were considered as the Control group. All patients in the Intervention group were treated with DUOLITH SD1 T‐TOP by a single expert urologist. Semen analysis and serum total testosterone dosage were performed before the start (T0) and 3 months after the end of extracorporeal shock wave therapy (T1) in Intervention group. The same parameters were evaluated after the extracorporeal shock wave therapy refusal (T0) and at the end of the following 3 months (T1) in Control group. Normozoospermia was chosen as the primary outcome, serum total testosterone concentration was selected as the secondary outcome.ResultsA total of 94 patients were enrolled in the study (48 Group A, 46 Group B). At T0, all patients were normozoospermic in both groups (p = 0.563), and no significant difference in mean ± SD total testosterone levels was recorded between the groups (582.5 ± 107.2 vs. 634.6 ± 108.4 ng/dl; p = 0.221). At T1, no significant deterioration (p > 0.05) in semen parameters was recorded in both groups. Only a statistically significant reduction in seminal pH was found after extracorporeal shock wave therapy compared to baseline (7.9 ± 0.3 vs. 7.5 ± 0.2; p < 0.001) and untreated patients (7.8 ± 0.2 vs. 7.5 ± 0.2; p < 0.001). No significant difference in total testosterone levels was recorded in Intervention group after extracorporeal shock wave therapy compared to baseline (p = 0.584).ConclusionExtracorporeal shock wave therapy in erectile dysfunction and Peyronie's disease patients does not seem to affect reproductive and hormonal testicular function.

Short-time intensive insulin therapy upregulates 3 beta- and 17 beta-hydroxysteroid dehydrogenase levels in men with newly diagnosed T2DM.

ObjectiveOur previous study has found that short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM) increased serum testosterone levels, but the underlying mechanisms remain unclear.Design and methodsIn this self-controlled study, 43 men with newly diagnosed drug naïve T2DM, aged 18-60 years, with HbA1c >9.0% were treated with continuous subcutaneous insulin infusion (CSII) to normalize blood glucose within one week. Venous blood specimens were collected for measuring of serum total testosterone, dehydroepiandrosterone sulfate (DHEA-S), 3β- and 17β-hydroxysteroid dehydrogenase (3β- and 17β-HSD) concentrations before and after insulin therapy.ResultsTestosterone increased from 13.0 (11.3, 14.6) nmol/L to 15.7 (13.9, 17.5) nmol/L after intensive insulin therapy (p<0.001), while the levels of DHEA-S decreased significantly after treatment (from 6.5 (5.7, 7.3) μmol/L to 6.0 (5.3, 6.7) μmol/L, p=0.001). The ratio of testosterone/DHEA-S increased significantly (2.4 (2.0, 2.8) vs. 3.1 (2.6, 3.7) nmol/μmol, p<0.001). After blood glucose normalization with the short-term CSII therapy, 3β-HSD increased from 11.0 (9.5, 12.5) pg/mL to 14.6 (13.5, 15.7) pg/mL, p=0.001, and 17β-HSD increased from 20.7 (16.3, 25.2) pg/mL to 28.2 (23.8, 32.5) pg/mL, p=0.009.ConclusionsBlood glucose normalization via short-term intensive insulin therapy increases plasma total testosterone levels in men with newly diagnosed type 2 diabetes, associated with a decreased level of DHEA-S, probably because of the enhanced conversion from DHEA to testosterone catalyzed by 3β-HSD and 17β-HSD.

Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men.

ObjectiveMen are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations and poorer COVID-19-related outcomes. We analysed the associations of premorbid serum testosterone concentrations, not confounded by the effects of acute SARS-CoV-2 infection, with COVID-19-related mortality risk in men.DesignThis study is a United Kingdom Biobank prospective cohort study of community-dwelling men aged 40–69 years.MethodsSerum total testosterone and sex hormone-binding globulin (SHBG) were measured at baseline (2006–2010). Free testosterone values were calculated (cFT). the incidence of SARS-CoV-2 infections and deaths related to COVID-19 were ascertained from 16 March 2020 to 31 January 2021 and modelled using time-stratified Cox regression.ResultsIn 159 964 men, there were 5558 SARS-CoV-2 infections and 438 COVID-19 deaths. Younger age, higher BMI, non-White ethnicity, lower educational attainment, and socioeconomic deprivation were associated with incidence of SARS-CoV-2 infections but total testosterone, SHBG, and cFT were not. Adjusting for potential confounders, higher total testosterone was associated with COVID-19-related mortality risk (overall trend P = 0.008; hazard ratios (95% CIs) quintile 1, Q1 vs Q5 (reference), 0.84 (0.65–1.12) Q2:Q5, 0.82 (0.63–1.10); Q3:Q5, 0.80 (0.66–1.00); Q4:Q5, 0.82 (0.75–0.93)). Higher SHBG was also associated with COVID-19 mortality risk (P = 0.008), but cFT was not (P = 0.248).ConclusionsMiddle-aged to older men with the highest premorbid serum total testosterone and SHBG concentrations are at greater risk of COVID-19-related mortality. Men could be advised that having relatively high serum testosterone concentrations does not protect against future COVID-19-related mortality. Further investigation of causality and potential underlying mechanisms is warranted.

Single-center real-life experience with testosterone treatment in adult men with Prader-Willi syndrome.

Hypogonadism is the most frequent hormonal deficiency in individuals with Prader‐Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide testosterone treatment in adult men with PWS. We aimed to evaluate the serum testosterone concentrations and adverse effects of testosterone treatment in individuals with PWS attending a specialist obesity management service. A retrospective audit was undertaken at Austin Health, Melbourne between January 2010 and April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and prevalence of polycythemia and behavioral disturbance. Data were available for eight individuals with median baseline age 19 years (range, 19–42) and BMI 37 kg/m2 (range, 27–71). Six men had obstructive sleep apnea; none were smokers. Baseline testosterone concentration was 1.8 nmol/L (IQR, 1.1–3.3) with hematocrit 0.43. Testosterone formulations were intramuscular testosterone undecanoate (TU) 1000 mg (n = 5), transdermal testosterone gel 50 mg daily (n = 1), and oral TU 80–120 mg daily (n = 2). Median total testosterone concentration was 9.7 nmol/L (IQR, 8.5–14.7). Nine of 25 (36%) hematocrit results in six patients measured >0.50 (range, 0.50–0.56). Intramuscular TU was well tolerated and was the only formulation to achieve serum total testosterone concentrations in the adult male reference range. Worsening behavioral disturbance resulted in treatment discontinuation in one individual. Our experience reinforces the need to regular monitoring of hematocrit in men with PWS treated with testosterone. However, a worsening of behavior problems was uncommon in this series.

Sexual activity of patients undergoing testicular sperm extraction

ABSTRACT Introduction For couples who wish for a baby, sexual activity (though 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. Objective To examine sexual activity among infertile men undergoing TESE and identify factors that influenced Methods Married 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. Results 226 married men who answered a questionnaire regarding sexual frequency were reviewed retrospectively. Patients’ mean age was 35.8 ± 7.5 years (range 23–67) and that of their partners was 32.9 ± 4.5 years (range 23–44). Most couples (n = 193) were in their first marriage, and 33 were re-married. The mean marriage duration was 52.6 ± 42.2 months (range 1–192). Micro-dissection 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 &amp;lt; .01). There were no correlations between sexual activity and patients’ age, partners’ age, marriage type (first marriage/re-married), testicular volume, or serum total testosterone concentration. Regression analysis showed marriage duration (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.003–1.019, P = .009) and testicular volume (OR 0.94, 95% CI 0.88–0.99, P = .033) were significant predictors of low sexual activity (0–1 times/month). There were no significant differences in sexual activity per month between patients treated with micro-TESE and c-TESE; between those in a first marriage and those re-married; and between patients with Klinefelter syndrome and patients who underwent c-TESE. Conclusions The sexual activity of patients undergoing TESE was almost the same as reported previously. Patients’ age, partners’ age, testicular volume, and serum total testosterone concentration had no correlations with the reported frequency of sexual activity. Disclosure Work supported by industry: no.

Subcutaneous Testosterone Enanthate and the Effect of Body Mass Index on Serum Testosterone in Men with Testosterone Deficiency

ABSTRACT Introduction Obesity (body mass index [BMI] ≥30 kg/m^2) in men is associated with low testosterone (T) levels, and the prevalence of testosterone deficiency (TD) is greater in obese men. Information is limited regarding how BMI affects the pharmacokinetic (PK) profile or dosing of testosterone therapies (TTh) in men with TD. Serum total testosterone (TT) trough concentration (C-trough)-guided dosing achieved physiological serum TT levels (300-1100 ng/dL) in a Phase 3 trial of subcutaneous (SC) testosterone enanthate (TE) administered weekly. Objective This post-hoc analysis evaluated the association between BMI and serum TT to assess PK parameters of weekly SC TE treatment in men with TD and varying BMIs. Methods Concentration-controlled SC TE was evaluated in a single-arm Phase 3 trial. The primary endpoint was the percentage of patients who received ≥1 dose of SC TE (Safety Population) achieving an average serum TT concentration of 300-1100 ng/dL over the 7-day dosing interval, C-avg (0-168h), at Week 12. The PK Population (n=142) included all patients in the Safety Population with ≥1 blood sample drawn post-dose. Patients in the PK Population who completed the study through Week 12 (n=137) were categorized into tertiles based on baseline BMI: Tertile 1 (BMI ≤29 kg/m^2; n=45), Tertile 2 (BMI &amp;gt;29-32 kg/m^2; n=33), and Tertile 3 (BMI &amp;gt;32 kg/m^2; n=59). Assessed PK parameters included C-trough, AUC-(0-168h), C-avg (0-168h), and C-max. Weeks 6 and 12 C-trough and C-avg (0-168h) were assessed by BMI tertiles. C-trough and C-avg (0-168h) were calculated according to their Week 12 treatment doses, and an overall dose-normalized linear regression model at Week 12 was used. Results At baseline, mean (SD) serum TT levels for patients in Tertiles 1-3 were 250.7 (101.3), 235.3 (91.2), and 226.4 (81.1) ng/dL, respectively. Prior to dosing adjustments at Week 6, Tertiles 2 and 3 mean (SD) C-trough (459.2 [157.0] and 453.2 [133.0] ng/dL) were lower than Tertile 1 (616.9 [181.6] ng/dL). At Week 6, 21.2% of the total variance in C-trough levels could be predicted from BMI (P&amp;lt;0.001). At Week 12, patients in Tertiles 2 and 3 had lower TT C-trough (494.8 [137.6] and 469.0 [146.2] ng/dL) compared to 517.7 (153.5) ng/dL in Tertile 1. Mean (SD) C-avg (0-168h) values were 585.2 (148.1), 554.2 (104.5), and 528.5 (118.0) ng/dL in Tertiles 1-3, respectively. Mean doses at Week 12 for Tertiles 1-3 were 65.0 (13.48), 78.0 (12.12), and 78.4 (12.68) mg, respectively. Thus, the patients in Tertiles 2 and 3 require higher final doses of SC TE compared to patients in Tertile 1. Using an overall dose-normalized linear regression model at Week 12, 9.36% (P&amp;lt;0.001) and 16.96% (P&amp;lt;0.001) of the total variance in C-trough and C-avg (0-168h), respectively, can be predicted from independent BMI and dose variables. Overall, 98.5% of Week 12 completers achieved C-avg (0-168h) of 300-1100 ng/dL. Conclusions Week 12 TT C-trough, C-avg (0-168h), and C-max were inversely related to BMI, suggesting an important role for BMI and final dose selection in SC TE exposure. Patients with higher BMI tertiles may require higher testosterone dosing to replete physiologic levels. Disclosure Yes, this is sponsored by industry/sponsor: Antares Pharma, Inc. Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma, Inc.

Changes in Organ Weight, Sperm Quality and Testosterone Levels After Aluminum (Al) and Indium (In) Administration to Wistar Rats.

Aluminum and indium are widely used in industrial manufacturing, in pharmaceutical products, in medical treatments, and in food packaging, so they could reach organisms by different way. In order to clarify whether these elements are dangerous, we already demonstrated the ultrastructural modifications observed in the testicles, the epididymides, and the seminal vesicles of rat. Their pro-oxidative effect was also confirmed concomitantly to a decrease in anti-oxidant defenses in the blood, the testicles, and the liver. Thus, it seemed very logic to evaluate damages in the reproductive organs, especially on the exocrine and endocrine functions of the testicles. Aluminum and indium were intraperitoneally administered to male Wistar rats. Sperm solution was obtained from cauda epididymides. Motility, viability, density, and malformation of spermatozoa solution were assessed. Serum total unconjugated testosterone concentrations were measured using RIA technique. Our results showed a decrease in weight of the testicles, epididymides, and seminal vesicles of indium-treated rats and an increase in the weight of their kidneys. A decrease in motility, viability, and density of epididymides stored sperm as well as generation of many spermatozoa malformations was also observed especially in indium-treated rats. Testosterone levels were increased in indium but were enhanced in aluminum group. This confirmed our previous studies showing that aluminum and indium are toxic for the testicular tissues. This could be explained by the generation of reactive oxygen species (ROS) affecting strongly the exocrine and the endocrine functions of the testicles. Aluminum and indium are disturbing elements for the exocrine and endocrine functions of rat testicles.

The Role of Sex Hormones on Bone Mineral Density, Marrow Adiposity, and Muscle Adiposity in Middle-Aged and Older Men.

PurposeThe etiology of age-related bone loss is less clear in men. This study is aimed to observe the variations of endogenous sex hormone concentrations with increasing of age in men, and investigate their relations to bone mass, marrow adiposity, and muscle adiposity.MethodsA total of 199 community-dwelling Chinese men (aged 41 to 82 years) were included and measured of serum total estradiol, total testosterone, and follicle-stimulating hormone (FSH) concentrations by enzyme-linked immunosorbent assay (ELISA). Vertebral trabecular volumetric bone mineral density (vBMD) was measured by quantitative computed tomography for all participants, and vertebral marrow fat content and erector muscle fat content were quantified by Chemistry-shift-encoding magnetic resonance imaging in 62 participants.ResultsIn this population, FSH concentration increased (p < 0.001) gradually with aging. Lower vBMD was independently associated with higher FSH concentration (β = -0.216, p < 0.001), but not with total estradiol or total testosterone. For each standard deviation increase in FSH there was a 50% higher risk of an individual having osteopenia or osteoporosis (vBMD < 120 mg/cm3). Marrow fat content and erector muscle fat content were greater in osteopenic and osteoporotic men, but there were no associations with sex hormones concentrations.ConclusionIn summary, FSH but not total estradiol or total testosterone is related to vertebral trabecular vBMD in middle-aged and older Chinese men. Neither marrow adiposity nor muscle adiposity is associated with sex hormones.

Testosterone concentrations and prescription patterns of 1% testosterone gel in transgender and gender diverse individuals.

Background:Masculinising hormone therapy with testosterone is used to align an individual’s physical characteristics with their gender identity. Standard testosterone doses and formulations recommended for hypogonadal cisgender men are typically administered, although there are currently limited data evaluating the use of 1% testosterone gel in gender-affirming hormone therapy regimens.Objectives:The objective of the study was to assess the prescription patterns and serum total testosterone concentrations achieved with 1% testosterone gel in trans and gender diverse individuals.Materials and Methods:A retrospective cross-sectional analysis was undertaken of trans individuals at a primary and secondary care clinic in Melbourne, Australia. Sixty-seven individuals treated with 1% testosterone gel were included. Primary outcomes were testosterone dose and serum total testosterone concentration achieved.Results:Median age was 25 (22–30) years and median duration of testosterone therapy was 12 (7–40) months. Thirty-five (52%) individuals had a nonbinary gender identity. Initial median testosterone dose was 25 mg (12.5–31.3) daily. Fifty-two (78%) individuals commenced doses <50 mg daily, the recommended starting dose for hypogonadal cisgender men. Median total testosterone concentration achieved was 11.9 nmol/l (7.3–18.6). Polycythaemia (haematocrit >0.5) was documented in eight of 138 (6%) laboratory results in six individuals.Discussion and Conclusions:One percent testosterone gel achieves serum total testosterone concentrations in the cisgender male reference range. A high proportion of individuals had a nonbinary gender identity and most individuals commenced a lower dose than that typically administered to hypogonadal cisgender men, potentially related to slow or ‘partial’ masculinisation goals.

Association of Macronutrients Composition, Physical Activity and Serum Androgen Concentration in Young Women with Polycystic Ovary Syndrome.

The roles of dietary macronutrients and physical activity (PA) in patients with PCOS have not been sufficiently reported, especially in adolescent girls. To address this knowledge gap, we evaluated the associations between serum concentrations of total testosterone (tT), free testosterone (fT), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and dietary macronutrients intake as well as different types and levels of PA. The study population consisted of 96 girls of Caucasian ancestry, aged 14–18 years: 61 participants with polycystic ovary syndrome (PCOS) and 35 healthy controls. Serum tT, fT, A, DHEA-S, and SHBG were determined in fasting blood. Macronutrient intake and PA levels were assessed by using the three-day food record method and the Beliefs and Eating Habits Questionnaire (KomPAN), respectively. We found several positive correlations between dietary macronutrients such as total fat, saturated fatty acids (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and hormonal parameters across the entire cohort and in healthy girls. A positive correlation between SHBG and total protein consumption as well as an inverse correlation between SHBG and carbohydrate intake could be determined. No correlation between androgens and macronutrients was found in the PCOS group. In contrast, we observed an inverse correlation between androgen concentrations (except of DHEA-S) and “work/school” and/or “leisure time” PA only in PCOS patients. Moreover, the hormone levels differed according to PA intensity. In conclusion, the impact of diet and PA was strikingly different in adolescents with and without PCOS. These findings indicate that disturbed hormonal homeostasis in PCOS, at least in the youngest patients, likely “overtrump” dietary influences, and otherwise, PA offers a therapeutic potential that requires further evaluation of the long-term effects in randomized studies. (ClinicalTrial.gov Identifier: NCT04738409.)

Longitudinal changes in serum testosterone and sex hormone-binding globulin in men aged 40-69 years from the UK Biobank.

Testosterone and sex hormone-binding globulin (SHBG) concentrations are reported to decline during male ageing, but whether these changes reflect physiological ageing or age-related comorbidities remains uncertain. We examined longitudinal changes in serum testosterone and SHBG concentrations in middle-aged to older men, concordance between baseline and follow-up valuesand relationships with concomitant changes in lifestyle and medical factors. Population-based longitudinal cohort study. Community-dwelling men aged 40-69 years. Immunoassay serum total testosterone (n = 7812) and SHBG (n = 6491) at baseline (2006-2010) and follow-up (2012-2013). Free testosterone (cFT) was calculated. Bland-Altman analyses and concordance correlation of repeated measurements were conducted. Associations of changes in hormone concentrations with lifestyle and medical factors were explored using Spearman's rank correlation. Over 4.3 years follow-up, there was a negligible mean change (±SE) in serum total testosterone concentration (+0.06 ± 0.03 nmol/L), whereas mean SHBG concentration increased (+3.69 ± 0.12 nmol/L) and cFT decreased (-10.7 ± 0.7 pmol/L). Concordance estimates were 0.67 (95% confidence interval [CI]: 0.66-0.69) for total testosterone, 0.83 (CI = 0.82-0.84) for SHBG and 0.56 (CI = 0.54-0.58) for cFT. Changes in serum total testosterone correlated with changes in SHBG (Spearman's rank ρ = 0.33, CI = 0.30-0.35), and inversely with changes in body mass index (BMI) (ρ = -0.18, CI = -0.20 to -0.16)and waist circumference (ρ = -0.13, CI = -0.15 to -0.11) and in SHBG with changes in BMI (ρ = -0.34, CI = -0.36 to -0.32) and waist circumference (ρ = -0.21, CI = -0.24 to -0.19). In relatively healthy middle-aged to older men, mean serum total testosterone concentration is stable with ageing, while mean SHBG concentration increases. Both total testosterone and SHBG concentrations were highly concordant over time.

Prevalence of polycythaemia with different formulations of testosterone therapy in transmasculine individuals.

Masculinising hormone therapy with testosterone is used to align an individual's physical characteristics with his or her gender identity. Testosterone therapy is typically administered via intramuscular or transdermal routes, and polycythaemia is the most common adverse event. To compare the risk of polycythaemia with different formulations of testosterone therapy in transmasculine individuals. A retrospective cross-sectional analysis was undertaken of transmasculine individuals at a primary and secondary care clinic in Melbourne, Australia. A total of 180 individuals who were on testosterone therapy for >6 months was included. Groups included those receiving: (i) intramuscular testosterone undecanoate (n = 125); (ii) intramuscular testosterone enantate (n = 31); or (iii) transdermal testosterone (n = 24). Outcome was prevalence of polycythaemia (defined as haematocrit > 0.5). Mean age was 28.4 (8.8) years, with a median duration of testosterone therapy of 37.7 (24.2) months; 27% were smokers. There was no difference between groups in serum total testosterone concentration measured. While there was no difference between groups in haematocrit, there was a higher proportion of patients with polycythaemia in those who were on intramuscular testosterone enantate (23.3%) than on transdermal testosterone (0%), P = 0.040. There was no statistically significant difference in polycythaemia between intramuscular testosterone undecanoate (15%) and transdermal testosterone, P = 0.066 nor between intramuscular testosterone enantate and undecanoate, P = 0.275. One in four individuals treated with intramuscular testosterone enantate and one in six treated with testosterone undecanoate had polycythaemia. No individual treated with transdermal testosterone had polycythaemia. This highlights the importance of regular monitoring of haematocrit in transmasculine individuals treated with testosterone, and findings may inform treatment choices.

Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women.

To assess the safety and serum estradiol (E2) and total testosterone (T) concentrations in postmenopausal women treated with Pellet Hormonal Therapy (PHT) and Food and Drug Administration approved Hormonal Therapy (FHT). A total of 539 postmenopausal women were identified, including 384 on PHT and 155 on FHT. Data extracted from medical records include demographics, indication for hormone therapy, treatment duration, side effects, serum E2 and T levels, and frequency of laboratory follow-up. The incidence of overall side effects was significantly higher in PHT compared with FHT (221 [57.6%] vs 23 [14.8%], P < 0.00001, odds ratio [95% CI] =8.0[4.5-14.2]). When examining women with an intact uterus prior to hormone therapy initiation, 55.3% (136/246) on PHT vs 15.2% (12/79) on FHT had at least one episode of abnormal uterine bleeding (P < 0.0001, odds ratio [95% CI] = 7.9[3.6-17.0]). Furthermore, a significantly higher proportion of women on PHT (20.3% [50/246]), compared with 6.3% (5/79) on FHT, had a hysterectomy (P = 0.036, odds ratio [95% CI] = 3.2[1.1-9.3]). Both mean (SD, Min-Max) peak E2 (pg/mL) and peak T (ng/dL) are significantly higher in the PHT group than those in the FHT group (E2: 237.70 [168.55, 10-1,111] vs 93.45 [130.77, 5.5-465.8], T: 194.04 [84.94, 4.3-599] vs 15.59 [19.52, 0.2-70], P < 0.00001). Of those on PHT, four women had E2 level > 1,000 pg/mL and nine women with T level > 400 ng/dL. Women on PHT had a significantly higher incidence of side effects than FHT as well as a significantly higher supraphysiological level of peak E2 and T during the treatment.

Ovarian Hyperandrogenism and Response to Gonadotropin-releasing Hormone Analogues in Primary Severe Insulin Resistance.

ContextInsulin resistance (IR) is associated with polycystic ovaries and hyperandrogenism, but underpinning mechanisms are poorly understood and therapeutic options are limited.ObjectiveTo characterize hyperandrogenemia and ovarian pathology in primary severe IR (SIR), using IR of defined molecular etiology to interrogate disease mechanism. To extend evaluation of gonadotropin-releasing hormone (GnRH) analogue therapy in SIR.MethodsRetrospective case note review in 2 SIR national referral centers. Female patients with SIR with documented serum total testosterone (TT) concentration.ResultsAmong 185 patients with lipodystrophy, 65 with primary insulin signaling disorders, and 29 with idiopathic SIR, serum TT ranged from undetectable to 1562 ng/dL (54.2 nmol/L; median 40.3 ng/dL [1.40 nmol/L]; n = 279) and free testosterone (FT) from undetectable to 18.0 ng/dL (0.625 nmol/L; median 0.705 ng/dL [0.0244 nmol/L]; n = 233). Higher TT but not FT in the insulin signaling subgroup was attributable to higher serum sex hormone–binding globulin (SHBG) concentration. Insulin correlated positively with SHBG in the insulin signaling subgroup, but negatively in lipodystrophy. In 8/9 patients with available ovarian tissue, histology was consistent with polycystic ovary syndrome (PCOS). In 6/6 patients treated with GnRH analogue therapy, gonadotropin suppression improved hyperandrogenic symptoms and reduced serum TT irrespective of SIR etiology.ConclusionSIR causes severe hyperandrogenemia and PCOS-like ovarian changes whether due to proximal insulin signaling or adipose development defects. A distinct relationship between IR and FT between the groups is mediated by SHBG. GnRH analogues are beneficial in a range of SIR subphenotypes.

Gonadotropins for testicular descent in cryptorchid congenital hypogonadotropic hypogonadism males beyond infancy.

To study the effect of combined gonadotropin therapy (CGT) on testicular descent±spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients with cryptorchidism beyond infancy. This retrospective cohort study included CHH patients with cryptorchidism [bilateral (n=5) or unilateral (n=1)] treated with CGT for testicular descent±pubertal induction. All participants were treated with CGT [human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG)] with hMG pretreatment in three and monitored for changes in testicular volume (TV), serum total testosterone (T), serum inhibin-B, and sperm concentration. Complete testicular descent to the scrotal position was achieved in 5/6 patients (10/11 testes) after 4.7±1.6months of treatment. There was 44±18%, 97.5% (IQR: 44-195), 10-fold (IQR: 3-19.6), and two-fold (IQR: 1.7-9.3) increase in stretched penile length, ultrasound measured TV, T level, and serum inhibin-B from baseline, respectively. In two pediatric cases, testicular descent occurred with isolated hMG therapy. At the last follow up (median: 23.5, IQR: 10.5-38.7months), all the descended testes remained in scrotal position. In four pubertal/postpubertal age patients, continuous CGT (18-60months) yielded T and inhibin-B levels of 16.64±1.46nmol/l and 106±32.6pg/mL, respectively. All the three patients with available semen analysis had sperm concentration of≥5 million/mL and one of them achieved paternity. A trial of CGT before orchiopexy may be considered in CHH males with cryptorchidism even beyond the narrow age-window of infancy. CGT may also have beneficial effects on future spermatogenesis and fertility outcomes in these patients.

The role of makorin ring finger protein-3, kisspeptin, and neurokinin B in the physiology of minipuberty.

There is no data regarding the interrelationships of circulating Makorin Ring Finger Protein-3 (MKRN3), Kisspeptin (KISS1), and Neurokinin B (NKB) concentrations during minipuberty in humans. To determine temporal changes in circulating concentrations of MKRN3, KISS1, NKB, and gonadotropins and investigate interrelationships between them in healthy full-term (FT) and preterm (PT) infants during minipuberty period. A prospective study of 6-month follow-up performed. Eighty-seven healthy newborns, 48 FT (19 boys/29 girls), and 39PT (21 boys/18 girls) (gestational age 31-37weeks), were included. Blood samples were taken at 7days (D7), 2months (M2), and 6months (M6) of age. Serum MKRN3, KISS1, NKB, LH, FSH, total testosterone (TT), and estradiol (E2) concentrations were measured. Seventy infants completed the study. MKRN3, KISS1, and NKB concentrations were similar in FT girls and boys. PT boys and girls also had similar concentrations of MKRN3, KISS1, and NKB. FT babies had significantly higher NKB concentrations than PT babies at D7, M2, and M6. MKRN3 and KISS1 concentrations do not differ between FT and PT babies. A strong positive correlation was found between MKRN3 and KISS1 at each time point and in all groups. FSH, LH, TT/E2 concentrations decrease while those of MKRN3 and KISS1 have a trend to increase toward the end of minipuberty. No correlation was detected between gonadotropins and MKRN3, KISS1, NKB concentrations. Strong positive correlation demonstrated between KISS1 and MKRN3 suggests that interrelationship between molecules controlling minipuberty is not similar to those at puberty.

A systematic review of antiandrogens and feminization in transgender women.

Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects of testosterone, but it is unclear which antiandrogen is most effective at feminization. A systematic review was performed using PRISMA guidelines. We searched online databases (Medline, Embase and PsycINFO) and references of relevant articles for studies of antiandrogens in transgender women aged 16+ years to achieve feminization (namely changes in breast size, body composition, facial or body hair) or changes in serum total testosterone concentration when compared to placebo, estradiol alone or an alternative antiandrogen. Four studies fulfilled eligibility criteria and were included in a narrative review. The addition of cyproterone acetate, leuprolide and medroxyprogesterone acetate may be more effective than spironolactone or estradiol alone at suppressing the serum total testosterone concentration. Body composition changes appear similar in transgender women treated with estradiol and additional cyproterone acetate or leuprolide. No eligible studies adequately evaluated the effects of antiandrogens on breast development or facial and body hair reduction. It remains unclear which antiandrogen is most effective at achieving feminization. Cyproterone acetate, medroxyprogesterone acetate and leuprolide may be more effective than spironolactone at suppressing the serum total testosterone concentration. However, due to spironolactone's antagonism of the androgen receptor, it is unclear whether this results in clinically meaningful differences in feminization. Further research with clinically meaningful endpoints is needed to optimize the use of antiandrogens in transgender women.

1639-P: Correlates and Prevalence of Hypogonadism in Male Patients with Latent Autoimmune Diabetes, Classic Type 1 Diabetes, and Classic Type 2 Diabetes

Objectives: The study aims to compare the prevalence of hypogonadism in male patients with latent autoimmune diabetes (LADA) and classic type 1 diabetes (T1DM) and type 2 diabetes (T2DM), and explore risk factors for hypogonadism in those patients. Methods: Form 1 January 2016 and 9 October 2019, a total of 399 male patients with LADA(n=71), T1DM (n=72) and T2DM (n=256) respectively were recruited from the endocrinology department in Shanghai Tenth People’s Hospital for this cross-sectional study. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. Results: The mean age of male patients with LADA, T1DM and T2DM was 54.44 ± 1.54, 47.50±1.83 and 56.55±0.74 years old, respectively. The serum total testosterone concentration in the LADA group was similar to the T1DM group, but higher than those in the T2DM group. The rate of hypogonadism in the LADA group, T1DM group, T2DM group were 1.6%, 2.4% and 20.8%, respectively (p &amp;lt;0.05). Total testosterone was positively correlated with SHBG and HDL-c, and negatively correlated with uric acid, HbA1c, BMI, SBP, DBP and TG in all, LADA, T1DM and T2DM groups. Logistic regression indicate that after adjusting for age, duration of diabetes, smoking, drinking and family history of diabetes, the independent risk factors for developing hypogonadism in male with diabetes were BMI (OR=1.31, P&amp;lt;0.05), C-peptide (OR=1.88, P&amp;lt;0.05), HDL-c (OR=0.41,P&amp;lt;0.05) and SBP (OR=1.01,P&amp;lt;0.05). Conclusion: Our results indicate that in a population of admission to a large urban hospital in China, the rate of hypogonadism was lower in LADA patients and T1DM patients than T2DM patients. High levels of BMI, C-peptide, SBP and low level of HDL-c are risk factors for developing hypogonadism in male with diabetes. Disclosure M. Cai: None. J. Gao: None. C. Sheng: None. H. Li: None. S. Qu: None. M. Zhang: None. Funding National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)

SUN-046 Prevalence of Polycythaemia with Different Formulations of Testosterone Therapy in Transmasculine Individuals

Background: Masculinising hormone therapy with testosterone is used to align an individual’s physical characteristics with their gender identity. Testosterone therapy is typically administered via intramuscular or transdermal routes and polycythaemia is the most common adverse event. Aims: To compare the risk of polycythaemia with different formulations of testosterone therapy in transmasculine individuals. Methods: A retrospective cross-sectional analysis was undertaken of transmasculine individuals at a primary and secondary care clinic in Melbourne, Australia. 180 individuals who were on testosterone therapy for >6 months were included. Groups included those receiving (1) intramuscular testosterone undecanoate (n=125), (2) intramuscular testosterone enantate (n=31), or (3) transdermal testosterone (n=24). Outcome was prevalence of polycythaemia (defined as haematocrit >0.5). Results: Mean age was 28.4 (8.8) years with a median duration of testosterone therapy 37.7 (24.2) months. 27% were smokers. There was no difference between groups in serum total testosterone concentration measured. Whilst there was no difference between groups in haematocrit, there was a higher proportion of patients with polycythemia in those who were on intramuscular testosterone enantate (23.3%) than on transdermal testosterone (0%), p=0.040. There was no statistically significant difference in polycythaemia between intramuscular testosterone undecanoate (15%) and transdermal, p=0.066 nor between intramuscular testosterone enantate and undecanoate, p=0.275. Conclusions: One in four individuals treated with intramuscular testosterone enantate and one in six treated with testosterone undecanoate had polycythaemia. No individual treated with transdermal testosterone had polycythaemia. This highlights the importance of regular monitoring of haematocrit in transmasculine individuals treated with testosterone and findings may inform treatment choices.