Symptoms Of Androgen Deficiency Research Articles

Evaluation of the effect of testosterone replacement therapy with a transdermal testosterone on glycemic control in men with type 2 diabetes mellitus

BACKGROUND: It is important to evaluate the effect of androgen replacement therapy on glycemic control.AIMS: Assessment of the effect of transdermal testosterone therapy on glycemic control in men with hypogonadism and T2DM.MATERIALS AND METHODS: The prospective, comparative study included 300 men aged 55[49;61] years: men receiving both glucose-lowering therapy (GLT) and transdermal testosterone; and patients receiving only GLT. Observation period 1 year. A medical history, a questionnaire for symptoms of androgen deficiency, and measurement of total testosterone and glycated hemoglobin were carried out. Groups were compared using nonparametric methods.RESULTS: Patients receiving androgen replacement therapy in combination with GLT at both 6 and 12 months from the moment of inclusion in the study, they had a statistically significantly higher level of total testosterone and less severity of symptoms of androgen deficiency. When assessing the magnitude of changes in the studied parameters, it was found that patients receiving testosterone replacement therapy (TRT) were characterized by a statistically significantly more pronounced decrease in the level of glycated hemoglobin (average difference 0,3%). In 29 (20,4% (95% ДИ 13,8–27,0)) men who received only GLT, hypogonadism was eliminated. In 3 patients from the TRT group, a pathological increase in the level of total blood PSA was observed, and therefore TRT was discontinued. An increase in hemoglobin above the reference value (>172 g/l) was detected in 8% and 1,3% of men on TRT and without correction of hypogonadism, respectively, p=0,011.CONCLUSIONS: The combination of transdermal TRT and GLT has a positive effect on glycemic control, which is manifested by a decrease in glycated hemoglobin to a greater extent than when using GLT alone. Normalization of testosterone levels leads to a decrease in the symptoms of androgen deficiency, which is accompanied by an improvement in quality of life. Elimination of hypogonadism only with GLT is possible in a small number of cases.

Symptomatic androgen deficiency and sexual dysfunctions in male patients receiving alectinib for ALK-positiveadvanced nonsmall cell lung cancer.

It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK-positive cancer and in murine models. In this study, three groups, including an experimental group of male patients with ALK-positive, advanced nonsmall cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK-positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK-negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist. Ninety-five patients were consecutively enrolled onto the study. Among sixty-eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p=.0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p=.0002) were significantly lower in ALK-positive ANSCLC patients in cohort A compared with ALK-negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p=.0059) and LH levels (4.72 vs. 7.49 mUI/ml; p=.0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK-positive male patients (74.3 vs. 44.24 pg/ml; p=.0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B. Symptoms of androgen deficiency should be tracked in male patients with ALK-positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate.

FRI434 Long-term Self-reported Outcomes Of Randomized Testosterone (T) vs Placebo (P) Treatment In The T4DM Study

Abstract Disclosure: D.J. Handelsman: None. M. Grossmann: None. B.B. Yeap: Consulting Fee; Self; Bayer, Inc., Lawley. Research Investigator; Self; Lawley. B.G. Stuckey: Speaker; Self; Lawley. N. Shankara-Narayana: None. A.J. Conway: None. W. Inder: None. R.I. McLachlan: None. C.A. Allan: None. A. Jenkins: None. D.R. Jesudason: None. K. Bracken: None. K. Robledo: None. G.A. Wittert: Research Investigator; Self; Bayer, Inc., Lilly USA, LLC. The T4DM study randomized 1007 men (age 50-74 yr, waist ≥95 cm, serum T ≤14.0 nmol/L, no pathological hypogonadism) with impaired glucose tolerance or newly diagnosed type 2 diabetes to T undecanoate (1000 mg) or matching placebo injections every 12 weeks for 24 months with a lifestyle program. At study’s end, T treatment reduced OGTT diabetes diagnosis by 40% without change in HbA1C. After a median of 5 years since last injection, a follow-up email survey obtained 705 responses (70%) comprising 599 completed surveys (316 T, 283 P, 10 deceased, 95 declining). Participants in follow-up survey were similar to non-participants in 23 anthropometric and demographic variables at entry to T4DM, but more in follow-up study were randomized to T (53 vs 46%%, p=0.038), had lower entry weight (107 vs 109 kg, p=0.026) and older school leaving age (16.7 vs 16.5 years, p=0.026) but remaining well matched for work status (46% retired, 35% full-time work, p=0.60), alcohol intake (69% nil or light, 3% heavy; p=0.12) and smoking (3% smoking, p=0.61). At long-term follow-up, randomization to T treatment was associated with stronger belief in benefits during study (64% vs 49%, p<0.001) with less for post-study benefits (44% vs 40%, p=0.07) but overall high interest in future studies (surveys 93%, clinical 76%). At entry, 35% had sleep apnea, most (71%) diagnosed pre-study, with new diagnosis more frequent on T during (9% vs 1%, p=0.03), but not before or after, the study. After study, T treatment was prescribed at a higher rate for men who had study T treatment (6% vs 2.8%, p=0.03), mostly using T injections with 81% continuing at 24 months (median) on post-study T treatment. In the long-term, study T treatment did not influence self-reported new post-T4DM study diagnosis of diabetes (19%, p=0.65) or diabetes drug treatments (22%, p=0.31; oral 18%, injectable 2%, both 2%), prostate disease (p=0.49; cancer 3%, non-cancer 8%) or cardiovascular disease (p=0.95; heart disease 13%, stroke 1%). Both groups had similar weight maintenance (maintained 24%, lost 22%, gain 24%, up/down 30%, p=0.91) and further attempts to lose weight (76%, p=0.29; diet 68%, exercise 57%, drugs 6%, surgery 2%). We conclude that randomized T (vs placebo) treatment for 24 months in men with impaired glucose tolerance or new diabetes but without pathological hypogonadism, was associated with higher rates of (a) self-reported benefits during, but not after the study, (b) of resuming T treatment after the study, consistent with androgen dependence due to withdrawal (androgen deficiency) symptoms and/or recalling perceived benefits of study T treatment, and (c) of sleep apnea diagnosis during, but not before or after the study. Five years after T treatment stopped, there was no difference in the long-term rates of self-reported new diagnosis of diabetes, prostate or cardiovascular disease nor change in weight maintenance or weight loss behaviors. Presentation: Friday, June 16, 2023

Leflutrozole in Male Obesity-Associated Hypogonadotropic Hypogonadism: Ph 2b Double-Blind Randomised Controlled Trial.

Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH). Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA. Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring. Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2, and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, 1.0 mg groups respectively, versus 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvement in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean -1.24%, -1.30%, -2.09%), and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function.

PD11-12 THE EFFECT OF CLOMIPHENE CITRATE ON PATIENT REPORTED OUTCOME MEASURES

You have accessJournal of UrologyCME1 Apr 2023PD11-12 THE EFFECT OF CLOMIPHENE CITRATE ON PATIENT REPORTED OUTCOME MEASURES Jessica Schardein, Kia Fendereski, Zane Randell, Soren Keihani, Joshua Horns, and James Hotaling Jessica SchardeinJessica Schardein More articles by this author , Kia FendereskiKia Fendereski More articles by this author , Zane RandellZane Randell More articles by this author , Soren KeihaniSoren Keihani More articles by this author , Joshua HornsJoshua Horns More articles by this author , and James HotalingJames Hotaling More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003251.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clomiphene Citrate (CC) is a medication that can be used in hypogonadal men in lieu of testosterone to increase testosterone levels while preserving or improving fertility. Patient reported outcome measures for this medication are limited, especially regarding sexual functioning. Our objective is to assess whether self-reported changes in androgen deficiency symptoms and erectile function are observed along with changes in hormone levels and semen parameters in men taking CC. METHODS: We performed a retrospective review of all patients on CC between 2014 and 2018 for hypogonadism and/or infertility. Patient characteristics including age and body mass index (BMI) along with hormone levels, semen parameters, and self-reported questionnaire scores were obtained. Patients who completed blood work for total testosterone and bioavailable testosterone, a semen analysis, and hypogonadism and erectile function questionnaires including Androgen Deficiency in Aging Male (ADAM) and Sexual Health Inventory for Men (SHIM) before and 3 months after the initiation of CC were included in the analysis. Patients with documented exogenous testosterone, human chorionic gonadotrophin, or anastrozole use were excluded. Changes in baseline and follow-up data were analyzed using paired-sample t-tests. RESULTS: A total of 97 men were identified and included in the analysis. The mean age and body mass index (BMI) were 33.7 ± 6 years and 31.2 ± 7.3 kg/m2, respectively. All patients were followed for at least 3 months. The use of CC significantly increased both mean total and bioavailable testosterone levels by 236.5 ng/dL and 115.6 ng/dL, respectively (p<0.05). Concentration, total progressive motility and morphology all significantly improved as well (p<0.05). Clinical manifestations included a significant improvement in ADAM scores (p=0.025) and no change in SHIM scores (p=0.278). CONCLUSIONS: As more men are placed on CC for hypogonadism and/or infertility, characterizing patient reported outcomes regarding androgen deficiency symptoms and erectile function are important. The medication is able to raise testosterone levels while increasing semen parameters in addition to improving self-reported hypogonadal symptoms and maintaining erectile function scores. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e337 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jessica Schardein More articles by this author Kia Fendereski More articles by this author Zane Randell More articles by this author Soren Keihani More articles by this author Joshua Horns More articles by this author James Hotaling More articles by this author Expand All Advertisement PDF downloadLoading ...

Diagnosis of hypogonadism in ageing men.

To make the diagnosis of hypogonadism in an ageing man, in absence of rare organic cause often referred to as functional or late onset hypogonadism (LOH), he should present with a clinical syndrome suggestive of androgen deficiency and have consistently low serum testosterone (T) levels. This does not differ from the diagnosis of any other form of hypogonadism. Particular to LOH diagnostic are uncertainties surrounding this entity: signs and symptoms of androgen deficiency (including sexual symptoms) are nonspecific in older men; clinical significance of only moderately low T levels is uncertain; comorbidity plays a substantial role with potential for reversibility; the place of T therapy in these men is debatable. This context demands for a pragmatic, but appropriately conservative approach to diagnosis. Evaluation should be stepwise with clinical evaluation, if suggestive for androgen deficiency, followed by measurement of a fasting morning serum T, if unequivocally low to be confirmed in a separate morning sample by a second low T or, if initial T borderline low or in presence of factors known to affect SHBG, by a low calculated free T level. All other (free) T results make hypogonadism an unlikely cause of the patient's symptoms. In the absence of consensus cut-off levels for total and free T in the published clinical guidelines for diagnosis of hypogonadism, it seems appropriate in the context of LOH to use stringent criteria indicating a convincingly low serum T. The approach to the diagnosis of LOH is not fundamentally different from that of other forms of hypogonadism but should put extra weight on prioritizing the shunning of overdiagnosis above the risk of underdiagnosis.

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

BackgroundAndrogen deprivation therapy (ADT) for prostate cancer (PCa) is accompanied by side effects affecting health-related quality of life (HRQL). ObjectiveTo assess the effects of the fetal estrogen estetrol (E4) on symptoms related to estrogen and androgen deficiency, and on HRQL measured using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Design, setting, and participantsThis was a phase 2, double-blind, randomized, placebo-controlled study in patients with advanced PCa. InterventionPatients receiving ADT were randomly assigned at a 2:1 ratio to daily treatment with a high dose of E4 (HDE4; n = 41) or placebo (n = 21) for 24 wk. Outcome measurements and statistical analysisThe primary outcome was the effect of HDE4 cotreatment on hot flushes (HFs). Secondary outcomes were the Q-Man questionnaire for evaluation of the effect on estrogen and androgen deficiency symptoms, and the FACT-P questionnaire for evaluating HRQL. Results and limitationsAt 24 wk, the number of patients experiencing HFs was significantly lower in the HDE4 group than in the placebo group (14.3% vs 60.0%; p < 0.001). HDE4 treatment was associated with lower incidence of night sweats, arthralgia, and fatigue, but more nipple tenderness and gynecomastia. At 24 wk, the mean HRQL score favored HDE4 over placebo for the FACT-P total score (122.2 ± 12.3 vs 118.7 ± 19.7) and for several other FACT subscales. ConclusionsDaily HDE4 coadministration almost completely prevented HFs in patients with advanced PCa treated with ADT. HDE4 also had positive effects on HRQL and counteracted other estrogen deficiency symptoms caused by ADT. These data support the dual efficacy concept of ADT and HDE4 to improve HRQL and increase the antitumor effect of ADT. Patient summaryFor patients on androgen deprivation therapy for advanced prostate cancer, cotreatment with a high dose of estetrol almost completely prevents the occurrence of hot flushes and improves quality of life and well-being, but nipple sensitivity and an increase in breast size may occur.

Novel testosterone gel improves aging males' symptoms in patients with late-onset hypogonadism: Active control equivalence, randomized, double-blind, crossover pilot study

ABSTRACT Introduction The standard treatment for late-onset hypogonadism (LOH) is testosterone replacement therapy (TRT). In Japan, testosterone enanthate intramuscular injection is recommended for LOH. But it needs regular clinic visits every 2-3 week, and it elicit pain. The 2% testosterone gel (AndroForte2®) is available for treatment LOH. Because of imported drug, AndroForte2® (AF2) is expensive. We have created a 2 % novel testosterone gel (NTG). Objective We hypothesized that our NTG improves Aging males' symptoms (AMS) scores, and serum testosterone in patients with LOH. Methods In this active control equivalence, randomized, double-blind, crossover study, it enrolled that were men with low serum free-testosterone (defined as below 11.8pg/mL), and symptoms of androgen deficiency (defined as AMS scores more than 27). The patients were randomly divided into two groups (A group, men receiving the NTG first; and B group, men receiving the AF2 first). Men with LOH received 2% AF2 for 28 days or 2% NTG for another 28 days separated by a 14-day washout period. The AMS score and serum hormonal data, and adverse events were assessed. Results Twenty-three patients aged 42–71 years old were enrolled in and concluded the study with no adverse events experienced. Serum testosterone and free-testosterone concentrations were significantly higher with NTG and AF2. And more, both concentrations were significantly higher in NTG than AF2. The AMS total score, physical subscore, mental subscore, and sexual subscore were significantly improved with NTG, but not significant with AF2. Conclusions This is the first study to show that our NTG may not be effective for improvement serum testosterone level but also for physical, mental, and sexual symptoms in patient with LOH. Disclosure Work supported by industry: no.

Testosterone improved the erectile dysfunction induced by anti-cancer agent doxolubicine in rats

ABSTRACT Introduction Many chemotherapeutic agents are administered to cancer patients worldwide. We previously reported at the world meeting on Sexual Medicine 2018 that doxorubicin (DOX) increased the risk of erectile dysfunction (ED) according to our analyses of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database. We also reported that DOX decreased erectile function in a study using rats. DOX also decreased rat testosterone levels. These studies suggest a need for a new treatment method for ED associated with anticancer drug treatment. Objective To investigate the effect of testosterone administration on DOX-induced ED in rats. Methods Twelve-week-old male Wistar ST rats were separated into Control, DOX, and DOX+T groups. DOX (3 mg/kg) was intravenously administered on days 1, 8, 15, and 22 in the DOX and DOX+T groups. Testosterone undecanoate (25 mg/kg) was administered to DOX+T rats on day 1. Erectile function was tested using ICP measurements, and endothelial function was tested by assessing isometric tension. Oxidative stress (NADPH oxidase), inflammation (IL-6), and smooth muscle factor (α-SMA, Cavin-1, and Cavin-2) mRNA expression levels were tested using real-time PCR. Results After the 4-week observation period, the ICP/MAP ratio in the DOX group (0.32 ± 0.03) was significantly decreased compared to the Control group (0.72 ± 0.05) (P &amp;lt;0.01). The ICP/MAP ratio in the DOX + T group (0.61 ± 0.07) was increased significantly compared to the DOX group (P &amp;lt;0.01). According to isometric tension measurements, reactivity to acetylcholine was significantly lower in the DOX group (35.0 ± 5.1%) than in the control group (77.6 ± 7.9%), whereas reactivity in the DOX + T group (69.8 ± 8.5%) was significantly improved (P &amp;lt;0.05). NADPH oxidase-1 and IL-6 mRNA levels were increased in the DOX group compared to the Control group (P &amp;lt;0.01), and levels were decreased relative to the DOX group in the DOX+T group. α-SMA, Cavin-1, and Cavin-2 mRNA levels were decreased in the DOX group compered to the Control group. These levels were improved in the DOX+T group. Conclusions We have demonstrated in rats that androgen replacement therapy may mitigate ED induced by DOX administration. We hypothesize that administration of testosterone improves smooth muscle function and vascular endothelial cell function by suppressing oxidative stress and inflammatory response in the corpus cavernosum, and maintaining normal levels of caveolin-related factors. When androgen deficiency symptoms are observed due to administration of anticancer drugs such as DOX, androgen replacement therapy is expected to be one viable treatment option. Our study sheds light on possible treatment strategies for improving quality of life for cancer survivors. Disclosure Work supported by industry: no.

Pituitary-gonadal system dysfunction in middle-aged men with an uncontrolled asthma

The functional state of the pituitarygonadal system is investigated in 90 middle-aged men with the uncontrolled asthma and 35 healthy volunteers. According to the severity of the disease, the patients were stratified into two groups: moderate and severe. To assess the symptoms of an androgen deficiency and sexual dysfunction, the Aging Males Symptoms and the International Index of the Erectile Function were used. The activity of the pituitarygonadal system was assessed by determining the serum levels of testosterone, sex hormone binding globulin, prolactin, estradiol, luteinizing and follicle-stimulating hormone as well as cortisol. It was found that in patients suffering from asthma, symptoms of androgen deficiency and sexual dysfunction are revealed significantly more often than in the healthy middle-aged men, and the severity of these disorders depends on the severity of the disease. At the same time, in patients suffering from asthma, before the treatment, there was a significant decrease in the serum level of androgens, cortisol, and an increase in the sex hormone binding globulin, luteinizing and follicle-stimulating hormone, depending on the severity of the disease, in comparison with healthy subjects. After the treatment, the levels of sex hormone binding globulin, luteinizing hormone and follicle-stimulating hormone were restored, while the levels of androgens and cortisol remained reduced. A significant decrease in the level of prolactin was detected only after the treatment in patients suffering from a severe asthma. Thus, in middle-aged men with an uncontrolled asthma, symptoms of androgen deficiency, and dysfunction of the pituitarygonadal and reproductive systems are significantly more common than in the healthy individuals of the same age. Moreover, the severity of these disorders is influenced not only by the severity of the asthma, but also by the treatment with the systemic corticosteroids.

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

BackgroundTo compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls.MethodsWe performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression.ResultsThe questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and less likely to suffer from lifetime depression.Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p < 0.001; cluster headache 5.62 ± 0.99, p < 0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p < 0.001; cluster headache: − 5.25 ± 0.56, p < 0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001).ConclusionMen with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.

Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone.

Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = -0.41; P = 0.002), and CRP (r = -0.28; P = 0.041). Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.

P0523 - Androgen receptor gene polymorphism modulates symptoms of androgen deficiency and erectile function in men with type 2 diabetes and hypogonadism

P0523 - Androgen receptor gene polymorphism modulates symptoms of androgen deficiency and erectile function in men with type 2 diabetes and hypogonadism

Management of late-onset hypogonadism: person-centred thresholds, targets, techniques and tools.

Late-onset hypogonadism (LOH) is a complex and highly debatable syndrome in ageing men, which is characterised by reduced testosterone levels associated with classical symptoms of androgen deficiency. This article discusses the complex issues surrounding its management related to patient-centric thresholds and therapeutic targets. It specifically highlights the need to consider symptoms as the starting point, the key milestones in the management and the target of treatment, while ensuring safety at all times. The diagnosis of LOH requires a high index of suspicion and early identification of symptoms followed by appropriate investigations. The threshold for initiation of treatment has to be person centric and requires individualised decisions. The dose, preparation, route and follow up after testosterone initiation also may vary among different people. A person-centred approach is key to the successful management of this complex, nebulous yet debilitating disease.

Clinical and biochemical correlates of hypogonadism in men with type 2 diabetes mellitus.

Introductionthere is an association between hypogonadism and obesity, chronic hyperglycaemia, and ageing in men with type 2 diabetes mellitus (T2DM). T2DM is known to be associated with low testosterone. There is a paucity of data on the risk factors of hypogonadism in Nigerian men with T2DM. The objective of this study was to determine the clinical and biochemical correlates of hypogonadism and clinical predictors of low total testosterone levels in men with T2DM.Methodsthis was a cross-sectional study consisting of 358 men with T2DM and 179 non-diabetic men (controls). Structured Androgen Deficiency in the Ageing Male questionnaire was administered. Clinical and biochemical parameters were measured. Free testosterone was calculated from albumin, SHBG and total testosterone using Vermeulen´s method. Hypogonadism was defined as fasting TT as < 8 nmol/L with or without symptoms or TT of 8-12 nmol/L with symptoms of androgen deficiency. Low testosterone was defined as serum total testosterone levels ≤ 12 nmol/L.Resultsthe mean (±SD) total testosterone of men with T2DM and controls were 8.79±3.35 nmol/L and 15.41±3.79 nmol/L respectively (p < 0.001). The risk of hypogonadism was associated with central obesity (Odds ratio [OR] 2.24, 95% confidence interval [CI] 0.38-13.07), systolic hypertension (OR 3.93, 95% CI 0.67-23.10), hyperglycaemia (OR 2.48, 95% CI 0.37-16.46) and hypercholesterolaemia (OR 2.50, 95% CI 0.43-14.61). In a multivariable regression analysis, there was a significant negative correlation between total testosterone and triglycerides (r -1.85, 95% CI -3.58 - 0.12, P = 0.04) and HDL cholesterol (r -1.25, 95% CI -5.95-3.45, P = 0.02).Conclusionthis study shows that in men with T2DM, triglycerides and HDL cholesterol are independent correlates of hypogonadism but not central adiposity, systolic blood pressure and glycaemia. Further large prospective studies are recommended.

Evaluation of predictors of erectile dysfunction and hypogonadism in men with types 2 diabetes mellitus

Background: Now a day erectile dysfunction (ED) and hypogonadism of the patients with type 2 diabetes mellitus (T2DM) become two common complaints. The association among hypogonadism, erectile dysfunction and type 2 diabetes of man seem to be increased. The aim of this study was to evaluate the predictors of erectile dysfunction and hypogonadism in men with types 2 diabetes mellitus (T2DM). Methods: This was a cross-sectional study which was conducted in the Department of Shaheed Monsur Ali Medical College Hospital, Dhaka, Bangladesh Hospital, Bangladesh during the period from January 2019 to December 2019. In total 352 newly detected T2DM male patients, with complete data were finalized as the study population. All data were processed by using SPSS program version 23.0.Results: In this study, according to complement fixation test (cFT) and androgen deficiency in the aging male (ADAM) criteria, 119 (33.81%) participant had low cFT&amp; ADAM positive under hypogonadal, 84 (23.86%) were with normal TT &amp; ADAM negative (eugonadal), 37 (10.51%) were with low TT &amp; ADAM negative (eugonadal), 112 (31.82%) were with normal TT &amp; ADAM positive (eugonadal). On the other hand, according to the cFT and ADAM score in total 119 (33.81%) hypogonadal patients were with low cFT &amp; ADAM positive. Besides this, 102 (43.78%) eugonadal patients were with normal cFT &amp; ADAM negative and 131 (56.22%) eugonadal patients were with normal cFT &amp; ADAM positive.Conclusions: Hence, universal screening of testosterone level and androgen deficiency symptoms is recommended in newly detected T2DM patients.

Patient-reported outcomes and biochemical alterations during hormonal therapy in men with hypogonadotropic hypogonadism who have finished infertility treatment.

Male hypogonadotropic hypogonadism (MHH) is effectively treated by gonadotropins with a high rate of ejaculate sperm and paternity; however, there is no information regarding the appropriate management, including patient-reported outcomes (PROs), of men with MHH who have finished infertility treatment. To compare health-related quality of life, erectile function and biochemical alterations in men with MHH who were treated with testosterone replacement therapy (TRT) or human chorionic gonadotropin (hCG). Twenty-six MHH patients (mean age: 34 years) who needed to improve their androgen deficiency symptoms underwent either hCG therapy (n = 16, started with self-injection of 2,000-7,500 IU per week) or TRT (n = 10, testosterone enanthate 250 mg every 3 weeks). The 36-item Short Form Health Survey (SF-36) questionnaire, five-item International Index of Erectile Function (IIEF-5) and hormonal and biochemical analyses were assessed every 3 months. Changes and comparison of each treatment regarding these parameters were analyzed. Both hCG and TRT significantly improved all domains of the SF-36, except for bodily pain and social functioning. hCG significantly improved the general and mental health domains compared with TRT. Significant improvements in IIEF-5 were observed with both treatments, showing significant improvement with hCG compared to TRT. TRT caused progressive testicular atrophy. There were significant decreases in waist circumference and triglycerides in both treatment groups and significant elevations in prostate-specific antigen and hematocrit. Both hCG and TRT are effective and safe, with preferable PROs by hCG, for treating androgen deficiency in men with MHH who do not need infertility treatment.

Three-dimensional simulation analysis of microdissection testicular sperm extraction for patients with non-obstructive azoospermia.

BackgroundMicrodissection testicular sperm extraction (microTESE) is considered the gold standard method of sperm retrieval from patients with non‐obstructive azoospermia (NOA). For careful and thorough examination of seminiferous tubules during microTESE, maximizing surface area of the testicles which we are able to search is essential.ObjectivesTo develop a systematic procedure for microTESE to maximize surface area and to achieve high sperm retrieval rate (SRR) in microTESE.Materials and methodsWe simulated microTESE using three‐dimensional (3D) simulation model and analyzed mathematically the sum of the surface area in various methods. The best method obtained from this simulation model was applied to 102 patients with NOA from 2014 to 2018. These new clinical results were compared with those of 56 patients who underwent a previous method of microTESE from 2011 to 2014.ResultsThe mathematical 3D simulation model of microTESE indicated that a longitudinal incision on the tunica albuginea and following transverse slicing incisions of testicular parenchyma maximized the surface area coverage. Forty‐six (45%) out of 102 patients who underwent microTESE with the new method had successful retrieval of testicular spermatozoa compared with 16 (29%) of 56 patients with the previous method of microTESE (P = .04).DiscussionTransverse resections of parenchyma in our method run parallel to the courses of intratesticular arteries and do not interfere with the blood supply. The small amount of extracted seminiferous tubules was equivalent to that of the previous method, and no patients exhibited post‐operative symptoms of androgen deficiency in our study. As for post‐operative pain, our new method was comparable with the previous method. Although our study needs a longer follow‐up, there will be limited effects on testicular functions.ConclusionLongitudinal incision on the tunica albuginea and following transverse slicing incisions in the testicular parenchyma maximized the surface area and improved the SRR of microTESE.

Androgen-Regulated Cardiac Metabolism in Aging Men.

The prevalence of cardiovascular mortality is higher in men than in age-matched premenopausal women. Gender differences are linked to circulating sex-related steroid hormone levels and their cardio-specific actions, which are critical factors involved in the prevalence and features of age-associated cardiovascular disease. In women, estrogens have been described as cardioprotective agents, while in men, testosterone is the main sex steroid hormone. The effects of testosterone as a metabolic regulator and cardioprotective agent in aging men are poorly understood. With advancing age, testosterone levels gradually decrease in men, an effect associated with increasing fat mass, decrease in lean body mass, dyslipidemia, insulin resistance and adjustment in energy substrate metabolism. Aging is associated with a decline in metabolism, characterized by modifications in cardiac function, excitation-contraction coupling, and lower efficacy to generate energy. Testosterone deficiency -as found in elderly men- rapidly becomes an epidemic condition, associated with prominent cardiometabolic disorders. Therefore, it is highly probable that senior men showing low testosterone levels will display symptoms of androgen deficiency, presenting an unfavorable metabolic profile and increased cardiovascular risk. Moreover, recent reports establish that testosterone replacement improves cardiomyocyte bioenergetics, increases glucose metabolism and reduces insulin resistance in elderly men. Thus, testosterone-related metabolic signaling and gene expression may constitute relevant therapeutic target for preventing, or treating, age- and gender-related cardiometabolic diseases in men. Here, we will discuss the impact of current evidence showing how cardiac metabolism is regulated by androgen levels in aging men.

Lipid accumulation product and late-onset hypogonadism in middle-aged and elderly men: results from a cross-sectional study in China

ObjectivesHypogonadism in men is related to the deterioration of general health. However, the association between lipid overaccumulation and ageing-related hypogonadism remains an undetermined concept. We aimed to provide an insight...