Total Testosterone Levels Research Articles

(155) Transcutaneous Electrical Neural Stimulation Improves Overall Satisfaction in Patients with Erectile Dysfunction

Abstract Introduction Transcutaneous electrical neural stimulation (TENS) therapy has demonstrated the potential to augment peripheral blood flow towards the musculature, thereby enhancing oxygen supply to the working muscles. Erectile dysfunction (ED) is a pathological condition characterized by compromised blood flow to the penis. In theory, TENS therapy can enhance penile blood circulation and alleviate the symptoms associated with ED. Objective Therefore, we aimed to assess the effects of penile TENS therapy on reducing ED symptoms and improving erectile function (EF). Methods We conducted a pilot cohort trial following approval from the Institutional Review Board (IRB), in which we enrolled patients presenting with clinical ED at our clinic. The TENS therapy intervention comprised ten sessions lasting 20 min each, administered over a period of 5 weeks. Two TENS patches were used, with one patch positioned at the base of the penis and the second patch placed on the perineum. The intensity of TENS therapy was determined using a scale ranging from 0 to 10, with the patients selecting the maximum intensity that they could tolerate without experiencing pain. Baseline and post-therapy questionnaires were administered using the International Index of Erectile Function (IIEF) as the primary outcome measure. A paired t-test was conducted to assess the results, which are presented as the mean difference (MD) along with a 95% confidence interval. Results Ten patients, all of whom were already receiving oral PDE5i medications ED were enrolled. However, specific drugs, dosages, and regimens were not standardized across patients, although they maintained the same treatment regimen throughout the study period. The mean baseline total testosterone level was at 527.9 ng/dL. On average, the intensity of TENS therapy administered to the patients was 6.58. A statistically significant improvement in the IIEF total score was seen with an MD of 5.6 (95% CI:0.35, 10.85; p = 0.03). Additionally, a statistically significant difference was observed in the IIEF overall satisfaction domain, with an MD of 1.20 (95% CI:0.14, 2.26; p = 0.03). However, no significant differences were found in IIEF erectile function, desire, orgasm, and intercourse satisfaction subdomain scores. Furthermore, none of the patients reported any adverse effects associated with TENS therapy. Conclusions These findings suggest that TENS therapy has the potential to improve the overall satisfaction of patients with ED. Further research with larger sample sizes and randomized controlled trials are warranted to validate these initial findings and to elucidate the full potential of TENS therapy in ED management. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Disclosures: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.

(170) Satisfaction with Penile Prosthesis Implantation among Patients with Peyronie’s Disease Using a Contemporary Questionnaire

Abstract Introduction The Satisfaction Survey for Inflatable Penile Implants (SSIPI) is a recently validated 16-question survey used to quantitatively measure patient outcomes after penile prosthetic surgery. The survey consists of four subdomain scores representing the appearance, pain, satisfaction, and function of the penile implant. Since its validation, there have been limited studies examining its use in patients with Peyronie’s disease (PD). Objective The objective of this study is to explore the use of the SSIPI in men with Peyronie’s Disease and to determine if any factors predict patient-perceived postoperative outcomes. Methods Preoperative, intraoperative, and postoperative data for patients with PD undergoing implantation of an inflatable penile prosthesis (IPP) by a single surgeon at a tertiary care institution was retrospectively collected into a secure database. Only those patients with at least one completed SSIPI postoperatively were included in the analysis. For those patients with multiple completed SSIPI’s, only the most recently completed one was used. Linear regression and Fischer’s exact test were used to determine if there were any significant relationships between variables and the SSIPI scores. Results There were a total of 44 men with PD who underwent surgery for an IPP. 31 of them were Caucasian, 11 were African-American, and one each were Hispanic and American Indian/Native American. Median time between surgery and completion of the SSIPI at a follow-up visit was 291 days (IQR 107.75-403.50). 35 men received a Coloplast Titan and 9 received an AMS 700 CX. There was no significant difference in the overall SSIPI score and any of the subdomains between men who received different types of implants or between men of different races. All four subdomains were significantly negatively correlated with the residual curvature which was measured intraoperatively after the IPP was implanted and any adjunctive straightening techniques were used (Fig 1a-d). The appearance domain was also significantly negatively correlated with the preoperative total testosterone indicating that men with a lower total testosterone level were more satisfied with the appearance of their penis. (p < 0.05, R2 = 0.32). Interestingly, those men who underwent manual modeling (n=36) had a significantly lower score in the appearance domain (p < 0.05). Conclusions Post-operative residual curvature in men with PD undergoing implantation of an IPP is a predictor of satisfaction with the IPP. The role of preoperative testosterone and intraoperative manual modeling in how men with PD perceive the appearance of their penis postoperatively requires further investigation. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific.

(341) First-time Orgasm in a Man with Flibanserin Use: A Case Report

Abstract Introduction Anorgasmia is a poorly understood phenomenon defined as either a lifelong or an acquired consistent inability to achieve ejaculation. Despite the prevalence of anorgasmia, there is currently no established treatment. Objective In this abstract, we present the unique case of a patient with lifelong anorgasmia who was able to achieve his first orgasm with off-label use of flibanserin. Methods A 28-year-old male presented to our office with complaints of lifelong anejaculation and anorgasmia, without any signs of erectile dysfunction. He reported good libido and energy levels and denied any urinary symptoms or history of depression. Physical examination revealed normal genital anatomy without lesions. Testicular size was within normal limits, and a palpable varicocele was noted. Hormonal evaluations revealed total testosterone levels of 590 ng/dl and prolactin levels of 12 ng/ml. The baseline International Index of Erectile Function (IIEF) score was 41, with an orgasmic function sub-domain (IIEF-OF) score of 2. The patient had no history of major surgeries. He denied any neurological, infectious, or endocrine cause of anejaculation or anorgasmia. He was not taking medications that could cause these symptoms, except for over-the-counter allergy medications. Upon further questioning, the patient equated orgasm with ejaculation and reported having never experienced any previous orgasms. Results The patient was prescribed 150 mg of bupropion daily, which was increased to 300 mg daily after two weeks, in combination with sex therapy. Despite having received four–five sex therapy sessions over three months, the patient reported that this treatment approach was not effective. Subsequently, bupropion was tapered and discontinued. The patient was then started on bremelanotide, administered at a dose of 10 mg/mL, injecting 0.2mL (2 mg) before sexual activity. Although various forms of stimulation were attempted, the patient was unable to achieve orgasm with bremelanotide, and experienced penile pain. Flibanserin was then initiated, and after 28-32 doses over four weeks, the patient achieved his first orgasm. Notably, the patient also experienced nocturia and insomnia after initiating this medication. The follow-up IIEF score marginally improved by two points without any improvement in IIEF-OF. Conclusions This case highlights the challenges in managing anorgasmia and anejaculation in a young male patient. A stepwise approach, involving pharmacotherapy and sex therapy, was unsuccessful. However, off-label use of flibanserin ultimately resulted in the patient achieving his first orgasm, albeit with some side effects. Further studies are required to evaluate the efficacy and safety of flibanserin for this indication. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.

Systematic review and meta-analysis of serum total testosterone and luteinizing hormone variations across hospitalized Covid-19 patients

A growing body of evidence suggests the role of male hypogonadism as a possible harbinger for poor clinical outcomes across hospitalized Covid-19 patients. Accordingly, we sought to investigate the impact of dysregulated hypothalamic-pituitary–gonadal axis on the severity of the clinical manifestations for hospitalized Covid-19 patients matched with healthy controls through a systematic review and meta-analysis. Databases were searched from inception to March 2022. A standardized mean difference (SMD) meta-analysis focused on hospitalized Covid-19 patients and healthy controls was developed for studies who reported total testosterone (TT) and luteinizing hormone (LH) levels at hospital admission. Overall, n = 18 series with n = 1575 patients between 2020 and 2022 were reviewed. A significant decrease in SMD of TT levels in Covid-19 patients compared to paired controls was observed (− 3.25 nmol/L, 95%CI − 0.57 and − 5.93). This reduction was even more consistent when matching severe Covid-19 patients with controls (− 5.04 nmol/L, 95%CI − 1.26 and − 8.82) but similar for Covid-19 survivors and non-survivors (− 3.04 nmol/L, 95%CI − 2.04 and − 4.05). No significant variation was observed for serum LH levels across studies. Patient related comorbidities, year of the pandemic, and total lymphocyte count were associated with the observed estimates. TT levels may be a useful serum marker of poor outcomes among Covid-19 patients. These findings may support the development of ad-hoc clinical trials in the Covid-19 risk-group classification and subsequent disease monitoring. The interplay between TT and immune response should be evaluated in future researches.

Oncostatin M Is Related to Polycystic Ovary Syndrome-Case Control Study.

Background: Oncostatin M, a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to polycystic ovary syndrome pathogenesis and related metabolic problems. Adipokines are believed to contribute to developing polycystic ovary syndrome and its accompanying metabolic parameters, such as dyslipidemia, insulin resistance, and cardiovascular diseases. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the polycystic ovary syndrome (n = 32) or the control group (n = 32). Serum levels of fasting glucose, insulin, C-reactive protein, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin, estradiol, homeostasis model assessment of insulin resistance, and oncostatin M were analyzed. Results: Oncostatin M levels were significantly lower, but C-reactive protein levels were substantially higher in the polycystic ovary syndrome group than in the control group (p = 0.002, p = 0.001, respectively). Oncostatin M was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = -0.329, p =0.017; ρ = -0.386, p = 0.005; ρ = -0.440, p = 0.001; ρ = -0.316, p = 0.023, respectively). Conversely, there was no correlation between oncostatin M and total testosterone level (ρ = 0.220; p = 0.118). In the context of inflammation and metabolic parameters, oncostatin M was inversely correlated with C-reactive protein, homeostatic model assessment for insulin resistance score, and low-density lipoprotein cholesterol (ρ = -0.353, p = 0.019; ρ = -0.275, p = 0.048; ρ = -0.470, p < 0.001, respectively). Conclusions: Plasma oncostatin M levels were considerably lower in patients with polycystic ovary syndrome than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of polycystic ovary syndrome. Thus, oncostatin M may be a novel therapeutic target for polycystic ovary syndrome and its metabolic parameters.

Type 2 Diabetes Mellitus and Erectile Dysfunction: A study on risk factors and their correlation to serum testosterone level.

Background &#x0D; Diabetes mellitus (DM) is one of the major cause of erectile dysfunction (ED). Testosterone regulates nearly every component of ED and this subnormal testosterone concentration con tribute to ED. &#x0D; The objective of our work was to study the age of the patient, duration of diabetes mellitus, body mass index (BMI), glycosylated haemoglobin (hbA1c) and urinary albumin creatinine ratio (uACR) in type 2 diabetic male patients as etiology for ED and their relation to the serum testosterone level. &#x0D; Methodology &#x0D; We studied 100 male type two diabetic patients selected from the outpatient department of the Family Medicine department in Olive Healthcare. We divided our patients into two groups. Group A: 50 patients with type 2 diabetes mellitus with ED and Group B: 50 patients with type 2 diabetes mellitus without ED. We assessed their history with special focus on the age of the patient, disease duration and lab investigations. The patients answered the five item version of the International Index of Erectile Function (IIEF-5) questionnaire. &#x0D; Results &#x0D; Total serum testosterone was significantly lower in type 2 diabetic male patients with ED compared to those without ED. HbA1c, diabetes duration and uACR were independently negatively correlated with testosterone level. &#x0D; Conclusion &#x0D; The duration of diabetes, glycemic control and uACR contributed to ED in type 2 diabetics and they are independently and negatively correlated with total serum testosterone level.

Exploring Hematological and Biochemical Disparities in Same-Sex and Opposite-Sex Females: A Cross-Sectional Twin Study in a Ghanaian Population.

There are sex-dependent differences in hematological and biochemical variables in adulthood attributed to the predominant effects of testosterone in males and estrogen in females. The Twin Testosterone Transfer (TTT) hypothesis proposes that opposite-sex females may develop male-typical traits due to exposure to relatively higher levels of prenatal testosterone than same-sex females. Additionally, prenatal testosterone exposure has been suggested as a correlate of current circulating testosterone levels. Consequently, opposite-sex females might exhibit male-typical patterns in their hematological and biochemical variables. Despite this hypothesis, routine laboratory investigations assign the same reference range to all females. Our cross-sectional study, conducted in Tamale from January to September 2022, included 40 twins, comprising 10 opposite-sex (OS) males (25%), 10 OS females (25%), and 20 same-sex (SS) females (50%), all aged between 18 and 27 years. Fasting venous blood samples were collected and analyzed using automated hematology and biochemistry laboratory analyzers. Results indicated that levels of hemoglobin, serum creatinine, gamma-glutamyl transferase, total protein, globulins, and total testosterone were significantly higher in OS males than OS females. Conversely, total cholesterol and low-density lipoprotein cholesterol were significantly higher in OS females than OS males. Unexpectedly, levels of low-density lipoprotein cholesterol and total testosterone were significantly higher in SS females than OS females. Contrary to expectations, opposite-sex females did not exhibit male-typical patterns in their hematological and biochemical variables. This suggests that the TTT effect may not occur or may not be strong enough to markedly affect hematological and biochemical variables in OS females.

Utilization of patient-reported outcomes to assess adherence to relugolix when combined with radiation therapy.

319 Background: Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy (RT). Relugolix is an oral GnRH receptor antagonist that achieves rapid testosterone suppression. Non-adherence to oral medications due to poor social support or bothersome side effects may increase the risk of cancer recurrence. This prospective study sought to evaluate early testosterone suppression and relugolix drug adherence when combined with RT. Utilization of patient-reported outcomes (PROs) to evaluate oral medication adherence and guide intervention may improve appropriate utilization of oral medications. This study focuses on the use of the Simplified Medication Adherence Questionnaire (SMAQ) as a tool to assess relugolix adherence. Methods: Relugolix was initiated at least 2 months prior to questionnaire administration. Adherence was assessed using the SMAQ. Total testosterone levels were obtained at the time of SMAQ administration. Castration was defined as serum testosterone ≤ 50 ng/dL. Poor drug adherence was delineated as failure to reach castration or non-adherence per the SMAQ (any non-adherence answer, missed &gt;2 doses in last week or since last visit). To compare the demographic and clinical characteristics of patients who adhered to treatment versus who did not, t-test, Wilcoxon rank sum test, Chi-square test, and Fisher’s exact test were used. A p-value &lt;0.05 determined statistical significance. Results: Between May 2021 and June 2023, 92 men were treated at Georgetown with relugolix and RT per an institutional protocol. The median age was 73 years, and 32% of patients were non-white. Patients initiated relugolix at a median of 5 months prior to the SMAQ (2-24 months). 97% of patients achieved castration (≤ 50 ng/dL) at the time of the SMAQ. 96% of men reported always taking relugolix at the appropriate time. 3% discontinued medication due to bothersome side effects, 18% reported forgetting to take the medication, and 2% reported missing a dose during the weekend. 99% and 97% did not miss a dose more than 2 times in the last week and since the last visit, respectively. Overall patient-reported drug adherence was 73%. Conclusions: Relugolix allows for high rates of castration and drug adherence when combined with RT. Monitoring drug adherence during treatment allows for prompt detection of non-adherence and timely intervention. Future studies should focus on how to optimally incorporate this questionnaire into patient management. [Table: see text]

Placental mRNA Expression of Neurokinin B Is Increased in PCOS Pregnancies with Female Offspring.

Current research suggests that polycystic ovary syndrome (PCOS) might originate in utero and implicates the placenta in its pathogenesis. Kisspeptin (KISS1) and neurokinin B (NKB) are produced by the placenta in high amounts, and they have been implicated in several pregnancy complications associated with placental dysfunction. However, their placental expression has not been studied in PCOS. We isolated mRNA after delivery from the placentae of 31 PCOS and 37 control women with term, uncomplicated, singleton pregnancies. The expression of KISS1, NKB, and neurokinin receptors 1, 2, and 3 was analyzed with real-time polymerase chain reaction, using β-actin as the reference gene. Maternal serum and umbilical cord levels of total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), androstenedione, dehydroepiandrosterone sulfate (DHEAS), Anti-Mullerian hormone (AMH), and estradiol were also assessed. NKB placental mRNA expression was higher in PCOS women versus controls in pregnancies with female offspring. NKB expression depended on fetal gender, being higher in pregnancies with male fetuses, regardless of PCOS. NKB was positively correlated with umbilical cord FAI and AMH, and KISS1 was positively correlated with cord testosterone and FAI; there was also a strong positive correlation between NKB and KISS1 expression. Women with PCOS had higher serum AMH and FAI and lower SHBG than controls. Our findings indicate that NKB might be involved in the PCOS-related placental dysfunction and warrant further investigation. Studies assessing the placental expression of NKB should take fetal gender into consideration.

The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40:1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria

Setting: Insulin resistance (IR) and compensatory hyperinsulinemia are considered contributing factors toward polycystic ovary syndrome (PCOS). Objectives: This study evaluates the frequency of metabolic abnormalities in PCOS patients and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio on hormonal and metabolic parameters. Participants: Thirty-four women with PCOS phenotype A (endocrine-metabolic syndrome [EMS-type 1]) between the ages of 20–40. Design: Open prospective study with phenotype A (EMS-type I, n = 34) supplemented with 2,255 mg/day of inositol (MI and DCI in a 40:1 ratio) for 3 months. Methods: The following were measured before and after treatment: serum levels of follicular stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), anti-Müllerian hormone, glucose, insulin, HOMA-IR, and body mass index (BMI). Results: 55.9% of the enrolled patients were overweight or obese, 50% affected by IR, 17.6% with a history of gestational diabetes mellitus, and 61.8% had familial diabetes mellitus. At the conclusion of the study, BMI (p = 0.0029), HOMA-IR (p < 0.001) significantly decreased, along with decreased numbers of patients with elevated insulin levels. The supplementation resulted in decreased total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001); increased SHBG (p < 0.001) and estradiol (p < 0.001). Limitations: The present analysis was limited to a 12-week follow-up, which precluded a long-term evaluation of the effects of MI and DCI combination. Also, this period was insufficient to achieve and analyze clinical changes such as restoration of the menstrual cycle, restoration of reproductive function, and clinical manifestations of hyperandrogenism. Conclusions: Supplementation improved metabolic and hormonal profile in PCOS phenotype A (EMS-type I) patients. This builds upon previous work that demonstrated that combined inositol treatment may be effective in PCOS. The study presented herein, used a reduced concentration than in prior literature; however, a significant change in hormonal and metabolic parameters was still observed.

Evaluation of the Incidence of Low Testosterone Levels in Young Male Adults with Moderate to Severe Obesity-Single-Centre Study from India.

With the increase in obesity epidemic among Asians, it is necessary to evaluate the impact of obesity on this population. Low testosterone levels are known to be associated with obesity. This is the 1st study from Asia to evaluate incidence and magnitude of hypotestosteronemia in young adults with BMI more than 32.5kg/m2 defined as moderate to severe obesity in Asians. One hundred thirty-four male patients with BMI more than 32.5kg/m2, between 18 and 30years old who visited a single bariatric facility between 2017 and 2020, were evaluated with BMI, total and free testosterone levels and clinical features of gynecomastia, hypogonadism, and thinning of pubic and armpit hair. Statistical analysis was performed using SPSS, Spearman's correlation coefficient, and ANOVA test. 60.4% of patients (84/134) had low testosterone levels (< 300ng/dl) and 23.9% (32/134) had levels between 300 and 400ng/dl. 89.6% patients (120/134 had gynecomastia, 60.4% (81/134) had thinning of pubic and arm pit hair, and 62.7% (84/134) had hypogonadism. Testosterone levels showed a decreasing trend with increasing BMI, but it was not statistically significant. Obesity is one of the important etiologies of hypotestosteronemia and its manifestations in young adults. The actual incidence may be significantly higher than what is reported in the literature. High-quality research is required to address questions of diagnosis and best treatment options.

Characteristics of bone mineral density in patients with functional hypothalamic amenorrhoea and its association with reproductive hormones and body composition.

Bone mineral density (BMD) is typically reduced in patients with female athlete triad (FAT) and anorexia nervosa (AN). However, bone health in most patients with functional hypothalamic amenorrhoea (FHA), who may not suffer from severe energy deficiency, has not received adequate attention in clinical practice. This study aimed to investigate BMD and its association with clinical and endocrine features in individuals with FHA and to provide clinical evidence for improving bone loss and preventing osteoporosis in FHA. To assess the bone status of patients with FHA and investigate its association with various clinical and endocrinological characteristics. We retrospectively analysed 80 patients with FHA who attended the Obstetrics and Gynecology Hospital of Fudan University from January 2022 to March 2023. The levels of reproductive hormones, including luteinising hormone (LH), follicle-stimulating hormone, oestradiol (E2 )and total testosterone (TT), were examined at the time of initial diagnosis, and a body composition analyser was used to measure body fat percentage (BF%), lean body mass (LBM)and segmental muscle/fat. Dual-emission X-ray absorptiometry was used to measure lumbar spine BMDand femoral neck BMDin patients with FHA, and the Z score was calculated. The study cohort consisted of 80 female patients with FHA. The average age of the patients was 24.64 ± 6.02 years, and their body mass index (BMI) was 19.47 ± 2.86 kg/m2 . The duration of weight loss was 12 (6, 24) months, while the duration of oligo/amenorrhoea was 12 (4.5, 24) months. The mean degree of weight loss was 18.39 ± 9.53%. Low BMD were present in 15% of patients with FHA at the lumbar spine and/or femoral neck; 12.5% and 10% had low bone mass at the lumbar spine and femoral neck, respectively. The low bone mass group experienced a longer period of weight loss than the normal group [24 (16.5, 60) vs. 12 (4.5, 24) months, p = .037]. In addition, the abnormal group had a lower BMR (basal metabolic rate, BMR) [1158 ± 85 vs. 1231 ± 91 kcal/day, p = .011] and lower bone mineral content [2.15 ± 0.26 vs. 2.43 ± 0.31 kg, p = .009] than the normal group. Both LBMD and femoral neck BMD (Fn BMD) were positively correlated with BMI, BF%, LBM, and regional muscle/fat mass (all p < .05). There was also a positive correlation between LBMD and basal LH levels (p = .009) and waist-to-hip ratio (p = .034), whereas Fn BMD was positively correlated with TT levels (p = .029). Multiple linear regression analysis showed that LBM was positively associated with LBMD (β = .007, 95% confidence interval [CI] = 0.004-0.009, p < .001), while trunk muscle mass was positively associated with Fn BMD (β = .046, 95% CI = 0.013-0.080, p = .008). Fifteen percent of the patients with FHA exhibited low bone mass, a condition associated with prolonged weight loss. The basal LH and TT levels showed positive correlations with LBMD and Fn BMD, respectively. Meanwhile, BMR levels, BMI, BF%, and muscle mass were all positively correlated with LBMD and Fn BMD. Clinically, we should be attentive to suboptimal bone health in patients with FHA and take early screening, diagnosis and intervention measures, especially appropriate muscle mass gain, to prevent the onset of osteoporosis and fragility fractures in the long term.

P-40 A rare cause of male infertility: 46, XX testicular disorder of sex development

Abstract Introduction 46, XX testicular disorder of sex development (DSD) is a rare condition with an estimated incidence of 1 per 20,000 individuals. The clinical spectrum ranges from ambiguous genitalia that is usually diagnosed at birth, to male infertility that is diagnosed in the adult years. However, the diagnosis of 46, XX DSD in an individual presenting with infertility may be challenging due to occult clinical findings. A thorough physical examination as well as clinical suspicion is required for diagnosis. Clinical Case A 22-year-old male presented to the urology clinic for infertility despite at least 3 years of regular unprotected intercourse. On physical examination, his testicles were palpable bilaterally in the scrotum with small volumes. Laboratory results revealed hypergonadotropic hypogonadism and his spermiogram revealed azoospermia. Abdominopelvic ultrosonagraphy (US) was reported normal except abdominal situs inversus. Tumor markers for a probable testicular tumor were negative. He was referred to medical genetic department. His family history was unremarkable except for parental consanguineouty. The chromosomal analyze revealed a 46, XX karyotype, and fluorescence in situ hybridization (FISH) disclosed that the SRY gene locus was translocated to the X chromosome: 46,x,der(x) t(x;Y) (sry+); SRY + AZF a,b,c microdeletion. The patient was consulted to the endocrinology department for further evaluation of hypogonadism. On physical exam, he had eunuchoid habitus with incomplete virilization, bilateral and symmetric gynecomastia. The height, and body mass index of the patient was 165 cm, and 29.2 kg/m2, respectively. The testicles were bilaterally palpable in the scrotum, with a volume of 4 mL each. His luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone levels were 14 mUI/mL (laboratory reference: 1.5–9 mUI/mL), 42 mUI/mL (1.4–18 mUI/mL), and 140 ng/dl (197-700 ng/dL), respectively. The bone age matched his chronological age. Bone densitometry revealed osteopenia. A direct X-ray of the thorax showed thoracic situs inversus, he diagnosed with situs inversus totalis. Detailed genetic analyses could not be done concerning this diagnosis due to financial constraints. He had no history of lung infections that ruled out Kartagener's syndrome. Treatment was started with monthly intramuscular testosterone injections of 250 mg/ml. The patient and his family received genetic counseling, including advice that assisted reproduction will not work owing to AZFabc deletion. Conclusion 46, XX DSD is an uncommon genetic disorder that is rarely identified during the evaluation of male infertility. Clinical suspicion and a comprehensive physical exam are keys for diagnosis. Genetic analysis is essential for definitive diagnosis. A multidisciplinary is required for treatment and follow-up. Psychological support and genetic counseling are also critical for the management of these patients.

P-35 Luteinized Thecoma in a postmenopausal woman with Hirsutism

Abstract Introduction We present a 59-year-old postmenopausal woman with a history of obesity and hypertension who sought medical attention due to severe hirsutism. She had been taking various medications, including levotiroksin for thyroid hormone replacement, asetyl salicylic acid as an antiplatelet agent, Betahistin for vertigo, and amlodipine 10 mg for hypertension. Clinical Case The patient had been experiencing severe hirsutism for a year and her complaining had been deteriorating. Her past medical history was significant for obesity and hypertension. She had undergone menopause ten years ago. Her hirsutism, and obesity prompted further investigation into her hormonal profile and pelvic health. On physical examination, the patient's height was 153 cm, and her weight was 109.7 kg, with a BMI of 46.6. Notably, she exhibited severe hirsutism, with Feriman Gallway score of 15. The patient's laboratory results revealed TSH level was elevated at 4.98 mIU/L, indicating subclinical hypothyroidism. Further hormonal evaluation showed increased FSH levels (40 IU/L) and LH levels (12 IU/L), consistent with diminished ovarian function. DHEAS (dehydroepiandrosterone sulfate) level was 121 µg/dL, PRL (prolactin) was 7 ng/mL and both were between normal ranges. Total testosterone level (416,09 ng/dL) and estradiol level was 34.11 pg/mL (0 - 32,2 pg/mL for postmenopausal women) were increased. Free testesteron was increased (22 nmol/L) and 17-α hydroxyprogesterone was 0,61 ng/mL. Cortisol after 1mg-dexamethasone suppression test (1-mg DST) was 0.65 ug/dl. In March 2021, the patient underwent a pelvic ultrasound, which was inconclusive due to obesity. However, no masses were detected in the ovaries. An abdominal MR was also performed, revealing no significant findings in the ovaries. She was prescribed spironolactone 100 mg per day and orlistat for weight loss. In November 2021, the patient underwent surgery due to the discovery of a left-sided sex cord-stromal tumor during the pelvic examination. The histopathological examination confirmed the diagnosis of "Luteinized Thecoma" in the left ovary. The tumor was composed of luteinized cells capable of producing androgens, explaining the patient's hirsutism. Following the surgery, the patient experienced a reduction in hirsutism, possibly due to the removal of the hormonally active tumor. Moreover, she exhibited weight loss since the last prescription, with her weight reducing to 98.3 kg, resulting in a BMI of 41.4. Conclusion Hyperthecosis is mostly reported in postmenopausal women, affecting less than 1% of women of reproductive age. This case illustrates the diagnostic journey of a postmenopausal woman with hirsutism. The discovery of a Luteinized Thecoma, a rare sex cord-stromal tumor, explains the patient's hirsutism.

Sex hormones and the total testosterone:estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men.

The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111±89vs. 191±143ng/dL; p<0.001), dehydroepiandrosterone (1.69±1.26vs. 2.96±2.64ng/mL; p<0.001), and dehydroepiandrosterone sulfate (91.72±76.20vs. 134.28±98.261μg/dL; p=0.009), significantly higher levels of estradiol (64.61±59.35vs. 33.78±13.78 pg/mL; p=0.001), and significantly lower total testosterone:estradiol ratio (0.28±0.31vs. 0.70±0.75; p<0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p=0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p<0.001). Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.

Hypogonadism and sexual function in men affected by adrenocortical carcinoma under mitotane therapy.

Adrenocortical carcinoma (ACC) is a rare and aggressive tumor. ACC male patients under adjuvant mitotane therapy (AMT) frequently develop hypogonadism, however sexual function has never been assessed in this setting. The aim of this retrospective study was to evaluate in AMT treated ACC patients the changes in Luteinizing hormone (LH), Sex Hormone Binding Globulin (SHBG), total testosterone (TT) and calculated free testosterone (cFT), the prevalence and type of hypogonadism and sexual function, the latter before and after androgen replacement therapy (ART). LH, SHBG, TT and cFT were assessed in ten ACC patients at baseline (T0) and six (T1), twelve (T2), and eighteen (T3) months after AMT. At T3, ART was initiated in eight hypogonadal patients, and LH, SHBG, TT and cFT levels were evaluated after six months (T4). In six patients, sexual function was evaluated before (T3) and after (T4) ART using the International Index of Erectile Function-15 (IIEF-15) questionnaire. Under AMT we observed higher SHBG and LH and lower cFT levels at T1-T3 compared to T0 (all p<0.05). At T3, hypergonadotropic hypogonadism and erectile dysfunction (ED) were detected in 80% and 83.3% of cases. At T4, we observed a significant cFT increase in men treated with T gel, and a significant improvement in IIEF-15 total and subdomains scores and ED prevalence (16.7%) in men under ART. AMT was associated with hypergonatropic hypogonadism and ED, while ART led to a significant improvement of cFT levels and sexual function in the hypogonadal ACC patients. Therefore, we suggest to evaluate LH, SHBG, TT and cFT and sexual function during AMT, and start ART in the hypogonadal ACC patients with sexual dysfunction.

Erectile function in men with COVID-19 six months after recovery

Background. Based on the results of epidemiological studies, it was found that coronavirus disease 2019 (COVID-19) affects men more often than women. Among COVID-19 complications, erectile dysfunction is considered a marker of endothelial dysfunction and one of the main factors for the development of cardiovascular diseases. Lower total and free testosterone levels are predictors of adverse prognosis in males with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Testosterone deficiency syndrome is considered an independent risk factor of cardiometabolic disorders. The purpose of the study is to investigate the state of erectile function in men who suffered from COVID-19 six months after recovery. Materials and methods. Seventy-two men suffering from COVID-19 and being treated in an infectious disease hospital were examined 6.90 ± 0.29 months after recovery. Their average age was 45.23 ± 3.01 years. The control group included 18 conditionally healthy men aged 43.18 ± 2.90 years. The state of erectile function was assessed using the International Index of Erectile Function (IIEF). The concentration of testosterone was determined by the enzyme-linked immunosorbent assay with DRG (Germany) and DiaMetra (Italy) kits. All measurements were performed on the Stat Fax 3200 analyzer. Statistical comparison of the obtained results between groups was performed according to the Student’s test. A value of p &lt; 0.05 was considered to be signifi­cant. Results. In addition to erectile dysfunction, as evidenced by a reduced corresponding integrative indicator “erectile function” of IIEF-15 in men with COVID-19, a decrease in sexual desire was found, as well as a deterioration of sensations in the form of a decrease in ejaculation frequency and orgasmic sensations during sex contacts. The average serum level of total testosterone was 10.9 nmol/l and was significantly reduced compared to that in the control group. Analysis of individual indicators showed that testosterone level was decreased in 10 patients and was within the normal range in 13 men with COVID-19. The average serum concentration of total testosterone in the examined men after the disease was 10.73 ± 1.07 nmol/l and was significantly reduced compared to that of the control group. Conclusions. There was an erectile dysfunction in men who suffered COVID-19, it was confirmed by a probable decrease in IIEF-15 score and integrative indicators of erectile function. A significant decrease in the blood concentration of total testosterone was detected in the examined men, which may be one of the causes of erectile dysfunction. Large-scale prospective, randomized, controlled trials in patients infected with SARS-CoV-2 are needed to provide an understanding of the molecular mechanisms that cause erectile dysfunction.

Association between ethylene oxide exposure and sex steroid hormone levels in male adults in the United States

Sex steroid hormones play important roles in maintaining our health systems, including reproductive function and developmental health. Ethylene oxide (EtO) is a reactive organic compound that is widely used in the gas sterilization of materials such as foods, spices, and medical devices. Previous studies have suggested that EtO exposure is associated with carcinogenic risk, neurotoxicity, and reproductive toxicity. However, no studies focusing on the relationship between EtO exposure and changes in sex steroid hormone levels have been performed in human. The present study investigated the association between blood EtO levels and serum sex steroid hormone levels in 1,635 adult men from the NHANES 2013-2016. Multivariate linear regression analyses, a positive correlation between blood EtO and total testosterone levels, and the testosterone to estradiol ratio. Moderate EtO exposure was associated with a decrease in estradiol levels, but no relationship was found at the highest exposure range. No significant associations were observed between EtO exposure and free testosterone, bioavailable testosterone, or sex hormone-binding globulin levels. These findings suggest EtO exposure could impact human sex steroid hormone production, although analysis in females and further verification through prospective studies should be performed.

Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis. Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G. Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans. LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.

Association between serum testosterone changes and parameters of the metabolic syndrome.

Testosterone production is important in males, and various physical and psychological abnormalities occur in individuals with low testosterone levels. In the present study, we aimed to examine the effects of longitudinal changes in total testosterone levels in the same cohort. We included 178 male subjects who visited our hospital multiple times between 2018 and 2023 for medical checkups for at least 3 years. The median baseline age and total testosterone level (TT) of the cohort were 61 years and 4.74 ng/mL, respectively. The patients were divided into four groups based on the difference in TT (ΔTT) between baseline and last visit (Q1, n = 45; Q2, n = 45; Q3, n = 44; Q4, n = 44). ΔTT values ranged from -3.07 to -0.78 ng/mL in Q1, from -0.75 to -0.05 ng/mL in Q2, from -0.03 to 0.73 ng/mL in Q3, and from 0.75 ng/mL to 3.4 ng/mL in Q4. The median ΔTT were -1.22 for Q1, -0.35 for Q2, +0.19 for Q3, and +1.43 for Q4. Decreased TT tended to increase body weight, body mass index, waist circumference, and visceral fat (p for trend 0.0136, 0.0272, 0.0354, and 0.0032, respectively), and decrease adiponectin level (p for trend 0.0219). Herein, we found that decreased TT increases visceral fat and decreases adiponectin levels.