Disorders of Sex Development (DSD)

Researchers are studying the impact of exposure to Endocrine-Disrupting Chemicals EDCs on the risk of hypospadias, a common birth defect affecting the external genital organs in boys. This multicenter case-control study compares biological mothers of boys with hypospadias Case Group to mothers of boys without malformations Control Group to better understand environmental and hormonal factors that might contribute to this condition. The study aims to clarify how exposure to these chemicals during pregnancy might influence hormonal changes in newborns. The study involves a single consultation visit where a pediatric urologist or endocrinologist will confirm the presence or absence of hypospadias. Mothers will complete a validated European questionnaire and an occupationexposure matrix to assess environmental and occupational exposure to EDCs during pregnancy. Hair samples will be collected from mothers to analyze accumulated toxic substances, and blood samples will be taken from the children to evaluate hormone levels during the neonatal mini-puberty period. For cases, an additional blood sample will be collected for DNA analysis. Participants will attend one visit where clinical examinations, interviews, and sample collections occur. Researchers will measure toxic exposures through hair analysis, assess environmental exposures using questionnaires and models, and evaluate hormonal levels in the children. The study will help improve understanding and prevention of hypospadias by linking environmental exposures and hormonal changes. The total participation involves this single visit, with careful monitoring and data collection during that time.

This research aims to evaluate Social Management Training SMT, a 10-session group-based psychosocial intervention, for adults aged 16 to 65 with sex chromosome aneuploidies SCAs. The study focuses on assessing whether SMT can improve mental health as the primary outcome, along with secondary outcomes related to executive functions and autism symptoms. The intervention builds on previous work with men with Klinefelter syndrome and adapts SMT to a digital format to reach a wider Norwegian population with various SCAs. Participants will take part in 10 group sessions delivered online, covering topics such as social information processing, emotion regulation, executive functions, and individual learning goals. The study uses a single-group multiple baseline design with measurements collected at six time points three before and three after the intervention, spanning 30 weeks. This design allows comparison of outcomes before and after SMT to examine feasibility, acceptability, and potential benefits. During the study, participants will complete questionnaires measuring mental health, social responsiveness, and executive function multiple times before and after the intervention. The Symptom Checklist 25 SCL-25 is the primary tool for mental health assessment, while the Social Responsiveness Scale and Behavior Rating Inventory of Executive Function are secondary measures. The study will monitor participants throughout the 30-week period and aims to include 20-30 adults with genetically confirmed SCAs.

Researchers are evaluating the safety, effectiveness, and how the body processes and responds to atumelnant treatment in children with classic congenital adrenal hyperplasia CAH. This Phase 23 study includes a double-blind, randomized portion and an open-label extension to better understand treatment effects in pediatric participants aged 1 to under 18 years. The study is designed with multiple parts, including sequential cohorts based on age groups to carefully monitor safety and outcomes. Participants will receive atumelnant tablets once daily by mouth with doses adjusted based on their weight. The study is divided into three parts Part A involves open-label, semi-sequential cohorts for children aged 12 to under 18 and later for those aged 1 to 11 Part B is a randomized, double-blind, placebo-controlled phase evaluating active treatment versus placebo and Part C is an open-label extension where participants from Parts A and B may continue treatment. Safety reviews guide progression between cohorts. Throughout the study, participants will have their hormone levels monitored, including morning serum androstenedione and 17-hydroxyprogesterone, along with blood concentration measurements of atumelnant. The trial tracks changes in glucocorticoid doses and hormone levels over time up to 260 weeks in the extension phase. The study also assesses treatment compliance and overall safety, with participation lasting from initial screening through extended follow-up.

Researchers are investigating atumelnant in adults aged 18 to under 75 years with classic congenital adrenal hyperplasia CAH caused by 21-hydroxylase deficiency 21-OHD. This Phase 3, global, randomized, double-blind, placebo-controlled study aims to assess the effectiveness, safety, pharmacokinetics, and pharmacodynamics of atumelnant in participants who have been on stable glucocorticoid GC therapy for at least two months. Eligible participants enter a screening period lasting 3 to 6 weeks to confirm suitability for the study. After screening, participants are randomly assigned in a 21 ratio to receive either 80 mg of atumelnant orally once daily, with a possible dose increase to 120 mg at Week 20, or a matching placebo once daily for 32 weeks. The study compares these two groups to evaluate the effects of atumelnant alongside usual GC treatment. During the study, participants will have regular assessments including blood tests to measure hormone levels such as androstenedione A4 and 17-hydroxyprogesterone 17-OHP at baseline and specified weeks. Researchers will monitor participants hormone control, GC doses, safety, and adherence. The main outcome is the proportion of participants achieving morning post-GC A4 levels within the normal range while on physiologic GC replacement at Week 32. The total participation duration includes the screening and 32-week treatment periods.

Researchers are evaluating different doses of Lu AG13909 in adults with congenital adrenal hyperplasia CAH, a rare genetic disorder that affects hormone production. The study aims to understand the safety, tolerability, how the body processes Lu AG13909, and the bodys response to this investigational drug. The research is conducted across multiple phases to assess these aspects carefully. Participants will receive multiple intravenous doses of Lu AG13909 according to specified dosing schedules divided into three parts Part A, Part B, and Part C. Each part starts after confirming the safety and tolerability of the dose from the previous part. After Part C, participants may have the option to continue treatment in an extension phase. The dosing and treatment schedules are carefully planned and monitored throughout the study. During the trial, participants will undergo regular assessments including blood tests to measure hormone levels like 17-hydroxyprogesterone and androstenedione, as well as monitoring for treatment-emergent adverse events and the presence of anti-drug antibodies. Pharmacokinetic parameters such as serum concentration and elimination half-life of Lu AG13909 will be tracked up to several months. The total participation duration can extend up to about a year or more depending on the study part and extension involvement.

Researchers are studying the long-term safety, tolerability, and efficacy of atumelnant CRN04894 in people with congenital adrenal hyperplasia CAH. This open-label extension study includes participants who completed a prior Crinetics atumelnant CAH study and were judged by investigators to have an acceptable benefit-risk profile and potential benefit from continued treatment. Approximately 150 to 200 participants are expected to enroll. Participants will receive atumelnant orally during an open-label treatment period lasting up to two years. The dose will not exceed the highest dose explored in the previous parent study. This study follows one treatment group only, with no placebo or comparator groups. During the study, participants will undergo regular safety and efficacy assessments including monitoring for adverse events, adrenal insufficiency, adrenal crisis, and hospitalizations related to CAH. Blood tests will measure hormone levels such as androstenedione and 17-hydroxyprogesterone, and glucocorticoid dosing will be tracked over time. The study aims to follow participants for up to 108 weeks to evaluate these outcomes.

Researchers are studying individuals with Androgen Insensitivity Syndrome AIS, a rare condition where the body cannot respond to male hormones due to differences in the androgen receptor gene. This natural history study aims to describe the overall health and characteristics of people with AIS, including hormone levels, bone strength, metabolic and cardiovascular health, quality of life, and tumor risk. The study also includes adult relatives without AIS to better understand genetic effects. Participants will undergo various tests and assessments, including medical history, physical exams, blood and urine tests, heart electrocardiograms, bone density scans, and imaging such as MRI or sonograms of the pelvis. Adults may receive additional scans like MR elastography, MR spectroscopy, and cardiac CT scans. Optional exams include genital exams and vaginal swabs. Participants have visits every 1 to 2 years, and adult relatives participate in one visit with selected tests. During the study, participants will provide samples and undergo physical measurements and questionnaires to track health changes over time. Researchers will monitor bone health, metabolic markers, tumor risks, and quality of life through repeated assessments. The study will continue indefinitely, allowing long-term observation, and aims to enroll about 500 individuals with AIS and their relatives for comprehensive data collection and future treatment research.

This research aims to find out whether a guided journaling program can reduce stress and anxiety in parents of children with urogenital conditions, such as differences of sex development and hypospadias. The study seeks to understand if journaling helps lower anxiety levels and gather parents views on group-based writing support programs for the future. Participants will receive a physical journal containing five writing prompts designed to help them process emotions related to their childs condition. They will complete five journal entries over several weeks, spending 15 to 20 minutes on each writing session at least once per week. This single-arm study includes baseline and follow-up anxiety assessments, plus a 30 to 45-minute interview after finishing the journaling to discuss effects on stress and gather feedback. During the study, parents will complete the General Anxiety Disorder-7 GAD-7 questionnaire at the start and after the journaling period, about six weeks later. They will also participate in an interview to assess changes in anxiety and coping strategies. Researchers will evaluate changes in anxiety scores and the acceptability of the journaling program. Total participation lasts about six weeks.

Researchers are investigating the cardiovascular health of transgender individuals undergoing gender-affirming care, specifically focusing on the effects of gender-affirming hormone therapy GAHT. This study aims to address gaps in knowledge about the long-term cardiovascular risks and mechanisms associated with GAHT, especially for people assigned female at birth AFAB receiving testosterone and those assigned male at birth AMAB receiving feminizing hormone therapy. The research highlights the need for robust, prospective data to better understand how GAHT impacts blood pressure, lipid profiles, and overall cardiovascular risk in transgender populations. The study observes transgender individuals receiving gender-affirming hormone therapy masculinizing GAHT with testosterone for AFAB participants and feminizing GAHT combining estradiol with anti-androgens like cyproterone acetate or GnRH analogues for AMAB participants. Some AMAB participants may receive estradiol alone after orchiectomy. Gender-affirming surgery is also part of the care pathway but is not the direct focus of the study. The investigation tracks changes in vital signs, blood tests, body composition, and insulin resistance over time while monitoring cardiovascular health outcomes. Participants will be followed from baseline through to study completion, estimated by 2035. They will undergo regular assessments including measurements of vital signs, anthropometric data, laboratory blood tests, and body composition analysis. Researchers will evaluate lifestyle habits and the presence or absence of cardiovascular disease, as well as how different GAHT regimens affect cardiovascular parameters. The study offers careful monitoring of cardiovascular risk factors in the context of gender affirmation, aiming to inform safer and more effective clinical guidelines for transgender health care.

Hypospadias is a common genital malformation in boys that is usually treated with surgery. Researchers are evaluating whether caudal anesthesia compared to dorsal penile block anesthesia affects the rate of surgical complications like urethrocutaneous fistulas and glans dehiscence after hypospadias repair. This pilot randomized controlled trial aims to determine if one anesthesia method leads to fewer complications and to test the feasibility of a larger study. Participants aged 6 to 48 months undergoing distal hypospadias repair will be randomly assigned to receive either a caudal block or a dorsal penile block anesthesia. Both methods use inhalation induction with airnitrous oxide and sevoflurane followed by an injection of bupivacaine without epinephrine. Additional pain management includes fentanyl, dexamethasone, ondansetron, acetaminophen, morphine, and post-discharge medications such as oral morphine, Ditropan, Tylenol, ibuprofen, and trimethoprim until catheter removal. During the study, children will be closely monitored for postoperative complications for up to one year. Researchers will assess safety and complication rates, medication usage, and recovery progress. This double-blind, randomized trial will provide detailed data on the impact of anesthesia type on surgical outcomes and help guide future treatment decisions.