SPIOMET4HEALTH-efficacy, tolerability and safety of lifestyle intervention plus a fixed dose combination of spironolactone, pioglitazone and metformin (SPIOMET) for adolescent girls and young women with polycystic ovary syndrome: study protocol for a multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO. DISCUSSION: The present study will be the first to evaluate-in a randomised, double-blind, placebo-controlled way-the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention. TRIAL REGISTRATION: EudraCT 2021-003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .

Worse Metabolic Control and Dynamics of Weight Status in Adolescent Girls Point to Eating Disorders in the First Years after Manifestation of Type 1 Diabetes Mellitus: Findings from the Diabetes Patienten Verlaufsdokumentation Registry.

OBJECTIVE: To assess indications of eating disorders in girls with type 1 diabetes mellitus (T1DM). STUDY DESIGN: In total 31 556 girls aged >6 months and <23 years of age with T1DM from the Diabetes Patienten Verlaufsdokumentation (DPV) cohort were analyzed including 155 (0.49%) girls with anorexia nervosa, 85 (0.27%) girls with bulimia nervosa, 45 (0.14%) girls with binge eating disorder, and 229 (0.73%) girls with eating disorders not otherwise specified. Patient characteristics, weight changes, numbers of patients with severe hypoglycemia and diabetic ketoacidosis (DKA), changes of glycosylated hemoglobin A1c (HbA1c) levels, use of pumps, and prevalence of celiac disease and autoimmune thyroiditis were compared between girls with and without eating disorders. Multiple logistic regression analyses were performed. RESULTS: Eating disorders were significantly associated with late pubertal age, nonusage of pumps, no migration background, increased HbA1c levels, increased frequencies of DKA and severe hypoglycemia, and celiac disease were not related to eating disorders. Significant differences in HbA1c levels, prevalence of DKA and severe hypoglycemia between girls with and without eating disorders were already detectable in the first years after onset of T1DM. A decrease of body mass index (BMI)-SDS increased the risk for comorbid anorexia nervosa (7.1-fold [95% CI 3.6-14.3] compared with stable BMI-SDS, 6.9-fold [95%CI 3.4-14.1] compared with increase of BMI-SDS). CONCLUSIONS: Poor metabolic control and increased rates of DKA and severe hypoglycemia in the first years after manifestation of T1DM can be hints for eating disorders in girls with T1DM, and weight loss is specific for anorexia nervosa. These clinical features should lead to screening for eating disorders especially at a late pubertal age.

Suicidal Ideation in Adult Patients with Atopic Dermatitis: A German Cross-sectional Study.

A cross-sectional study was performed to assess symptoms of suicidality, depression and anxiety in adult patients with atopic dermatitis. The study describes the relationships between these psychiatric symptoms and skin-specific factors, such as atopic dermatitis severity and skin satisfaction. A sample of 181 German patients with atopic dermatitis was compared with a control group of 64 persons with healthy skin with a similar age and sex distribution. Standardized questionnaires were used to assess suicidality (Pöldinger's Scale), depression and anxiety (Hospital Anxiety and Depression Scale; HADS), quality of life (Dermatology Life Quality Index; DLQI), atopic dermatitis severity (Patient-Oriented Scoring Atopic Dermatitis; PO-SCORAD) and skin satisfaction (Skin Satisfaction Questionnaire; SSQ). The prevalence of suicidal ideation among patients with atopic dermatitis was high (21.3%); 3.9% scored above the cut-off that might be an indicator for acute suicidality. Depression symptoms, high severity of atopic dermatitis, lower age, and little touching within the family were identified as significant factors to predict suicidality in atopic dermatitis. Psychiatric screening in dermatological treatment of atopic dermatitis is discussed.