12 research outputs found
Quality of Life in Men With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a disorder of adrenal steroid biosynthesis, leading to hypocortisolism, hypoaldosteronism, and hyperandrogenism. Impaired quality of life (QoL) has been demonstrated in women with CAH, but data on men with CAH are scarce. We hypothesized that disease severity and poor treatment control are inversely associated with QoL. In this study, 109 men (16-68 years) with 21OHD were included. The WHOQOL-BREF questionnaire was used to measure self-reported QoL domain scores on a 0-100 scale, where higher scores reflect better QoL. QoL domain scores were compared to published data on healthy and chronically ill reference populations from France, Germany, the Netherlands, and the United Kingdom. Differences in QoL scores among groups of disease severity and treatment control were tested within the study population. Overall, the men with CAH in this study appeared to rate their QoL as good. Median domain scores were 78.6 (IQR: 67.9-85.7) for physical health, 79.2 (IQR: 66.7-87.5) for psychological health, 75.0 (IQR: 58.3-83.3) for social relationships, and 81.3 (IQR: 71.9-90.6) for environment. In general, these scores were similar to WHOQOL-BREF domain scores in healthy references and higher compared to chronically ill reference populations. The domain scores did not differ among genotype groups, but patients with undertreatment or increased 17-hydroxyprogestrone concentrations scored higher on several QoL domains (p<0.05). Patients treated with dexamethasone or prednisone scored higher on the physical health, psychological health, and social relationships domains, but not on the environmental domain. In conclusion, QoL domain scores appeared to be comparable to healthy reference populations and higher compared to patients with a chronic illness. QoL was not influenced by genotype, but undertreatment and use of dexamethasone or prednisone were associated with higher QoL
Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine
Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe
Le syndrôme triple-A (maladie d'allgrove, de l'anomalie fonctionnelle nucléaire aux neuropathiques périphériques)
La maladie d'Allgrove (syndrome Triple-A) se caractérise par une triade symptomatologique composée d'une alacrymie, une achalasie du cardia et d'une insuffisance surrénalienne. A ce tableau clinique se surajoutent des atteintes neuropathiques périphériques. Celles-ci sont très diverses entre les patients mais induisent toutes une atteinte invalidante à long terme. Le diagnostic est alors essentiellement clinique. Les mutations touchant le gène AAAS codant pour la protéine ALADIN, nucléoporine appartenant à la macrostructure du complexe du pore nucléaire, engendrent un défaut d'importation de molécules antioxydantes au niveau du nucléoplasme. Ce déficit entraîne une détoxification moins importante des espèces réactives de l'oxygène au sein du noyau, ne permettant plus aux cellules et notamment aux neurones de lutter efficacement contre le stress oxydatif physiologique. Les cellules développent ainsi une sénescence prématurée induite par un niveau de stress oxydatif sub-toxique continu. La méta-analyse réalisée sur 89 patients permet d'affiner la prévalence des trois symptômes de la triade AAA au sein de la maladie. De plus, l'étude a permis de mettre en lumière l'absence de corrélation entre le génotype et le phénotype exprimé par les patients. Ceci engendre une complexité évidente lors de l'établissement du diagnostic. La maladie d'Allgrove est une pathologie neuro-endocrine complexe et invalidanteLYON1-BU Santé (693882101) / SudocSudocFranceF
Body Image and Quality of Life in Women with Congenital Adrenal Hyperplasia
Objective: Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) may have poor quality of life (QoL) and low satisfaction with body appearance. We investigated the influence of the patients’ satisfaction with their support on their QoL and body image. Design: Retrospective, comparative, Europe-wide study as part of the multicenter dsd-LIFE study. Methods: 203 women with CAH were included in this study. We investigated the patients’ QoL and body image compared to a healthy control group. The patients’ satisfaction with their treatment and support in childhood and adolescence as well as in adulthood was assessed by questionnaire and its influence on the patients’ body image and QoL was analyzed by multiple regression models. Results: Women with CAH showed worse body image and poorer physical, psychological and social QoL compared to a healthy reference population. The patients’ satisfaction with professional care in the last 12 months was a significant positive predictor for all four domains of QoL (psychological, physical, social, environmental). Dissatisfaction with care in childhood and adolescence and with general support through different stages of life was a significant negative predictor for QoL and body image. Conclusions: These results show that women with CAH have poor QoL and body image compared to a healthy reference population. Psychosocial factors such as general and family support, and social interactions with professionals have a substantial impact on QoL and body image in adult females with CAH. This should be taken into account regarding patient care and multimodal therapy
Hormone therapy and patient satisfaction with treatment, in a large cohort of diverse disorders of sex development
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Fertility outcome and information on fertility issues in individuals with different forms of disorders of sex development: findings from the dsd-LIFE study
International audienceOBJECTIVE:To investigate fertility outcome in individuals with different forms of disorders of sex development (DSD), if assisted reproductive technology (ART) was used, and the patients' satisfaction with the information they had received.DESIGN:A cross-sectional multicenter study, dsd-LIFE.SETTING:Not applicable.PATIENT(S):A total of 1,040 patients aged ≥16 years with different DSD diagnoses participated.INTERVENTION(S):A web-based questionnaire was filled out by all participants. The participants could chose to take part in somatic investigations including ultrasonography.MAIN OUTCOME MEASURE(S):Information on partner, number of children, ART, adoption and step-children, general health, presence of gonads and uterus, current education and economic situation, received information on fertility issues, and satisfaction with the information, was collected.RESULT(S):In the total cohort, mean age 32 years, 33% lived with a partner, but only 14% reported having at least one child including 7% with ART, 4% adopted. Only 3.5% of the total cohort had been able to reproduce without ART, most frequently women with congenital adrenal hyperplasia, and only 0.7% of participants with other diagnoses. Of the participants, 72% had received information on fertility, but 17% were not satisfied with the information.CONCLUSION(S):Fertility outcome is significantly reduced in all types of DSD; however, fertility potential should be assessed individually. The satisfaction with how fertility problems have been discussed can be improved. The care of patients with DSD is complex, should be individualized, and new treatment possibilities incorporated. A close collaboration in multidisciplinary teams is therefore essential to improve the situation for individuals with DSD
Sexuality in Adults with Differences/Disorders of Sex Development (DSD): Findings from the dsd-LIFE Study
For various reasons, sexuality of individuals with differences/disorders of sex development (DSD) may be affected. The aim of the study was to describe sexual activity, satisfaction with sex life, satisfaction with genital function, and sexual problems in people with different DSD conditions. Data were collected from 1,040 participants in Europe. Many people with a variety of DSD conditions do not appear to be satisfied with their sex life, experience a variety of sexual problems, and are less sexually active than the general population; therefore sexuality should be explicitly addressed in the care of people with DSD
Gender Dysphoria and Gender Change in Disorders of Sex Development/Intersex Conditions: Results From the dsd-LIFE Study
© 2018 International Society for Sexual Medicine Background: Information on the psychosexual outcome of individuals with disorders of sex development (DSDs) and intersex conditions is of great importance for sex assignment at birth of newborns with DSD. Aim: To assess gender change and gender dysphoria in a large sample of individuals with different DSDs. Methods: A cross-sectional study was conducted in 14 European centers with 1,040 participants (717 female-identifying and 311 male-identifying persons and 12 persons identifying with another gender) with different forms of DSD. The cohort (mean age = 32.36 years, SD = 13.57) was divided into 6 major subgroups: women with 45,X DSD and variants (Turner syndrome; n = 325), men with 47,XXY DSD and variants (Klinefelter syndrome; n = 219), women with XY DSD without androgen effects (n = 107) and with androgen effects (n = 63), men with XY DSD (n = 87), and women with 46,XX congenital adrenal hyperplasia (n = 221). Data on psychosexual outcome were gathered by medical interviews and questionnaires. Outcomes: Gender change and gender dysphoria. Results: Although gender changes were reported by 5% of participants, only in 1% (3% if those with Klinefelter and Turner syndromes—conditions in which gender issues are not prominent—are excluded) did the gender change take place after puberty and was likely initiated by the patient. 39 participants (4%) reported gender variance: between male and female, a gender other than male or female, or gender queer, alternating gender roles, or a gender expression that differed from the reported gender. This group had lower self-esteem and more anxiety and depression than the other participants. Clinical Implications: Clinicians should be aware of and sensitive to the possibility that their patients with DSD not only might have transgender feelings and a desire to change gender, but also identify as different from male or female. The complexity of their feelings might require counseling for some patients. Strengths and Limitations: The study is unique in the large number of participants from many different clinics, with sizable numbers in most subgroups, and in the large number of aspects that were measured. However, the very broadness of the study made it impossible to focus in detail on gender issues. Also, there is a need for instruments specifically measuring gender dysphoria in individuals with DSD that take non-binary genders into account. Conclusion: To make appropriate gender care possible for people with DSD, the gender-normative and gender-variant development of children with DSD should be studied in longitudinal studies. Kreukels BPC, Köhler B, Nordenström A, et al. Gender Dysphoria and Gender Change in Disorders of Sex Development/Intersex Conditions: Results From the dsd-LIFE Study. J Sex Med 2018;15:777–785