Family building after diagnosis of premature ovarian insufficiency: a cross-sectional survey in 324 women.

OBJECTIVE: The diagnosis of premature ovarian insufficiency (POI) is a traumatic event for many patients that involves poor fertility prognosis. After such diagnosis, spontaneous pregnancies are rare. The alternatives for building a family are oocyte donation, embryo donation, and adoption. However, we have few information on how many women with POI finally built a family after the diagnosis and which alternative they chose. DESIGN: We performed a cross-sectional, descriptive study. METHODS: We conducted a survey of all the women who consulted for POI in the department of endocrinology and reproductive medicine at la Pitié Salpêtrière between May 31, 1991, and January 12, 2021. We included patients who continued to be followed up regularly by our department or were contacted by mail or phone between June and September 2021. We excluded patients with Turner syndrome and POI secondary to oncological treatment and patients under 18 at the time of the survey. RESULTS: 985 patients were referred to the department for POI, and 324 patients were finally analyzed. 41% of the women who wanted to build a family had children after the diagnosis: 53.9% by oocyte donation, 1 woman by embryo donation, 5.6% after ovarian stimulation, 13.5% by adoption, and 25.8% who had spontaneous pregnancy after a mean time of 2.5 years. Spontaneous pregnancy rate was 8.6% in the whole cohort. CONCLUSIONS: Having children after a diagnosis of POI is not uncommon but more often results from oocyte donation. This study will provide enlightened information for newly diagnosed women on the possibilities to build a family after POI diagnosis.

Fertility and pregnancy outcomes in women with nonclassic 21-hydroxylase deficiency.

INTRODUCTION: Overall fertility and pregnancy outcomes in patients with nonclassic congenital adrenal hyperplasia (NCCAH) have been poorly studied. It has been suggested that hydrocortisone (HC) may decrease the time to conceive (TTC) and the rate of miscarriage in these patients. OBJECTIVES: To describe fertility and pregnancy outcomes in a large cohort of NCCAH women. The secondary objective was to identify factors that could impact reproductive outcomes, with a particular focus on HC dose and genetic status. DESIGN: Retrospective study in a referral center for congenital adrenal hyperplasia. PATIENTS AND MEASUREMENTS: One hundred seventy-three female patients with NCCAH confirmed by genetic testing, followed in our center between 2010 and 2019. RESULTS: Among the 173 patients, 95 women had a parental project, 86 of whom presented 176 pregnancies, 56% under glucocorticoid (GC) treatment and 44% without, and 76 women obtained 128 live births. Two-thirds of the patients regularized their cycle under GC treatment, with significant decrease of androgens and progesterone levels. This treatment was associated with a shortening of TTC (coef ß = -.196, information coefficient [IC] = [-10.7; -0.91], p = .021). Androgen levels and TTC were positively correlated to the rate of miscarriage (OR = 4.8, IC = [1.15; 20.34], p = .021 for testosterone, OR = 1.4, IC = [1.05; 1.81], p = .02 for androstenedione, and OR = 1.03, IC = [1.01; 1.06], p = .015 for TTC). There was no difference in terms of obstetric outcomes between patients with or without GC treatment. CYP21A2 genotype had no impact on pregnancy outcome or TTC. CONCLUSIONS: Infertility is relative in patients with NCCAH. HC seems beneficial for fertility and pregnancy outcomes, especially for patients with menstrual disorders and high preconceptional androgen levels.

Classical and non-classical congenital adrenal hyperplasia: What is the difference in subsequent fertility?

21-Hydroxylase deficiency (21OHD) is the most common cause of congenital adrenal hyperplasia. Increased production of adrenal-derived androgens and progesterone in 21OHD women interfere with their reproductive function and their fertility in many different ways, depending on the severity of the disease. Sexuality and fertility in women with classic 21OHD is impaired, due to several issues such as disrupted gonadotropic axis due to androgen and progesterone overproduction, and mechanical, psychological factors related to genital surgery. Fertility and fecundity in these women get better over the years. Subfertility seems contrariwise to be relative in non-classic 21OHD women. Before pregnancy, genotyping the partner and genetic counselling is mandatory.

Evaluation of a new transition organization for young adults with endocrine or metabolic diseases.

OBJECTIVE: To evaluate the effect of a new care organization on multiple outcomes of transition success and its cost-effectiveness in patients with any endocrine or metabolic disease diagnosed during childhood and transferred to adult care. DESIGN: Non-randomized controlled trial in a French university hospital. METHODS: Patients transferred to adult care during the control period (04/2014-08/2016) and the intervention period (09/2016-06/2018) were included. The intervention is based on case management involving liaising with pediatric services, personalizing care pathways, and liaising with structures outside hospital (general practitioner, educational and social sector). The primary endpoint was the percentage of patients lost to follow-up at 24 months post transfer. Other outcomes were collected from medical files, consultation software, and questionnaires. A cost analysis was performed. RESULTS: Two hundred two patients were included (101 per period), the most represented pathologies were congenital and non-congenital hypopituitarism (respectively n = 34 (17%) and n = 45 (22%)) and thyroid diseases (n = 21, 10%). Patients were aged 22.5 in median at 24 months post transfer where 12 were lost to follow-up in the control group vs 9 with the intervention (P = 0.49). The percentage of honored consultation among those planned during 24 months was higher with intervention (P = 0.0065). Patient satisfaction, physician trust, and transfer delay did not differ between the groups. The incremental cost-effectiveness ratio was €179 per patient not lost to follow-up. CONCLUSIONS: At 24 months post transfer, the rate of lost to follow-up did not differ significantly, but indicators of a steadier follow-up were increased and the intervention appeared to be cost-effective.

Transition of young adults with endocrine and metabolic diseases: the 'TRANSEND' cohort.

OBJECTIVE: The transition from paediatric to adult medicine involves risks of poor patient outcomes and of significant losses of patients to follow up. The research aimed to analyse the implementation in an initial cohort of patients of a new programme of transition to adult care based on a case management approach. DESIGN: A longitudinal study of the case management approach to transition, initiated in a university hospital in France in September 2016. METHODS: Patients with the endocrine or metabolic disease diagnosed during childhood and transferred to adult care were included. The transition programme includes three steps based on case management: liaising with paediatric services, personalising care pathways, and liaising with structures outside the hospital (general practitioners, agencies in the educational and social sector). RESULTS: The cohort included 500 patients, with malignant brain tumour (n = 56 (11%)), obesity (n = 55 (11%)), type 1 diabetes (n = 54 (11%)), or other disease (n = 335 (67%)). Their median age at transfer was 19, and the sex ratio was 0.5. At median 21 months of follow-up, 439 (88%) had a regular follow-up in or outside the hospital, 47 (9%) had irregular follow-up (absence at the last appointment or no appointment scheduled within the time recommended), 4 had stopped care on doctor's advice, 4 had died, 3 had moved, and 3 had refused care. The programme involved 9615 case management actions; 7% of patients required more than 50 actions. Patients requiring most support were usually those affected by a rare genetic form of obesity. CONCLUSIONS: Case managers successfully addressed the complex needs of patients. Over time, the cohort will provide unprecedented long-term outcome results for patients with various conditions who experienced this form of transition.

Positive association between progestins and the evolution of multiple fibroadenomas in 72 women.

OBJECTIVE: Multiple fibroadenomas (MFA) of the breast is a rare benign disease, thus its natural history is poorly understood. The aim of our study was to describe the radiological evolution of MFA and to evaluate the influence of different factors on this evolution. METHODS: This was a longitudinal cohort study. All patients included had two clinical and radiological assessments (breast ultrasound (US) and/or MRI) at least 5 years apart. RESULTS: Seventy-two women were followed for 7.6 ± 2.1 years. The radiological evolution showed a decrease or stability in the number of fibroadenomas (FA) in 26/44 cases on the MRI and in 38/64 cases on the US. There was a decrease of size in 35/44 cases on the MRI and in 53/64 cases on the US. An increase in the number of FAs was found in 18/44 cases in the MRI and 26/64 cases in the US with, for the majority, a decrease of size (19/26 by MRI and 16/18 by MRI). Older age at the first FA (P < 0.0001) and at the diagnosis of MFA (P < 0.0001), pregnancy (P = 0.003) and progestin use (P < 0.001), particularly lynestrenol (P < 0.0001), had a beneficial effect on the evolution of MFA. CONCLUSION: This is the first longitudinal study describing women with MFA. The radiological evolution of MFA seamed favorable and similar to that expected for a single FA. We identified factors influencing the evolution of the disease, including progestin treatments such as lynestrenol, which could have a beneficial effect. Our cohort should be followed further in order to expand our knowledge of MFA, especially concerning the risk of breast cancer.

Impact of transition on quality of life in patients with congenital adrenal hyperplasia diagnosed during childhood.

BACKGROUND: Health-related quality of life (QoL) in adult patients with congenital adrenal hyperplasia (CAH) has been variously reported. However, there is no study evaluating the impact of transition on quality of life. METHODS: Adult patients with classic or non-classic CAH diagnosed during childhood CAH, born between 1970 and 1990, were recruited from the registers of Pediatric departments belonging to the French reference center for endocrine rare disease. Primary end point was the quality of life (WHOQoL -BREF). RESULTS: Seventy three patients were included in the study, among them 59/73 (81%) were transferred to adult endocrinologist by their pediatricians for transition. WHOQoL -BREF scores were similar between patients with or without transition to specialist adult services, except for environment dimension score, which was slightly higher in CAH patients without transition. However, CAH patients with a regular follow-up had a better physical health, psychological health and environment score and item global quality of life than the group without regular follow-up after transition. CONCLUSION: Regular medical follow-up in adulthood is associated with the transition between pediatric and adult care and with better QoL in adults with CAH.

Gain-of-function Prolactin Receptor Variants Are Not Associated With Breast Cancer and Multiple Fibroadenoma Risk.

CONTEXT: In a cohort of 95 women with multiple breast fibroadenomas (MFAs), we recently identified patients harboring germline heterozygous variants of the prolactin receptor (PRLR) exhibiting constitutive activity (PRLRI146L and PRLRI176V). OBJECTIVE: This study sought to better delineate the potential role of PRLR gain-of-function variants in benign and malignant mammary tumorigenesis. DESIGN: This was an observational study and transgenic mouse model analysis. SETTING: The study took place at the Department of Endocrinology, Reproductive Disorders and Rare Gynecologic Diseases, Pitié Salpêtrière, Paris, and Inserm Unit 1151, Paris. PATIENTS OR OTHER PARTICIPANTS: We generated a second MFA cohort (n = 71) as well as a group of control subjects (n = 496) and a cohort of women with breast cancer (n = 119). We also generated two transgenic mouse models carrying the coding sequences of human PRLRI146L or PRLRWT. INTERVENTION: We aimed to determine the prevalence of PRLR variants in these three populations and to uncover any association of the latter with specific tumor pattern, especially in patients with breast cancer. RESULTS: This study did not highlight a higher prevalence of PRLR variants in the MFA group and in the breast cancer group compared with control subjects. Transgenic mice expressing PRLRI146L exhibited very mild histological mammary phenotype but tumors were never observed. CONCLUSION: PRLRI146L and PRLRI176V variants are not associated with breast cancer or MFA risk. However, one cannot exclude that low but sustained PRLR signaling may facilitate or contribute to pathological development driven by oncogenic pathways. Long-term patient follow-up should help to address this issue.

[Therapeutic education programme for patients with chronic endocrine conditions: Transition from paediatric to adult services]. / Un programme d'éducation thérapeutique centré sur la transition des patients, avec endocrinopathie chronique, entre les services d'endocrinologie pédiatrique et adulte.

UNLABELLED: The purpose of this study is to contribute to better identifying the transition of patients with chronic endocrine conditions from paediatric to adult department. The aim was to specify the means and the competences that must be used by patients and health care teams and which could be help to the best quality care. METHOD: We propose group sessions and individual interviews. A thematic analysis of the sessions and the responses to questionnaires have enabled the development of individual educational diagnosis and assess the autonomy of young adolescents. RESULTS: Fifty of 214 patients from paediatric services participated to therapeutic education program (TEP) in the last four years. This program is based on the psychic movements of adolescence. One year after the therapeutic education program session, 48 patients came to all the medical consultations and we observed a greater autonomy in adolescent patients. CONCLUSION: However, we must improve the modalities for including patients in this "transition program".

Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition.

OBJECTIVES: Our aim was to analyze a large cohort of childhood onset GH deficiency (CO-GHD) adults from a unique adult center, in order to analyze their clinical management and to study the metabolic and bone status in relation to GHD and to the other pituitary deficits, and to evaluate these parameters during the long-term follow-up. DESIGN AND METHODS: Observational retrospective cohort study on 112 consecutive CO-GHD adults transferred to our unit from 1st January 1994 to 1st March 2012. Evaluation of GHD in pediatrics and after transition was conducted following consensus guidelines. Data recorded from pediatric and adult files were GH doses, pituitary magnetic resonance imaging and function, and metabolic and bone status. RESULTS: Most patients presented with severe CO-GHD (64%) associated with other pituitary deficits (66%). CO-GHD was acquired in 56%, congenital in 33%, and idiopathic in 11% cases. Most patients (83%) stopped GH before transfer, at 16.3 years (median), despite persistence of GHD. Median age at transfer was 19.4 years. After transfer, GHD persisted in 101 patients and four of the 11 resolutive GHD were non idiopathic. IGF1 level was <-2 SDS in 70% of treated patients at transfer and in 34% of them after 3 years of treatment. Follow-up showed improvement in lipid profile and bone mineral density in severely persistent GHD patients under GH therapy. In multivariate analysis, the associated pituitary deficits seemed stronger determinant factors of metabolic and bone status than GHD. CONCLUSIONS: This study raises concern about discontinuation of GH replacement therapy in pediatrics in severely persistent GHD patients and about the often insufficient dose of GH in the treatment of adult patients.

Transition from pediatric to adult healthcare: assessment of specific needs of patients with chronic endocrine conditions.

BACKGROUND/AIM: Transition from pediatric to adult care is a challenging turning point. The aim was to evaluate the transition process and needs expressed by patients with chronic endocrine conditions at transition in order to ensure program optimization. METHODS: Prospective assessment of the transition period was conducted through completion of standardized questionnaires given to targeted patients. Two types were created: (1) a general questionnaire (GQ) addressing universal aspects of transition, and (2) a specific questionnaire (SQ) exploring concerns related to each endocrine condition. Three endocrinopathies (congenital adrenal hyperplasia, hypogonadotropic hypogonadism and growth hormone deficiency) were selected for assessment since they present specific challenges requiring characterization. RESULTS: Over the last decade, 244 patients in transition were registered in our department and 153 were included since they presented one of the endocrinopathies selected. A total of 73 subjects completed both the GQ and the SQ. Over 80% of the patients were satisfied with the transition process in terms of organization, accessibility and medical care. The actual age of transition corresponded for most to the age considered by patients as ideal for transition. SQs identified psychosexual issues that must be addressed more systematically. CONCLUSION: This study identified key elements allowing the creation of an improved transition program tailored for our center and for each endocrine condition studied.

Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients.

CONTEXT: Craniopharyngiomas are often associated with an unfavorable prognosis, but data on their long-term consequences are sparse. OBJECTIVE: The aim of the study was to identify markers of recurrence and factors associated with compromised social rehabilitation and altered quality of life in a large cohort of patients with either childhood-onset (CO) or adult-onset craniopharyngioma. METHODS: Retrospective analysis was performed for 171 patients treated for craniopharyngioma in two academic centers in France between 1972 and 2009. For each subject, data were collected concerning clinical presentation, imaging features, visual sequelae, endocrine and metabolic impact, treatment modalities (surgery, radiotherapy), recurrence-free survival rate, and social insertion, as well as answers to the WHO-QOL BREF questionnaire. RESULTS: A total of 65 CO and 106 adult-onset patients were reviewed. If CO was diagnosed before the age of 10 yr, this was associated with a higher incidence of obesity, blindness, and panhypopituitarism, and only 40.7% of subjects had adequate work or school attendance compared to 72.4% of patients with later disease onset. Initial symptoms of intracranial hypertension (SIHT), pterional surgery, and multiple surgery were associated with obesity and poorer social insertion. No determinant of quality of life was identified. In the subgroup of patients treated in the 1990s and later, the progression rate was 59.4% in patients with residual tumor on magnetic resonance imaging compared with a 19.8% recurrence rate in the group with apparently complete resection. Recurrence/progression correlates significantly with male gender, early onset (before 10 yr), and SIHT, but only SIHT at presentation remained a significant predictor with multivariate analysis. CONCLUSIONS: Craniopharyngioma continues to be associated with severe outcomes. Higher morbidity rates are found in patients with early-onset disease (before 10 yr), initial SIHT, or in whom pterional surgery was required. Markers of recurrence are difficult to identify, with SIHT being the most powerful predictor.