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International audience; In Euro-EWING99-R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard-risk Ewing sarcoma (SR-EWS) after a common induction with VIDE (vincristine-ifosfamide-doxorubicin-etoposide). We present the results of the late effects analysis of VAC (vincristine-dactinomycin-cyclophoshamide) vs VAI (vincristine-dactinomycin-ifosfamide) conducted in Euro-EWING99-R1 French cohort. Of 267 French randomized patients, 204 were alive and free-of-relapse at 5-years including 172 with available long-term follow-up data concerning cardiac, renal and/or gonadal functions (sex-ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m2, ifosfamide = 59.4 g/m2) and 88 in VAI (ifosfamide = 97.1 g/m2). With a median follow-up of 10 years (range = 5-17), five late relapses and five second malignancies were recorded. The 10-year event-free survival among 5-year free-of-relapse survivors was similar between VAC and VAI (93% vs 95%, P =.63). We estimated the 10-year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval [95% CI] = 1.1%-7.6%) and 34.8% (95% CI = 26.8%-42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P =.02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P

La demande d’une contraception par l’adolescente permet de plus au praticien d’évaluer et rediscuter avec elle la vaccination contre le papillomavirus (HPV) et la prévention des infections sexuellement transmissibles (IST), mais aussi de détecter les possibles maltraitances que l’adolescente subit. L’optimisation de l’utilisation de la contraception reste l’objectif prioritaire de la consultation. Toutes les méthodes peuvent être proposées. L’adhésion à telle ou telle méthode est améliorée par une information préalable et un choix qui sera personnalisé. En dehors du risque vasculaire de la contraception œstroprogestative, la contraception hormonale a des effets gynécologiques bénéfiques. L’efficacité des méthodes de longue durée d’action est supérieure à celle des méthodes ponctuelles, mais leur tolérance reste imparfaite. Une contraception d’urgence sera prescrite à l’avance, afin de prévoir tout évènement pouvant survenir de façon inopinée. Des mesures de délivrance sont facilitées pour les mineures.

To assess the user profiles of copper intrauterine devices (Cu-IUD) and levonorgestrel intrauterine systems (LNG-IUS) in France in 2019 and the rates of continuation 1 year later.A population-based study was conducted of all French women aged 13-49 years for whom an IUD was dispensed in 2019. Information was collected from the French National Health Data System about their characteristics at the time of dispensation and indicators of continued use 1 year later. Associations between these characteristics and the type of IUD were analyzed using multivariate regressions.A total of 477 705 Cu-IUDs and 355 242 LNG-IUSs (mean age 32.5 ± 7.3 and 36.4 ± 7.7 years, respectively) were dispensed in 2019. After adjustment, having a LNG-IUS rather than a Cu-IUD was associated with being aged 35-44 years compared to 25-35 years (odds ratio [ORTwo different patterns of use of Cu-IUDs and LNG-IUSs in France are highlighted.

Objectives To examine the changes in diagnostic practices and clinical management of patients with 5α-reductase type 2 (SRD5A2) or 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency since molecular diagnoses became available. Methods Clinical, laboratory, and therapeutic data were retrieved from the medical records of 52 patients with a molecular diagnosis of SRD5A2 (n = 31) or HSD17B3 (n = 21) deficiency. Temporal trends regarding age at assessment and initial sex assignment over 1994–2020 were qualitatively analyzed. Age at molecular diagnosis was compared between two subgroups of patients according to their year of birth. Results Fifty-eight percent (n = 30) patients were diagnosed during the perinatal period, 33% (n = 17) during infancy, and 9% (n = 5) during adolescence or adulthood. Over the studied period, the patients’ age at initial assessment and diagnosis frankly decreased. The median (range) age at diagnostic confirmation was 10.5 (0–53.2) years for patients born before 2007 and 0.4 (0–9.3) years for those born in 2007 or later (P = 0.029). Genetic testing identified 27 different variants for the SRD5A2 gene (30% novel, n = 8) and 18 for the HSD17B3 gene (44% novel, n = 8). Before 2002, most patients were initially assigned as females (95%, n = 19), but this proportion dropped for those born later (44%, n = 14; P < 0.001). The influence of initial genital appearance on these decisions seemingly decreased in the most recent years. Therapeutic interventions differed according to the sex of rearing. Ten percent (n = 2) patients requested female-to-male reassignment during adulthood. Conclusion This study showed, over the past two decades, a clear trend toward earlier diagnosis and assignment of affected newborns as males.

International audience; Objectives: To assess the impact of the COVID-19 pandemic on the use of reimbursed contraceptives in France after 15 months of the pandemic, according to age-group and updating previous data only pertaining to the first lockdown (2 months). Study design: We conducted a national register-based study by extracting all reimbursements of oral contraceptives (OC), emergency contraception (EC), intrauterine devices (IUD), and implants from the French National Health Insurance database (SNDS), which includes and covers 99.5% of the French population, in 2018, 2019, 2020 and from January 1, 2021 to April30, 2021. We calculated the expected use of contraceptives in 2020 and 2021 in the absence of the pandemic, based on 2018 and 2019 usage and taking annual trends into account. We assessed the difference between observed and expected dispensing rates by contraceptive type and by age-group (≤18 years old, 18< age ≤25, 25< age ≤35, >35). Results: Dispensing of all contraceptives decreased compared to expect dispensing numbers: −2.0% for OC, −5.3% for EC, −9.5% for LNG-IUS, −8.6% for C-IUD, and −16.4% for implant. This decrease in the dispensing of contraceptives was observed in all age-groups, but mainly concerned women under the age of 18 years (−22% for OC, −10% for EC, −37.2% for LNG-IUS, −36.4% for C-IUD, −26.4% for implant) and those aged 18 to 25 (−5.1% for OC, −11.9% for EC, −18.1% for LNG-IUS, −15.9% for C-IUD, −17.6% for implants). Conclusions: Our study showed that the dispensing of contraceptives in France was markedly impacted by the COVID-19 pandemic. Prescriptions for long-acting contraceptive use and women under the age of 25 years were the most substantially impacted. Ensuring access to contraceptive methods during health emergencies must be a public health policy priority. Implications: The COVID-19 pandemic strongly impacted the dispensing of contraceptives in France with varying degrees of decreased dispensing according to the type of contraceptive, the age-group and the level of pandemic-related restrictions. The impact of these restrictions on unintended pregnancy at the population level remains undetermined.

Representatives for congenital adrenal hyperplasia (CAH) continue to desire early feminizing surgery in girls with 46,XX-CAH. The aim of this analysis, which included 174 46,XX- individuals with salt-wasting (SW) or simple-virilizing (SV) CAH, a female gender identity, and an age > 16 years participating in a multicenter cross-sectional clinical evaluation study (dsd-LIFE), was to evaluate the long-term results of surgery and patient-reported outcomes (PRO). The gynecological examination (n = 84) revealed some shortcomings concerning surgical feminization. A clitoris was absent in 9.5% of cases, while a clitoral hood was missing in 36.7% of cases. Though all women had large labia, they didn’t look normal in 22.6% of cases. Small labia were absent in 23.8% of cases. There was no introitus vaginae, and the urethra and vagina had no separate opening in 5.1% of cases. A mucosal lining was missing in 15.4% of cases. Furthermore, 86.2% of the women had scars at the region of their external genitalia. A vaginal stenosis was described in 16.5% of cases, and a meatal stenosis was described in 2.6% of cases. Additionally, PRO data showed a very-/high satisfaction rate of 21.3%/40.2% with cosmesis and 23.8%/38.1% with functionality, while 3.3%/10.7% showed a very-/low satisfaction with cosmesis as well as 5.6%/10.3% with functionality. The remaining women—24.6% and 23.8%—were indifferent. Satisfaction concerning sex life was very-/high in 9.6%/27.7%. In 12.0%/16.9% it was very-/low. Furthermore, 33.7% had no opinion. Furthermore, 27.0%/31.6% of the women reported that clitoriplasty, but not clitoridectomy, had a very-/positive influence on their lives, while 1.3%/8.9% felt it to be very-/negative, and 28.4% were indifferent. Vaginoplasty had a very-/positive influence in 25.7%/33.8% and a very-/negative effect in 3.6%/6.8%. 29.7% had no opinion. Additionally, 75.7% of the women preferred feminizing surgery during infancy/childhood, especially concerning clitoreduction. In conclusion, though the majority of the participants (76%) preferred early feminizing surgery and 60% described a positive effect on their lives, about 10% felt it to have been negative. About 15% of the women suffered from insufficient cosmesis and functionality after surgery. Sex life was even described as poor in nearly 30%. Therefore, the decision about early genital surgery in 46,XX-CAH girls should be considered carefully. Parents should get detailed information about possible complications of surgery and should receive support to understand that postponing surgery does not inevitably cause harm for their child. Importantly, genital surgery when performed in children should only be performed in expert centers with a specialized team including surgeons who are trained in feminizing surgery.

This matched-cohort study uses data from the French National Health Insurance database to assess whether a 19.5-mg levonorgestrel intrauterine system, vs a 52-mg system, is associated with increased use of antidepressant, hypnotic, and anxiolytic medications.

The request for a contraception in adolescent women makes it possible to address HPV vaccination and prevention of STIs and to search for abuse. Optimizing the use of contraception is the priority. Any contraceptive methods can be offered. Adhesion is improved by prior information and individualized counselling. Apart from the vascular risk associated with the combined hormonal contraception, hormonal contraception provides gynecologic benefits. The efficacy of long-acting methods is higher compared to short-acting methods but their tolerance is a sensitive matter. Emergency contraception can be prescribed in advance. There are measures to facilitate the delivery to minors.Contraception dans le contexte de l’adolescente.La demande d’une contraception par l’adolescente permet de plus au praticien d’évaluer et rediscuter avec elle la vaccination contre le papillomavirus (HPV) et la prévention des infections sexuellement transmissibles (IST), mais aussi de détecter les possibles maltraitances que l’adolescente subit. L’optimisation de l’utilisation de la contraception reste l’objectif prioritaire de la consultation. Toutes les méthodes peuvent être proposées. L’adhésion à telle ou telle méthode est améliorée par une information préalable et un choix qui sera personnalisé. En dehors du risque vasculaire de la contraception œstroprogestative, la contraception hormonale a des effets gynécologiques bénéfiques. L’efficacité des méthodes de longue durée d’action est supérieure à celle des méthodes ponctuelles, mais leur tolérance reste imparfaite. Une contraception d’urgence sera prescrite à l’avance, afin de prévoir tout évènement pouvant survenir de façon inopinée. Des mesures de délivrance sont facilitées pour les mineures.

Summary Background Surgery is performed in many individuals with disorders/differences of sex development (DSD). Irreversibility of some surgical procedures, lack of information about the procedures, and lack of follow-up care for physical and psychological outcomes, lead to wish for more knowledge from both surgeons and patients. After the consensus conference in 2006, multidisciplinary care is provided to a higher degree with psychological support and more restricted surgical procedures. Outcome studies after genital surgery often lack of patient's perspective. Objective To describe surgical procedures in relation to diagnosis, to evaluate the outcomes of surgery through genital examination, and through patient's and observer's satisfaction with the anatomical and functional result after genital surgery. Study design In a cross-sectional clinical study performed in six European countries in 2014/15, we have included 500 participants where surgery was performed, from a total of 1040 adolescents (≥16years) and adults with a DSD. Diagnoses included Turner syndrome (n = 301), mixed gonadal dysgenesis (45,XO/46,XY; n = 45), Klinefelter syndrome (n = 218), XYY (n = 1), 46, XY DSD (n = 222) and 46, XX DSD (n = 253). Study protocol included clinical report files, an optional gynecological or urological examination, patient reported outcomes including received surgical interventions, satisfaction with appearance and function after surgery, and impact of the surgical procedure on life. Results Five hundred participants had received genital or breast surgery, with the highest rate in 46, XY DSD and the lowest in Turner syndrome. Altogether; 240 participants had feminizing surgery, 112 had masculinizing surgery, and 217 underwent gonadectomy. Physicians evaluated anatomical appearance at genital examination as poor in less than 10%. Dissatisfaction with anatomical appearance was reported by 22% of the participants, dissatisfaction with function by 20%. Being (very) dissatisfied with anatomical appearance and function was reported by 13% of the study participants. Most participants reported no impact, or positive impact, of the surgical procedures on their lives, but 29% experienced a negative effect of gonadectomy on their life. Discussion There might be a selection bias and/or a recall bias for participating in our studies. Due to poor data quality about surgical procedures performed in the past, we also relied on participants memory about surgical procedures in their past. Ideally, patient reported outcomes should be evaluated both before and after surgical procedures. Conclusion A vast majority are satisfied with appearance and function, but still genital or breast surgery have a long-lasting effect on patient's life. Self-reported satisfaction is usually lower than the observer's evaluation regarding both appearance and function. Download : Download high-res image (217KB) Download : Download full-size image Summary Figure . Satisfaction with anatomy and function after genital surgery in individuals with DSD (appearance: n = 244; function: n = 257) (n = total number of participants).

Objectives To report the long-term follow-up outcomes of masculinizing surgery in disorders/differences of sex development (DSD), including both physicians' and patients' perspectives on appearance and functional outcome, including sexuality. Patients and methods In total, 1040 adolescents (age ≥16 years) and adults with a DSD took part in this multicentre cross-sectional clinical study in six European countries in 2014/2015. Of those, 150 living in other than the female gender had some kind of masculinizing surgery: hypospadias repair, orchidopexy, breast reduction and/or gonadectomy. The study protocol included medical data collection, an optional genital examination, and patient-reported outcomes including satisfaction with appearance and current sexual functioning. Results Diagnoses included partial and mixed gonadal dysgenesis (45,XO/46,XY; n = 38), Klinefelter syndrome/46,XX males (n = 57), and various 46,XY DSDs (n = 42; e.g. partial androgen insensitivity syndrome, severe hypospadias) and 13 with other diagnoses. Of the participants, 84 underwent hypospadias surgery, 86 orchidopexy, 52 gonadectomy and 32 breast reduction (combinations possible). Physicians evaluated anatomical appearance at genital examination as poor in approximately 11% of patients. After hypospadias surgery, 38% of participants reported that they were (very) dissatisfied with anatomical appearance and 20% with function. The physician and patient evaluations were moderately correlated (r = 0.43). Conclusion The majority of participants were neutral to satisfied with the appearance and function in the long-term after masculinizing surgery. Given the initial severe phenotype and a risk of unsatisfactory results after masculinizing surgery in DSD, treatment should be handled by experienced multidisciplinary teams in order to optimize the postoperative results.

Objective To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism. Design Observational cohort study. Setting Data from SNDS, the French administrative healthcare database, between 2007 and 2015. Participants 253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis. Main outcome measure Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas. Results Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years). Conclusions A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.

International audience; Premature ovarian insufficiency (POI) is a rare pathology affecting 1-2% of under-40 year-old women, 1 in 1000 under-30 year-olds and 1 in 10,000 under-20 year-olds. There are multiple etiologies, which can be classified as primary (chromosomal, genetic, auto-immune) and secondary or iatrogenic (surgical, or secondary to chemotherapy and/or radiotherapy). Despite important progress in genetics, more than 60% of cases of primary POI still have no identifiable etiology; these cases are known as idiopathic POI. POI is defined by the association of 1 clinical and 1 biological criterion: primary or secondary amenorrhea or spaniomenorrhea of>4 months with onset before 40 year of age, and elevated follicle-stimulating hormone (FSH)>25IU/L on 2 assays at>4 weeks' interval. Estradiol level is low, and anti-Müllerian hormone (AMH) levels have usually collapsed. Initial etiological work-up comprises auto-immune assessment, karyotype, FMR1 premutation screening and gene-panel study. If all of these are normal, the patient and parents may be offered genome-wide analysis under the "France Génomique" project. The term ovarian insufficiency suggests that the dysfunction is not necessarily definitive. In some cases, ovarian function may fluctuate, and spontaneous pregnancy is possible in around 6% of cases. In confirmed POI, hormone replacement therapy is to be recommended at least up to the physiological menopause age of 51 years. Management in a rare diseases center may be proposed.

Background Patients with disorders/differences of sex development (DSD), especially those possessing the Y chromosome, have a higher risk of gonadal germ-cell tumours (GCTs). We aimed to examine the incidence of different types of gonadal neoplasia and associated risk factors. Methods A total of 1040 DSD patients aged ≥16 years participated in a cross-sectional multicentre European study (dsd-LIFE). Data on medical history were gathered from the patients’ archival medical documents. A web-based questionnaire was filled out individually by the participants. A physical examination was performed in all, while ultrasonography of gonads was carried out in 214 and semen analysis was performed for 53 patients. Results Germ-cell neoplasia was present in 12 % of patients with DSD and in 14 % of those with XY DSD. The highest risk (36 %) was observed in 46,XY patients with gonadal dysgenesis (GD): complete GD (33 %) and partial GD (23 %), but also in mixed GD (8 %) and complete androgen insensitivity syndrome (AIS) (6%). It was not reported in partial AIS, XX male, 46,XX DSD and congenital adrenal hyperplasia, Turner and Klinefelter syndromes, or in androgen biosynthesis defects. Benign sex cord-stromal tumours (Sertoli- and Leydig-cell tumours) were noted only in patients with complete AIS (3.1 %) and Klinefelter syndrome (14.3 %). A relationship between risk factors for GCT and gonadal neoplasia appearance, other than the Y chromosome, was not found. Conclusion Adult patients with GD and the Y chromosome have the highest risk of GCT and should be kept under thorough medical control and receive special medical follow-up to prevent the development of gonadal tumours.

Purpose To evaluate the validity and reproducibility of magnetic resonance (MR) imaging-based ovarian morphologic measurements for diagnosis of polycystic ovary syndrome (PCOS) in adolescents. Materials and Methods This case-control study included 110 adolescent girls (age range, 13-17 years) who underwent pelvic MR imaging in 2006-2015. The case group included girls with high (n = 40, hyperandrogenism and oligomenorrhea or amenorrhea), intermediate (n = 8, hyperandrogenism), or low (n = 7, oligomenorrhea or amenorrhea) suspicion of PCOS. Control subjects were 55 age-matched (± 2 years) girls with no clinical hyperandrogenism, oligomenorrhea, or amenorrhea. The validity (sensitivity, specificity, and area under the receiver operating characteristic curve [AUC]) of the number of follicles per ovary (FPO) measuring 9 mm or smaller (FPO-9) and FPO measuring 5 mm or smaller (FPO-5), ovarian volume (OV), sphericity index, peripheral distribution of follicles, and absence of a dominant follicle were determined, with girls who were highly suspected of having PCOS compared with control subjects as the reference. Two radiologists independently measured these criteria in 50 girls who were suspected of having PCOS to assess reproducibility (κ and intraclass correlation coefficients [ICCs]). Results All criteria except sphericity index and absence of a dominant follicle were significantly associated with the level of suspicion of PCOS (P ≤ .05). The AUCs for FPO-9 (0.78; 95% confidence interval [CI]: 0.68, 0.87), FPO-5 (0.73; 95% CI: 0.62, 0.83), and OV (0.77; 95% CI: 0.68, 0.87) were significantly greater than 0.5; that was not true for sphericity index (AUC, 0.58; 95% CI: 0.47, 0.70). Sensitivity and specificity for peripheral distribution of follicles were 33% (95% CI: 19%, 49%) and 95% (95% CI: 85%, 99%), respectively; for absence of a dominant follicle, they were 90% (95% CI: 76%, 97%) and 27% (95% CI: 16%, 41%), respectively. Reproducibility was almost perfect for OV (ICC, 0.89), substantial for absence of a dominant follicle (κ, 0.74), moderate for FPO-9 (ICC, 0.54) and FPO-5 (ICC, 0.61), and fair for peripheral distribution of follicles (κ, 0.37). Conclusion The most accurate MR imaging-based diagnostic criteria for PCOS were OV, FPO-9, and peripheral distribution of follicles; however, reproducibility of these measures was moderate, except that for OV (ICC, 0.89).

Background Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacologic challenges. Methods In this prospective case–control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10 ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 age- and body mass index-matched healthy women with 17OHP after Synacthen® Findings The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference –47 ng/mL, 90% CI, –66, P = 0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (P = 0.0039). Twenty-four hours after sodium depletion, blood pressure, plasma sodium, potassium, and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (P = 0.0044). Interpretation Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions.

Background: Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacological challenges. Methods: In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 ageand BMI-matched healthy women with 17OHP after Synacthen®

What should be done in clitoral hypertrophy ? Clitoral hypertrophy is an infrequent variation/disorder of the sex development which requires a careful assessment. It should never be disregarded because it can reveal a congenital pathology that will have immediate vital consequences and result in low self-esteem, sexuality and fertility. This justifies an early multidisciplinary care and careful psychological support.Que faire en cas de clitoris augmenté de volume chez une petite fille ? L’hypertrophie clitoridienne est une variation/anomalie du développement des organes génitaux externes peu fréquente qui nécessite un bilan soigneux. Elle ne doit jamais être négligée parce qu’elle peut révéler une pathologie congénitale qui aura des conséquences vitales immédiates et futures en termes d’estime de soi, de sexualité et de fertilité. Cela justifie une prise en charge précoce multidisciplinaire et un accompagnement psychologique soigneux.

Given the excellent survival rate of children and teenagers treated for cancer, careful should be given in order to minimize long-term late effects of treatments and to improve quality of life. In this regard, fertility preservation is particularly important. Age, sex and concomitant therapies have an impact on the level of risk of hypofertility, with a stronger risk for chemotherapeutic regimens including alkylating agents, and gonads or hypothalamo-pituitary axis radiotherapy. Assessment of gonadotoxic impact of treatment strategy and fertility preservation techniques are crucial for limiting late effects. The objective of this literature review is to develop guidance for pediatric oncologists and hematologists relative to fertility preservation methods, in children and teenagers receiving gonadotoxic treatment. Specific follow-up after treatment is also proposed.

International audience; Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and "non-hormonal/non chromosomal" DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts. Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should lead to design collaborative prospective studies involving all parties and using consensual protocols of evaluation.

Resume Les hypothyroidies et les hyperthyroidies sont les deux grands ambassadeurs des dysfonctionnements thyroidiens. La glande thyroide peut, par ailleurs, etre le siege d’un processus cancereux. Les principaux medicaments des dysfonctionnements thyroidiens que le pharmacien dispense couramment a l’officine sont representes par les hormones thyroidiennes, principalement la levothyroxine, et les antithyroidiens de synthese.

Given the excellent survival rate of children and teenagers treated for cancer, careful should be given in order to minimize long-term late effects of treatments and to improve quality of life. In this regard, fertility preservation is particularly important. Age, sex and concomitant therapies have an impact on the level of risk of hypofertility, with a stronger risk for chemotherapeutic regimens including alkylating agents, and gonads or hypothalamo-pituitary axis radiotherapy. Assessment of gonadotoxic impact of treatment strategy and fertility preservation techniques are crucial for limiting late effects. The objective of this literature review is to develop guidance for pediatric oncologists and hematologists relative to fertility preservation methods, in children and teenagers receiving gonadotoxic treatment. Specific follow-up after treatment is also proposed.

ObjectiveCongenital cardiovascular malformations and aortic dilatation are frequent in patients with Turner syndrome (TS). The objective of this study was to investigate the cardiovascular findings and management in a large cohort of patients, including children and adults.Design/methodsWe recruited 336 patients with TS from a network of tertiary centers. We reviewed their files, checking for cardiovascular events, cardiac valve abnormalities, and aortic diameters indexed to body surface area (BSA) from magnetic resonance imaging (n=110) or echocardiography (n=300).ResultsInformative cardiovascular data were available for only 233 patients. Vascular surgery was reported in 7.4% of the cohort. The first cause of surgery was aortic coarctation, detected in 6.9% at a median age of 9.5 (range: 0–60) years. Bicuspid aortic valve (BAV) was detected in 21% at a median age of 20 years (25th–75th percentiles: 15–30). At least one aortic diameter exceeded 32 mm in 12% of the cohort. This was detected at a median age of 19 (7–30) years. When indexed to BSA, at least one aortic diameter exceeded 20 mm/m2 in 39% of the cohort.ConclusionOur study shows that cardiovascular monitoring for TS patients is currently insufficient in France. BAV is present at birth, but often remains undiagnosed until later in life. Therefore, improved management in cardiovascular monitoring is required and a more systematic approach should be taken.

Kuhn JM, Duranteau L, Rieu MA, Lahlou N, Roger M, Luton JP. Evidence of oestradiol-induced changes in gonadotrophin secretion in men with feminizing Leydig cell tumours. Eur J Endocrinol 1994;131:160–6. ISSN 0804–4643 To study the sex steroid-gonadotrophin relationship, plasma oestradiol (E2), testosterone and gonadotrophin-releasing hormone (GnRH)-induced (100 μg iv) gonadotrophin response were measured in 42 male partners of infertile couples with normal sperm count (group I) and in 21 men with Leydig cell tumour (LCT, group II) in which a basal evaluation was repeated after tumour removal. Plasma free α-subunit (FAS), immunoreactive α-inhibin and luteinizing hormone (LH) pulse analysis were assessed in 10 LCT before and in six of them after surgery. Testosterone was significantly (p < 0.01) lower whereas E2 was significantly (p < 0.001) higher in group II than in group I. Gonadotrophin data were similar in both groups. The mean FAS was higher in group II than in group I and α-inhibin was higher than the normal range in 6/10 LCT. In group II, E2 levels were significantly (p < 0.01) and negatively correlated with testosterone, FSH, GnRH-induced gonadotrophin rise and LH pulse amplitude but not frequency. Significant (p < 0.001) changes were observed after surgery: E2 and α-inhibin fell; testosterone, LH and FSH rose; whereas FAS did not change significantly. The LH pulse amplitude but not frequency increased significantly (p < 0.05). In conclusion E2 oversecreted by LCT decreased LH and testosterone levels concomitantly. The GnRH-induced gonadotrophin level rose and the LH pulse amplitude decreased when the plasma E2 level rose, whereas the pulse frequency remained unaffected. A concomitant increase in α-inhibin and E2 is likely to be responsible for the drop in plasma FSH levels. These data support an action of excessive amounts of E2 at pituitary level, perhaps by decreasing the sensitivity of gonadotrophs to GnRH. JM Kuhn, Service d'Endocrinologie, Hôpital de Bois Guillaume, 147 avenue du Maréchal Juin, 76230 Bois Guillaume, France

Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10% and to reduce tumour size in one-third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long-term effects of bromocriptine and CV 205-502 (a non-ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine-resistant prolactinomas. Bromocriptine reduced significantly (P less than 0.001) plasma prolactin levels (from 2307 +/- 518 to 568 +/- 279 micrograms/l) (conversion to Sl units: 1 microgram/l = 20 mU/l). Visual field defects observed in five patients improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side-effects at the beginning of the treatment, CV 205-502 was well tolerated in five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205-502 and it was necessary to reduce the daily dose. CV 205-502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205-502 was more potent than bromocriptine as demonstrated by the further 90% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205-502 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a novel mutant of the luteinizing hormone receptor (LHR) in a case of familial Leydig cell hypoplasia and pseudohermaphrotidism. The proband was homozygous for two missense mutations, T1121C and C1175T, causing substitutions I374T and T392I. The molecular effects of the mutations were investigated by heterologous expression of the WT LHR, the double mutant LHR, or receptors with either the I374T or the T392I mutation, and measuring hormone binding and cAMP signaling. All mutant LHRs exhibited severe defects, including loss of ligand binding and cAMP production. Immunoblots showed little difference in protein levels between the WT and mutant receptors.

Contexte Le risque d’insuffisance surrenale chez les femmes atteintes d’un deficit en 21-hydroxylase non classique (D21OH-NC) est inconnu. L’indication d’un traitement substitutif reste controversee. Objectif Evaluer la fonction glucocorticoide et mineralocorticoide de la surrenale des femmes avec un D21OH-NC. Protocole Etude prospective controlee chez 20 patientes avec un D21OH-NC avec mutations bi-alleliques de CYP21A2 et une 17-hydroxyprogesterone plasmatique sous Synacthene > 10 ng/mL, et chez 20 femmes volontaires saines appariees. Etude des reponses a l’hypoglycemie insulinique et a la depletion sodee (furosemide et un regime pauvre en sel). PHRC AOR11-111, ClinicalTrials.gov Id: NCT01862380 . Resultats Les resultats des 13 premieres patientes et 7 volontaires saines sont presentees ici : – le pic de cortisolemie sous hypoglycemie insulinique etait significativement plus bas chez les patientes que chez les femmes controles : 18,0 μg/dL (14,2–22,8) vs 23,2 μg/dL (18,4–28,7), p = 0,0022. Un pic de cortisolemie ≥ 18 μg/dL etait obtenu chez tous les controles et seulement chez 50 % de patientes D21OH-NC ; – apres 15 heures de depletion sodee, l’aldosterone plasmatique etait comparable entre les deux groupes mais la renine active etait plus elevee chez les D21OH-NC que chez les femmes saines : 99 mUI/L (52–146) vs 42 mUI/L (24–62), p = 0,0152. Les resultats de l’ensemble des patients seront detailles lors du congres. Conclusion Un sous groupe de femmes avec un D21OH-NC a une reserve glucocorticoide et mineralocorticoide de la surrenale diminuee. La signification clinique de ce deficit partiel et inconstant n’est pas etablie. Mais par precaution, un traitement substitutif dans les situations de stress aigu pourrait etre propose.

The receptor for luteinizing hormone and chorionic gonadotropin plays a major part in normal and abnormal reproductive function.1–4 In males, activation of the receptor regulates the development and function of Leydig cells.5 Testosterone secreted by Leydig cells promotes male sexual differentiation, pubertal androgenization, and fertility. The human luteinizing hormone receptor is a G protein–coupled receptor with a transmembrane domain composed of seven segments. Activation of the receptor by luteinizing hormone leads to activation of Gs, the G protein that is coupled to adenylyl cyclase, and to an increase in cyclic AMP (cAMP). High concentrations of luteinizing hormone . . .

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 μg per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.

Introduction-ObjectiveThe subdermal contraceptive implant is a long-acting reversible method of contraception. It is available on the French market since 2011 but is used only by a minority of women of reproductive age. Due to the absence of impact of compliance, it is one of the most effective method of contraception. However, early removals are not rare. The main objective of the study was to evaluate the knowledge and to know women's representations related to the subdermal implant, in order to understand the obstacles to its use in order to adapt the information given to women and to achieve a better acceptability.Secondly, analyzed women’s opinion about anticipating the contraceptive choice by discussing about available methods, during pregnancy. MethodsA questionnaire was distributed to women staying in the three units of diapers at Antoine Béclère Hospital from December 2017 to March 2018. 175 questionnaires were given. The results are quantitative and expressed in numbers and percentages.Results and conclusionStudy shows that the contraceptive implant is associated with a significant lack of knowledge and misinformation that lead to unfavorable features which impact the contraceptive choice. Also, the role of general practitioners and midwives remains unknown to women. The resumption of contraception is considered as an important decision in 50% of women and a first approach of contraceptive methods during pregnancy seems appropriate for 80% women.; Introduction-Objectifs L’implant contraceptif sous cutané fait partie des nouvelles méthodes contraceptives réversibles de longue durée d’action. Mis sur le marché français en 2011, il n’est utilisé que par une minorité de femmes en âge de procréer et les retraits précoces ne sont pas rares. Il s’agit pourtant d’une des méthodes de contraception les plus efficaces puisque son efficacité est indépendante de l’observance. D’autre part, les retraits précoces ne sont pas rares. L’objectif principal de cette étude était d’évaluer les connaissances et de connaître les représentations des femmes à propos de l’implant sous-cutané, afin de mieux comprendre les freins à son utilisation et ainsi d’adapter l’information faite aux femmes et d’atteindre une meilleure tolérance. Nous analyserons de plus l’avis des femmes sur le fait d’anticiper la réflexion contraceptive en l’abordant au cours de la grossesse. Matériel et méthodesUn questionnaire a été distribué aux femmes séjournant dans les trois unités de suites de couches de l’hôpital Antoine Béclère entre décembre 2017 et mars 2018. 175 questionnaires ont été exploités. Les résultats sont quantitatifs et exprimés en effectifs et pourcentages. Résultats et ConclusionSelon les résultats, un défaut de connaissances et des informations erronées relatives à l’implant attribuent à cette méthode contraceptive des critères défavorables au moment du choix contraceptif. D’autre part, le rôle des médecins généralistes et des sages-femmes dans la prescription de la contraception est peu connu des femmes. La reprise de la contraception est une décision importante pour une femme sur deux et l’abord des méthodes contraceptives pendant la grossesse paraît judicieux chez 80% des femmes.

Le syndrome de Turner caractérisé par l'absence de la totalité ou d'une partie d'un chromosome X chez une fille, est une affection rare dont la prévalence est estimée actuellement à 1/2500 naissances féminines. Il associe une petite taille et une insuffisance ovarienne avec des anomalies du développement pubertaire et une infertilité. De façon inconstante, l'apparence physique peut également être modifiée. Face à une condition médicale complexe telle que le syndrome de Turner, notre objectif était d'évaluer le bien être physique et psychique des patientes. Ce travail est fondé sur un questionnaire anonyme et a inclus 61 patientes de 15 à 35 ans présentant un syndrome de Turner suivies dans des services d'endocrinologie adulte et pédiatrique (Centres Hospitalo-Universitaires de Nice, de Paris Sud et de Marseille). L'évaluation de la qualité de vie, de l'état psychologique, de l'image corporelle et de la sexualité des patientes a été comparée à celle de 33 témoins issues du même environnement social. L'image corporelle et la perception de leur féminité semblent altérées chez les patientes par rapport aux témoins (p < 0.01), ceci de façon corrélée avec la qualité de vie et l'état anxio-dépressif. L'entrée dans la vie sexuelle est plus tardive et la sexualité nettement inférieure chez les patientes (p < 0.01). Cependant, la qualité de vie générale évaluée par le SF 36 est similaire entre les deux groupes (p=0.5). L'intérêt porté à la sexualité et la satisfaction qu'elle peut apporter paraissent identiques chez les patientes et les témoins ayant une activité sexuelle (p=0.1 et p=0.8). Par ailleurs, 64% des patientes bénéficient d'un suivi gynécologique : 40% déclarent avoir eu des informations sur la sexualité et 80% sur les possibilités de procréation médicale assistée. Néanmoins, d'après ces résultats, une meilleure prise en charge par l'information et l'accompagnement des patientes semble nécessaire, afin d'améliorer leur relation avec elles-mêmes, leurs interactions avec autrui et leurs attentes en tant que jeunes femmes.