S Christin-Maitre

Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien), Lutetia Parisorum, Île-de-France, France

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Publications (128)443.42 Total impact

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    Annales de biologie clinique 08/2014; 72(4):385-389. · 0.30 Impact Factor
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    ABSTRACT: Context: Mutations in CHD7, a gene previously implicated in CHARGE syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating versus non-truncating mutations in KS and CHH patients is still unknown. Objective: To determine the nature, prevalence, mode of transmission, and clinical spectrum of CHD7 mutations in a large series of patients. Design: We studied 209 KS and 94 CHH patients. These patients had not been diagnosed as CHARGE syndrome according to the current criteria. We searched for mutations in 16 KS and CHH genes including CHD7. Results: We found presumably pathogenic mutations in CHD7 in 24 KS patients, but not in CHH patients. Non-truncating mutations (16 missense, and a two-codon duplication) were more prevalent than truncating mutations (three nonsense, three frame-shift, and a splice site), which contrasts with patients presenting with typical CHARGE syndrome. Thus the clinical spectrum associated with CHD7 mutations may be partly explained by genotype/phenotype correlations. Eight patients also had congenital deafness and one had a cleft lip/palate, whereas six had both. For 10 patients, the presence of diverse features of the CHARGE spectrum in at least one relative argues against a de novo appearance of the missense mutation, and this was confirmed by genetic analysis in five families. Conclusion: Considering the large prevalence and clinical spectrum of CHD7 mutations, it will be particularly relevant to genetic counseling to search for mutations in this gene in KS patients seeking fertility treatment, especially if KS is associated with deafness and cleft lip/palate.
    The Journal of clinical endocrinology and metabolism. 07/2014;
  • Célia Ravel, Capucine Hyon, Jean-Pierre Siffroi, Sophie Christin-Maitre
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    ABSTRACT: DAX-1 stands for Dosage sensitive sex-reversal, Adrenal hypoplasia congenital (AHC), on the X chromosome. DAX-1 mutations usually cause primary adrenal insufficiency or congenital adrenal hypoplasia in early childhood and hypogonadotropic hypogonadism (MIM # 300200). DAX-1 protein is necessary to maintain normal spermatogenesis. In humans, male fertility has been studied in few patients carrying DAX-1 mutations. Cases of azoospermia have been reported, as well as unsuccessful gonadotropin treatments. The clinician should be informed that TESE-ICSI technique carries a potential hope to father non-affected children, as shown in this review.
    Annales d Endocrinologie 04/2014; · 1.02 Impact Factor
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    ABSTRACT: Background: The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However, ketoconazole is frequently used as a drug to lower circulating cortisol levels. Several pharmacological agents have recently been approved for the treatment of Cushing's disease (CD) despite limited efficacy and significant side effects. Ketoconazole has been used worldwide for more than 30 years in CD but in the absence of large scale study, its efficacy and tolerance are still under debate. Patients and methods: We conducted a French retrospective, multicenter study reviewing data from patients treated by ketoconazole as a single agent for CD, with the aim of clarifying efficacy and tolerance in order to better determine the benefits/risk balance. Results: Data from 200 patients were included in this study. At the last follow-up, 49.3% of patients had normal urinary free cortisol (UFC) levels, 25.6% had at least a 50% decrease, and 25.4% had unchanged UFC levels. The median final dose of ketoconazole was 600 mg/day. Forty patients (20%) received ketoconazole as a pre-surgical treatment; 40-50% of these patients showed improvement of hypertension, hypokalemia and diabetes, and 48.7% had normal UFC before surgery. Overall, 41 patients (20.5%) stopped the treatment due to poor tolerance. Mild (< 5N) and major (>5N) increases in liver enzymes were observed in 13.5 % and 2.5% of patients respectively. No fatal hepatitis was observed. Conclusions: Ketoconazole is an effective drug with acceptable side effects. It should be used under close liver enzyme monitoring. Hepatotoxicity is usually mild and resolutive after drug withdrawal.
    The Journal of Clinical Endocrinology and Metabolism 01/2014; · 6.31 Impact Factor
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    ABSTRACT: Contexte La néoplasie endocrinienne multiple de type 1, NEM1, est une affection à transmission autosomique dominante qui associe chez un même patient ou ses apparentés des tumeurs des parathyroïdes, du pancréas endocrine et de l’hypophyse. Des données controversées suggèrent que le variant Ala541Thre pourrait avoir un rôle pathogénique, et pourrait être associé à un risque accru de développer des lésions de MEN1. Objectifs Le but de cette étude était d’évaluer les atteintes cliniques et fonctionnelles du variant p.Ala541Thr. Patients et méthodes Nous avons analysé une série de 55 patients porteurs du variant p.Ala541Thr. Leur présentation clinique a été comparée à celle de 117 patients MEN1. L’effet biologique de ce variant sur la croissance cellulaire a été également étudié dans un modèle cellulaire issus de tumeurs de cellules de Leydig déficientes en MEN1 (LCT10). Résultats L’âge moyen à la première lésion est similaire dans les 2 groupes p.Ala541Thr et MEN1, mais aucun des patients p.Ala541Thr n’avait plus d’une lésion au diagnostic. Une deuxième lésion a été diagnostiquée chez 13 % des MEN1 et 7 % des p.Ala541Thr l’année qui a suivi le diagnostic initial. Les études fonctionnelles montrent que la réexpression du variant p.Ala541Thr ne permet pas d’inhiber la croissance cellulaire, contrairement à ce qui a été observé avec la protéine sauvage. Conclusions Ce travail vient perturber le concept de polymorphisme et de leur potentielle non-pathogénicité. Des études complémentaires sont cependant nécessaires afin de déterminer si ce variant peut-être impliqué dans la survenue d’un phénotype MEN1 de faible pénétrance.
    Annales d'Endocrinologie. 01/2014;
  • Célia Ravel, Capucine Hyon, Jean-Pierre Siffroi, Sophie Christin-Maitre
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    ABSTRACT: DAX-1 signifie inversion sexuelle dosage sensible, hypoplasie congénitale des surrénales sur le chromosome X. Les mutations de DAX-1 entraînent une insuffisance surrénale primitive ou une hypoplasie congénitale des surrénales dans la petite enfance ainsi qu’un hypogonadisme hypogonadotrope (MIM#300200). La protéine DAX-1 est nécessaire au maintien d’une spermatogénèse normale. Chez l’homme la fertilité masculine a été étudiée chez quelques patients porteurs de la mutation. Des cas d’azoospermis ont été rapportés ainsi que des échecs de traitement par les gonadotrophines. Le clinicien doit être informé que la technique TESE-ICSI offre un espoir de paternité permettant la naissance d’enfants non atteints comme il est montré dans cette revue.
    Annales d'Endocrinologie. 01/2014;
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    ABSTRACT: Background Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands. Methods We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients. Results The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion. Conclusions Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of steroidogenic cells in the hyperplastic adrenals. Thus, the hypercortisolism associated with bilateral macronodular adrenal hyperplasia appears to be corticotropin-dependent. (Funded by the Agence Nationale de la Recherche and others.).
    New England Journal of Medicine 11/2013; 369(22):2115-2125. · 54.42 Impact Factor
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    ABSTRACT: Premature ovarian failure (POF) is clinically suspected by amenorrhea and confirmed by an elevated FSH serum level above 40mUI/L (even 20mUI/L) twice, in a woman before the age of 40. Prevalence of POF is between 1 to 2% in women. In 90% of cases, no aetiology is identified. Obvious causes are chemotherapy, pelvic radiotherapy, ovarian surgery and diethylstilbestrol exposure in utero. A karyotype should be performed as Turner Syndrome is the most frequent genetic cause of POF. Some X abnormalities such as X deletion or X autosome translocation can be found. FMR1 pre-mutation (fragile X syndrome) should be searched for, even though no cases of mental retardation are known, in the family. Other genetic abnormalities can be suggested by associated symptoms (i.e.: FOXL2, SF1 mutations). Auto-immune aetiology can be suspected if other auto-immune features are present, however, there are no reliable auto-antibodies to confirm auto-immunity in POF. Treatment of POF is based on hormonal replacement therapy in order to avoid estrogen deficiency, suppress vasomotor symptoms and avoid bone loss as well as cardiovascular risk. Estrogens should be associated with progesterone or a progestin, at least up to the age of 51. Patients with POF should be informed that spontaneous pregnancies may occur (in 5% of cases). In case of desire of pregnancy, the patient should be oriented to a specialized unit for in vitro fertilization with oocyte donation. Psychological support is essential and should be part of the treatment. POF is associated with an increased risk of emotional distress and depression. No preventive treatment of POF is available so far.
    La Presse Médicale 10/2013; · 0.87 Impact Factor
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    ABSTRACT: Context:The association of primary amenorrhea, gonadotropin levels at menopausal range, and normal antral follicle endowment is a rare clinical condition that suggests unresponsiveness of antral follicles to follicle-stimulating hormone (FSH). Patients suffering from this affection are usually referred to egg donation to treat their infertility.Objective:To test the effectiveness of in vitro maturation (IVM) of oocytes to treat the infertility of a woman endowed with multiple antral follicles unresponsive to FSH.Design:Case report.Setting:University hospital.Patient:A young, amenorrheic woman having high serum FSH (40.3 and 38.4 mIU/mL) and LH (35.7 and 31.7 mIU/mL) levels but normal serum anti-Müllerian hormone (AMH; 4.50 and 4.36 ng/mL) levels and total counting of antral follicles (23 and 18 follicles).Intervention:Aspiration of oocytes from small antral follicles and subsequent IVM, fertilization, and embryo transfer.Main Outcome Measure:Live birth.Results:Fifteen immature oocytes were retrieved. Following IVM, 12 of them reached metaphase II. Seven embryos were obtained and 3 of them were transferred into the uterus. This patient became pregnant and delivered a healthy baby at term.Conclusions:We obtained the first pregnancy and live birth achieved using IVM in a woman endowed with multiple antral follicles unresponsive to endogenous and exogenous FSH. Therefore, IVM may constitute a viable alternative to egg donation for treating the infertility of women suffering from such a condition.
    The Journal of Clinical Endocrinology and Metabolism 08/2013; · 6.31 Impact Factor
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    ABSTRACT: Laminopathies, due to mutations in LMNA, encoding A type-lamins, can lead to premature ageing and/or lipodystrophic syndromes, showing that these diseases could have close physiopathological relationships. We show here that lipodystrophy and extreme insulin resistance can also reveal the adult progeria Werner syndrome linked to mutations in WRN, encoding a RecQ DNA helicase. We analysed the clinical and biological features of two women, aged 32 and 36, referred for partial lipodystrophic syndrome which led to the molecular diagnosis of Werner syndrome. Cultured skin fibroblasts from one patient were studied. Two normal-weighted women presented with a partial lipodystrophic syndrome with hypertriglyceridemia and liver steatosis. One of them had also diabetes. Both patients showed a peculiar, striking lipodystrophic phenotype with subcutaneous lipoatrophy of the four limbs contrasting with truncal and abdominal fat accumulation. Their oral glucose tolerance tests showed extremely high levels of insulinemia, revealing major insulin resistance. Low serum levels of sex-hormone binding globulin and adiponectin suggested a post-receptor insulin signalling defect. Other clinical features included bilateral cataracts, greying hair and distal skin atrophy. We observed biallelic WRN null mutations in both women (p.Q748X homozygous, and compound heterozygous p.Q1257X/p.M1329fs). Their fertility was decreased, with preserved menstrual cycles and normal follicle-stimulating hormone levels ruling out premature ovarian failure. However undetectable anti-mullerian hormone and inhibin B indicated diminished follicular ovarian reserve. Insulin-resistance linked ovarian hyperandrogenism could also contribute to decreased fertility, and the two patients became pregnant after initiation of insulin-sensitizers (metformin). Both pregnancies were complicated by severe cervical incompetence, leading to the preterm birth of a healthy newborn in one case, but to a second trimester-abortion in the other. WRN-mutated fibroblasts showed oxidative stress, increased lamin B1 expression, nuclear dysmorphies and premature senescence. We show here for the first time that partial lipodystrophy with severe insulin resistance can reveal WRN-linked premature aging syndrome. Increased expression of lamin B1 with altered lamina architecture observed in WRN-mutated fibroblasts could contribute to premature cellular senescence. Primary alterations in DNA replication and/or repair should be considered as possible causes of lipodystrophic syndromes.
    Orphanet Journal of Rare Diseases 07/2013; 8(1):106. · 4.32 Impact Factor
  • E. Laroche, L. Bricaire, S. Christin-Maitre
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    ABSTRACT: Amenorrhea in adolescents can be primary, with or without breast development, or secondary. Whether amenorrhea is primary or secondary, height, body mass index, food intake, the level of physical activity per week, the presence of hirsutism or galactorrhea, pelvic pain and past history of intercourse need to be investigated. Initially, blood tests should include hCG, FSH, estradiol, testosterone and prolactin serum levels. This screening will discriminate between hypogonadotropic hypogonadism and amenorrhea from primary ovarian insufficiency (POI). In case of primary amenorrhea, hypogonadism may be due to congenital hypogonadotropic hypogonadism (HH) or more rarely acquired HH. If FSH is elevated, amenorrhea is due to primary ovarian failure, mainly related to Turner syndrome. If pubertal development is normal, a pelvic ultrasound should be performed. It may visualize a hindering of menses output or less frequently an absence of uterus, as in Rokitansky syndrome or androgen insentivity syndrome. The most frequent etiologies of secondary amenorrhea are polycystic ovarian syndrome (PCOS), functional hypothalamic amenorrhea and less frequently POI and hyperprolactinemia. The differential diagnoses of PCOS are late-onset 21-hydroxylase deficiency and very rare ovarian or adrenal tumors. When contraception is not necessary, hormonal replacement therapy, including estrogen and progestins should be administered in order to avoid hypoestrogenism. In case of PCOS, sequential progestins can be prescribed. A contraceptive pill can be considered when contraception is needed and/or when hyperandrogenism needs to be treated.
    Archives de Pédiatrie. 07/2013; 20(7):817–822.
  • L Bricaire, E Laroche, S Christin-Maitre
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    ABSTRACT: Menometrorrhagia is a common symptom in adolescents. It is idiopathic in most cases. In case of menometrorrhagia, it is necessary to exclude a pregnancy, a disorder of hemostasis, particularly the von Willebrand disease, as it represents the most common inherited disorder, and more rarely a chronic disease or an endocrinopathy. History of the bleedings, menstrual blood loss quantification by the Higham score and tolerance of the bleedings (blood pressure) should be evaluated. Laboratory testing includes hCG, ferritin level, a complete blood count, a prothrombin time, an activated partial thromboplastin. Management of menometrorrhagia is related to the severity of the blood loss. It associates antifibrinolytics or non-steroidal anti-inflammatory agents (NSAIDS) with hormonal treatments, such as estrogen-progestin oral contraceptive pill or cyclic oral progestins. Primary or functional dysmenorrhea concerns 40 to 90% of the teenagers and represents a frequent cause of school absenteeism. Management of primary dysmenorrhea is primarily based on a treatment by NSAIDS. In case of its inefficacy or if contraception is needed hormonal treatments, such as estrogen-progestin combined pill should be prescribed. It is very important when pelvic pain is chronic and not soothed by simple medications to look for a secondary dysmenorrhea, mainly endometriosis. In such cases, pelvic magnetic resonance imaging should be performed.
    Archives de Pédiatrie 05/2013; · 0.36 Impact Factor
  • E Laroche, L Bricaire, S Christin-Maitre
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    ABSTRACT: Amenorrhea in adolescents can be primary, with or without breast development, or secondary. Whether amenorrhea is primary or secondary, height, body mass index, food intake, the level of physical activity per week, the presence of hirsutism or galactorrhea, pelvic pain and past history of intercourse need to be investigated. Initially, blood tests should include hCG, FSH, estradiol, testosterone and prolactin serum levels. This screening will discriminate between hypogonadotropic hypogonadism and amenorrhea from primary ovarian insufficiency (POI). In case of primary amenorrhea, hypogonadism may be due to congenital hypogonadotropic hypogonadism (HH) or more rarely acquired HH. If FSH is elevated, amenorrhea is due to primary ovarian failure, mainly related to Turner syndrome. If pubertal development is normal, a pelvic ultrasound should be performed. It may visualize a hindering of menses output or less frequently an absence of uterus, as in Rokitansky syndrome or androgen insentivity syndrome. The most frequent etiologies of secondary amenorrhea are polycystic ovarian syndrome (PCOS), functional hypothalamic amenorrhea and less frequently POI and hyperprolactinemia. The differential diagnoses of PCOS are late-onset 21-hydroxylase deficiency and very rare ovarian or adrenal tumors. When contraception is not necessary, hormonal replacement therapy, including estrogen and progestins should be administered in order to avoid hypoestrogenism. In case of PCOS, sequential progestins can be prescribed. A contraceptive pill can be considered when contraception is needed and/or when hyperandrogenism needs to be treated.
    Archives de Pédiatrie 05/2013; · 0.36 Impact Factor
  • S Christin-Maitre
    Gynécologie Obstétrique & Fertilité 04/2013; · 0.55 Impact Factor
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    ABSTRACT: OBJECTIVE: DAX1/NR0B1 mutations cause primary adrenal insufficiency in early childhood and hypogonadotropic hypogonadism, leading to absent or incomplete sexual maturation. The aim of the study was to prospectively investigate gonadotrope and testicular functions in a patient carrying a DAX1 mutation, who had spontaneous puberty and normal virilization but oligospermia. CASE REPORT: The proband was referred for infertility at age 32. He reported adrenal insufficiency diagnosed at age 19. Puberty started at age 13, with spontaneous virilization, growth spurt and testicular growth. He reported normal libido and sexual function. Physical examination showed normal virilization, penile length and testicular volume. However, semen samples showed severe oligospermia. Hormonal measurements confirmed adrenal insufficiency but showed a preserved hypothalamic-pituitary-gonadal axis with normal testosterone and inhibin B; basal and GnRH-stimulated gonadotropin levels and LH pulsatility were also normal. He fathered a first boy by in vitro fertilization and a second boy without medical assistance. As a nephew also had early adrenal insufficiency, the possibility of DAX1 mutation was raised. The same recurrent hemizygous nonsense mutation W39X was found in the proband, his nephew and in an apparently asymptomatic brother who was found to have adrenal insufficiency, mild hypogonadotropic hypogonadism and azoospermia. Several evaluations of the proband over 20 years showed preserved testosterone levels and LH secretion but deteriorating oligospermia. CONCLUSION: Long-term preservation of normal hypothalamic-pituitary-gonadal function in this patient, contrasting with his severe oligospermia, strongly suggests that DAX1 is required for human spermatogenesis, independently of its known role in gonadotropin secretion.
    European Journal of Endocrinology 02/2013; · 3.14 Impact Factor
  • Sophie Christin-Maitre
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    ABSTRACT: The first hormonal pill, called Enovid(®), was approved by the Federal Drug Administration (FDA) in May 1960. It contained mestranol and norethisterone. Over the years, oral contraceptives have evolved through gradual lowering of ethinyl estradiol (EE) content, introduction of 17β estradiol, and many different progestins. The standard regimen allows for 21 days of pill containing steroids and a pill-free interval of 7 days. Recently, continuous or extended regimens have been approved. In order to improve compliance, alternative routes of combined oral contraceptive (COC) administration have been developed such as vaginal or transdermal routes. In 2009, according to the United Nations, the mean global percentage using contraception in women who are married or in union was 62.7%. COC represented 8.8% of contraceptive prevalence, reaching 15.4% in more developed countries. More than 100 million women worldwide use COCs. However, each year, many unintended pregnancies occur, indicating that contraception still needs to be promoted.
    Best practice & research. Clinical endocrinology & metabolism. 02/2013; 27(1):3-12.
  • Sophie Christin-Maitre
    Best practice & research. Clinical endocrinology & metabolism. 02/2013; 27(1):1-2.
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    ABSTRACT: L’insuffisance ovarienne prématurée (IOP) est suspectée cliniquement devant une aménorrhée et affirmée biologiquement chez une femme âgée de moins de 40 ans par un taux de FSH > 40 mUI/L (voire 20 mUI/L) à deux reprises. Sa prévalence est estimée à 1 à 2 % chez les femmes de moins de 40 ans. Dans 90 % des cas, aucune étiologie n’est retrouvée. Il convient d’éliminer une cause secondaire (radiothérapie pelvienne, chimiothérapie, chirurgie ovarienne, exposition in utero au distilbène) et d’effectuer un caryotype pour rechercher un syndrome de Turner (cause génétique la plus fréquente) ou une anomalie de l’X. Une recherche de pré-mutation du gène FMR1 (syndrome de l’X fragile) est souhaitable, même en l’absence de retard mental dans la famille. D’autres anomalies génétiques pourront être recherchées en fonction des symptômes associés (ex. : mutation de FOXL2, SF1). Une origine auto-immune est évoquée dans un contexte d’auto-immunité associé car il n’existe pas de dosage d’anticorps fiable pour établir le diagnostic d’IOP auto-immune. La prise en charge thérapeutique repose sur le traitement hormonal substitutif pour pallier la carence estrogénique : faire disparaître les bouffées de chaleur, diminuer la perte osseuse et le risque cardiovasculaire. Il associe des estrogènes à de la progestérone ou un progestatif jusqu’à l’âge d’au moins 51 ans. Il est souhaitable d’informer les patientes que le taux de grossesses spontanées n’est pas nul (5 %). En cas de désir de grossesse, elles doivent être adressées dans un centre spécialisé pour bénéficier d’une fécondation in vitro avec don d’ovocytes. La prise en charge psychologique doit faire intégralement partie du traitement. Les taux d’anxiété et de dépression sont, chez ces femmes, supérieurs à la population générale. Aucun traitement préventif efficace n’est à ce jour disponible.
    La Presse Médicale. 01/2013; 42(11):1500–1507.
  • Sophie Christin-Maitre, Emmanuelle Laroche, Léopoldine Bricaire
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    ABSTRACT: Most combined oral contraceptive pills contain ethinyl estradiol (EE) with progestins. In order to minimize the pill's cardiovascular risks, the concept of using 17β-estradiol (E2), the endogenous estradiol, arose in the 1970s. Many attempts to develop a pill containing 17β-E2 have failed as cycle control was low. The first pill containing 17β-E2 was launched in 2011. This monophasic pill contains 24 pills with 1.5 mg 17β-E2 and 2.5 mg nomegestrol acetate, and four placebo pills. Studies conducted in Europe and the USA demonstrate that its Pearl index is 0.38 and 1.13, respectively. It has less influence on hemostasis, fibrinolysis markers, lipids and carbohydrate metabolism than the combined oral contraceptive levonorgestrel/EE (150 g/30 g and 100 µg/20 µg). Withdrawal bleedings are shorter and lighter as compared with women using drospirenone/EE (3 mg/ 30 µg). The number of women without withdrawal bleeding is approximately 30% after 12 months. Even though its contraindications are identical to other combined oral contraceptives, this nomegestrol acetate/E2 pill should be considered to be of interest for many women.
    Women s Health 01/2013; 9(1):13-23.
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    ABSTRACT: OBJECTIVE: To determine whether NR5A1 (SF-1) variants are a cause of primary ovarian insufficiency (POI) in 26 young women with similar genetic background. DESIGN: Genetic and functional mutation study. SETTING: University hospitals. PATIENT(S): Genetic analysis of the NR5A1 gene in 26 XX girls with POI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): NR5A1 molecular and functional analysis. RESULT(S): Genetic analysis revealed a new c.763C>T (p.Arg255Cys) mutation and a recurrent c.437G>C (p.Gly146Ala) variant. Functional analysis of the p.Arg255Cys mutant showed a marked decrease in transactivation on the Cyp11a1 and Amh promoters. The p.Gly146Ala variant was identified significantly more often in the patients (46.1%) than in ancestry-matched control subjects (10%). CONCLUSION(S): We identified one new NR5A1 mutation in a patient of our POI cohort (prevalence 3.8%). Moreover, although our study is limited in the number of cases, we report the high frequency of the p.Gly146Ala variant in this cohort compared with the ancestry-matched control subjects. This work highlights the important role of SF-1 in ovarian function.
    Fertility and sterility 11/2012; · 3.97 Impact Factor

Publication Stats

1k Citations
443.42 Total Impact Points

Institutions

  • 2007–2013
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2000–2013
    • Pierre and Marie Curie University - Paris 6
      • Équipe Génétique de la reproduction (EA 1533)
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2008
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 1998–2008
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1999
    • Hôpital Saint-Vincent-de-Paul – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 1996
    • Massachusetts General Hospital
      • Department of Medicine
      Boston, MA, United States