Sophie Ouzounian

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

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Publications (14)12.57 Total impact

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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
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    ABSTRACT: During pregnancy, the production rate of thyroid hormone increases when iodine intake is sufficient. However, the appropriateness of the free thyroxin (FT4) immunoassay is questionable. We have therefore evaluated prospectively the thyroid function in pregnancy and the relevance of the FT4 immunoassay. The thyroid function of 114 pregnant, healthy Parisian women with mild iodine deficiency was studied at the third trimester of pregnancy, 55 of whom served as their own control three months after delivery, and the results were compared to North American reference values. All French pregnant women showed an increase in thyroxin binding globulin (TBG) serum levels. FT4 levels decreased by about 30% at the third trimester of pregnancy, as compared to 10-15% in the American population. Moreover, the increase in total thyroxin (TT4) secretion represented only 27%, as compared to 50% in the American population. Linear regression model analysis showed a positive correlation between levels of TT4 and TBG, TT4 and FT4, as well as FT4 and free thyroxin index (FTI). The hypothyroxinemia at the third trimester of pregnancy was more prominent in the Parisian population and insufficient iodine intake could be responsible for the deficient increase in TT4. It is therefore concluded that the inability of the thyroid to establish the required equilibrium could be corrected by systematic iodine supplementation before pregnancy. Finally, the strong correlation between FT4 and FTI suggests that the quality of FT4 test immunoassay is appropriate for estimating FT4 serum levels during pregnancy.
    Annales d Endocrinologie 09/2010; 71(6):519-24. · 1.02 Impact Factor
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    ABSTRACT: We report the case of a 21-year-old pregnant women (36 WA) presenting intensive headaches and visual disturbances. Those sellar compression symptoms have made us suppose the diagnosis of autoimmune hypophysitis. MRI has confirmed the typical aspect of symmetric enlargement of the pituitary gland with a strong and homogenous enhancement after gadolinium. This pathology associated to a high morbidity and mortality due to partial or complete deficit of the anterior pituitary hormones, shall be reminded more often.
    Gynécologie Obstétrique & Fertilité 04/2010; 38(4):278-82. · 0.55 Impact Factor
  • J Hugon, S Ouzounian, S Christin-Maître
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    ABSTRACT: Müllerian inhibiting substance (MIS) has been discovered by Alfred Jost at the beginning of the fifties. MIS is a glycoprotein belonging to the TGF-beta family. Its various functions differ between males and females and according to the age of the individual. In male, the protein is synthesized by Sertoli's cells and induces the disappearance of Müllerian's ducts, the development of the male genital tract. Its role in adult males remains quite unknown. In female, the protein is secreted by granulosa cells and plays a role during folliculogenesis as it regulates the initial and cyclic recruitment of ovarian follicles. MIS is also a good marker of follicular reserve and ovarian function. Therefore, it plays a role in different areas such as assisted medical reproduction and oncology. This protein represents a potential major diagnosis as well as prognostic tool in reproduction.
    Annales d Endocrinologie 02/2010; 71(2):83-8. · 1.02 Impact Factor
  • J. Hugon, S. Ouzounian, S. Christin-Maître
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    ABSTRACT: Müllerian inhibiting substance (MIS) has been discovered by Alfred Jost at the beginning of the fifties. MIS is a glycoprotein belonging to the TGF-β family. Its various functions differ between males and females and according to the age of the individual. In male, the protein is synthesized by Sertoli's cells and induces the disappearance of Müllerian's ducts, the development of the male genital tract. Its role in adult males remains quite unknown. In female, the protein is secreted by granulosa cells and plays a role during folliculogenesis as it regulates the initial and cyclic recruitment of ovarian follicles. MIS is also a good marker of follicular reserve and ovarian function. Therefore, it plays a role in different areas such as assisted medical reproduction and oncology. This protein represents a potential major diagnosis as well as prognostic tool in reproduction.
    Annales D Endocrinologie - ANN ENDOCRINOL. 01/2010; 71(2):83-88.
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    ABSTRACT: We report the case of a 21-year-old pregnant women (36WA) presenting intensive headaches and visual disturbances. Those sellar compression symptoms have made us suppose the diagnosis of autoimmune hypophysitis. MRI has confirmed the typical aspect of symmetric enlargement of the pituitary gland with a strong and homogenous enhancement after gadolinium. This pathology associated to a high morbidity and mortality due to partial or complete deficit of the anterior pituitary hormones, shall be reminded more often.
    Gynecologie Obstetrique & Fertilite - GYNECOL OBSTET FERTIL. 01/2010; 38(4):278-282.
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    ABSTRACT: Mifepristone is the only available glucocorticoid receptor antagonist. Only few adult patients with hypercortisolism were treated to date by this drug. Our objective was to determine effectiveness and tolerability of mifepristone in Cushing's syndrome (CS). Retrospective study of patients treated in seven European centers. Twenty patients with malignant (n=15, 12 with adrenocortical carcinoma, three with ectopic ACTH secretion) or benign (n=5, four with Cushing's disease, one with bilateral adrenal hyperplasia) CS were treated with mifepristone. Mifepristone was initiated with a median starting dose of 400 mg/day (200-1000). Median treatment duration was 2 months (0.25-21) for malignant CS, and 6 months (0.5-24) for benign CS. Clinical (signs of hypercortisolism, blood pressure, signs of adrenal insufficiency), and biochemical parameters (serum potassium and glucose) were evaluated. Treatment was stopped in one patient after 1 week due to severe uncontrolled hypokalemia. Improvement of clinical signs was observed in 11/15 patients with malignant CS (73%), and 4/5 patients with benign CS (80%). Psychiatric symptoms improved in 4/5 patients within the first week. Blood glucose levels improved in 4/7 patients. Signs of adrenal insufficiency were observed in 3/20 patients. Moderate to severe hypokalemia was observed in 11/20 patients and increased blood pressure levels in 3/20 patients. Mifepristone is a rapidly effective treatment of hypercortisolism, but requires close monitoring of potentially severe hypokalemia, hypertension, and clinical signs of adrenal insufficiency. Mifepristone provides a valuable treatment option in patients with severe CS when surgery is unsuccessful or impossible.
    European Journal of Endocrinology 04/2009; 160(6):1003-10. · 3.14 Impact Factor
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    ABSTRACT: Currently developed progesterone receptor modulators (PRMs) are steroid-derived compounds with mild or potent antiprogestin activity. PRMs may exert a contraceptive activity by different mechanisms such as blockade of ovulation and endometrial desynchronization. Their potential clinical applications are manifold and are very promising in major public health areas, including emergency contraception, long term oestrogen-free contraception (administered alone, or in association with a progestin-only pill to improve bleeding patterns), endometriosis and myoma treatment. The mechanisms of their anti-ovulatory effects and of the endometrial modifications elicited during long term PRM treatment are still not fully elucidated. In future clinical applications, PRMs will be administered orally, via intrauterine systems or vaginal rings.
    The European Journal of Contraception and Reproductive Health Care 10/2008; 13(3):222-30. · 1.81 Impact Factor
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    ABSTRACT: Progesterone-receptor modulators (PRMs) are progesterone-receptor ligands that can exert agonistic, antagonistic or mixed agonist-antagonist effects depending on the cellular context. The mechanisms of action of these compounds are still incompletely understood. PRMs already have several applications in women's health such as emergency contraception, pregnancy termination, management of early fetal demise and cervical maturation. The main indications that will be developed in the future include dysfunctional bleeding and preoperative treatment of uterine myomas. Other future indications may include estrogen-free contraception, treatment of endometriosis and prevention and treatment of breast cancer. However, the available data from mid- to long-term continuous administration studies has raised the issue of endometrial safety. For this reason, long-term applications of PRMs are currently postponed, although windows of treatment with a short course of progestin therapy, or even by a short interruption of treatment, could improve endometrial aspects if needed.
    Women s Health 06/2008; 4(3):269-80.
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    ABSTRACT: Third-generation oral contraceptives are an association of low-dose ethinyl estradiol and potent testosterone-derived progestins, developed in order to improve general and vascular tolerance. They are highly efficient and well tolerated by most users. Their extensive use has provided different key information: oral contraceptives (as well as non-oral ethinyl estradiol-containing contraceptives) can be used in women under the age of 35 years with well-controlled metabolic risk factors and high familial risk of breast cancer. On the other hand, ethinyl-estradiol containing contraceptives are not indicated in women with a high risk of deep venous thrombosis, or noncontrolled metabolic and vascular risk factors (including being over the age of 35 years or cigarette smoking), or with a history of breast cancer. Progestin-only contraception is not well tolerated owing to bleeding. Future hormonal contraception for women with a high vascular risk may contain nontestosterone-derived progestins and 17 estradiol, or antiprogestins.
    Expert Review of Obstetrics &amp Gynecology 02/2008; 3(2):189-201.
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    ABSTRACT: Progesterone antagonists belong to the family of selective progesterone receptor modulators. SPRMs already have several applications in women's health. Their main value lies in their effect on endometrium. For example, they can be used to reduce tumor volume and uterine bleeding before uterine myoma surgery. They are also being evaluated for the treatment of endometriosis, and for estrogen-free contraception.
    Bulletin de l'Académie nationale de médecine 01/2008; 192(6):1159-71; discussion 1172-3. · 0.16 Impact Factor
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    ABSTRACT: The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well.
    Gynécologie Obstétrique & Fertilité 04/2007; 35(3):240-8. · 0.55 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia…) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2,5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well.
    Gynecologie Obstetrique & Fertilite - GYNECOL OBSTET FERTIL. 01/2007; 35(3):240-248.
  • Sophie Ouzounian, Nathalie Chabbert-Buffet
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    ABSTRACT: Postmenopausal age women have an increased risk of cardiovascular diseases, osteoporosis, and gynaecological cancers. A regular follow up is necessary to evaluate the interest of HRT, and for screening cardiovascular diseases and gynaecologic cancers. Patient counselling includes life style modifications, follow-up and regular evaluation of risk factors and potential benefit of HRT for each woman.
    La Revue du praticien 03/2005; 55(4):403-9.