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See detailA novel mutation of the luteinizing hormone/choionic gonadotrophin receptor gene leading to Leydig cell hypoplasia type I
Potorac, Iulia ULg; Rivero-Muller, A; Pintiaux, Axelle ULg et al

in The International Journal of The Romania Society of Endocrinology - Abstract book (2015, June)

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See detailA novel mutation of the luteinizing hormone/choionic gonadotrophin receptor gene leading to Leydig cell hypoplasia type I
Potorac, Iulia ULg; Rivero-Müller, A; Pintiaux, Axelle ULg et al

in Symposium "Perspectives in Endocrinology" - 5ème édition (2015, February 07)

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See detailA novel inactivating mutation of the LH/chorionic gonadotrophin receptor with impaired membrane trafficking leading to Leydig cell hypoplasia type 1.
Rivero-Muller, Adolfo; Potorac, Iulia ULg; Pintiaux, Axelle ULg et al

in European journal of endocrinology / European Federation of Endocrine Societies (2015), 172(6), 27-36

OBJECTIVE: The LH/chorionic gonadotrophin receptor (LHCGR) is a G protein-coupled receptor (GPCR) that plays a central role in male sexual differentiation, regulation of ovarian follicular maturation ... [more ▼]

OBJECTIVE: The LH/chorionic gonadotrophin receptor (LHCGR) is a G protein-coupled receptor (GPCR) that plays a central role in male sexual differentiation, regulation of ovarian follicular maturation, ovulation and maintenance of corpus luteum and pregnancy, as well as maintenance of testicular testosterone production. Mutations in the LHCGR gene are very rare. The aim of this work was to study the clinical and molecular characteristics of a rare familial LHCGR mutation. METHODS: Five affected members of a family, including a phenotypically female, but genotypically male (46,XY), patient with Leydig cell hypoplasia type 1 and four genotypically female siblings with reproductive abnormalities, were studied genetically. Cell trafficking studies as well as signalling studies of mutated receptor were performed. RESULTS: The five affected patients were all homozygous for a novel mutation in the LHCGR gene, a deletion of guanine in position 1850 (1850delG). This resulted in a frameshift affecting most of the C-terminal intracellular domain. In vitro studies demonstrated that the 1850delG receptor was completely incapable of transit to the cell membrane, becoming trapped within the endoplasmic reticulum. This could not be rescued by small-molecule agonist treatment or stimulated intracellularly by co-expression of a yoked human chorionic gonadotrophin. CONCLUSIONS: This novel LHCGR mutation leads to complete inactivation of the LHCGR receptor due to trafficking and signalling abnormalities, which improves our understanding of the impact of the affected structural domain on receptor trafficking and function. [less ▲]

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See detailRestoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: II. Clinical effects.
Zimmerman, Y.; Foidart, Jean-Michel ULg; Pintiaux, Axelle ULg et al

in Contraception (2015), 91(2), 134-42

OBJECTIVES: Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that ... [more ▼]

OBJECTIVES: Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that 'co-administration' of dehydroepiandrosterone (DHEA) to a drospirenone (DRSP)-containing COC restored total T levels to baseline and free T levels by 47%. Here we describe the effects on sexual function, mood and quality of life of such an intervention. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study in 99 healthy COC starters. A COC containing 30mcg ethinylestradiol (EE) and 3mg DRSP was used for three cycles, followed by six cycles of the same COC combined with 50mg/day DHEA or placebo. Subjects completed the Moos Menstrual Distress Questionnaire (MDQ), the McCoy Female Sexuality Questionnaire and the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Safety and tolerability, including effects on skin, were evaluated. RESULTS: The addition of DHEA induced small but significant improvements compared to placebo in the MDQ score for autonomic reactions during the menstrual (-2.0 vs. 0.71; p=0.05) and the premenstrual phase (-3.1 vs. 2.9; p=0.01) and for behavior during the intermenstrual phase (-1.4 vs. 3.6; p=0.02). A significant difference was found in the MDQ score for arousal during the premenstrual phase in favor of placebo (-5.0 vs. 1.0; p=0.01). There were no statistically significant differences between groups for the MSFQ and Q-LES-Q scores. DHEA 'co-administration' resulted in an acceptable safety profile. DHEA negated the beneficial effect of the COC on acne according to the subjects' self-assessment. CONCLUSIONS: 'Co-administration' with DHEA did not result in consistent improvements in sexual function, mood and quality of life indicators in women taking EE/DRSP. Retrospectively, the 50 mg dose of DHEA may be too low for this COC. IMPLICATIONS: A well-balanced judgment of the clinical consequences of normalizing androgens during COC use may require complete normalization of free T. [less ▲]

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See detailRestoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: I. Endocrine effects.
Zimmerman, Y.; Foidart, Jean-Michel ULg; Pintiaux, Axelle ULg et al

in Contraception (2015), 91(2), 127-33

OBJECTIVES: Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of ... [more ▼]

OBJECTIVES: Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). STUDY DESIGN: In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34kg/m(2)), a COC containing 30mcg ethinylestradiol (EE) and 3mg drospirenone (DRSP) was used for 3cycles, followed by 6cycles of the same COC combined with either 50mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Delta4-androstenedione (AD), 3alpha-androstanediol glucuronide (ADG) and estradiol (E2) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo). RESULTS: During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period - 1.3+/-1.2nmol/L vs. 0.0+/-0.4nmol/L; p<.0001) - and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E2. CONCLUSIONS: An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG. IMPLICATIONS: When using a COC that increases SHBG considerably, a daily dose of 50mg DHEA is insufficient to normalize free T levels completely. [less ▲]

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See detailA novel mutation of the luteinizing hormone/choionic gonadotrophin receptor gene leading to Leydig cell hypoplasia type I
Potorac, Iulia ULg; Rivero-Müller, Adolfo; Pintiaux, Axelle ULg et al

in Abstract book - 24th Meeting of the Belgian Endocrine Society (2014, October 18)

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See detailLE MÉDICAMENT DU MOIS L’acétate d’ulipristal (Esmya®) : un modulateur sélectif des récepteurs à la progestérone, nouveau traitement de la fibromatose utérine
Nisolle, Michelle ULg; CLOSON, François ULg; FIRQUET, Anne ULg et al

in Revue Médicale de Liège (2014), 69(4), 220-225

Ulipristal acetate (Esmya®) : a selective modulator of progesterone receptors, new treatment of uterine fibromatosis Summary : Uterine fibromatosis is a frequent benign gynaecological disease causing ... [more ▼]

Ulipristal acetate (Esmya®) : a selective modulator of progesterone receptors, new treatment of uterine fibromatosis Summary : Uterine fibromatosis is a frequent benign gynaecological disease causing heavy menstrual bleeding and in some cases anaemia. Until now, medical treatment aimed to obtain amenorrhea by administration of progestins or Gn-RH agonists. By inducing hypo-oestrogenism, a reduction of myoma size is observed with Gn-RH agonists but after cessation of the treatment, initial myoma size is noted. The impact of progesterone in myoma growth is nowadays demonstrated and use of selective modulators of progesterone receptors represents a new medical approach of this disease. [less ▲]

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See detailPrise en charge du diabete gestationnel.
Philips, J. C.; EMONTS, Patrick ULg; Pintiaux, Axelle ULg et al

in Revue medicale de Liege (2013), 68(9), 489-96

Pregnancy is associated with relative carbohydrate intolerance and insulin resistance. Gestational diabetes mellitus (GDM) is recognized as a risk factor for a number of adverse outcomes during pregnancy ... [more ▼]

Pregnancy is associated with relative carbohydrate intolerance and insulin resistance. Gestational diabetes mellitus (GDM) is recognized as a risk factor for a number of adverse outcomes during pregnancy, including excessive fetal growth, increased incidence of birth trauma and neonatal metabolic abnormalities. This recognition has led to recommendations to screen all pregnant women for GDM and to treat those whose glucose tolerance tests exceed threshold criteria. Numerous epidemiological studies show that GDM affects between 1 and 25% of pregnancies, depending on the ethnicity of the population studied and the diagnostic criteria. Intervention to change lifestyle and, if maternal hyperglycemia persists, treatment with additional oral medication or insulin injections have shown to improve perinatal outcomes. Patients with GDM have a high risk of developing type 2 diabetes in the years after delivery and these women are encouraged to practice specific health behaviours (dietary habits, physical activity) during the postpartum period. The present article discusses the management of GDM in the light of data from the latest studies and international recommendations. [less ▲]

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See detailInsuffisance ovarienne prématurée : de la génétique à la clinique
Rege, G; Foidart, Jean-Michel ULg; NISOLLE, Michelle ULg et al

in Revue Médicale de Liège (2012), 67(7-8), 413-419

L’Insuffisance Ovarienne Prématurée (IOP) est une pathologie dont la présentation clinique est complexe. Elle survient chez 1% des femmes avant 40 ans, 0,1% avant 30 ans. Les causes sont multiples : les ... [more ▼]

L’Insuffisance Ovarienne Prématurée (IOP) est une pathologie dont la présentation clinique est complexe. Elle survient chez 1% des femmes avant 40 ans, 0,1% avant 30 ans. Les causes sont multiples : les anomalies génétiques, les maladies auto-immunes, les atteintes ovariennes iatrogènes secondaires à la chirurgie, radiothérapie, chimiothérapie, aux facteurs environnementaux tels que les virus, les toxines, le tabac, et aux facteurs métaboliques. Cependant, dans la majorité des cas, l’étiologie de l’IOP est idiopathique. [less ▲]

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See detailLe médicament du mois. Zoely®, une association monophasique d’estradiol et d’acétate de nomégestrol
PINTIAUX, Axelle ULg; Gaspard, Ulysse ULg; Nisolle, Michelle ULg

in Revue Médicale de Liège (2012), 67(3), 152-6

SUMMARY : A new combined oral contraceptive called Zoely® has just been marketed in Belgium. It contains nomegestrol acetate, a progestin known for its high contraceptive reliability based on its ... [more ▼]

SUMMARY : A new combined oral contraceptive called Zoely® has just been marketed in Belgium. It contains nomegestrol acetate, a progestin known for its high contraceptive reliability based on its antigonadotropic power and long half-life. This progestin is associated with estradiol and Zoely® is devoid of ethinyl estradiol, which is the usual component of the majority of combined oral contraceptives and is primarily responsible for thrombotic side effects of the pill. The compositon and type of regimen of this new oral contraceptive contribute to its efficacy and excellent clinical tolerance. [less ▲]

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See detailL’interruption médicamenteuse de grossesse : applications cliniques de la mifépristone et des prostaglandins.
FIRQUET, Anne ULg; BELIARD, Aude ULg; Chabbert-Buffet, N et al

in Revue Médicale de Liège (2011), 66(12), 614-618

summarY : mifepristone is one of the most common selective progesterone receptor modulator. its use in abortion in first and second trimester of pregnancy is well known. this type of molecule has also ... [more ▼]

summarY : mifepristone is one of the most common selective progesterone receptor modulator. its use in abortion in first and second trimester of pregnancy is well known. this type of molecule has also been studied in several diseases such as endometriosis, myomas, breast cancer and meningioma. only practical management of abortion using mifepristone will be described here. [less ▲]

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See detailPrise en charge des consequences de la carence oestrogenique apres cancer du sein.
BLERET, Valerie ULg; PINTIAUX, Axelle ULg; BELIARD, Aude ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 385-92

The prevention and the treatment of oestrogen deficiency induced by breast cancer treatments are crucial in the management of patients. The impacts of this deficiency must not be neglected: quality of ... [more ▼]

The prevention and the treatment of oestrogen deficiency induced by breast cancer treatments are crucial in the management of patients. The impacts of this deficiency must not be neglected: quality of life impairments inducing eventually premature withdrawal of hormonotherapies, and excess of bone and cardio-vascular morbidities and mortalities, especially in good prognosis young women. Management strategies of short and long term effects of this deficiency are reviewed and discussed here. [less ▲]

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See detailLe médicament du mois. Nouvelle contraception orale combinée au valerate d'estradiol et au dienogest (Qlaira).
Gaspard, Ulysse ULg; PINTIAUX, Axelle ULg; Kridelka, Frédéric ULg

in Revue Médicale de Liège (2010), 65(12), 706-13

In combined oral contraception (OC), a drastic reduction of both ethinylestradiol and androgenic progestins mostly derived from 19 NOR testosterone, allowed to moderately reduce the adverse impact of ... [more ▼]

In combined oral contraception (OC), a drastic reduction of both ethinylestradiol and androgenic progestins mostly derived from 19 NOR testosterone, allowed to moderately reduce the adverse impact of classical combined pills on metabolism and circulation (both arterial and venous). However, the marked hepatic action of ethinylestradiol, even in small dosages, lessens the expected risk reduction. For the first time, an OC has been developed, which contains estradiol valerate (with reduced hepatic action because of lack of a 17alpha ethinyl group) with dienogest, a 19 NOR testosterone-derived nonandrogenic progestin, which powerfully inhibits endometrial proliferation. Thanks to a dynamic modulation of estrogen and progestin doses (26 active days + 2 placebo days), an adequate contraceptive effectiveness, a good cycle control and drug tolerance are achieved, similar to those obtained with a classical low-dose OC. Recent data indicate that this new combination reduces the usually observed metabolic impact. An adequate cycle control (with 20% amenorrhea) is achieved for the first time with estradiol valerate + progestin,, in opposition with prior catastrophic results with other formulations containing 17beta-estradiol. A second combination containing estradiol + nomegestrol acetate (monophasic, 24 active days + 4 placebo days) is under study and seems also to yield promising results. Of course, in-depth study of metabolic and vascular effects of these new combinations is mandatory - and ongoing. [less ▲]

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See detailL'inertie thérapeutique en contraception.
Pintiaux, Axelle ULg; Bouüaert, Corine ULg; Habay, Nathalie ULg et al

in Revue Médicale de Liège (2010), 65(5-6), 391-4

The efficiency of contraception is linked to the method and the patient's compliance. The advice given by the physician about contraception use is essential to avoid unintended pregnancy. The accuracy of ... [more ▼]

The efficiency of contraception is linked to the method and the patient's compliance. The advice given by the physician about contraception use is essential to avoid unintended pregnancy. The accuracy of contraceptive choice and the individualized adaptation over time contribute to safe contraception. [less ▲]

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See detailDiabete et grossesse: impact de l'inertie medicale et de l'observance therapeutique.
Pintiaux, Axelle ULg; Chabbert-Buffet, N.; Philips, Jean-Christophe ULg et al

in Revue Médicale de Liège (2010), 65(5-6), 399-404

Pregnancy and infant outcomes are related to maternal blood glucose profile. Managing preexisting diabetes and achieving euglycaemia before and during the pregnancy reduce the risk for complications ... [more ▼]

Pregnancy and infant outcomes are related to maternal blood glucose profile. Managing preexisting diabetes and achieving euglycaemia before and during the pregnancy reduce the risk for complications. Screening, diagnosis and treatment of gestational diabetes are important issues from a public health point of view, more particularly because of the progression of this disease due to obesity epidemics among young people. Pregnancy in a diabetic woman is a critical situation where neither clinical inertia nor patient's non-compliance could be accepted. [less ▲]

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See detailLes indications de l'androgénothérapie chez la femme
DE GOTTAL, Emilie ULg; PINTIAUX, Axelle ULg; BELIARD, Aude ULg et al

in Réalités en Gynécologie-Obstétrique (2009), 138

Les taux d’androgènes peuvent être diminués dans de nombreuses situations pathologiques et iatrogènes, mais également physiologiquement chez la femme âgée. La déficience androgénique affecte de nombreux ... [more ▼]

Les taux d’androgènes peuvent être diminués dans de nombreuses situations pathologiques et iatrogènes, mais également physiologiquement chez la femme âgée. La déficience androgénique affecte de nombreux systèmes. La supplémentation androgénique améliorerait les fonctions cognitives, l’humeur, la libido, la qualité osseuse, la force et la fonction musculaire. Toutefois, ce traitement, n’est actuellement pas recommandé en routine par les Guidelines de l’Endocrine Society. Les androgènes peuvent entraîner de l’acné, une augmentation de la pilosité, une raucité de la voix et une clitorimégalie, ces deux derniers effets indésirables étant rares. Ils influencent également le système cardiovasculaire en modifiant le profil lipidique, mais les données restent controversées. La supplémentation par DHEA a été étudiée chez des femmes atteintes d’insuffisance surrénalienne. Il semblerait que 50 mg/j de DHEA soit la dose adéquate pour restaurer des taux d’androgènes physiologiques et améliorer ainsi les symptômes sans observer d’effets secondaires majeurs. Il est toutefois recommandé de poursuivre les recherches parmi les groupes de patientes atteintes de déficience androgénique afin d’en définir précisément le syndrome clinique et d’étudier les effets de l’androgénothérapie. [less ▲]

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See detailNouveautés en contraception d'urgence.
Pintiaux, Axelle ULg; Foidart, Jean-Michel ULg

in Gunaïkeia (2009), 14(1), 18-20

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See detailEffects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old.
De Groote, D.; PERRIER d'HAUTERIVE, Sophie ULg; Pintiaux, Axelle ULg et al

in Contraception (2009), 80(2), 187-93

Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ... [more ▼]

Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. Results Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of β-carotene (−41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log2 fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log2 fold change=−0.24, p<.05) in the OCU compared to the NCU. Conclusions The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk. [less ▲]

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