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F Kuttenn

Publications and source records attributed to F Kuttenn.

At least 19 recordsLinked to original sources
PubMed2006

Serum anti-Müllerian hormone expression in women with premature ovarian failure.

BACKGROUND: Premature ovarian failure (POF) is generally irreversible. However, developing follicles up to the antral stage are reported in POF and anti-Müllerian hormone (AMH) might be a good indicator of follicular presence. This study analysed serum AMH, ovarian histology and AMH immunoexpression in POF patients. METHODS: A cross-sectional study of 48 POF patients in an Endocrinology Department setting. Patients had an ovarian biopsy simultaneously with serum AMH sampling and/or ovarian AMH immunostaining. RESULTS: Mean serum AMH was 1.04 +/- 1.66 ng/ml. Serum AMH was significantly higher in women with 15 or more follicles at ovarian histology (P = 0.001). Comparison of ovarian AMH immunostaining from POF patients and 10 normal controls revealed a normal AMH expression in POF pre-antral follicles, but a decreased expression at the early antral stages. Serum AMH was undetectable in 77% of the patients with 0-5 AMH immunopositive follicles and detectable in 100% of the patients with more than 15 AMH immunopositive follicles. CONCLUSIONS: AMH levels in POF patients could identify women with persistent follicles. The decrease of AMH immunoexpression in POF antral follicles could suggest a defect of antral development.

Adolescent↗
PubMed2006

Idiopathic premature ovarian failure in 63 young women.

BACKGROUND: Premature ovarian failure (POF) in adolescents is defined as primary or secondary amenorrhea associated with high follicle-stimulating hormone (FSH) levels. In normal 46,XX patients, its etiology is most often unknown. We have evaluated the clinical, hormonal and ovarian phenotypes in patients with a normal karyotype who were diagnosed with POF before the age of 18. METHODS: Sixty-three patients were included in this retrospective study. RESULTS: The mean patient age was 20.4 years. The patients presented with three clinical patterns: lack of pubertal development (n = 23), primary amenorrhea with interrupted puberty (n = 18), and secondary amenorrhea with normal puberty (n = 22). Ten patients had a familial history of POF and 6 presented with hypothyroidism. The FSH, estradiol and inhibin B levels were not statistically different in the three clinical groups. Fifty percent of the patients presented small ovaries (length <2 cm) at ultrasonography. The presence of follicles was found at histology in only 7 of the 27 patients who underwent an ovarian biopsy. CONCLUSION: 46,XX patients presenting with early POF rarely presented a specific, identifiable disorder. We discuss the clinical management and different diagnosis strategies to improve our current knowledge of this syndrome.

Adolescent↗
PubMed2005

Breast inflammatory gigantomastia in a context of immune-mediated diseases.

CONTEXT: Localized breast lesions have been described in lupic or diabetic patients. However, the description of breast gigantomastia in women presenting with autoimmune diseases has not been reported. SETTING: The study took place within the Department of Endocrinology and Reproductive Medicine, Necker Hospital, Paris, France. PATIENTS: We describe eight patients with inflammatory gigantomastia, occurring in a context of immune-mediated diseases: myasthenia, chronic arthritis, or thyroiditis. MAIN OUTCOME MEASURES: Together with hormonal, immunological, and breast magnetic resonance imaging (MRI) evaluation, breast histology enabled us to perform immunocytochemical and indirect immunofluorescence studies. Control sera were obtained from patients with (n = 10) and without (n = 7) antinuclear antibodies. RESULTS: Six of the eight patients developed gigantomastia either at puberty or during pregnancy. Neither a hormonal oversecretion nor a specific immunological pattern was observed. All patients except one presented antinuclear antibodies. Histological study revealed a diffuse, stromal hyperplasia and a severe atrophy of the lobules. A rarefaction of adipocytes was also noted, as previously suggested on MRI. There was a perilobular lymphocytic infiltrate made of CD3+ lymphocytes. Study of sera from five of six cases of gigantomastia showed a nuclear immunofluorescence pattern in normal mammary ductal and lobular glandular epithelium, as well as in kidney and intestine epithelial cells. In control sera, a nuclear signal was observed only when antinuclear antibodies were present. CONCLUSIONS: We suggest that breast tissue may be a target tissue in autoimmune diseases, this process being favored by the hormonal milieu. However, the precise mechanism of such association is not individualized. The fact that stromal hyperplasia is the main histological feature justifies the search for the involvement of growth factors in such a process.

Adolescent↗
PubMed2004

Significance of ovarian histology in the management of patients presenting a premature ovarian failure.

BACKGROUND: Premature ovarian failure (POF) is a heterogeneous syndrome, possibly due to mutations of genes involved in the normal development of the ovary and/or follicles. Based essentially on animal models, these mutations are associated with various ovarian phenotypes, from a complete absence of follicles to a partial follicular maturation. The aim of the present study was to determine whether ovarian histology, compared to pelvic ultrasonography, would be helpful in identifying which patients display an impaired follicular reserve and/or growth, and in orientating the search for POF aetiology. METHODS AND RESULTS: We studied a cohort of 61 patients suffering from POF with a normal karyotype. Their median age (range) at diagnosis was 26 years (15-39). The FSH plasma level was high, 67.0 IU/l (13-155). Estradiol and inhibin B plasma levels were low: 18.5 pmol/l (18.5-555) and 5 pg/ml (5-105) respectively. Both pelvic ultrasonography and ovarian biopsies were performed in each patient. The presence of follicles suggested at ultrasonography was confirmed at histology in 56% of the patients. Ovarian histology led to the distinction of two phenotypes: (i) small-sized ovaries, deprived of follicles; and (ii) normal-sized ovaries with partial follicular maturation. To confirm the value of ovarian biopsies, samples from 20 normal women were studied. These demonstrated that ovarian biopsy at random enables reliable assessment of follicular presence, especially when their size is <2 mm. CONCLUSION: Ovarian histology appears to be a reliable tool in evaluating the follicular reserve, and helpful and complementary to clinical and hormonal phenotyping in orienting the search for the various genetic causes of POF syndrome.

Adolescent↗
PubMed2004

[Conservation of human embryos in straws: safety in terms of human immunodeficiency virus 1].

OBJECTIVE: The possibility of offering assisted reproductive technologies (ART) to HIV-positive couples has revived questions concerning the safety of the gametes and embryos cryopreservation in liquid nitrogen tanks. PATIENTS AND METHODS: We evaluated the safety of three types of straws - polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG) and so-called 'high-security' ionomeric resin (IR) - containing HIV-1 under standard conditions of cryopreservation. Potential HIV contamination was assessed by RT-PCR and then nested PCR. RESULTS: Under cryopreservation conditions, the sealed open ends of PVC and PETG straws were not safe. The ultrasound sealing system seems to be the weak link in obtaining total imperviousness of the straws. In contrast, both ends of the IR straws were safe for HIV in the framework of their use for ART. CONCLUSION: Sealing cryopreservation straws ultrasonically could incur the risk of not assuring their impermeability. Under standard cryopreservation conditions thermosealing of IR straws appears to be safe for HIV.

Cryopreservation↗
PubMed2003

Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies.

Inactivating mutations of the FSH receptor have been described in rare cases of premature ovarian failure. Only one mutation was associated with a complete phenotype, including delayed puberty, primary amenorrhea, and small ovaries. We describe here a new patient presenting a similar complete phenotype of premature ovarian failure, with high plasma FSH levels associated with very low estrogen and inhibin B levels. No biological response to high doses of recombinant FSH was detected. A novel homozygous Pro(519)Thr mutation was found in this patient. This mutation is located in the second extracellular loop of the FSH receptor, within a motif highly conserved in gonadotropin and TSH receptors. The mutation totally impairs adenylate cyclase stimulation in vitro. FSH binding experiments and confocal microscopy showed that this mutation alters the cell surface targeting of the mutated receptor, which remains trapped intracellularly. Histological studies of the ovaries of the patient showed an increase in the density of small follicles compared with age-matched normal women. A complete block in follicular maturation after the primary stage was also observed. Immunocytochemical studies allowed detection of the expression of c-Kit and proliferation cellular nuclear antigen, whereas no apoptosis was shown by the 3'-end-labeling method. This observation supports the concept that in humans FSH seems mandatory for the initiation of follicular growth only after the primary stage. In our patient complete FSH resistance yields infertility, which is remarkably associated with the persistence of a high number of small follicles.

Adult↗
PubMed2002

[Effects of hormone replacement therapy in menopause on cardiovascular risk. Need for a European study].

The increased risk of coronary heart disease (CHD) after menopause is currently attributed to estrogen deficiency. Many epidemiological (case-control and prospective) studies have reported a decreased risk (0.5-0.7) of CHD in postmenopausal women receiving hormone replacement therapy (HRT). However, there are some discordant studies, among which the Framingham study. Moreover, the observational studies were subject to several biases that may have falsely elevated the apparent benefit of estrogen: women taking estrogen tend to be wealthier, more educated and healthier than untreated women. Large randomized clinical trials of secondary (HERS, WEST) or primary (WHI) prevention have not confirmed cardioprotection with HRT. However, these studies used orally administered estrogens, while the non-oral route of administration is frequently used in Europe. From a biological point of view, estrogen has multiple effects that would be expected to be cardioprotective, including favorable changes in lipids, endothelial function, vascular reactivity and blood flow. However, concerning hemostasis factors, a pro-coagulant effect can be induced by the first pass liver effect of estrogen when administered orally, which is not observed with the non oral routes of administration. In addition, the synthetic progestin medroxy-progesterone acetate (MPA) inhibits the beneficial effects of estrogen on the arterial wall, whereas natural progesterone does not. It is therefore urgent that Europeans undertake a European "HERS study" in order to investigate the possible beneficial effect of non-oral estrogens (administered percutaneously or transdermally) associated with natural progesterone.

Administration, Cutaneous↗
PubMed2002

Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women.

The largest-to-date randomized trial (Women's Health Initiative) comparing the effects of hormone replacement therapy (HRT) and a placebo concluded that the continuous use of an oral combination of conjugated equine estrogens (CEE) and medroxy-progesterone acetate (MPA) increases the risk of breast cancer. This conclusion may not apply to women taking other estrogen and progestin formulations, as suggested by discrepancies in the findings of in vitro studies, epidemiological surveys and, mostly, in vivo studies of human breast epithelial cell proliferation showing opposite effects of HRT combining CEE plus MPA or estradiol plus progesterone. To evaluate the risk of breast cancer associated with the use of the latter combination, commonly prescribed in France, a cohort including 3175 postmenopausal women was followed for a mean of 8.9 years (28 367 woman-years). In total, 1739 (55%) of these women were users of one type of estrogen replacement with systemic effect during at least 12 months, any time after the menopause, and were classified as HRT users. Among them, 83% were receiving exclusively or mostly a combination of a transdermal estradiol gel and a progestin other than MPA. Some 105 cases of breast cancer occurred during the follow-up period, corresponding to a mean of 37 new cases per 10 000 women/year. Using multivariate analysis adjusted for the calendar period of treatment, date of birth and age at menopause, we were unable to detect an increase in the relative risk (RR) of breast cancer (RR 0.98, 95% confidence interval (CI): 0.65-1.5) in the HRT users. The RR of breast cancer per year of use of HRT was 1.005 (95% CI 0.97-1.05). These results do not justify early interruption of such a type of HRT, which is beneficial for quality of life, prevention of bone loss and cardiovascular risk profile, without the activation of coagulation and inflammatory protein synthesis measured in users of oral estrogens.

Administration, Cutaneous↗
PubMed2001

Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype--phenotype correlation.

Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II the eyelid defect occurs as an isolated entity. In this study, we describe the identification of novel mutations in the FOXL2 gene in BPES types I and II families, in sporadic BPES patients, and in BPES families where the type could not be established. In 67% of the patients studied, we identified a mutation in the FOXL2 gene. In total, 21 mutations (17 of which are novel) and one microdeletion were identified. Thirteen of these FOXL2 mutations are unique. In this study, we demonstrate that there is a genotype--phenotype correlation for either types of BPES by the finding that mutations predicted to result in a truncated protein either lacking or containing the forkhead domain lead to BPES type I. In contrast, duplications within or downstream of the forkhead domain, and a frameshift downstream of them, all predicted to result in an extended protein, cause BPES type II. In addition, in 30 unrelated patients with isolated POF no causal mutations were identified in FOXL2. Our study provides further evidence that FOXL2 haploinsufficiency may cause BPES types I and II by the effect of a null allele and a hypomorphic allele, respectively. Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect.

Alleles↗
PubMed2001

Estrogen and antiestrogen actions on transforming growth factorbeta (TGFbeta) in normal human breast epithelial (HBE) cells.

We have previously shown that estradiol (E2) increases the growth of normal human breast epithelial (HBE) cells and the antiestrogen 4-hydroxytamoxifen (4-OHT) inhibits estrogen-induced proliferation. These effects of estrogens and antiestrogens on proliferation have also been well documented in breast cancer cells. One mechanism for the antiproliferative effects of antiestrogens is the stimulation of TGFbeta in hormone-dependent MCF-7 and T47D cells. The role of this inhibitory growth factor in normal human breast cells has not been well studied. Accordingly, we measured the amounts of total and active TGFbeta1 and TGFbeta2 by specific E(max) immunoassay (EIA) in culture medium from normal breast cells (epithelial and fibroblasts) and from various ER- and ER+ breast cancer cell lines. We established that HBE cells are sensitive to the antiproliferative effect of TGFbetas, and studied the effect of E2 and 4-OHT, alone or in combination, on the secretion and activation of TGFbetas by HBE cells. HBE cells secrete TGFbeta1 and even more TGFbeta2, and are sensitive to these factors. However, in contrast to MCF-7 cells, TGFbeta secretion in normal breast cells is not regulated by E2 and 4-OHT.

Adolescent↗
PubMed2001

Resumption of luteinizing hormone pulsatility and hypogonadotropic hypogonadism after endoscopic ventriculocisternostomy in a hydrocephalic patient.

OBJECTIVE: To study gonadotropin pulsatility before and after surgical cure of hydrocephalus. DESIGN: Case report. SETTING: Department of Endocrinology and Centre d'Investigations Cliniques, Necker Hospital, Paris, France. PATIENT(S): A 29-year-old woman who presented with secondary amenorrhea. INTERVENTION(S): The patient underwent an endoscopic ventriculocisternostomy that led to restoration of normal menses and resolution of hypogonadism. MAIN OUTCOME MEASURE(S): A gonadotropin pulse study was performed before and 2 and 5 months after surgery. RESULT(S): No LH pulse was observed before surgery. Emergence of pulsatility was observed 2 months after surgery, and pulses became clearly individualized after 5 months. CONCLUSION(S): This observation strongly suggests that amenorrhea, in case of chronic hydrocephalus, is indeed due to a hypothalamic dysfunction of the GnRH pulse generator.

Adult↗
PubMed2001

Long-term follow-up of 246 hyperprolactinemic patients.

BACKGROUND: We wanted to evaluate the very long-term effects of bromocriptine on prolactin (PRL) levels and pituitary tumor size in a large cohort of hyperprolactinemic patients. METHODS: We conducted a retrospective cohort study in the Department of Endocrinology from Necker Hospital in Paris, France. Two hundred and forty-six patients consulted primarily for menstrual disorders, with diagnosis of hyperprolactinemia. Patients were followed-up for 99.9+/-3.6 months. One hundred and ninety-one were treated with bromocriptine, 32 underwent surgery, and 23 received no treatment. RESULTS: The mean initial plasma PRL level was 135.0+/-20.2 ng/ml. Presence of an adenoma was detected in 60% of our patients and comprised a microadenoma in 64% of cases. Compared to oligomenorrheic women, amenorrheic patients had significantly higher levels of PRL and larger pituitary tumor size. In the bromocriptine group, PRL levels decreased from 99.6+/-7.9 to 20.0+/-1.5 ng/ml (p=0.00001). The medical treatment was associated with disappearance of the adenoma in 45% of the women and with stabilization of pituitary tumor size in 40% of patients. Surgery led to disappearance of the adenoma in almost all cases, but failed to definitively cure hyperprolactinemia. CONCLUSION: In this large-scale retrospective study, the medical treatment of mild hyperprolactinemia was shown to be effective and sufficient after 9 years of follow-up.

Adenoma↗
PubMed2001

Phenotype-genotype correlation in 56 women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Complete analysis of the CYP21 gene was performed in 56 unrelated French women with symptomatic nonclassical congenital adrenal hyperplasia. The mutational spectrum and the phenotype-genotype correlation were examined. The overall predominant mutation was V281L, which was present on 51% of alleles and in 80% of women. Three novel mutations were found: L317M, R435C, and a 5'-end gene conversion. Sixty-three percent of the women were carrying a severe mutation of the CYP21 gene, and hence risk giving birth to children with a classical form of the disease. In such cases, screening for heterozygosity in the partner is crucial. Potential genotype/phenotype correlations were examined by classifying the patients into three groups according to the CYP21 allelic combinations: A (mild/mild), B (mild/severe), and C (severe/severe). Primary amenorrhea was more frequent, and mean basal and stimulated 17-hydroxyprogesterone levels were higher in compound heterozygotes for mild and severe mutations (group B) compared with women with two mild mutations (group A), but there was a considerable overlap for individual values. Surprisingly, in two women, a severe mutation was found on both alleles (group C). Therefore, the phenotype cannot be accurately predicted from the genotype. Variability in phenotypic expression may be conditioned by mechanisms other than genetic heterogeneity at the CYP21 locus.

17-alpha-Hydroxyprogesterone↗
PubMed2001

[Hormone replacement therapy of menopause, heart and blood vessels].

The incidence of coronary heart disease (CHD) is lower in premenopausal women than in men and post-menopausal women of the same age. The higher CHD rate after menopause is currently attributed to estrogen deficiency: many epidemiological (case-control and prospective) studies have reported a reduced risk (0.5-0.63) of CHD in post-menopausal women receiving hormone replacement therapy (HRT). Moreover, estrogens have multiple effects that would be expected to be cardioprotective, including favorable changes in lipids, endothelial function, vascular reactivity and blood flow. However, the observational studies are subject to several biases that could falsely elevate the apparent benefit of estrogens: women taking estrogens tend to be wealthier, more educated and healthier than untreated women. The american HERS (Heart and Estrogen-progestin Replacement Study; 2.763 women) is a large multicenter randomized study of secondary prevention, designed to evaluate the efficacy of HRT. Results are disappointing, since no reduced risk was observed, and the risk of CHD was even higher in women receiving HRT during the first year: 1.52 (CI 95%: 1.01-2.29). In HERS study, the treatments consisted of conjugated equine estrogens and the synthetic progestin medroxyprogesterone acetate (MPA) which are rarely used in Europe. Indeed, the effects of HRT are not equivalent depending on the dose, the route of administration, the type of progestogen. It should be emphasized that MPA, contrarily to progesterone, inhibits the beneficial effect of estrogens on lipids and experimental atherosclerosis. The route of administration of estrogens is also involved: estrogens alter hemostasis factors, and when orally administered, they have a first pass liver effect, which favors hypercoagulability. It is therefore urgent that Europeans undertake a European "HERS study" in order to investigate the possible beneficial effect of non oral estrogens (gel or patch) associated with natural progesterone.

Clinical Trials as Topic↗
PubMed2000

Progesterone effect on cell growth, ultrastructural aspect and estradiol receptors of normal human breast epithelial (HBE) cells in culture.

The stimulating effect of estradiol (E2) on breast cell growth is well documented. However, the actions of progesterone (P) and its derivatives remain controversial. Additional information is therefore necessary. On a culture system of normal human breast epithelial (HBE) cells, we observed an inhibitory effect on cell growth of a long-term P treatment (7 days) in the presence or absence of E2, using two methods: a daily cell count providing a histometric growth index, and [3H]-thymidine incorporation during the exponential phase of cell growth. A scanning electron microscopy study confirmed these results. Cells exhibited a proliferative appearance after E2 treatment, and returned to a quiescent appearance when P was added to E2. In both studies, P proved to be as efficient as the synthetic progestin R5020. Moreover, the immunocytochemical study of E2 receptors indicated that E2 increases its own receptor level whereas P and R5020 have the opposite effect, thus limiting the stimulatory effect of E2 on cell growth. In the HBE cell culture system and in long-term treatment, P and R5020 appear predominantly to inhibit cell growth, both in the presence and absence of E2.

Adolescent↗
PubMed2000

Safety of cryopreservation straws for human gametes or embryos: a preliminary study with human immunodeficiency virus-1.

The aim of this preliminary experimental study was to test the stability of cryopreservation straws to human immunodeficiency virus-1 (HIV-1). Three kinds of straws were tested: four polyvinyl chloride (PVC), four polyethylene terephthalate glycol (PETG) and 20 high-security ionomeric resin (IR). The PVC and PETG straws were sealed ultrasonically, and the IR straw by thermosoldering. Each sealed straw was cut in half to produce two demi-straws and then filled with 100 microl of HIV-1-containing supernatant (reverse transcriptase activity: 15 000 c.p.m./50 microl). The unsealed cotton end of PVC and PETG straws and the two halves of the IR straws (cotton and plastic plug ends) were tested. Each demi-straw was two- thirds submerged in RPMI medium at 37 degrees C, and RPMI samples were withdrawn on days 3, 7 and 11. Viral RNA was extracted from the medium and then amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by nested PCR using primers specific to HIV-1 protease. On day 7, no HIV-1 RNA was detected in any of the different samples of medium that had surrounded the unsealed PVC and PETG straws with cotton ends, but three IR specimens were positive. On day 11, PVC and PETG remained negative but HIV-1 RNA was detected in RPMI samples for two more IR demi-straws (n = 5). In conclusion, under these experimental conditions (at 37 degrees C), the unsealed cotton end PVC, PETG and thermosoldered cotton end IR demi-straws appeared to be safe for HIV-1, while IR straws, sealed or unsealed with a plastic plug and with unsealed cotton ends, leaked.

Cryopreservation↗