Idiopathic Premature Ovarian Failure in 63 Young Women

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

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.

Related collections

Most cited references 18

Record: found
Abstract: found
Article: not found

The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance.

Dirk Schmidt, Catherine Ovitt, Katrin Anlag … (2004)

Human Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) type I is an autosomal dominant disorder associated with premature ovarian failure (POF) caused by mutations in FOXL2, a winged-helix/forkhead domain transcription factor. Although it has been shown that FOXL2 is expressed in adult ovaries, its function during folliculogenesis is not known. Here, we show that the murine Foxl2 gene is essential for granulosa cell differentiation and ovary maintenance. In Foxl2(lacZ) homozygous mutant ovaries granulosa cells do not complete the squamous to cuboidal transition leading to the absence of secondary follicles and oocyte atresia. We further demonstrate that activin-betaA and anti-Mullerian inhibiting hormone expression is absent or strongly diminished in Foxl2(lacZ) homozygous mutant ovaries. Unexpectedly, two weeks after birth most if not all oocytes expressed Gdf9 in Foxl2(lacZ) homozygous mutant ovaries, indicating that nearly all primordial follicles have already initiated folliculogenesis at this stage. This activation, in the absence of functional granulosa cells, leads to oocyte atresia and progressive follicular depletion. In addition to providing a molecular mechanism for premature ovarian failure in BPES, these results suggest that granulosa cell function is not only crucial for oocyte growth but also to maintain follicular quiescence in vivo.

0 comments Cited 148 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure.

Kristiina Aittomäki, JoséLuis Dieguez Lucena, Pirjo Pakarinen … (1995)

Hypergonadotropic ovarian dysgenesis (ODG) with normal karyotype is a heterogeneous condition that in some cases displays Mendelian recessive inheritance. By systematically searching for linkage in multiplex affected families, we mapped a locus for ODG to chromosome 2p. As the previously cloned follicle-stimulating hormone receptor (FSHR) gene had been assigned to 2p, we searched it for mutations. A C566T transition in exon 7 of FSHR predicting an Ala to Val substitution at residue 189 in the extracellular ligand-binding domain segregated perfectly with the disease phenotype. Expression of the gene in transfected cells demonstrated a dramatic reduction of binding capacity and signal transduction, but apparently normal ligand-binding affinity of the mutated receptor. We conclude that the mutation causes ODG in these families.

0 comments Cited 124 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor.

I Beau, P Touraine, G. Meduri … (1998)

A single natural loss of function mutation of the follicle stimulating hormone receptor (FSHR) has been described to date. Present in the Finnish population it markedly impairs receptor function, blocking follicle development at the primary stage and presenting as primary amenorrhea with atrophic ovaries. When Western European women with this phenotype were examined for FSHR mutations the result was negative, suggesting that other etiologies corresponding to this clinical pattern are markedly more frequent. We now describe a novel phenotype related to mutations provoking a partial loss of function of the FSHR. A woman with secondary amenorrhea had very high plasma gonadotropin concentrations (especially FSH), contrasting with normal sized ovaries and antral follicles up to 5 mm at ultrasonography. Histological and immunohistochemical examination of the ovaries showed normal follicular development up to the small antral stage and a disruption at further stages. The patient was found to carry compound heterozygotic mutations of the FSHR gene: Ile160Thr and Arg573Cys substitutions located, respectively, in the extracellular domain and in the third intracellular loop of the receptor. The mutated receptors, when expressed in COS-7 cells, showed partial functional impairment, consistent with the clinical and histological observations: the first mutation impaired cell surface expression and the second altered signal transduction of the receptor. This observation suggests that a limited FSH effect is sufficient to promote follicular growth up to the small antral stage. Further development necessitates strong FSH stimulation. The contrast between very high FSH levels and normal sized ovaries with antral follicles may thus be characteristic of such patients.

0 comments Cited 39 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): HRE

Journal ID (nlm-ta): Horm Res Paediatr

Journal ID (doi): 10.1159/issn.1663-2818

Title: Hormone Research in Paediatrics

Publisher: S. Karger AG

ISSN (Print): 1663-2818

ISSN (Electronic): 1663-2826

Publication date Subscription-year: 2006

Publication date (Print): February 2006

Publication date (Electronic): 23 February 2006

Volume: 65

Issue: 2

Pages: 89-95

Affiliations

Departments of ^aEndocrinology and Reproductive Medicine, and ^bPediatrics, Necker-Enfants Malades Hospital, Faculty of Medicine, Paris V University, Paris, France

Article

Publisher ID: 91177 Other ID: Horm Res 2006;65:89–95

DOI: 10.1159/000091177

PubMed ID: 16439854

SO-VID: 5434faea-eecd-45e2-9d6a-675aeb6f61ea

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 18 October 2005

Date accepted : 13 December 2005

Page count

Figures: 2, Tables: 1, References: 26, Pages: 7

Comments

Comment on this article

scite_

Cited by 2

See all cited by

Most referenced authors 271

See all reference authors

- Version 1

Idiopathic Premature Ovarian Failure in 63 Young Women

Read this article at

Abstract

Related collections

Karger: Endocrinology

Most cited references 18

The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance.

Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure.

A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor.

Author and article information

Journal

Affiliations

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 149

Cited by 2

Most referenced authors 271