Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure.
OBJECTIVE
Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis.


METHODS
We performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center.


RESULTS
Seventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turner's syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1.


CONCLUSIONS
A genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.
AP-HP, Department of Endocrinology and Reproductive Medicine, Centre de référence des Maladies Endocriniennes rares de la croissance, Groupe Hospitalier Pitié-Salpétrière, University Pierre et Marie Curie, Paris VI, 75013 Paris, France.
Anne
A
Bachelot
Agnès
A
Rouxel
Nathalie
N
Massin
Jérome
J
Dulon
Carine
C
Courtillot
Christine
C
Matuchansky
Yasmina
Y
Badachi
Anne
A
Fortin
Bernard
B
Paniel
Fabrice
F
Lecuru
Marie-Aude
MA
Lefrère-Belda
Elisabeth
E
Constancis
Elisabeth
E
Thibault
Géri
G
Meduri
Anne
A
Guiochon-Mantel
Micheline
M
Misrahi
Frédérique
F
Kuttenn
Philippe
P
Touraine
D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D015519:Bone Density / Q000235:genetics; D002648:Child; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007247:Infertility, Female / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D028322:Inhibin-beta Subunits / Q000097:blood; D008875:Middle Aged; D010053:Ovary / Q000000981:diagnostic imaging / Q000473:pathology; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics; D011237:Predictive Value of Tests; D016649:Primary Ovarian Insufficiency / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011627:Puberty / Q000235:genetics; D011628:Puberty, Delayed / Q000235:genetics / Q000473:pathology; D014463:Ultrasonography; D055815:Young Adult
C422402:INHBB protein, human; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits