ABSTRACT
The FSH receptor presents several polymorphisms. Two of them, located at codon 307 and 680, are the most frequent. Threonine can be substituted by alanine at position 307 and serine can be substituted by asparagine at position 680. The two most frequent allelic combinations are Thr(307) -Asn (680) (60%) and Ala(307) -Ser (680) (40%). As the allelic variants at codon 307 and 680 are almost invariably associated, most of the studies assessed only one codon (680) and classified the women as homozygous (Ser/Ser ou Asn/Asn) or heterozygous (Asn/Ser). Several studies aimed to correlate the follicle-stimulating hormone receptor polymorphism and ovarian function. Women homozygous for the Ser (680) variant have higher follicular FSH levels and longer follicular phase length, which suggest a lower sensitivity to FSH. The FSH receptor genotype would also influence the sensitivity to exogenous FSH: as regards ovarian stimulation, higher recombinant FSH doses are needed for Ser/Ser homozygous women. The analysis of polymorphism in women with premature ovarian failure did not show a link with any particular allelic variant. In women with polycystic ovaries, the distribution of the allelic variants greatly varies from one study to another.
Subject(s)
Follicle Stimulating Hormone/physiology , Infertility, Female/genetics , Ovary/physiology , Polymorphism, Genetic , Receptors, FSH/genetics , Codon , Female , Follicle Stimulating Hormone/metabolism , Gene Frequency , Humans , Polycystic Ovary Syndrome/genetics , Serine , ThreonineABSTRACT
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.
