Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Premature ovarian failure (POF) causing hypergonadotrophic hypogonadism occurs in 1% of women. In majority of cases the underlying cause is not identified. The known causes include: (a) Genetic aberrations, which could involve the X chromosome or autosomes. A large number of genes have been screened as candidates for causing POF; however, few clear causal mutations have been identified. (b) Autoimmune ovarian damage, as suggested by the observed association of POF with other autoimmune disorders. Anti-ovarian antibodies are reported in POF by several studies, but their specificity and pathogenic role are questionable. (c) Iatrogenic following surgical, radiotherapeutic or chemotherapeutic interventions as in malignancies. (d) Environmental factors like viral infections and toxins for whom no clear mechanism is known. The diagnosis is based on finding of amenorrhoea before age 40 associated with FSH levels in the menopausal range. Screening for associated autoimmune disorders and karyotyping, particularly in early onset disease, constitute part of the diagnostic work-up. There is no role of ovarian biopsy or ultrasound in making the diagnosis. Management essentially involves hormone replacement and infertility treatment, the only proven means for the latter being assisted conception with donated oocytes. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation hold promise in cases where ovarian failure is foreseeable as in women undergoing cancer treatments.
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PMID:Premature ovarian failure. 1591 82

Premature ovarian failure (POF) is an unexplained amenorrhoea (>6 months) with raised levels of gonadotropins (FSH>40 U/L) occurring before the age of 40 years. Recent studies have elucidated the role of oocyte derived growth factors (BMP15 and GDF9) in maintenance of folliculogenesis, granulosa cell (GC) proliferation and overall fertility. Our recently published work showed presence of two rare missense variants in the GDF9 gene associated with ovarian failure (Dixit et al. 2005, Menopause 12:749-754). The present case-control study has been structured to establish the role of BMP15 germline status associated with ovarian failure. Sequence analysis of the coding region of the BMP15 gene was carried out in a cohort of women with POF (n=133), primary amenorrhoea (n=60), and secondary amenorrhoea (n=9) compared with control females (n=197). This study revealed a total of 18 germline variants in the coding region of BMP15 gene, including 16 novel variants. These novel variants include one intronic variant, one 3' flanking variant, one silent variant, and 13 missense variants. Eleven missense variants were present only in cases with complete absence in the control females. The remaining two missense variants viz. c.308A>G (p.Asn103Ser) and c.788_789insTCT (p.Leu263_Arg264insLeu) were present both in the cases and in the controls. The c.788_789insTCT variant was significantly higher in primary amenorrhoea cases than in the controls (Fisher's exact test, P=0.034). Three frequent variants c.-9C>G, c.308A>G, and c.852C>T were chosen for haplotyping. The haplotype G-G-C was found to be significantly associated with ovarian failure (P=0.0075). In a nutshell, the BMP15 gene is highly associated with etiology of ovarian failure.
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PMID:Missense mutations in the BMP15 gene are associated with ovarian failure. 1650 50

Premature ovarian failure in the early age 20s is a very rare phenomenon. In a woman presenting with amenorrhea and symptoms of hypoestrogenism, the confirmatory diagnosis of premature ovarian failure relies upon the finding of postmenopausal level of the follicle-stimulating hormone (FSH > 40 mIU/ml). Three women at the age of 25, 30 and 32 years presented with 5, 6 and 10 years secondary amenorrhea, respectively. They used to have regular menses, and two of them gave birth to a healthy baby(ies). Although the etiology remains enigmatic, their gonadotropin and estradiol serum values were found to be in the postmenopausal range. Serum FSH values in the three cases were 135.4, 41.9 and 86.5 mlU/ml. Both combined oral contraceptive pills and progesterone challenge test were administered but couldn't bring about recommencement of menstrual flow. These three women who were diagnosed as a case of premature ovarian failure, evidenced by long standing secondary amenorrhea, secondary infertility, signs and symptoms of postmenopause and biochemical evidences of hypergonadotropic hypoestrogenism, were put on continuous combined oral contraceptive pills and felt better. Literature on the potential serious complications of premature menopause and treatment options in low setting areas is revised.
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PMID:Premature ovarian failure in the early age 20s: 3 case reports. 1652 51

Testosterone therapy for postmenopausal women and women with surgical menopause, albeit controversial, is becoming more widespread. However, only limited data are available to support its use in premenopausal women. Androgens have important biological roles in young women, influencing bone and muscle mass, mood and well-being, and libido. Pathophysiological states affecting ovarian and adrenal function or both may result in androgen deficiency in premenopausal women. Young women with hypothalamic amenorrhea, premature ovarian failure, oophorectomy, premenstrual syndrome, acquired immunodeficiency wasting syndrome, adrenal insufficiency, and hypopituitarism may have testosterone deficiency. Young women with loss of libido may also have testosterone deficiency. Medications that may lead to testosterone insufficiency include oral estrogen, oral contraceptives, and corticosteroids. Testosterone deficiency in young women may be underdiagnosed because the symptoms generally are nonspecific and the measurement of total and free testosterone is inaccurate with commonly used techniques. Only a few studies investigating the effects of testosterone therapy have been performed thus far in premenopausal women. Long-term trials evaluating safety and effectiveness of testosterone therapy in premenopausal women are lacking. Common adverse effects include hirsutism and acne, which reverse with discontinuation of treatment. The availability of testosterone regimens specifically designed for women is expected to help maintain testosterone levels within the normal range and clarify whether the apparent beneficial effects of testosterone therapy are physiological or pharmacological.
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PMID:Testosterone therapy in premenopausal women. 1663 84

Premature ovarian failure (POF) is a common condition, affecting approximately 1:100 women. It is characterised by amenorrhea, hypoestrogenism, and elevated gonadotrophin levels in women under the age of 40. It is often an unexpected and distressing diagnosis, which coincides with infertility and menopausal symptoms. There is a well recognised genetic basis to the development of POF. Our laboratory has identified several candidate genes associated with POF.
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PMID:The genetic basis of premature ovarian failure. 1670 81

Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea). It is a heterogeneous disorder affecting approximately 1% of women <40 years, 1:10,000 women by age 20 and 1:1,000 women by age 30. The most severe forms present with absent pubertal development and primary amenorrhea (50% of these cases due to ovarian dysgenesis), whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion. As in the case of physiological menopause, POF presents by typical manifestations of climacterium: infertility associated with palpitations, heat intolerance, flushes, anxiety, depression, fatigue. POF is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Beyond infertility, hormone defects may cause severe neurological, metabolic or cardiovascular consequences and lead to the early onset of osteoporosis. Heterogeneity of POF is also reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. POF has a strong genetic component. X chromosome abnormalities (e.g. Turner syndrome) represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.
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PMID:Premature ovarian failure. 1672 28

Premature ovarian failure (POF) is characterized by elevated gonadotropins and amenorrhea in women aged <40 years. In a Lebanese family with five sisters who received the diagnosis of POF, we established linkage to the long arm of the X chromosome (between Xq21.1 and Xq21.3.3), using whole-genome SNP typing and homozygosity-by-descent mapping. By sequencing one candidate gene within that region, POF1B, we identified a point mutation localized in exon 10. This substitution of a nucleotide (G-->A), at position 1123, results in an arginine-->glutamine mutation of the protein sequence at position 329 (mutation R329Q). All the affected family members were homozygous for the mutation, whereas the unaffected members were heterozygous. Because POF1B shares high homology with the tail portion of the human myosin, we assessed the ability of both wild-type and mutant POF1B proteins to bind nonmuscle actin filaments in vitro. We found that the capacity of the mutant protein to bind nonmuscle actin filaments was diminished fourfold compared with the wild type, suggesting a function of POF1B in germ-cell division. Our study suggests that a homozygous point mutation in POF1B influences the pathogenesis of POF by altering POF1B binding to nonmuscle actin filaments.
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PMID:Disruption of POF1B binding to nonmuscle actin filaments is associated with premature ovarian failure. 1677 70

Premature ovarian failure (POF) is characterized by amenorrhea and high serum levels of follicle-stimulating hormone (FSH). POF causes female infertility and represents a substantial women's health risk affecting 1% of women by age 40. Although ovarian autoimmunity has been associated with POF, the identity of ovarian Ags recognized is unknown. In this study, we show that autoimmune-targeted disruption of the pituitary-ovarian axis leads to POF. Immunization of SWXJ female mice with the p215-234 peptide derived from mouse inhibin-alpha activates CD4(+) T cells and induces experimental autoimmune oophoritis with a unique biphasic phenotype characterized by an early stage of enhanced fertility followed by a delayed stage of POF. Affected mice show high serum levels of inhibin-alpha-neutralizing Abs that prevent inhibin-mediated down-regulation of activin-induced pituitary FSH release. The loss of activin/FSH down-regulation leads to prolonged metestrus-diestrus, superovulation, increased numbers of mature follicles, increased offspring, accelerated depletion of primordial follicles, and ultimately premature infertility. Thus, inhibin-alpha-targeted experimental autoimmune oophoritis is initiated by CD4(+) Th1 T cells that stimulate B cells to produce inhibin-alpha-neutralizing Abs directly capable of mediating POF and transferring disease into naive recipients. Our inhibin-alpha autoimmune model of POF shows how premature infertility may develop in the context of elevated FSH levels thereby closely mimicking the hallmark features of human POF.
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PMID:Autoimmune targeted disruption of the pituitary-ovarian axis causes premature ovarian failure. 1684 13

Premature ovarian failure (POF) is defined by at least four months of amenorrhea with elevated gonadotropins (usually above 40 UI/L) detected on two occasions a few weeks apart, in a woman before the age of 40. It occurs in 1 out of 10,000 in women below the age of 20, 1/1,000 below 30 and 1% in women before the age of 40. In 80% of POF cases, the etiology is unknown, except for Turner syndrome. The different etiologies identified are 1) iatrogenic following chemotherapy and/or radiotherapy, 2) autoimmune, 3) viral, 4) genetic (RFSH, FOXL2, FRAXA, BMP15, GDF9, GALT, 17 hydroxylase...). Management of these patients includes hormone replacement therapy in order to avoid an increase in cardiovascular risk and osteoporosis related to hypoestrogenism. Infertility is common, as only 3 to 10% of the patients will have natural conception. When fertility is desired, women with POF should be oriented towards oocyte donation centers. Research is currently performed in order to identify new genes involved in POF.
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PMID:[Premature ovarian failure]. 1719 65

Premature ovarian failure (POF) is defined as the cessation of ovarian function under the age of 40 years and is characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotropin concentrations. POF affects 1% of all women and occurs in approximately 0.1% before the age of 30 years. To date, mutations associated with POF have been identified in a small number of genes, including those encoding inhibin alpha (INHA), the FSH receptor and the LH/chorio gonadotrophin receptor. Germ cell specific genes such as Gdf9, Bmp15, and Rfpl4 may also play important roles in human oogenesis. Transcription factors that regulate oocyte gene expression in animal models and include Nobox, Taf4b, Figla, Lhx8, Sohlh1 and Sohlh2 are likely to be key mediators of fertility in humans. In this review, after summarizing the general background on human POF, we focus on insights gained from the animal models with regards to mammalian folliculogenesis. Studies in animal models provide new candidate genes for ovarian failure in humans.
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PMID:Candidate genes for premature ovarian failure. 1730 37


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