Premature Ovarian Failure Women Research Articles

The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5.

Premature ovarian failure (POF) is a complication of ovarian dysfunction resulting from the depletion or dysfunction of primordial follicles (PFs) in the ovaries. However, residual follicles that have the potential to be activated are present in POF or aged women. Little is known about the mechanisms by which the remaining dormant PFs in POF patients are activated. Using mass spectrometry, we screened differentially generated peptides extracted from the ovarian cortical tissue biopsies of patients with or without POF, during which we identified PFAP1, a peptide that significantly promoted the activation of PFs in the ovaries of 3 dpp mice in vitro. PFAP1 reversed age-related fertility damage in vivo to a certain extent, promoted estrogen (E2) and anti-mullerian hormone (AMH) production (p < .05), and decreased the levels of follicle-stimulating hormone (FSH) (p < .05). In newborn mouse ovaries, PFAP1 could bind to the protein minichromosome maintenance protein 5 (MCM5) and inhibit its ubiquitination and degradation. In addition, PFAP1 promoted the proliferation of GCs, probably by regulating the function and production of MCM5. In conclusion, PFAP1 could promote the activation of PFs in the ovaries of newborn mice, partially restore the ovarian function of aged mice, and increase the proliferation of primary granulosa cells (GCs) by regulating the function of MCM5. PFAP1 is a promising novel peptide that may be developed into a new therapeutic agent for POF and other ovarian diseases.

Biochemical and Genetic Studies on Inhibin as a Hormonal Candidate in Prediction and Diagnosis of Premature Ovarian Failure in the Egyptian Women

Background: Recent studies have implicated a role for inhibin alpha (INHα) gene abnormalities in the etiology of premature ovarian failure (POF).The present study aimed at demonstrating the possibility that -16C>T polymorphism of INHα gene may enhance susceptibility to this disease among Egyptian women undergoingt in-vitro fertilization(IVF) technique. Methods: A total of 50 POF Egyptian women at age (31.5±7.3) and 50 control women at age (29.1 ± 6.8) were included in this study. Genotyping of INHα-16C>T gene was performed by restriction fragment length polymorphism. Levels of inhibin, activin, FSH and LH were also assessed. Results: Serum levels of FSH and LH showed significant increase coupled by decrease in serum inhibin and inhibin/activin ratio, however, levels of activin were within normal values in POF women comparing to control ones. The frequencies of CC, CT and TT genotypes showed no significant changes in POF women compared to control group. Moreover, there were no significant differences in frequency of C and T alleles among the POF women in comparison to controls. Conclusion: Obtained data indicated that -16C>T polymorphism of INHα gene can not imply a functional effect on the current decline of serum inhibin and hence the risk of developing POF in the studied Egyptian women. Further studies on POF women are needed to expand the present data.

FMR1 premutation: not only important in premature ovarian failure but also in diminished ovarian reserve

It is recognized that FMR1 premutation expansions are associated with premature ovarian failure (POF), but their role in diminished ovarian reserve (DOR) is not clearly established. Moreover, the impact of smaller repeats at the boundary of premutation and normal is less clear. Therefore, we have compared the frequency of these intermediate (45–54 repeats) and premutation (>55) sized FMR1 CGG repeats among a patients group including 188 DOR and 173 POF women and 200 controls. FSH and LH concentrations were also compared between intermediate and premutation ranges in patients. The 5′ UTR of FMR1 gene was amplified using PCR. The numbers of trinucleotide repeats were confirmed by the Sanger sequencing method. The frequency of premutation was higher in POF and DOR patients in comparison with controls, but the difference in the incidence of intermediate alleles was not statistically significant among these groups. The mean level of serum FSH was higher in patients with premutation than patients with intermediate alleles. Based on the current evidence, we concluded that intermediate-sized FMR1 CGG repeat alleles should not be considered as a high-risk factor for POF and DOR.

Investigation of some genetic variations in BMP15 accompanied with premature ovarian failure (POF) in Syrian women

Abstract Background Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles. Bone morphogenetic protein 15 (BMP15) is an oocyte-derived growth factor acting as a major player in follicle differentiation in mammals. Mutations in this gene, lead to defective secretion of bioactive dimmers. The present study was to verify the involvement of BMP15 variations in POF women in Syria. Results Genetic screening of 65 patients with POF, 55 primary amenorrhea (PA), 10 secondary amenorrhea (SA) and 100 controls of Syrian origin was done. Five variants in six patients were observed, including two missense substitutions: p. N103S (308A > G), p. A180T (538G > A), one silent variation p.S284S (852C > T), one insertion of three nucleotides (788 insTCT), and one novel intronic variant c. (851 + 13G > A). Variant (308A > G) was observed at the heterozygous state in one patient, variant (538G > A) was found at the heterozygous state in another patient, variant (852C > T) was identified in four patients: two patients at the heterozygous, the third patient had the variant (852C > T) associated with the insertion of three nucleotides [788insTCT]/(+)[852C > T]. This compound variant was detected for the first time in our study, and the fourth patient who had the variant (852C > T) was associated with novel intronic variant (851 + 13G > A) [851 + 13G > A](+)[852C > T]. In our controls the variant (852C > T), was observed in three controls, but the variant (308A > G) was detected in one control. Conclusion Several data indicate that POF has a strong genetic component; these findings are consistent with the critical role played by BMP15 in human folliculogenesis.

Relationship between Serum Estrogen, Magnesium and Body Mass Index in premature Ovarian Failure Women in Tikrit City/ Iraq .

This study was conducted to evaluate serum estrogen, magnesium level and body mass index of 30 women with premature ovarian failure and 30 women as control group attended to emergency department/ Tikrit teaching hospital in Tikrit City Their ages ranged between 40-48 years. The samples collection started from October /2012 till January /2013. The results showed that serum estrogen level of premature ovarian failure women was statistically significantly P ˂0.05 lower than in control group. Also the mean serum magnesium in premature ovarian failure women was significantly lower than in normal group p˂0.01 .This study showed that body mass index in patient women was significantly higher when compared with control group p˂0.05.

FSH receptor gene variants are rarely associated with premature ovarian failure

FSH receptor (FSHR) gene variants have been associated with premature ovarian failure (POF). Genomic DNA from New Zealand women with POF (n=80) and control women (n=80) was screened for variants in FSHR exons 7 and 10. FSHR exon 7 variants, including the c.566C>T Finnish founder mutation (p.Ala189Val), were not detected. Previously reported FSHR exon 10 polymorphisms were identified in both groups with similar allelic distributions. A novel heterozygous FSHR exon 10 variant c.1411A>T, p.Ile471Phe was observed in one woman with a family history of POF, but not her affected siblings. It is concluded that variants in exons 7 and 10 of FSHR are not frequently associated with the development of POF in the New Zealand population.

Estrogen receptor α gene (ESR1) polymorphisms associated with idiopathic premature ovarian failure in Chinese women

Objective: To evaluate the relationship between Estrogen receptor α gene (ESR1) polymorphisms and idiopathic premature ovarian failure (POF) in Chinese women. Methods: 155 idiopathic POF and 150 healthy controls were recruited in this study. All subjects were analyzed at the PvuII and XbaI loci of the ESR1 gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Results: The frequency of the P allele of the PvuII polymorphisms was 38.1% in POF women, which was significantly higher than controls (28.0%) (p = 0.008). And for the XbaI polymorphisms, the X allele was 21.0% in POF patients, compared to 13.3% in control women (p = 0.013). Carriers of the PP genotype had higher increased risk of POF than those of the pp genotypes (p = 0.011), whereas in three genotypes of the XbaI polymorphisms, no difference was found in the prediction value of POF. In addiction, the P-X haplotype was associated with a significantly increased risk for idiopathic POF. Conclusion: These data suggest that the PvuII and XbaI polymorphisms of ESR1 gene are associated with POF, which may be a potential genetic risk factor of idiopathic POF. More researches are needed to determine whether the findings are generalizable to other populations.

Blood Cell Mitochondrial DNA Content and Premature Ovarian Aging

Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.

Premature menopause: a comprehensive understanding of psychosocial aspects

ABSTRACTObjective To compare experience of premature menopause (PM), information sources, treatments, depression, anxiety, body image, sexual function and self-efficacy, between women with premature ovarian failure (POF), surgically induced menopause (SIPM), chemically induced menopause (CIPM), and controls.Design Cross-sectional observational pilot study using validated and devised questionnaires in 77 Australian women (POF, n = 25; SIPM, n = 17; CIPM, n = 12; controls, n = 23).Results The average age of all women was 34.8 years (standard deviation (SD) ± 5.7 years), and time since PM diagnosis was 3.8 years (SD ± 4.4 years, p = 0.19). The gynecologist (69%) and internet (67%) were the best expected sources of information. Women with PM feared osteoporosis more than controls (p < 0.0001). Women with SIPM (p = 0.006) and POF (p = 0.01) had higher rates of depression compared to controls. SIPM women were more anxious than women with POF (p = 0.04) and both SIPM (p = 0.002) and CIPM (p = 0.02) women were more anxious than controls. Women with POF had higher health evaluation (p = 0.03), fitness evaluation (p = 0.01) and fitness orientation (p = 0.01) than women with SIPM. Controls had higher health evaluation than women with SIPM (p = 0.001) and CIPM (p = 0.04), higher fitness evaluation than women with SIPM (p = 0.02) and CIPM (p = 0.04), and higher fitness orientation than SIPM women (p < 0.0001). Sexual dysfunction (p < 0.0001) and dyspareunia (p = 0.001) were higher in CIPM women than controls. Controls were more sexually responsive than POF women (p = 0.008). SIPM (p = 0.008) and POF (p = 0.04) women reported decreased confidence to manage disease.Conclusion Depression, anxiety, body image, sexual dysfunction and self-confidence are compromised for women across different groups of premature menopause. Understanding these differences is important to the development of individual management plans based on the needs of women.

New candidate gene POU5F1 associated with premature ovarian failure in Chinese patients

Premature ovarian failure (POF) is defined as a cessation of ovarian function in women before the age of 40 years. POU5F1 has a critical role in regulating pluripotency in embryonic development and POU5F1 transcription factor is down-regulated more than 30-fold in the POF candidate gene Nobox knockout ovaries. In order to identify the potential correlation between POU5F1 and the development of POF, the exon regions of POU5F1 were amplified and sequenced in 115 POF patients and 149 healthy controls. One non-synonymous variant of POU5F1 (c. C37A, p. Pro13Thr) was identified and confirmed in one of the POF patients. The substitution replacing a hydrophobic amino acid, proline, with a hydrophilic amino acid, threonine. As far as is known, the present study is the first to identify a potential association between POU5F1 and the development of POF. It has been estimated that up to 30% of POF (premature ovarian failure) cases may result from genetic causes. Until now, some mutations associated with POF have been located in autosomal genes. The present study explored the potential role of POU5F1 in POF development. The primary finding of the present study is a potential pathogenic mutation of POU5F1 in 115 Chinese POF women. A substitution was located at the 13th amino acid, replacing a hydrophobic amino acid, proline, with a hydrophilic amino acid, threonine. The present study firstly identified a non-synonymous variation in POU5F1 in a Chinese POF patient.

Breast density in women with premature ovarian failure or postmenopausal women using hormone therapy: analytical cross-sectional study.

Studies on postmenopausal women have reported increased risk of breast cancer relating to the type and duration of hormone therapy (HT) used. Women with premature ovarian failure (POF) represent a challenge, since they require prolonged HT. Little is known about the impact of prolonged HT use on these women's breasts. This study aimed to evaluate the effects of one type of HT on the breast density of women with POF, compared with postmenopausal women. Cross-sectional study at the Department of Obstetrics and Gynecology, Universidade Estadual de Campinas (Unicamp). 31 women with POF and 31 postmenopausal women, all using HT consisting of conjugated equine estrogen combined with medroxyprogesterone acetate, and matched according to HT duration, were studied. Mammography was performed on all subjects and was analyzed by means of digitization or Wolfe's classification, stratified into two categories: non-dense (N1 and P1 patterns) and dense (P2 and Dy). No significant difference in breast density was found between the two groups through digitization or Wolfe's classification. From digitization, the mean breast density was 24.1% ± 14.6 and 18.1% ± 17.2 in the POF and postmenopausal groups, respectively (P = 0.15). Wolfe's classification identified dense breasts in 51.6% and 29.0%, respectively (P = 0.171). There was no difference in breast density between the women with POF and postmenopausal women, who had used HT for the same length of time. These results may help towards compliance with HT use among women with POF.

Array Comparative Genomic Hybridization Profiling Analysis Reveals Deoxyribonucleic Acid Copy Number Variations Associated with Premature Ovarian Failure

Premature ovarian failure (POF) is defined by amenorrhea of at least 4- to 6-month duration, occurring before 40 yr of age, with two FSH levels in the postmenopausal range. Its etiology remains unknown in more than 80% of cases. Standard karyotypes, having a resolution of 5-10 Mb, have identified critical chromosomal regions, mainly located on the long arm of the X chromosome. Array comparative genomic hybridization (a-CGH) analysis is able to detect submicroscopic chromosomal rearrangements with a higher genomic resolution. We searched for copy number variations (CNVs), using a-CGH analysis with a resolution of approximately 0.7 Mb, in a cohort of patients with POF. We prospectively included 99 women. Our study included a conventional karyotype and DNA microarrays comprising 4500 bacterial artificial chromosome clones spread on the entire genome. Thirty-one CNVs have been observed, three on the X chromosome and 28 on autosomal chromosomes. Data have been compared to control populations obtained from the Database of Genomic Variants (http://projects.tcag.ca/variation). Eight statistically significantly different CNVs have been identified in chromosomal regions 1p21.1, 5p14.3, 5q13.2, 6p25.3, 14q32.33, 16p11.2, 17q12, and Xq28. We report the first study of CNV analysis in a large cohort of Caucasian POF patients. In the eight statistically significant CNVs we report, we found five genes involved in reproduction, thus representing potential candidate genes in POF. The current study along with emerging information regarding CNVs, as well as data on their potential association with human diseases, emphasizes the importance of assessing CNVs in cohorts of POF women.

Telomere Length and Reproductive Aging

Previous studies have suggested an association between rates of biological and reproductive aging. Short telomere length is a marker for cellular aging and may occur more frequently in women with poor oocyte quality and a history of premature reproductive senescence. Telomere length, however, has been both positively and negatively associated with different measures of reproductive aging in a number of studies. In the present study, the investigators tested the hypothesis that women with a history of premature reproductive aging have a shorter average telomere length than women without such a history. Telomere length in peripheral blood leukocytes was measured in 2 groups of women with evidence of premature reproductive aging: Group 1 (n = 34) was comprised of women with idiopathic premature ovarian failure (POF) who experienced menopause before 40 years of age and group 2 (n = 95) contained women with a history of recurrent miscarriage (RM). The 2 control groups were healthy women of reproductive age from the general population (C1, n = 108) and women who had had a healthy pregnancy after 37 years of age (C2, n = 46). Telomere length was measured using telomere-specific quantitative PCR. The age-adjusted mean telomere length was shorter among women in the RM group than among those in both control groups (8.46 kb for RM vs. 8.92 kb for C1, [P = 0.0004] and 9.11 kb for C2, [P = 0.02]), respectively. However, this effect was not specifically confined to women known to have experienced trisomic pregnancies. Contrary to expectation, women in the POF group did not have a shorter age-adjusted mean telomere length than those in the controls: Telomere length in POF women was longer compared to C1 (9.58 vs. 8.92 kb, P = 0.01) and not significantly different than C2. These findings suggest that both the opposing association of RM and POF with telomere length, and lack of an association of trisomic pregnancy―as manifestations of different types of reproductive aging―may result from unique physiological factors. The results require confirmation in studies with larger and more defined patient populations.

Decreased androgen concentrations and diminished general and sexual well-being in women with premature ovarian failure

To describe general and sexual well-being in women with premature ovarian failure (POF) and to investigate whether there is a relationship between androgen levels and sexual functioning. Women with POF and healthy volunteers with regular menstrual cycles participated. Participants completed a written questionnaire and underwent hormonal screening. The questionnaire included standardized measures: the Questionnaire for Screening Sexual Dysfunctions, the Shortened Fatigue Questionnaire, and the Symptom Check List-90. Serum hormone measurements included estradiol, total testosterone, bioavailable testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Eighty-one women with POF and 68 control women participated in the study. Compared with control women, women with POF reported more complaints of anxiety, depression, somatization, sensitivity, hostility, and psychological distress. Overall women with POF were less satisfied with their sexual life. They had fewer sexual fantasies and masturbated less frequently. Sexual contact was associated with less sexual arousal, reduced lubrication, and increased genital pain. However, the frequency of desire to have sexual contact and the frequency of actual sexual contact with the partner did not differ between women with POF and control women. Women with POF had lower levels of estradiol, total testosterone, and androstenedione. Multiple regression analysis revealed that androgen levels had only a weak influence on sexual functioning; higher total testosterone levels were associated with increased frequency of desire for sexual contact, and higher androstenedione levels were associated with elevated frequency of sexual contact. Women with POF have diminished general and sexual well-being and are less satisfied with their sexual lives than control women. Although women with POF had lower androgen levels, we did not find an important independent role for androgens in various aspects of sexual functioning.

Analysis of LHX8 mutation in premature ovarian failure

The LHX8 (LIM homeobox 8) gene encodes a LIM homeodomain transcriptional regulator that is preferentially expressed in germ cells and critical for mammalian oogenesis. The authors investigated whether nucleotide changes were present in the LHX8 gene of Caucasian women with premature ovarian failure (POF), as compared with control women. When the authors sequenced 95 Caucasian women with POF, they discovered two novel single-nucleotide polymorphisms (SNPs) in intron 3 (c.769+10G>T) and 3' untranslated region (c.1787A>G) of the LHX8 gene. These polymorphisms also were found in controls (n = 94), at frequencies that were not statistically different from those in POF women. Mutations in the LHX8 exons are uncommon in Caucasian women with POF.

Molecular cytogenetic studies of Xq critical regions in premature ovarian failure patients

Premature ovarian failure (POF) is defined as amenorrhoea for more than 6 months, occurring before the age of 40, with an FSH serum level higher than 40 mIU/ml. Cytogenetically visible rearrangements of the X chromosome are associated with POF. Our hypothesis was that cryptic Xq chromosomal rearrangements could be an important etiological contributor of POF. Ninety POF women were recruited and compared to 20 control women. Peripheral blood samples were collected and metaphase chromosomes were prepared using standard cytogenetic methods. To detect Xq chromosomal micro-rearrangements, fluorescence in situ hybridization (FISH) analysis was performed using a selection of 30 bacterial artificial chromosome (BAC) and P1 artificial chromosome clones, spanning Xq13-q27. We further localized the translocation breakpoints by FISH with additional BAC clones. Chromosomal abnormalities were identified in 8.8% of our 90 patients [one triple X, three large Xq deletions 46,X,del(X)(q22.3), 46,X,del(X)(q21.2) and 46,X,del(X)(q21.32), two balanced X;autosome translocations 46,X,t(X;1) (q21.1;q32) and 46,X,t(X;9)(q21.31;q21.2) and two Robertsonian translocations 45,XX,der(15;22)(q10;q10) and 45,XX,der(14;21)(q10;q10)]. The two Xq translocation breakpoints were among a cluster of repetitive elements without any known genes. FISH analysis did not reveal any Xq chromosomal micro-rearrangement. Karyotyping is definitely helpful in the evaluation of POF patients. No submicroscopic chromosomal rearrangements affecting Xq region were identified. Further analysis using DNA microarrays should help delineate Xq regions involved in POF.

Adipokine Dysregulation in Turner Syndrome: Comparison of Circulating Interleukin-6 and Leptin Concentrations with Measures of Adiposity and C-Reactive Protein

Women with Turner syndrome (TS) have increased risks of atherosclerosis, diabetes mellitus, and obesity. We hypothesized that women with TS have adverse metabolic or inflammatory markers for cardiovascular disease compared with normal women and estrogen-deficient controls. This was a cross-sectional study conducted at University College London Hospitals, UK. One hundred seventeen estrogen-treated women with TS and normal fasting blood glucose were compared with 30 age-matched normal controls and 31 estrogen-treated women with 46,XX premature ovarian failure (POF). The main outcome measures were markers of the metabolic syndrome, including the adipokines IL-6 and leptin, and C-reactive protein (CRP). TS women were more obese than controls (waist circumference, 79.9 +/- 12.4, 73.5 +/- 6.9, and 74.7 +/- 8.6 cm in TS, normal subjects, and POF controls, respectively; P = 0.005; body mass index, 26.8 +/- 5.8, 23.7 +/- 3.2, and 22.9 +/- 3.4 kg/m2; P < 0.001). This obesity was associated with increased CRP (2.9 +/- 1.5, 0.8 +/- 1.0, and 1.2 +/- 0.9 mg/liter; P < 0.001) and IL-6 concentrations (1.5 +/- 0.7, 1.0 +/- 1.5, and 1.2 +/- 0.5 pg/ml; P = 0.014), but lower fasting serum insulin (4.7 +/- 2.3, 6.3 +/- 3.0, and 6.9 +/- 2.9 mIU/ml; P = 0.004), glucose (83 +/- 11, 90 +/- 7, and 90 +/- 7 mg/dl; P < 0.001), and leptin (10.2 +/- 6.3, 14.4 +/- 7.6, and 14.8 +/- 8.1 ng/ml; P = 0.048). Triglyceride concentrations were similar in TS and POF women and were greater than in normal controls (97 +/- 53, 97 +/- 53, and 71 +/- 27 mg/dl; P = 0.024). We conclude that women with TS have various physical and biochemical features suggestive of the metabolic/insulin resistance syndrome, but there is a discrepancy among CRP, IL-6, and leptin, with leptin and fasting insulin concentrations being lower than expected for the degree of obesity. Obesity and estrogen therapy do not fully explain these findings. Women with TS may have specific metabolic defects contributing to cardiovascular risk.

Relationship of Estradiol and Inhibin to the Follicle-Stimulating Hormone Variability in Hypergonadotropic Hypogonadism or Premature Ovarian Failure

Recent studies have demonstrated the presence of ovarian follicular development in up to 78% of women with premature ovarian failure (POF). The purpose of this study was to examine the control of FSH by estradiol and inhibin secretion from these follicles. Weekly blood samples were collected in conjunction with assessment of ovarian follicle development by ultrasound for at least 12 wk in 49 subjects with POF. Results were compared with those of 44 normal cycling women. Ovulatory cycles occurred in 24 subjects (49%) with POF. These ovulatory cycles were characterized by higher FSH and lower inhibin B and inhibin A levels, whereas estradiol levels were higher compared with those in normal women. Follicles developed in the absence of ovulation in 18 women (37%) with POF, whereas the ovaries were inactive in seven women (14%). FSH levels were lower in POF women with ovulatory or anovulatory follicle development compared with levels in women with inactive ovaries. These findings demonstrate that ovulatory cycles in women with POF are characterized by a persistent elevation in FSH compared with levels in normal cycling women. The association of increased FSH with lower levels of inhibin B and inhibin A, but higher estradiol levels provides additional evidence for an important physiological role of the inhibins in the negative feedback control of FSH. These data also demonstrate the variability in FSH levels as a function of underlying follicular development in women with POF.

Low levels of serum inhibin A and inhibin B in women with hypergonadotropic amenorrhea and evidence of high levels of activin A in women with hypothalamic amenorrhea

Objective: To examine serum levels of inhibin A, inhibin B, and activin A in women with secondary hypergonadotropic or hypothalamic amenorrhea. Design: Retrospective study. Setting: Universities of Udine, Pisa, and Modena in Italy, and of Wien in Austria. Patient(s): Forty women with idiopathic premature ovarian failure (POF), 23 women with hypogonadotropic hypothalamic amenorrhea, 40 healthy postmenopausal women, and 40 age-matched women with normal ovarian function (controls). Intervention(s): Blood samples were collected between 8 and 9 am. Main Outcome Measure(s): Serum levels of inhibin A, inhibin B, and activin A. Result(s): Women with POF had lower concentrations of serum inhibin A and inhibin B than women with hypothalamic amenorrhea and fertile controls, and the difference between these concentrations was statistically significant. Levels of inhibin A and inhibin B were low in postmenopausal women and were no different than in women with POF. Serum levels of activin A were not significantly different among women with POF, fertile controls, and postmenopausal women. Women with hypogonadotropic hypothalamic amenorrhea had higher activin A values than did controls. No significant correlation was found between the level of inhibin A or inhibin B and the length of amenorrhea or the level of FSH. Conclusion(s): Low levels of circulating inhibins A and B, but not activin A, reflect ovarian failure in women with POF, whereas women with hypogonadotropic hypothalamic amenorrhea have normal levels of inhibins A and B and high levels of activin A.

Prevalence, Specificity and Significance of Ovarian Antibodies During Spontaneous Premature Ovarian Failure

Fenichel, Patrick; Sosset, Catherine; Barbarino-Monnier, Patricia; Gobert, Bernard; Hieronimus, Sylvie; Bene, Marie-Christine; Harter, Michel Author Information