Premature Ovarian Failure

Gynecol Endocrinol. 1999 Jun;13(3):189-95.

Premature ovarian failure.

Falsetti L, Scalchi S, Villani MT, Bugari G.

Source

Department of Gynecological Endocrinology, University of Brescia, Italy.

Abstract

Forty women with premature ovarian failure (POF) arising post-puberty (PPOF) during the reproductive lifespan, underwent karyotyping, pelvic ultrasonography, hormonal assays, hematochemical and immunological examinations. In 52.5%, PPOF was idiopathic, while in 45% the cause was immunological and in 2.5% chromosomal. The hormonal parameters were characterized by elevated plasma levels of gonadotropins (especially follicle-stimulating hormone, FSH), insulin and thyroid-stimulating hormone (TSH) and low levels of 17 beta-estradiol, prolactin, androstenedione, testosterone and dehydroepiandrosterone sulfate. One or more autoantibodies were present in 18 subjects (45%). Among the antibodies, the most representative were: antithyroid microsomal (27.5%), antinuclear antibody (20%) and antithyroid globulin (12.5%). Ultrasound showed that the ovaries were of normal volume (3.1 +/- 0.3 cm3) in 14 women (35%) and significantly smaller (1.4 +/- 0.4 cm3) in 26 (65%). Follicles were present in 10 women (25%). In patients with autoantibodies, ovaries were of small volume (n = 15, 83.3%) and had follicles (n = 6, 33.3%) in a significantly greater percentage compared to those without autoimmune etiology (n = 11, 50%; n = 4, 18.2%, respectively). Women with PPOF, all having secondary amenorrhea, presented significantly higher levels of total cholesterol, and low-density lipoproteins and lower levels of high-density lipoproteins.

PMID:10451811

Arq Bras Endocrinol Metabol. 2007 Aug;51(6):920-9.

Premature ovarian failure: steroid synthesis and autoimmunity.

Doldi N, Belvisi L, Bassan M, Fusi FM, Ferrari A.

Source

Department of Obstetrics and Gynecology, University of Milan, H. San Raffaele Scientific Institute, Italy.

Abstract

The androgen biosynthesis and autoimmunity of 25 patients with premature ovarian failure (POF) and 18 control subjects with normal cycles were examined. Serum levels of dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone were analyzed in POF patients with or without organ-specific autoimmunity, and the results compared with those of women with normal ovarian function. The comparative analysis of DHEAS, 17-OHP, androstenedione and testosterone showed that POF patients had significantly lower values than normal women (DHEAS, androstenedione and testosterone p < 0.01, 17-OHP p < 0.05). Furthermore, we found one or more organ-specific autoantibodies in 11 patients with POF (44%), while only one woman in the control group showed autoimmunity (antithyroid microsome) (5.5%). Only one patient had both anti-ovarian and anti-adrenal antibodies (4%). The comparison of androgen levels in POF patients with or without autoimmunity revealed a statistically significant reduction of DHEAS levels in POF patients with organ-specific autoimmunity (p < 0.01). These data reveal the reduction in androgen synthesis in POF patients, particularly in those with organ-specific autoimmunity.

PMID: 9526706

J Endocrinol Invest. 1993 Dec;16(11):889-92.

Impact of systemic lupus erythematosus on ovarian reserve in premenopausal women: evaluation by using anti-Muellerian hormone.

Lawrenz B, Henes J, Henes M, Neunhoeffer E, Schmalzing M, Fehm T, Kïtter I.

Source

University Hospital for Women, Tuebingen University Hospitals, Tuebingen, Germany.

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease which may negatively influence fertility. Treatment with cyclophosphamide can damage the ovaries. The ovarian function can also be reduced by autoimmune oophoritis in lupus patients. We analysed the influence of SLE on the ovarian reserve against disease intensity and duration of illness. We determined the ovarian reserve in 33 premenopausal SLE patients without previous cyclophosphamide-treatment by measuring the anti-Muellerian hormone (AMH) and compared these with the AMH values of 33 age-matched healthy controls. Numbers of children and miscarriages were reported. Disease intensity of the SLE patients was determined using SLEDAI and ECLAM and duration of illness was taken into account. We found that the AMH values in the SLE group were significantly lower than in the healthy control group. No significant differences between the groups regarding number of children and miscarriages were noted and no correlation between the AMH value and the duration of illness or the SLEDAI as an indicator of disease activity was found. Despite mild disease activity SLE patients had a significantly lower ovarian reserve than age-matched healthy women. This could be a sign that SLE itself has a negative influence on the ovarian reserve.

PMID: 21768179 -

Curr Opin Obstet Gynecol. 2010 Aug;22(4):277-82.

Serum anti-Müllerian hormone levels are lower in reproductive-age women with Crohn's disease compared to healthy control women.

Senateş E, Colak Y, Erdem ED, Yeşil A, Coşkunpınar E, Sahin O, Altunöz ME, Tuncer I, Kurdaş Övünç AO.

Source Haydarpaşa Numune Education and Research Hospital, Department of Gastroenterology, Turkey.

Abstract

BACKGROUND AND AIM: Crohn's disease (CD) decreases fertility both directly, by inducing inflammation in the fallopian tubes and ovaries, and indirectly, through the surgical interventions and tubal adhesions associated with disease treatment. Anti-müllerian hormone (AMH) is a reliable indicator of ovarian reserve in women. We aimed to compare serum AMH levels between reproductive-age women with CD and healthy controls.

METHODS: Serum AMH levels were measured by ELISA in 35 women with CD and 35 age-matched healthy women controls.

RESULTS: CD patients and controls were similar in terms of age, height, weight and BMI. Mean CD duration was 60 months. CRP, ESR and leukocyte counts were significantly higher in CD patients compared to the controls (p<0.001, p=0.004 and p=0.04, respectively). AMH levels in CD patients (1.02±0.72) were significantly lower compared to the controls (1.89±1.80) (p=0.009). Serum AMH levels in CD patients with active disease (0.33±0.25) were significantly lower compared to CD patients who were in remission (1.53±0.49) (p=0.001). Serum AMH levels were similar in CD patients with a disease duration of less than 5 years (17 patients) and CD patients with a disease duration of greater than 5 years (18 patients) (p=0.8). In CD patients, a negative correlation between CDAI and serum AMH levels was found (r=-0.718, p<0.001). Serum AMH levels were similar in CD patients who had (6 patients) and had not undergone (29 patients) surgical treatment (p=0.2).

CONCLUSION: Serum AMH levels of reproductive-age women with CD were significantly lower compared to the controls. CDAI and AMH are inversely correlated.

Inflamm Bowel Dis. 2011 Sep 20. doi: 10.1002/ibd.21872. [Epub ahead of print]

progressive decline of residual follicle pool after clinical diagnosis of autoimmune ovarian insufficiency.

Falorni A, Brozzetti A, Aglietti MC, Esposito R, Minarelli V, Morelli S, Tomaro ES, Marzotti S.

Source Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy.

Abstract

CONTEXT: In approximately 5-8% patients with primary ovarian insufficiency (POI), the disease is caused by an autoimmune process made evident by the appearence of autoantibodies against steroidogenic enzymes (SCA-POI). Anti-müllerian hormone (AMH) is the best marker of the residual follicular pool.

OBJECTIVE: To evaluate the rate of loss of the residual follicle pool in women with SCA-POI after clinical diagnosis.

DESIGN AND METHODS: 132 women with POI were tested for 21-hydroxylase autoantibodies, 17α-hydroxylase autoantibodies and P450scc autoantibodies and 35 patients with SCA-POI were identified. AMH was analyzed at the time of the first visit in all women with POI and in follow-up serum samples taken 1 to 3 years afterwards in 11 women with SCA-POI and detectable AMH.

RESULTS: 12/35 (35%) women with SCA-POI had AMH levels within the normal range at the time of first sampling, as compared to 6/97 (6%) with idiopathic POI (p<0.001). 11/17 (65%) women with SCA-POI with less than 6 years disease duration had normal serum AMH concentration. A progressive decline in AMH concentration was observed at longitudinal follow-up in all 11 AMH-positive women with SCA-POI, at an estimated average rate of 1.6 μg/L AMH/year (corresponding to an average 57% of preserved follicle pool/previous year) (R2=0.219, p=0.028). After 6 years of disease duration, only 1/18 (6%) women with SCA-POI had detectable levels of AMH, similar to women with idiopathic POI (5/78, 6%).

CONCLUSION:

Most women with SCA-POI present at clinical diagnosis with a preserved follicle pool that is progressively lost within a few years.

Autoantibody responses in autoimmune ovarian insufficiency and in Addison's disease are IgG1 dominated and suggest a predominant, but not exclusive, Th1 type of response.

Brozzetti A, Marzotti S, La Torre D, Bacosi ML, Morelli S, Bini V, Ambrosi B, Giordano R, Perniola R, De Bellis A, Betterle C, Falorni A; Italian Addison Network.

Source

Department of Internal Medicine, University of Perugia, Perugia, Italy.

Abstract

OBJECTIVE:

Steroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantibodies (21OHAbs), 17alpha-hydroxylase autoantibodies (17OHAb), and cholesterol side-chain cleavage enzyme (side-chain cleavage autoantibodies, P450sccAb) characterize autoimmune primary ovarian insufficiency (SCA-POI). The aim of the study was to analyze IgG subclass specificity of autoantibodies related to adrenal and ovarian autoimmunity.

DESIGN:

We studied 29 women with SCA-POI, 30 women with autoimmune Addison's disease (AAD) without POI, and 14 patients with autoimmune polyendocrine syndrome type 1 (APS1). 21OHAb isotypes were also analyzed in 14 subjects with preclinical AAD. Samples from 30 healthy women served as control group to determine the upper level of normality in the isotype assays.

METHODS:

Immunoradiometric assays with IgG subclass-specific secondary antibodies.

RESULTS:

In 21OHAb-positive sera, IgG1 isotype was detected in 90% SCA-POI and non-POI AAD sera and 67% APS1 patients. IgG1 isotype was found in 69% 17OHAb-positive SCA-POI and 100% 17OHAb-positive APS1 sera, and in 60% P450sccAb-positive SCA-POI and 80% P450sccAb-positive APS1 sera. For 21OHAb, IgG4 isotype was detected in 17% SCA-POI, 7% non-POI AAD, and 8% APS1 sera. None of the 17OHAb-positive sera was positive for IgG4. In P450sccAb-positive sera, 15% POI and 20% APS1 sera were positive for IgG4. Two 21OHAb-positive SCA-POI (7%), one 21OHAb-positive AAD (3%), three P450sccAb-positive SCA-POI (15%), and two P450sccAb-positive APS1 (20%) sera were positive for IgG4, in the absence of IgG1. All preclinical AAD sera resulted as positive for IgG1-21OHAb, but not for IgG4-21OHAb.

CONCLUSIONS:

The autoantibody responses in POI and AAD are IgG1 dominated, which suggests a predominant Th1 response. Selective IgG4 isotype specificity identified a small subset of patients with Th2-oriented response.

PMID: 20498138

Reprod Biomed Online. 2010 Sep;21(3):360-5. Epub 2010 Apr 18.

Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation.

Gleicher N, Weghofer A, Barad DH.Source Center for Human Reproduction, New York and Foundation for Reproductive Medicine, New York, NY, USA.

Abstract Dehydroepiandrosterone (DHEA) has been reported to improve oocyte/embryo yields and oocyte/embryo quality in women with diminished ovarian reserve. Whether DHEA objectively improves ovarian reserve is, however, unknown. This study investigated 120 consecutive patients with diminished ovarian reserve, supplemented for 30-120 days (mean 73+/-27) with DHEA (25mg three times daily). Anti-Müllerian hormone (AMH) concentrations were determined in relationship to DHEA supplementation using linear regression and, longitudinally, by examining interaction between days of DHEA treatment and pregnancy success in respect to changes in AMH. AMH concentrations significantly improved after DHEA supplementation over time (P=0.002). Women under age 38 years demonstrated higher AMH concentrations and improved AMH concentrations more than older females. AMH improved longitudinally by approximately 60% (P<0.0002). Women reaching IVF experienced a 23.64% clinical pregnancy rate and conceiving women showed significantly improved AMH concentrations compared with those who did not (P=0.001). DHEA supplementation, thus, significantly improved ovarian reserve in parallel with longer DHEA use and was more pronounced in younger women.

http://www.ncbi.nlm.nih.gov/pubmed/20638339

Clin Chem. 2000 Apr;46(4):523-8.

Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and pregnenolone sulfate concentrations in patients with hyperthyroidism and hypothyroidism.

Tagawa N, Tamanaka J, Fujinami A, Kobayashi Y, Takano T, Fukata S, Kuma K, Tada H, Amino N.Source Clinical Chemistry Laboratory, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.t-noriko@kobe pharma-u.ac.jp

BACKGROUND: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to have protective effects against cardiovascular disease, cancer, immune-modulated diseases, and aging. We examined serum concentrations of DHEA, DHEA-S, and pregnenolone sulfate (PREG-S) in patients with thyroid dysfunction.

METHODS: Steroids extracted with methanol from serum sample were separated into an unconjugated fraction (DHEA) and a monosulfate fraction (DHEA-S and PREG-S), using a solid-phase extraction and an ion-exchange column. After separation of unconjugated steroids by HPLC, the DHEA concentration was measured by enzyme immunoassay. The monosulfate fraction was treated with arylsulfatase, and the freed steroids were separated by HPLC. The DHEA and PREG fractions were determined by gas chromatography-mass spectrometry, and the concentrations were converted into those of DHEA-S and PREG-S.

RESULTS: Serum concentrations of DHEA, DHEA-S, and PREG-S were all significantly lower in patients with hypothyroidism (n = 24) than in age- and sex-matched healthy controls (n = 43). By contrast, in patients with hyperthyroidism (n = 22), serum DHEA-S and PREG-S concentrations were significantly higher, but the serum DHEA concentration was within the reference interval. Serum concentrations of these three steroids correlated with serum concentrations of thyroid hormones in these patients. Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentration of steroids.

CONCLUSIONS: Serum concentrations of DHEA, DHEA-S, and PREG-S were decreased in hypothyroidism, whereas serum DHEA-S and PREG-S concentrations were increased but DHEA was normal in hyperthyroidism. Thyroid hormone may stimulate the synthesis of these steroids, and DHEA sulfotransferase might be increased in hyperthyroidism.

Immunoprotective steroids and SHBG in non-treated hypothyroidism and their relationship to autoimmune thyroid disorders.

Drbalová K, Matucha P, Matejková-Behanová M, Bílek R, Kríz L, Kazihnitková H, Hampl R.

Source Institute of Endocrinology, Prague, Czech Republic.

Abstract Immunomodulatory steroids, dehydroepiandrosterone and its 7-hydroxylated metabolites and sex hormone-binding globulin (SHBG) were determined in sera of 88 women aged 18-75 years. The group consisted of 34 healthy women, 37 women with subclinical and 17 women with manifest hypothyroidism. In all subjects the laboratory parameters of thyroid function (thyrotropin, free thyroxine and triiodothyronine) and thyroid autoantibodies to thyroid peroxidase and thyroglobulin were determined. The aim was to find out 1) whether the above steroids and SHBG levels differ in individual groups according to thyroid status, 2) whether correlations exist among investigated steroids and thyroid laboratory parameters, and 3) whether the respective steroid and SHBG levels differ according to the presence of principal thyroid autoantibodies. With the exception of 7beta-hydroxy-dehydroepindrosterone levels, which were decreased in patients with manifest hypothyroidism (p<0.05), no significant differences in steroid and SHBG levels among groups according to diagnosis were found. On the other hand, significantly decreased levels of all the immunomodulatory steroids studied were found in subjects with positive titres of thyroid autoantibodies. This finding was supported by a tight negative correlation among the above steroids and thyroid autoantibodies. In addition, these steroids correlated negatively with thyrotropin and positively with free thyroid hormones. The results point to a negative relationship between the above mentioned immunoprotective steroids and the extent of the autoimmune process in hypothyroidism.