Anti-mullerian hormone and ovarian reserve in systemic lupus erythematosus.
ABSTRACT OBJECTIVES: To study the level of anti-mullerian hormone (AMH) and its relationship with age and previous cyclophosphamide (CYC) exposure in patients with systemic lupus erythematosus (SLE). METHOD: Consecutive female patients aged 18-52 years who had menstruation in the preceding 12 months and fulfilled ?4 ACR criteria for SLE were recruited. AMH was assayed by an ELISA kit (Beckman Coulter, Inc., USA). Serum AMH level was compared between patients with and without previous use of immunosuppressive agents. The relationship of AMH level to age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis. RESULTS: 216 patients were studied (age 35.1?10.1 years, SLE duration 7.6?5.9 years). AMH level was significantly lower in patients with previous CYC exposure than those without, adjusted for age (1.58?2.92 vs 1.73?2.11 ng/mL; p=0.04). The median time interval between AMH assay and last dose of CYC administered was 6.7 years (inter-quartile range 3.4-8.5). AMH levels were not statistically different between users and non-users of other immunosuppressive agents that included mycophenolate mofetil, azathioprine and the calcineurin inhibitors. Linear regression revealed increasing age (Beta -0.32; p=0.02) and each 5g of CYC exposure (Beta -0.28; p=0.047) were independently associated with lower AMH level. In patients aged ?30 years, a cumulative CYC dose cut-off of 5.9g yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis. CONCLUSION: AMH is a sensitive marker for ovarian damage due to previous CYC exposure in SLE patients. © 2012 American College of Rheumatology.
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ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that mainly affects women of reproductive age. Emerging data from recent molecular studies show us that estrogen hormone plays a central role in the development of this disease. By acting via its cognate receptors ERα and ERβ expressed on immune cells, estrogen can modulate immune function in both the innate and adaptive immune responses. Interestingly, estrogen may also evoke autoimmune responses after binding to B lymphocytes leading to the generation of high-affinity autoantibodies and proinflammatory cytokines (so-called estrogen-induced autoimmunity). Unfortunately, reproductive function of young female patients with this disease is commonly compromised by different pathophysiologic processes. First, ovarian reserve is diminished even in the presence of mild disease suggesting a direct impact of the disease itself on ovarian function possibly due to ovarian involvement in the form of autoimmune oophoritis. Second, SLE patients with severe manifestations of the disease are treated with alkylating chemotherapy agent cyclophosphamide. Cyclophosphamide and other drugs of alkylating category have the highest gonadotoxicity. Therefore, SLE patients exposed to cyclophosphamide have a much higher risk of developing infertility and premature ovarian failure than do the counterparts who are treated with other less toxic treatments. Third, the functions of the hypothalamic pituitary ovarian axis are perturbed by chronic inflammatory state. And finally adverse pregnancy outcomes are more commonly observed in SLE patients such as fetal loss, preterm birth, intrauterine fetal growth restriction, preeclampsia-eclampsia, and fetal congenital heart block. We aimed in this review article to provide the readers an update on how estrogen hormone closely interacts with and induces lupus-prone changes in the immune system. We also discuss ovarian function and other reproductive outcomes in SLE patients and the current strategies to preserve their fertility in the light of the most recent evidence-based findings of the clinical trials and molecular studies.Obstetrical and Gynecological Survey 03/2015; 70(3):196-210. DOI:10.1097/OGX.0000000000000160 · 2.36 Impact Factor
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ABSTRACT: Since serum anti-Müllerian hormone (AMH) levels enable quantitative evaluation of ovarian damage, we conducted a computer-based search, using key words, of all articles published in English through the PubMed database from inception until September 2013 to summarize available studies evaluating ovarian reserve after ovarian toxic interventions to discuss the usefulness of serum AMH levels. We found that most of the studies demonstrated a decline in serum AMH levels when compared to control or pretreatment levels, with levels dependent on the type of treatment modality. Measurement of serum AMH levels enables quantitative evaluation of ovarian damage caused by ovarian toxic interventions, such as chemotherapy and radiotherapy, instead of qualitative evaluation using menstrual condition or basal follicle-stimulating hormone levels. Serum AMH levels are becoming indispensable to assess the ovarian reserve of patients who desire preservation of ovarian function for fertility and endogenous sex steroid hormones.Reproductive sciences (Thousand Oaks, Calif.) 09/2014; 22(5). DOI:10.1177/1933719114549856 · 2.18 Impact Factor
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ABSTRACT: Purpose of reviewTo provide an update on the latest clinical applications of serum antimüllerian hormone (AMH) testing with practical approaches to mitigate the impact of significant variability in AMH results.Recent findingsRecent studies continue to demonstrate that AMH is the best single serum test for ovarian response management with, at most, a weak-to-moderate age-independent association with live-birth rate and time to conception. Data confirm serum AMH levels improve menopause prediction, monitoring of ovarian damage, and identification of women at risk for several ovary-related disorders such as polycystic ovary syndrome and premature or primary ovarian insufficiency. However, it is now recognized that serum AMH results can have dramatic variability due to common, biologic fluctuations within some individuals, use of hormonal contraceptives or other medications, certain surgical procedures, specimen treatment, assay changes, and laboratory calibration differences. Practical guidelines are provided to minimize the impact of variability in AMH results and maximize the accuracy of clinical decision-making.SummaryAMH is an ovarian biomarker of central importance which improves the clinical management of women's health. However, with the simultaneous rapid expansion of AMH clinical applications and recognition of variability in AMH results, consensus regarding the clinical cutpoints is increasingly difficult. Therefore, a careful approach to AMH measurement and interpretation in clinical care is essential.Current Opinion in Obstetrics and Gynecology 06/2014; 26(4). DOI:10.1097/GCO.0000000000000087 · 2.37 Impact Factor