Anti-mullerian hormone and ovarian reserve in systemic lupus erythematosus
Department of Medicine, Tuen Mun Hospital, Hong Kong, China. . Arthritis & Rheumatology
(Impact Factor: 7.76).
10/2012; 65(1). DOI: 10.1002/art.37719
To study the level of anti–müllerian hormone (AMH) and its relationship to age and previous exposure to cyclophosphamide (CYC) in patients with systemic lupus erythematosus (SLE).
Consecutive female patients ages 18–52 years who had menses at least once during the preceding 12 months and fulfilled ≥4 American College of Rheumatology criteria for SLE were recruited. AMH was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum AMH levels were compared in patients with and without previous use of immunosuppressive agents. The relationship of the AMH level to the patient's age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis.
A total of 216 patients were studied (mean ± SD age 35.1 ± 10.1 years, mean ± SD SLE duration 7.6 ± 5.9 years). The mean ± SD AMH level was significantly lower in patients previously exposed to CYC therapy than in those who had not been exposed after adjustment for age (1.58 ± 2.92 versus 1.73 ± 2.11 ng/ml; P = 0.04). The median time interval between the AMH assay and the last dose of CYC administered was 6.7 years (interquartile range 3.4–8.5). AMH levels in users versus nonusers of other immunosuppressive agents, including mycophenolate mofetil, azathioprine, and the calcineurin inhibitors, were not statistically different. Linear regression revealed increasing age (beta −0.32, P = 0.02) and each 5 gm of CYC exposure (beta −0.28, P = 0.047) were independently associated with a lower AMH level. In patients ages 30 years and younger, a cumulative CYC dose cutoff of 5.9 gm yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis.
AMH is a sensitive marker for ovarian damage due to previous CYC exposure in women with SLE.
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- "Numerous cancer therapy publications have demonstrated the dramatic effects of various chemotherapeutics in reducing serum AMH levels. Some of these studies have demonstrated that AMH testing can improve treatment selection by identifying which therapies are most toxic to the ovary and which patients are most at risk for postchemotherapy ovarian insufficiency [77▪,78▪▪,79–84]. Furthermore, numerous reports are confirming that after some ovarian-related surgeries such as removal of benign cysts and endometriomas, significant reductions in AMH are observed which may persist [72▪,73▪▪,74–76] with a recent study demonstrating similar reductions with benign cysts and endometriomas and more severe reductions with bilateral procedures . "
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ABSTRACT: Purpose of review
To 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 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.
AMH 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.
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ABSTRACT: Context:Cyclophosphamide is used for renal and major extrarenal involvement in systemic lupus erythematosus (SLE), and is associated with a risk of premature ovarian failure. There is no data available about the relation between anti-müllerian hormone (AMH) serum levels and the probability of subsequent pregnancy in SLE patients.Objective:We analysed AMH levels and probability of pregnancy in SLE women exposed to cyclophosphamide.Design:Matched cohort study.Setting:Referral centers for SLEPatients:56 cyclophosphamide-exposed SLE women aged younger than 40 and 56 control SLE women matched for age within 6 months.Main outcome measures:AMH was measured in samples from the PLUS study (ClinicalTrials.gov NCT00413361). All patients were interviewed in May 2012 regarding their obstetric status.Results:The mean age of the 112 patients was 31.6±5.8 years. The mean AMH level was low (1.21±1.01 ng/mL) and was significantly lower in patients exposed to cyclophosphamide (p=0.03) and in patients older than 30 years (p=0.02). During a median follow-up (interval between sampling and the interview) period of 4.2 [2.5-4.8] years, 38 patients sought to become pregnant and 32 succeeded (84.2%). In the univariate analysis, the risk of failure was associated with cumulative cyclophosphamide dose (p=0.007) and older age (p=0.02), but not with AMH.Conclusion:We confirmed that AMH levels are low in SLE patients and decrease significantly with age and cyclophosphamide exposure. Nonetheless, the risk of failure to conceive was low and was predicted by cyclophosphamide exposure and age, but not by AMH levels.
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