The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer

Abstract

AimChemotherapy results in permanent loss of ovarian function in some premenopausal women. Accurate identification in women with hormone-sensitive early breast cancer (eBC) would allow optimisation of subsequent endocrine treatment. We sought to assess whether analysis of anti-Müllerian hormone (AMH) using a sensitive automated assay could identify women who would not regain ovarian function after chemotherapy.MethodsData from women in the Ovarian Protection Trial in Premenopausal Breast Cancer Patients (OPTION) trial of goserelin (a gonadotrophin-releasing hormone (GnRH) analogue) for ovarian protection were analysed. Women were assessed for premature ovarian insufficiency (POI: amenorrhoea with elevated follicle-stimulating hormone (FSH)) at 24 months after diagnosis. The accuracy of AMH for the diagnosis of POI and its prediction from measurement at the end of chemotherapy was calculated.ResultsAMH below the level of detection showed good diagnostic accuracy for POI at 24 months (n = 73) with receiver operating characteristic (ROC) area under the curve of 0.86, sensitivity 1.0 and specificity 0.73 at the assay limit of detection. In women aged >40 at diagnosis who did not receive goserelin, AMH measured at end of chemotherapy also gave good prediction of POI at 24 months (area under the curve (AUC) 0.89 95% CI 0.75–1.0, n = 32), with sensitivity 0.91, specificity 0.82, diagnostic odds ratio (DOR) 42.8. FSH gave slightly lower AUC, and specificity was low at 0.55. Age but not tamoxifen impacted on AMH levels.ConclusionUsing this sensitive AMH assay, the finding of an undetectable AMH level in women aged >40 at the end of chemotherapy for eBC gave a good prediction that ovarian function would not return. This may allow alterations in post-chemotherapy endocrine management.

The role of antimullerian hormone in assessing ovarian damage from chemotherapy, radiotherapy and surgery

“…AMH is undetectable and shows no recovery in women receiving high-risk treatment: women and children treated with alkylating agents in high doses showed only little recovery of AMH [ 9 , 16 ]. Age has an important impact, with younger women have a higher pretreatment AMH, and a lower risk of undetectable AMH at the end of treatment chemotherapy (65% in women treated for breast cancer aged over 40; 16% in women aged ≤40 years) [ 22 ▪▪ ]. Younger age and higher pretreatment AMH brings a lower risk of chemotherapy-related amenorrhoea [ 17 , 19 , 22 ▪▪ , 23 ] and higher chance of return of menstruation [ 24 , 25 ].…”

Post-chemotherapy serum anti-Müllerian hormone level predicts ovarian function recovery

“…In a study by Chai et al ., levels of AMH measured at 2 years after diagnosis had a sensitivity of 96% in predicting menstruation for the subsequent 3 years ( 31 ). In another study by Anderson et al , a sensitivity of 84% was reported for AMH level at the end of chemotherapy to predict premature ovarian insufficiency at 2 years ( 32 ). However, only a few studies have measured ovarian function at 5 years after diagnosis ( 33 ); most studies have less than 2 years of follow-up ( 15 , 18 , 34 , 35 , 36 ), but ovarian function can be recovered 3 years after treatment ( 37 ).…”

Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin's lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial

“…Previous analyses in women with breast cancer have shown that receiving treatment at a young age and high concentrations of antimüllerian hormone before treatment are predictive of recovery of ovarian function after chemotherapy, albeit with variable relative contributions. 5 , 9 , 14 , 15 Women with breast cancer are generally older (approximate mean age 40 years 5 , 9 , 14 , 15 ) than those with Hodgkin's lymphoma and treatment involves more gonadotoxic alkylating agent-based regimens, resulting in a high probability of premature loss of ovarian function, particularly in women older than 40 years. These differences emphasise the need for defined populations and treatment regimens to analyse the toxic effects of chemotherapeutic regimens on the ovaries and, particularly, recovery.…”

“… 5 , 6 , 7 , 8 In the past 5 years, refinements in assay methods have improved their sensitivity, and thus their ability to detect low circulating concentrations of antimüllerian hormone in women after chemotherapy, which were previously undetectable. 13 , 14 How the pretreatment ovarian reserve and the patient's age influence recovery of ovarian function after chemotherapy is unclear, with most data derived from women who have been treated for breast cancer. 5 , 9 , 15 , 16 In this study, we aimed to determine the effect of response-adapted chemotherapy regimens on ovarian function in adult women with Hodgkin's lymphoma, since they are both a younger population and often treated with less gonadotoxic drugs than women with breast cancer.…”