Chemotherapy related amenorrhea and hormonal measures of ovarian reserve in young breast cancer patients

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OBJECTIVE: To determine if post-chemotherapy levels of anti-Mullerian hormone (AMH), inhibin B and follicle stimulating hormone (FSH) are associated with chemotherapy related amenorrhea (CRA) in breast cancer patients. To compare these hormones and stages of reproductive aging between breast cancer patients and age-matched healthy controls. DESIGN: Prospective cohort. MATERIALS AND METHODS: A cohort study 127 breast cancer patients with Stages I-III disease, premenopausal at diagnosis, were enrolled 1-4 years from chemotherapy. The primary endpoint was CRA (> 12 months of amenorrhea after chemotherapy). Cancer patients were age-matched to healthy controls. Menstrual patterns and clinical factors were collected prospectively. Bloods were assayed for hormones. Bivariable associations between AMH, inhibin B, FSH, demographics and chemotherapy regimen with CRA were assessed. Poisson regression models examined independent predictors of CRA and controlled for confounding. Matched pair analyses compared cancer to control subjects. RESULTS: Median age at chemotherapy was 43.2 (range 26.7-57.8). Median years of follow up since chemotherapy were 5.2 (range 0.4-7.6). At enrollment, 55% (70/127) of subjects had CRA. Compared to subjects without CRA, subjects with CRA had higher FSH and lower AMH and inhibin B even after controlling for confounders (all p<0.001). While most CRA subjects had undetectable levels of AMH (< 40 pg/mL), 42% had detectable AMH. Compared to controls, breast cancer subjects had significantly higher FSH and lower AMH and inhibin B (all p<0.001). Cancer subjects also had more advanced stages of reproductive aging compared to controls (p<0.001). Nine subjects (13%) with CRA at enrollment resumed menstrual bleeding. Compared to women who did not resume menstruating, these nine subjects were younger and were more likely to have had dose dense therapy. AMH, inhibin B and FSH at the time of enrollment did not predict resuming menses. CONCLUSIONS: AMH, inhibin B and FSH were significantly associated with CRA in breast cancer patients. Compared to age-matched controls, cancer patients had lower hormonal measures of ovarian reserve. Interestingly, a large proportion of CRA subjects had detectable levels of AMH, suggesting continued presence of ovarian follicles despite significant amenorrhea. These hormones did not predict resumption of menses after CRA. The utility of using these hormones for predicting CRA after cancer therapy is yet to be established.