Acute onset of ovarian dysfunction in young females after start of cancer treatment (original) (raw)
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Decreased serum anti-Mullerian hormone levels in girls with newly diagnosed cancer
Human Reproduction, 2014
study question: Are anti-Müllerian hormone (AMH) levels reduced in girls with newly diagnosed cancer before the start of treatment? summary answer: AMH levels are already compromised in girls at the time of cancer diagnosis compared with healthy girls. what is known already: In women diagnosed with cancer, evidence of reduced ovarian function has been described even before treatment has started. In girls with newly diagnosed cancer, no data are available. study design, size, duration: We performed an age-matched case-control study in girls with newly diagnosed cancer. participants/materials, setting, methods: We determined serum AMH levels in a cohort of 208 girls with newly diagnosed cancer, up to 18 years of age at diagnosis, and compared them with AMH levels of 250 age-matched healthy girls. The diagnoses included were acute lymphoblastic leukaemia, acute myeloid leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, nephroblastoma, sarcoma and neuroblastoma. main results and the role of chance: The median age was 6.6 years (range 0.0-17.4), comparable with that in the control group (median 6.3 years, range 0.3-18.0). Girls with childhood cancer presented with significantly lower serum AMH levels compared with healthy age-matched controls (standard deviation scores (SDS) 20.8, P , 0.001). Median AMH level in patients was 1.4 mg/l (0.1-10.2) versus 3.0 mg/l (0.1-18.3) in controls. Specifically, 84% of all patients had AMH levels below the 50th percentile of normal AMH levels, and 19% below the 10th percentile. Surrogate markers of general health status (temperature, C-reactive protein and haemoglobin levels at diagnosis) were significantly correlated with AMH SDS. limitations, reasons for caution: Some caution is warranted because AMH levels increase with age in healthy children but the cases and controls were age-matched in our study. Although our sample size was large, additional studies are still required in an independent cohort. wider implications of the findings: Our study shows that AMH levels are reduced in girls with newly diagnosed cancer even before the cancer treatment has started. AMH levels correlate with impairment of general health status in girls. Therefore, besides (pre) antral follicle number, other factors may influence serum AMH levels. Longitudinal studies during and after childhood cancer are currently being performed in order to evaluate possible ovarian recovery after discontinuation of treatment. study funding/competing interest(s): W.v.D. is supported by the Paediatric Oncology Centre Society for Research (KOCR),
Anti-Müllerian Hormone as a Sensitive Marker of Ovarian Function in Young Cancer Survivors
International Journal of Endocrinology, 2013
We evaluated ovarian function by measuring the levels of anti-Müllerian hormone (AMH), estradiol, and gonadotropins in 83 young women treated for cancer during childhood and adolescence, and classified according to post-treatment gonadal toxicity versus 38 healthy females. Results. The mean AMH values were lower in the entire cohort independently of the risk group as compared to the control, whereas FSH was elevated only in the high risk group. The lowest AMH values were noted in patients after bone marrow transplantation (BMT) and those treated for Hodgkin lymphoma (HL). Nineteen patients (22.9%) had elevated FSH. They all had low AMH values. Lowered AMH values (but with normal FSH and LH) were observed in 43 patients (51.8%). There was no effect of age at the time of treatment (before puberty, during or after puberty) on AMH levels. Conclusion. Our results show the utility of AMH measurement as a sensitive marker of a reduced ovarian reserve in young cancer survivors. Patients after BMT and patients treated for HL, independently of age at treatment (prepuberty or puberty), are at the highest risk of gonadal damage and early menopause.
Human Reproduction, 2008
BACKGROUND: In female cancer survivors, the accelerated loss of primordial follicles as a result of gonadal damage may lead to premature ovarian failure (POF). However, the extent of the damage is unpredictable. Anti-Mü llerian hormone (AMH) constitutes a sensitive marker of ovarian reserve. Serum AMH levels were measured to assess sub-clinical ovarian damage in patients treated with gonadotoxic therapy. METHODS: In 25 patients with haematological malignancies, serum AMH concentrations were measured prior to and after cancer therapy and were compared with normo-ovulatory controls. RESULTS: In all patients, AMH concentrations were lower than controls prior to treatment. Thirteen patients were treated with multi-drug chemotherapy. Although in most patients treated with chemotherapy menstrual cyclicity was restored, median serum AMH levels were lower than in controls. Twelve patients had stem cell transplantation (SCT) after total body irradiation. They all developed POF and their serum AMH concentrations were undetectable. CONCLUSIONS: Female cancer survivors treated with SCT all developed POF. Hence, in these patients fertility preservation should be considered. In patients treated with chemotherapy, ovarian reserve seems to be compromised as well.
Reproductive Biology and Endocrinology, 2014
Anti-Müllerian hormone (AMH) is a very sensitive indicator of the ovarian follicular content. Chemotherapeutic agents are notoriously ovariotoxic in that they damage follicles. The aim of this systematic review was to investigate the interest of serum AMH variations in determining the acute and long-term effects of chemotherapy on the ovarian reserve. According to the PRISMA guidelines, searches were conducted on PubMed for all English language articles until December 2013. Fifteen articles that focused on dynamic variations of AMH levels before and after chemotherapy were selected. Cancer patients have significantly lower AMH after chemotherapy than age-matched controls. Longitudinal studies of AMH variations before, during and after chemotherapy provide information about the degree of follicle loss for each patient according to different chemotherapy regimens. Different patterns of AMH levels during the ovarian recovery phase make it possible to discriminate between high and low gonadotoxic chemotherapy protocols. In addition, pretreatment AMH levels are shown to predict the long-term ovarian function after the end of treatment. These results may help to better understand the ovarian toxicity mechanisms of chemotherapy and to predict the degree of the ovarian follicle loss. Therefore, it can be useful for fertility preservation strategies, fertility counseling and future family planning.
Longitudinal observation of serum anti-Müllerian hormone in three girls after cancer treatment
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 2016
Gonadal dysfunction and infertility are major endocrinological late effects among childhood cancer survivors. Chemotherapy and radiation have gonadotoxic effects and diminish the ovarian reserve. The serum concentration of anti-Müllerian hormone (AMH) is a useful marker of ovarian reserve in survivors. We conducted a longitudinal study to investigate the variations of AMH in evaluating the acute and chronic effects of cancer therapy on the ovary. Three young female patients with different hematological diseases were registered, and their medical records were reviewed. Patient 1 with myelodysplastic syndrome received reduced-intensity hematopoietic stem cell transplantation (HSCT) at 10 yr of age. Breast development and menarche occurred spontaneously after HSCT; however, AMH level became undetectable and gonadotropin did not increase. Patient 2 with acute lymphoblastic leukemia had been receiving chemotherapy since 11 yr of age. AMH level became undetectable but increased after chem...
Anti-müllerian hormone compared with other ovarian markers after childhood cancer treatment
Acta Oncologica, 2018
Background: Gonadal dysfunction is one of the major late complications after cancer diagnosis and treatment. The best markers of ovarian reserve in clinical practice are antral follicle count (AFC) and ovarian volume. We aimed to study the prevalence of premature ovarian insufficiency (POI) and evaluate anti-M€ ullerian hormone (AMH) and other serum markers for ovarian function in adult women who were childhood cancer survivors (CCS) in comparison with a control group. Material and methods: Altogether, 167 female CCS were compared to 164 matched controls. Prevalence of POI was documented and serum levels of AMH, inhibin B, follicle stimulating hormone (FSH), and estradiol (E2) were compared with AFC and ovarian volume. Results: POI was reported in 22 (13%) of the CCS and in none of the controls. Serum levels of AMH, inhibin B, and FSH, but not E2, correlated significantly with AFC and ovarian volume; AMH showed the highest correlation. There was no difference between CCS and controls regarding the different serum markers as measured by linear regression analysis. ROC curve AUC for primary POI showed the highest values for AMH (0.930) and AFC (0.944). For AFC <10, ROC curve AUC showed highest value for AMH for CCS (0.866) and controls (0.878). In a subgroup of female CCS <40 years (n ¼ 120), the results were similar. Conclusion: We found POI in 13% among CCS, slightly more than in other studies. Serum levels of AMH, inhibin B, and FSH correlated significantly with AFC and ovarian volume, and no difference was noted between CCS and controls. AMH was the most reliable serum marker for ovarian function in terms of POI and low AFC.
Fertility and Sterility, 2014
Objective: To evaluate the utility of a hypersensitive assay for measuring low antim€ ullerian hormone (AMH) levels in young cancer patients during the ovarian recovery phase of their chemotherapy. Design: Retrospective study. Setting: Academic medical center. Patient(s): Fifty-eight samples drawn at least 3 months after the end of chemotherapy in 30 women having either breast cancer (n ¼ 13) or hematologic malignancies (n ¼ 17) were selected to constitute two equally size groups: amenorrhea (n ¼ 30 samples) or spontaneous cycle (n ¼ 28 samples). Intervention(s): None. Main Outcome Measure(s): Serum AMH levels were measured by a conventional AMH ELISA (EIA AMH/MIS) and a hypersensitive ELISA (PicoAMH, AnshLabs) on the same sample. Result(s): Using a conventional assay, serum AMH was detectable (R3 pmol/L) in 6.7% and in 10.7% of the samples corresponding to amenorrheic or cycling patients, respectively (nonsignificant). By contrast, with PicoAMH, serum AMH was detectable (R0.07 pmol/L) in 71.4% of the samples from cycling women vs. 16.7% of the samples from amenorrheic patients. Multivariate regression analysis showed that among putative contributors, only the menstrual status (r ¼ 0.307) and serum FSH level (r ¼ À0.546) were independently correlated to a detectable serum AMH with the picoAMH assay exclusively. Conclusion(s): The picoAMH assay, allowing measurement of very low AMH concentrations in human serum, should refine postchemotherapy ovarian follow-up in young women. (Fertil Steril Ò 2014;102:483-7.
Human Reproduction, 2016
Is the long-term decline of ovarian function, as reflected by a decrease in serum anti-Müllerian hormone (AMH) concentration, accelerated over time in female childhood cancer survivors (CCS) as compared to healthy women of the same age? SUMMARY ANSWER: The median decline of AMH levels in long-term female CCS is not accelerated and similar to that observed in healthy controls. WHAT IS KNOWN ALREADY: Gonadal function is compromised in female CCS treated with chemotherapy and/or radiation therapy. Ovarian function is most compromised in survivors treated with total body irradiation, abdominal or pelvic irradiation, stem cell transplantation or high doses of alkylating agents.