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Blood, 1 January 2008, Vol. 111, No. 1, pp. 101-108. Prepublished online as a Blood First Edition Paper on September 21, 2007; DOI 10.1182/blood-2007-05-090225.
CLINICAL TRIALS AND OBSERVATIONS Treatment-related risk factors for premature menopause following Hodgkin lymphoma1 Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam; 2 Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht; 3 Department of Bioinformatics and Statistics, the Netherlands Cancer Institute, Amsterdam; 4 Department of Hematology, Erasmus Medical Center (MC), Daniel den Hoed Cancer Center, Rotterdam; and 5 Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands
We conducted a cohort-study among 518 female 5-year Hodgkin lymphoma (HL) survivors, aged 14 to 40 years (median: 25 years) at treatment (1965-1995). Multivariable Cox regression was used to quantify treatment effects on risk of premature menopause, defined as cessation of menses before age 40 years. After a median follow up of 9.4 years, 97 women had reached menopause before age 40 years. Chemotherapy was associated with a 12.3-fold increased risk of premature menopause compared with radiotherapy alone. Treatment with MOPP (mechlorethamine, vincristine, procarbazine, prednisone)/ABV (doxorubicine, bleomycine, vinblastine) significantly increased the risk of premature menopause (hazard ratio [HR]: 2.9), although to a lesser extent than MOPP treatment (HR: 5.7). Alkylating agents, especially procarbazine (HR: 8.1) and cyclophosphamide (HR: 3.5), showed the strongest associations. Ten years after treatment, the actuarial risk of premature menopause was 64% after high cumulative doses (> 8.4 g/m2) and 15% after low doses (
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