Treatment-related risk factors for premature menopause following Hodgkin lymphoma.
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/m(2)) and 15% after low doses (<or= 4.2 g/m(2)) of procarbazine. The cumulative risk of menopause at age 40 years did not differ much according to age, but time to premature menopause was much longer in women treated at early ages. As long as alkylating agents will be used for curing HL, premature menopause will remain a frequent adverse treatment effect, with various clinical implications.
De Bruin
Marie L
ML
Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam.
Huisbrink
Jeannine
J
Hauptmann
Michael
M
Kuenen
Marianne A
MA
Ouwens
Gabey M
GM
van't Veer
Mars B
MB
Aleman
Berthe M P
BM
van Leeuwen
Flora E
FE
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000453:epidemiology* / Q000532:radiotherapy; D006801:Humans; D008466:Mechlorethamine / Q000009:adverse effects; D008499:Medical Records; D008594:Menopause, Premature; D015999:Multivariate Analysis; D011241:Prednisone / Q000009:adverse effects; D011344:Procarbazine / Q000009:adverse effects; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D014747:Vinblastine / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects
D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D011241:Prednisone