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.