Risk of Premature Menopause Raised by Some but Not All Hodgkin Lymphoma Therapies

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An analysis of nonsurgical menopause risk among 2,127 women treated for Hodgkin lymphoma found that “risk of premature menopause increased more than 20-fold” after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (carmustine [BiCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation but was not statistically significantly raised after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Results were reported in the Journal of the National Cancer Institute by Anthony J. Swerdlow, DSc, of the Institute of Cancer Research, Surrey, United Kingdom, and colleagues in the England and Wales Hodgkin Lymphoma Follow-up Group.

The authors concluded that patients treated for Hodgkin lymphoma “need to plan intended pregnancies using personalized information on their risk of menopause by different future time points” and provided tables to give individualized information to women based on the type of treatment, dose, and age at treatment.

The women were first treated from 1960 through 2004, mainly in the 1980s and 1990s, and were followed to 2003 through 2012. All the women were younger than 36 years when treated, with 5.5% younger than 15 and 50% aged 15 to 24 years. With increasing age at treatment, there was a moderate but statistically significant increased risk of premature menopause.

“During follow-up, 605 patients underwent nonsurgical menopause before age 40 years,” the investigators reported. Menopause generally occurred sooner after ovarian radiotherapy (with 62.5% of women experiencing menopause within 5 years of ≥ 5 Gy treatment), and after BEAM (with 50.9% of women experiencing menopause within 5 years), than after alkylating chemotherapy (with 24.2% of women experiencing menopause within 5 years of at least six cycles).

“Compared with women who had received neither alkylating chemotherapy nor pelvic radiotherapy, risk of premature nonsurgical menopause was increased about 20-fold in women who had received pelvic radiotherapy or classic alkylating chemotherapy, 36-fold in women who had received both, and over 50-fold in those who had received a stem cell transplant (more again if they had also received pelvic radiotherapy),” the investigators reported.

“Risk was greatly raised after treatment with each common classic alkylating regimen,” the researchers added. The risk was greatest with mechlorethamine, vinblastine, procarbazine, prednisone (hazard ratio [HR] = 37.1, 95% CI = 21.2–65.0, P < .001) and least for chlorambucil, vincristine, procarbazine, prednisone (HR = 17.9, 95% CI = 10.8–29.9, P < .001).

“Risk was greater again after BEAM, the most common regimen for stem cell transplantation; almost all BEAM-treated patients had also received other classic alkylating treatments. Risk was also statistically significantly raised in patients treated with etoposide who had not received classic alkylating chemotherapy or pelvic radiotherapy (HR = 6.1, 95% CI = 1.7–21.4, P < .001).” ■

Swerdlow AJ, et al: J Natl Cancer Inst 106(9):dju207, 2014.




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