To improve fertility advice in HL patients before treatment and counseling during survivorship, detailed information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal function in survivors after treatment of early favorable, early unfavorable and advanced stage HL.
Women <40 years and men <50 years at diagnosis in ongoing remission at least one year after treatment within the GHSG HD13–15 trials were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, measures to preserve fertility, pregnancies, and offspring were evaluated.
A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis. In women and men, mean age at fertility assessment was 32 and 38 years and mean observation time from the end of treatment was 46 and 48 months, respectively. Comparison of the participating and non-participating patients qualifying for our analysis showed no relevant differences. Hormone levels correlated significantly with therapy intensity (p<.001). After 6–8 cycles BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone), mean Anti-Muellerian hormone (AMH) levels in females were 0μg/l and 88.8% of males had Follicle-stimulating hormone (FSH) and inhibin B levels corresponding to oligospermia. Furthermore, low birth rates were observed in survivors after advanced-stage treatment within the observation time (women: 6.5%, men: 3.3%). Regular menstrual cycle was reported by >90% of early-stage HL female survivors and time to resumption of menstrual activity was mostly reached within one year. After advanced-stage treatment, menstrual activity was strongly related to age. 82% of women younger than 30 years had a regular cycle, compared to only 45% in the older age group (p<.001) and time to recovery was considerably longer than in early-stage patients. 34% of women >30 years suffered severe menopausal symptoms (3–4 fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism.
The present analysis in a large group of female and male HL survivors provides well-grounded information on gonadal toxicity of the currently used treatment regimens. Accordingly, the results allow a risk adapted planning of fertility preservation before therapy and a comprehensive support during survivorship.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.