Female cancer survivors exposed to alkylating-agent chemotherapy have unique reproductive hormone profiles

Objective To evaluate reproductive hormone patterns in women exposed to alkylating-agent chemotherapy. Design Prospective cohort. Setting University hospital. Patient(s) Normally menstruating mid-reproductive-age women (20–35 years old) who had previously been exposed to alkylating-agent chemotherapy for cancer treatment were compared with two healthy control populations: similarly-aged women and late-reproductive-age women (43–50 years old). Intervention(s) Subjects collected daily urine samples for one cycle. Main Outcome Measure(s) Integrated urinary pregnanediol glucuronide (PDG) and estrone conjugate (E1c) and urinary excretion of gonadotropins (FSH and LH). Result(s) Thirty-eight women (13 survivors, 11 same-age control subjects, 14 late-reproductive-age control subjects) provided 1,082 urine samples. Cycle length, luteal phase length, and evidence of luteal activity were similar among the groups. As expected, ovarian reserve was impaired in cancer survivors compared with same-age control subjects but similar between survivors and late-reproductive-age control subjects. In contrast, survivors had total and peak PDG levels that were similar to same-age control subjects and higher than those observed in late-reproductive-age control subjects. Survivors had higher E1c levels than both same-age and late-reproductive-age control subjects. There was no difference in urinary gonadotropins among the groups. Conclusion(s) Women exposed to alkylating agents have a unique reproductive hormone milieu that is not solely explained by age or ovarian reserve. The urinary hormone profile observed in survivors appears more similar to same-age control subjects than to late-reproductive-age women with similar ovarian reserve, which may suggest that age plays a more important role than ovarian reserve in the follicular dynamics of survivors.