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Keywords:

  • Inhibin A;
  • gonadotoxicity;
  • premature ovarian failure;
  • hypergonadotropic amenorrhea;
  • chemotherapy;
  • GnRH-a

PROBLEM: Inhibin A concentrations in serum may reflect the ovarian granulosa cell compartment. To characterize the correlation between ovarian function after gonadotoxic chemotherapy for Hodgkin's or non-Hodgkin's lymphoma in young women, the immunoreactive inhibin A concentrations in the sera of these patients was measured before, during, and after the gonadotoxic chemotherapy.

METHOD OF STUDY: A prospective clinical protocol was undertaken in 20 cycling women with lymphoma, aged 15–40 years. A monthly injection of depot D-TRP6 -GnRH-a (Decapeptyl CR, Ferring) was administered from before starting the chemotherapy until its conclusion, up to a maximum of six monthly injections. Most of the patients were treated with the mustargen-oncovin-procarbazine-prednisone (MOPP)/actinomycin D-bleomycinvincristine (ABV) chemotherapy combination; 13 with and 7 without radiotherapy. A hormonal profile [follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-β-estradiol (E2), testosterone (T), progesterone (P4), insulin-like growth factor (IGF)-1, IGF-bp3, and prolactin (PRL)] was taken before starting the gonadotropin-releasing hormone agonist (GnRH-a)/chemotherapy co-treatment and monthly thereafter until resuming spontaneous ovulation and menstrual cyclicity. This group of prospectively treated lymphoma patients was compared with a control group of 22 regularly cycling women who had been treated with chemotherapy (mostly MOPP/ABV) with or without radiotherapy for Hodgkin's or non-Hodgkin's lymphoma. Inhibin A immunoactivity developed by Nigel Groome was measured by an enzyme-linked immunoadsorbent assay (ELISA) commercial kit (Serotec).

RESULTS: Whereas all but one (40 years of age) of the surviving patients in the GnRH-a/chemotherapy co-treatment group resumed spontaneous ovulation and menses within 6 months, only one half of the patients in the “control” group (chemotherapy without GnRH-a co-treatment) resumed ovarian function and regular cyclic activity (P < 0.05). The remaining 50% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by approximately one third of the patients resuming cyclic ovarian function, suggesting a reversible ovarian damage in a larger proportion of women than those experiencing POF. The inhibin A immunoactive concentrations decreased during the GnRH-a/chemotherapy co-treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared to low levels in menopausal women and those who had developed POF.

CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, inhibin A concentration may serve as a prognostic factor for predicting the resumption of ovarian function, in addition to the levels of FSH, LH, and E2.