PROSPECTIVE-STUDY OF PITUITARY-GONADAL FUNCTION TO EVALUATE SHORT-TERM EFFECTS OF ABLATIVE CHEMOTHERAPY OR TOTAL-BODY IRRADIATION WITH AUTOLOGOUS OR ALLOGENIC MARROW TRANSPLANTATION IN POST-MENARCHEAL FEMALE-PATIENTS

Pituitary-gonadal (P-G) function was evaluated 0-3 months before and 3-4 months after bone marrow transplantation (BMT) in 15 post-menarcheal females aged 17-30 (21.6 +/- 0.34) years with haematological malignancies. All patients had evidence of gonadal insufficiency prior to BMT in that their basal and human menopausal gonadotrophin (HMG)-stimulated oestradiol (E2) levels were significantly lower than those of control subjects. The patients also had markedly higher basal FSH levels and exaggerated responses to 100 mu g iv gonadotrophin release hormone bolus compared with those of control subjects. However, the conditioning regimens employed prior to BMT, i.e. cytotoxic chemotherapy (CT) and total body irradiation (TBI), acting either singly or in combination, caused further ovarian damage. As a result, their gonadotrophins rose further into the menopausal range. Their oestradiol secretion diminished and ovaries became almost unresponsive 3-4 months after BMT. Pelvic ultrasound undertaken in 5 patients before and after BMT demonstrated a reduction in ovarian size associated with follicular depletion. All patients developed menopausal symptoms and became amenorrhoeic during this period. Contrary to expectation, the hormonal changes occurring acutely were similar in patients undergoing radiation-based regimens and those conditioned with high-dose chemotherapy alone. Also, the severity of ovarian dysfunction appeared independent of age at transplantation, the nature of the conditioning-regimen or the type of transplant. Gonadotrophic, thyrotrophic, lactotrophic and adrenocorticotrophic secretions were unaffected. These data indicate that the ovary suffers an acute insult during short-term chemotherapy but the anterior pituitary gland retains its trophic hormone reserve and secretory capacity.