Subnormal androgen levels in young female bone marrow transplant recipients with ovarian dysfunction, chronic GVHD and receiving glucocorticoid therapy.

Abstract

Ovarian function and sex hormone production with special focus on androgens (testosterone, androstenedione, dehydroepiandrosterone and its sulfate, DHEAS) was followed up during 1.5-20 (mean 9) years after bone marrow transplantation (BMT) in 24 female subjects aged 16-33 (mean 21) years at the last follow-up. All patients had received TBI and high-dose chemotherapy as the preparative regimen. A total of 24 female patients with conventionally treated pediatric hematologic malignancies served as controls. Four of 24 transplanted patients had spontaneous menstruation several years post transplantation, but in only one of them were serum FSH levels normal. Androgen levels of the BMT patients were lower than those of the conventionally treated patients. Subnormal testosterone levels were observed in 43% of BMT patients and subnormal DHEAS levels in 34% of BMT patients, the latter being a constant finding during glucocorticoid therapy for chronic GVHD (cGVHD). These results indicate that ovarian damage is a common late effect in patients transplanted at a young age, still having a seemingly normal pubertal development. Ovarian damage and cGVHD with glucocorticoid therapy are strongly associated with subnormal androgen levels. The clinical consequences of these changes and possible benefits of putative androgen replacement therapy remain to be elucidated.