Gonadal function in young patients successfully treated for Hodgkin disease.
BACKGROUND
Gonadal function in pediatric and young adult survivors of Hodgkin disease is not very well defined. This study evaluates the outcome following the Multiple Drug Protocol (MDP) and the results are compared to the published experience.


METHODS
Ovarian and testicular function was assessed in 65 patients (36 males) with Hodgkin disease in first or second complete remission after treatment with either radiation (RT, n = 13), chemotherapy (CT, n = 9), or both (n = 43). Chemotherapy consisted of six cycles of the MDP (doxorubicin, procarbazine, prednisone, vincristine, and cyclophosphamide). Median age at diagnosis was 13.1 years (range, 2.4-22.6) and median age at evaluation was 22.6 years (range, 15.1-33.7), which was 6.7 years (range, 2.0-19.8) after the completion of all treatments. For the purpose of analysis, patients were divided into three groups: group A, patients who received only RT that did not include the pelvis (8 females, 5 males); group B, patients who received CT but no pelvic RT (15 females, 25 males); and group C, patients who received CT plus pelvic RT (6 females, 6 males).


RESULTS
All patients progressed spontaneously through puberty and evaluable patients were found to be sexually mature (Tanner stage IV and V). Serum follicle stimulating hormone (FSH) was increased in 0/5, 13/25, and 5/6 and testicular volume was decreased in 1/3, 4/11, and 2/3 group A, B, and C male patients, respectively. Leydig cell dysfunction was uncommon; 91% and 88% of males had normal serum concentrations of luteinizing hormone (LH) and testosterone, respectively. FSH and LH were increased in 0/8, 3/15, and 2/6 group A, B, and C female patients, respectively, at last follow-up, indicating a 17% prevalence of ovarian dysfunction. Serial data in seven females whose initial levels of FSH/LH were elevated revealed normalization in four. Six females delivered eight normal children.


CONCLUSIONS
The majority of males who received CT +/- RT have evidence of germ cell dysfunction, while Leydig cell function is unaffected in most. In females, although abnormal function early after the end of treatment was observed, ovarian function remained or returned to normal in most young women. Thus, in females the results of hormone testing performed early after treatment may not be predictive of their eventual reproductive potential.
Papadakis
V
V
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Vlachopapadopoulou
E
E
Van Syckle
K
K
Ganshaw
L
L
Kalmanti
M
M
Tan
C
C
Sklar
C
C
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D010049:Ovarian Diseases / Q000139:chemically induced / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D013733:Testicular Diseases / Q000139:chemically induced / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000502:physiology*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D011344:Procarbazine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone