Gonadal function following chemotherapy for Hodgkin's disease: a comparative study of MVPP and a seven-drug hybrid regimen.
OBJECTIVE
Gonadal function was assessed in 89 patients after chemotherapy for Hodgkin's disease (HD). Thirty-seven patients had received mechlorethamine, vinblastine, prednisolone, and procarbazine (MVPP) and 52 patients, a hybrid combination of chlorambucil, vinblastine, prednisolone, procarbazine, doxorubicin, vincristine, and etoposide (ChIVPP/EVA). Fifty men (MVPP, n = 21; ChIVPP/EVA, n = 29) with a median age of 26 years (range, 16 to 54) and 39 women (MVPP, n = 16; ChIVPP/EVA, n = 23) with a median age of 30 years (range, 15 to 47) were studied at a median of 30 months (range, 4 to 83) following chemotherapy.


RESULTS
Semen analysis showed azoospermia in 35 of 37 men, and increased serum follicle-stimulating hormone (FSH) levels in this group confirmed severe germinal epithelial damage. Analysis of pretreatment semen in 28 men showed azoospermia in one, oligospermia in four (sperm count < 20 x 10(6)/mL), and a normal sperm count in the remaining 23. In the women, 26 of 34 (76%) with a regular menstrual cycle before commencing chemotherapy became amenorrheic following treatment. Menses returned in 10 women, who had a median age of 25 years (range, 21 to 34), and there were two pregnancies in this group. In the other 16, with a median age of 36 years (range, 27 to 47), amenorrhea persisted and premature ovarian failure was confirmed by increased serum gonadotrophins and reduced estradiol (E2) concentrations. Of the original eight women in whom menses were maintained following treatment, two subsequently developed amenorrhea and the clinical and biochemical features of an early menopause. In total, 18 of 34 women (53%) required hormone replacement therapy for chemotherapy-induced ovarian failure.


CONCLUSIONS
There was no statistically significant difference in the frequency or severity of gonadal dysfunction between MVPP- and ChIVPP/EVA-treated patients. We conclude that both of these chemotherapy schedules cause substantial damage to gonadal function in both sexes.
Clark
S T
ST
Department of Endocrinology, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Radford
J A
JA
Crowther
D
D
Swindell
R
R
Shalet
S M
SM
D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002699:Chlorambucil / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D005047:Etoposide / Q000009:adverse effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007989:Libido / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008466:Mechlorethamine / Q000009:adverse effects; D008597:Menstrual Cycle / Q000187:drug effects; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced; D011344:Procarbazine / Q000009:adverse effects; D011446:Prospective Studies; D012661:Semen / Q000187:drug effects*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013076:Sperm Count / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014747:Vinblastine / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects
D012738:Sex Hormone-Binding Globulin; D002699:Chlorambucil; D011344:Procarbazine; D013739:Testosterone; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D011239:Prednisolone