Reduction of testosterone synthesis after high dose interleukin-2 therapy of metastatic cancer.
We have investigated the effect of high dose iv bolus interleukin-2 (IL-2) therapy on sex hormone and adrenal steroid concentrations in six men treated for metastatic renal cell carcinoma or malignant melanoma. Blood concentrations of testosterone, 17 beta-estradiol, LH, FSH, cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) were measured before and after a 5-day course of IL-2 therapy. Cortisol levels rose and DHEA-S decreased insignificantly. DHEA declined, reaching a nadir (P less than 0.001) on day 6, and testosterone decreased significantly on day 2 and reached a nadir on day 6 (P less than 0.0001). Concentrations of both steroids then gradually rose. Estradiol rose on day 4 (P less than 0.001) and then declined. Neither LH nor FSH was affected significantly, although there was a rise in the mean level of LH after IL-2 therapy. Our results suggest that high dose IL-2 therapy in men affects both adrenal and testicular androgen production without inhibiting pituitary trophic hormone secretion. These effects of IL-2 on plasma sex steroids may be the result of cytokines stimulated by IL-2 therapy, rather than direct responses to IL-2.
Meikle
A W
AW
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City 84132.
Cardoso de Sousa
J C
JC
Ward
J H
JH
Woodward
M
M
Samlowski
W E
WE
D000328:Adult; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000628:therapy*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000627:therapeutic use; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood*; D013997:Time Factors
D007376:Interleukin-2; D011994:Recombinant Proteins; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone