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Reduction of Testosterone Synthesis after High Dose Interleukin-2 Therapy of Metastatic Cancer^*

Department of Internal Medicine and Clinical Research Center, University Of Utah School of Medicine Salt Lake City, Utah 84132 the University of Utah/Veterans Administration Medical Center Cancer Immunotherapy Program and the Salt Lake City Department of Veterans Affairs Medical Center Salt Lake City, Utah 84132

Address all correspondence and requests for reprints to: A. Wayne Meikle, M.D., Clinical Research Center, 50 North Medical Drive, Salt Lake City, Utah 84132.

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, 17β-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 < 0.001) on day 6, and testosterone decreased significantly on day 2 and reached a nadir on day 6 (P < 0.0001). Concentrations of both steroids then gradually rose. Estradiol rose on day 4 (P < 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.

^* This work was supported in part by NIH Grant RR-00064, Cancer Center Core Grant CA-42014, and Department of Veterans Affairs Medical Research Funds.

Received December 3, 1990.

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