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Maintenance of the Ratio of Bioactive to Immunoreactive Follicle-Stimulating Hormone in Normal Men During Chronic Luteinizing Hormone-Releasing Hormone Agonist Administration^*

SPYROS N. PAVLOU, KRISTINE D. DAHL, GAIL WAKEFIELD, JEAN RIVIER, WYLIE VALE, AARON J. W. HSUEH and JILL LINDNER

Department of Medicine, Vanderbilt University School of Medicine Nashville, Tennessee 37232
The Salk Institute La Jolla, California 92037
The Department of Reproductive Medicine, University of California La Jolla, California 92093

Address all correspondence and requests for reprints to: Spyros, N. Pavlou, M.D., Division of Endocrinology, AA-4206 MCN, Vanderbilt University Medical Center, Nashville, Tennessee 37232.

Chronic administration of LHRH agonist analogs to humans reduces gonadal function through pituitary desensitization. Serum immunoreactive gonadotropin levels are modestly reduced, whereas serum bioactive LH levels are drastically suppressed. The effects on bioactive FSH levels, however, are not known. In this study, serum bioactive FSH was measured using an in vitro granulosa cell aromatase bioassay in four normal men given a LHRH agonist, [D-Trp⁶,Pro⁹-NEt]LHRH (LHRH_A; 500 µg/day for 16 weeks), by sc infusion and testosterone enanthate (TE; 100 mg, im every 2 weeks) and in five men given 500 µg/day LHRH_A by daily sc injection for 20 weeks and TE (100 mg every 2 weeks) from weeks 10 through 20. During the first study, serum immunoreactive FSH levels (IR-FSH) decreased by 56.5 ± 4.8% (±SEM),and serum bioactive FSH (Bio-FSH) level decreased by 57.6 ± 6.4%. The ratio of Bio-FSH to IR-FSH did not change. During the second study, both serum IR-FSH and Bio-FSH levels followed a triphasic pattern, decreasing slightly but not significantly immediately after initiation of LHRH_A administration, progressively increasing to a peak (P < 0.5 vs, baseline) at week 10, and then, after addition of TE to this regimen, decreasing slightly again. The Bio-FSH to IR-FSH ratio, as in the first study, did not change. When serum obtained at week 10 during the second study, just before initiation of TE, was chromatographed on a Sephadex G-100 column, IR-LH eluted in two distinct peaks, while IR-FSH eluted as a single peak. These results demonstrate that in normal men chronic LHRH_A administration alone for up to 10 weeks or LHRH_A plus TE for up to 16 weeks does not alter the qualitative characteristics of secreted FSH, since there was no dissociation between serum IR- and Bio-FSH levels.

^* This work was supported by the following grants and grants-in-aid: NIH HD-16453, HD-23273 (to A.J.W.H.); Ford Foundation Grant 810-0297; a Mellon Foundation grant (to A.J.W.H.); Clinical Research Center Grant-in-Aid 5-M01-RR-95 and Population Center Grant-in-Aid HD-05797.

Recipient of NIH Postdoctoral Fellowship HD-06875.

Received July 16, 1987.