Prostate-sparing effects in primates of the potent androgen 7α-methyl-19-nortestosterone:: A potential alternative to testosterone for androgen replacement and male contraception

被引:61
作者
Cummings, DE
Kumar, N
Bardin, CW
Sundaram, K
Bremner, WJ
机构
[1] Univ Washington, Sch Med, Populat Ctr Res Reprod,Dept Med, Div Endocrinol & Metab,Seattle Vet Adm Med Ctr, Seattle, WA 98108 USA
[2] Vet Affairs, Puget Sound Hlth Care Syst, Dept Med, Div Endocrinol & Metab, Seattle, WA 98108 USA
[3] Populat Council, Ctr Biomed Res, New York, NY 10021 USA
关键词
D O I
10.1210/jc.83.12.4212
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
7 alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen that cannot be converted to dihydrotestosterone. In this study we determined the relative androgenic, antigonadotropic, and anabolic potencies of testosterone vs. MENT in the nonhuman primate M. fascicularis. In castrated monkeys, dose-response relationships were generated for the effects of testosterone and MENT on gonadotropin levels, prostate growth, body weight, and lipid metabolism. In a pilot study, four monkeys were castrated, and magnetic resonance imaging (MRI) was used to document a 50% loss of prostate volume within 8 weeks, verifying that MRI is a reliable means to measure prostate size in this species. Two additional groups of six monkeys each mere then castrated and serially administered four graded dosages of testosterone or MENT via osmotic minipumps over 20 weeks. Complete suppression of LH was achieved with a minimum of 0.3 mg/day MENT, compared to 3.0 mg/day testosterone. MENT supported body weight 10 times more potently than did testosterone. Baseline prostate volumes were maintained with 0.1-0.2 mg/day MENT vs. 0.3 mg/day testosterone. Thus, in monkeys, MENT is 10 times more potent than testosterone with regard to the clinically desirable end points of gonadotropin suppression and anabolism, but only twice as potent at stimulating prostate growth. These results suggest that MENT may have a wider therapeutic index than testosterone for human androgen replacement and male contraception.
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页码:4212 / 4219
页数:8
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共 76 条
  • [21] HIGHLY SENSITIVE IN VITRO BIOASSAY FOR LUTEINIZING-HORMONE AND CHORIONIC-GONADOTROPIN - TESTOSTERONE PRODUCTION BY DISPERSED LEYDIG CELLS
    DUFAU, ML
    MENDELSON, CR
    CATT, KJ
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1974, 39 (03) : 610 - 613
  • [22] *END SOC, 1997, J CLIN ENDOCR METAB, V82, pA40
  • [23] HIGH-DENSITY LIPOPROTEIN CHOLESTEROL IS NOT DECREASED IF AN AROMATIZABLE ANDROGEN IS ADMINISTERED
    FRIEDL, KE
    HANNAN, CJ
    JONES, RE
    PLYMATE, SR
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 1990, 39 (01): : 69 - 74
  • [24] EFFECT OF LONG-ACTING GONADOTROPIN-RELEASING HORMONE ANALOG (LEUPROLIDE) THERAPY ON PROSTATIC SIZE AND SYMPTOMS IN 15 MEN WITH BENIGN PROSTATIC HYPERTROPHY
    GABRILOVE, JL
    LEVINE, AC
    KIRSCHENBAUM, A
    DROLLER, M
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1989, 69 (03) : 629 - 632
  • [25] GHANADIAN R, 1981, EUR UROL, V7, P89
  • [26] THE EFFECT OF FINASTERIDE IN MEN WITH BENIGN PROSTATIC HYPERPLASIA
    GORMLEY, GJ
    STONER, E
    BRUSKEWITZ, RC
    IMPERATOMCGINLEY, J
    WALSH, PC
    MCCONNELL, JD
    ANDRIOLE, GL
    GELLER, J
    BRACKEN, BR
    TENOVER, JS
    VAUGHAN, ED
    PAPPAS, F
    TAYLOR, A
    BINKOWITZ, B
    NG, J
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (17) : 1185 - 1191
  • [27] EFFECT OF THE NEW POTENT LHRH ANTAGONIST ANTIDE
    HABENICHT, UF
    SCHNEIDER, MR
    ELETREBY, MF
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1990, 37 (06) : 937 - 942
  • [28] PHARMACOKINETICS AND PHARMACODYNAMICS OF TESTOSTERONE PELLETS IN MAN
    HANDELSMAN, DJ
    CONWAY, AJ
    BOYLAN, LM
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1990, 71 (01) : 216 - 222
  • [29] EFFECT OF LONG-TERM ORAL TESTOSTERONE UNDECANOATE TREATMENT ON PROSTATE VOLUME AND SERUM PROSTATE-SPECIFIC ANTIGEN CONCENTRATION IN EUGONADAL MIDDLE-AGED MEN
    HOLMANG, S
    MARIN, P
    LINDSTEDT, G
    HEDELIN, H
    [J]. PROSTATE, 1993, 23 (02) : 99 - 106
  • [30] INDUCTION OF BENIGN PROSTATIC HYPERTROPHY IN BABOONS
    KARR, JP
    KIM, U
    RESKO, JA
    SCHNEIDER, S
    CHAI, LS
    MURPHY, GP
    SANDBERG, AA
    [J]. UROLOGY, 1984, 23 (03) : 276 - 289