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Submitted on April 29, 2004
Accepted on February 9, 2005
Center for Research in Reproduction and Contraception, Geriatric Research Education and Clinical Center, Veteran Affairs Puget Sound Health Care System (AMM), and Department of Medicine, University of Washington School of Medicine (ADC, WJB, JKA, BDA, PLS), Seattle, WA; Department of Medicine, Charles R. Drew University (KLH), Los Angeles, CA; Department of Urology, Johns Hopkins University School of Medicine (XY, JPJ), Baltimore, MD; Division of Reproductive Biology, Department of Biochemistry and Molecular Biology Johns Hopkins University School of Public Health (WWW, TRB, XY, BRZ, JPJ), Baltimore, MD
* To whom correspondence should be addressed. E-mail: a-coviello{at}northwestern.edu.
In previous studies of testicular biopsy tissue from healthy men, intratesticular testosterone (ITT) has been shown to be much higher than serum testosterone (T), suggesting that high ITT is needed relative to serum T for normal spermatogenesis in men. However, the quantitative relationship between ITT and spermatogenesis is not known. To begin to address this issue experimentally we sought to determine the dose response relationship between human chorionic gonadotropin (hCG) and ITT to determine the minimum dose needed to maintain ITT in the normal range. Twenty-nine men with normal reproductive physiology were randomized to receive 200 mg T enanthate (TE) weekly in combination with either saline placebo or hCG 125 IU, 250 IU, or 500 IU every other day for 3 weeks. ITT was assessed in testicular fluid obtained by percutaneous fine needle aspiration at baseline and the end of treatment. Baseline serum T (14.1 nmol/L) was 1.2% of ITT (1174 nmol/L). LH and FSH were profoundly suppressed to 5% and 3% of baseline respectively, and ITT was suppressed by 94% (1234 nmol/L to 72 nmol/L) in the TE/placebo group. ITT increased linearly with increasing hCG dose (P < 0.001). Post-treatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group, and 26% greater than baseline in the 500 IU hCG group. These results demonstrate that relatively low dose hCG maintains ITT within the normal range in healthy men with gonadotropin suppression. Extensions of this study will allow determination of the ITT concentration threshold required to maintain spermatogenesis in man.
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