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Submitted on November 19, 2007
Accepted on April 21, 2008
Reproductive Endocrine Unit of the Department of Medicine (NP, AAD, SD, PAB, WFC, FJH), and the Department of Biostatistics and General Clinical Research Center (HL), Massachusetts General Hospital, Boston, MA 02114
* To whom correspondence should be addressed. E-mail: Hayes.Frances{at}MGH.Harvard.edu.
Objective: To determine the importance of testosterone (T), estradiol (E2) and GnRH pulse frequency to FSH regulation in men.
Design: Prospective study with 4 arms.
Setting: General Clinical Research Center.
Patients or Other Participants: 20 normal (NL) men and 15 men with idiopathic hypogonadotropic hypogonadism (IHH) completed the study.
Intervention: Medical castration and inhibition of aromatase were achieved using ketoconazole (KC) x 7 d with: 1) no sex steroid addback; 2) T addback starting on D4; 3) E2 addback starting on D4. IHH men in these arms received GnRH every 120 min. In a further 6 IHH men receiving KC with no addback, GnRH frequency was increased to 35 min for D4-D7. Blood was drawn every 10 min x 12 h at baseline (BL), overnight on D3-4 and D6-7.
Main Outcome Measures: Mean FSH calculated from the pool of each frequent sampling study.
Results: In NL men FSH levels increased from 5.1 ± 0.7 to 8.7 ± 1.3 and 9.7 ± 1.5 IU/L (P<0.0001). T caused no suppression of FSH. E2 reduced FSH from 12.4 ± 1.8 to 9.3 ± 1.3 IU/L (P<0.05). In IHH men on GnRH every 120 min, FSH levels went from 6.0 ± 1.6 to 9.0 ± 3.0 and 11.9 ± 4.3 (P=0.07). T caused no suppression of FSH. E2 decreased FSH such that levels on D6-7 were similar to BL. Increasing GnRH frequency to 35 min had no impact on FSH.
Conclusions: 1) The sex steroid component of FSH negative feedback in men is mediated by E2; 2) Increasing GnRH frequency to castrate levels has no impact on FSH in the absence of sex steroids; 3) When inhibin B levels are normal, sex steroids exert a modest effect on FSH.
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