The relative role of gonadal sex steroids and gonadotropin-releasing hormone pulse frequency in the regulation of follicle-stimulating hormone secretion in men.
OBJECTIVE
Our objective was to determine the importance of testosterone (T), estradiol (E(2)), and GnRH pulse frequency to FSH regulation in men.


METHODS
This was a prospective study with four arms.


METHODS
The study was performed at the General Clinical Research Center.


METHODS
There were 20 normal (NL) men and 15 men with idiopathic hypogonadotropic hypogonadism (IHH) who completed the study.


METHODS
Medical castration and inhibition of aromatase were achieved using ketoconazole x 7 d with: 1) no sex steroid addback, 2) T addback starting on d 4, and 3) E(2) addback starting on d 4. IHH men in these arms received GnRH every 120 min. In a further six IHH men receiving ketoconazole with no addback, GnRH frequency was increased to 35 min for d 4-7. Blood was drawn every 10 min x 12 h at baseline, overnight on d 3-4 and 6-7.


METHODS
Mean FSH was 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/liter (P < 0.0001). T caused no suppression of FSH. E(2) reduced FSH from 12.4 +/- 1.8 to 9.3 +/- 1.3 IU/liter (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. E(2) decreased FSH such that levels on d 6-7 were similar to baseline. Increasing GnRH frequency to 35 min had no impact on FSH.


CONCLUSIONS
The sex steroid component of FSH negative feedback in men is mediated by E(2). Increasing GnRH frequency to castrate levels has no impact on FSH in the absence of sex steroids. When inhibin B levels are NL, sex steroids exert a modest effect on FSH.
Pitteloud
Nelly
N
Reproductive Endocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Dwyer
Andrew A
AA
DeCruz
Suzzunne
S
Lee
Hang
H
Boepple
Paul A
PA
Crowley
William F
WF
Hayes
Frances J
FJ
D000328:Adult; D004958:Estradiol / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011446:Prospective Studies; D013739:Testosterone / Q000502:physiology*
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone