Relationship between GH activity and reproductive hormones: a randomized cross-over study in healthy male volunteers treated with GH and a GH receptor antagonist for three weeks

M. Andreassen; J. Frystyk; A. Juul; J. Faber; L. Kristensen

P1001

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Endocrine Abstracts (2012) 29 P1001

ICEECE2012 Poster Presentations Growth hormone IGF axis - basic (23 abstracts)

Relationship between GH activity and reproductive hormones: a randomized cross-over study in healthy male volunteers treated with GH and a GH receptor antagonist for three weeks

M. Andreassen ¹ , J. Frystyk ² , A. Juul ³ , J. Faber ¹ & L. Kristensen ¹

Err

Author affiliations

¹Herlev Hospital, University of Copenhagen, Herlev, Denmark; ²Arhus University Hospital, Arhus, Denmark; ³Rigshospitalet, Uiversity of Copenhagen, Copenhagen, Denmark.

Introduction: The GH/insulin-like growth factor 1 (IGF1) system may modulate the pituitary-gonadal axis in males. Direct pituitary and/or testicular effects might be involved, as well as indirect effects on sex hormone binding globulin (SHBG) and aromatase activity.

Methods/design: Nine healthy male volunteers (mean age 37, range 29–49 years) were treated in random order with increasing doses of GH for three weeks (1st week 0.01, 2nd week 0.02, 3rd 0.03 mg/kg per day) or a GH receptor antagonist (pegvisomant; 1st week 10, last 2 weeks 15 mg/day), separated by eight weeks of wash-out. Before and after three weeks of GH treatment or GH receptor blockage circulating levels of testosterone, estradiol, LH and SHBG were measured.

Results: During GH treatment IGF1 increased ((mean±1S.D.) 140±41 vs 448±97 μg/l, P<0.001) together with estradiol (77±22 vs 107±30 pmol/l, P=0.015) and the estradiol/testosterone ratio (P=0.001). By contrast LH tended to decrease (4.3±1.9 vs 3.6±1.7 U/l, P=0.053). The opposite was found during pegvisomant treatment where IGF1 (151±35 vs 103±29 μg/l, P=0.001) and estradiol (86±27 vs 79±23 pmol/l, P=0.038) decreased. No changes in testosterone, SHBG or calculated free testosterone (testosterone×100/SHBG) occurred during the two treatment regimens.

Conclusions: High GH/IGF1 activity was positively associated with serum estradiol. The study supports that GH/IGF1 action stimulates aromatase activity in vivo with subsequent increased conversion of testosterone to estradiol during GH treatment and visa versa during GH receptor blockage. The decrease in LH during GH treatment may support increased oestrogen activity with increased negative feedback at the pituitary gland. High levels of endogenous GH/IGF1 during puberty might chance the estradiol/testosterone-ratio thereby contributing to development of pubertal gynaecomastia.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.