Document Detail

Effects of selective testosterone and estradiol withdrawal on skeletal sensitivity to parathyroid hormone in men.
MedLine Citation:
PMID:  16352679     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Gonadal steroid withdrawal increases bone turnover and causes bone loss in men, but the underlying mechanisms have not been defined. We previously reported that gonadal steroid deprivation increases the skeletal sensitivity to the bone resorbing properties of PTH infusion in men, but it is not known whether this effect is mediated by the absence of androgens, estrogens, or both. OBJECTIVE: The objective of the study was to determine the selective effects of testosterone and estradiol withdrawal on the skeletal sensitivity to PTH infusion in healthy adult men. DESIGN AND SETTING: We randomly assigned 58 healthy men between the ages of 20 and 45 yr to receive treatment with combinations of a GnRH analog, an aromatase inhibitor, and hormone add-back therapy to produce the following treatment groups: group 1 (testosterone and estradiol deficient, n = 16); group 2 (testosterone sufficient but estradiol deficient, n = 12); group 3 (testosterone deficient but estradiol sufficient, n = 14); and group 4 (testosterone and estradiol sufficient, n = 16). Twenty-four-hour PTH infusions were performed at baseline and after 6 wk of therapy. Serum N-telopeptide (NTX), C-telopeptide (CTX), osteocalcin (OC), and amino-terminal propeptide of type I procollagen (P1NP) were measured every 6 h during the PTH infusions. RESULTS: Serum testosterone levels fell into the castrate range in groups 1 and 3, whereas estradiol levels were similarly reduced in groups 1 and 2. Gonadal steroid levels in the replaced groups were unchanged from baseline. Serum NTX levels measured before PTH infusion did not change in group 4 (+T, +E) but increased significantly in all other groups. A similar pattern was observed in serum CTX, although the increase in group 2 (+T, -E) was not significant (P = 0.12). Preinfusion concentrations of both OC and P1NP fell in most groups, but these changes were significant in group 2 (+T, -E) for both OC and P1NP and group 4 (+T, +E) for P1NP only. Serum NTX and CTX increased during PTH infusions in all groups at all time points (P < 0.001). In the eugonadal group (group 4 +T+E), the increase in NTX was the same at wk 0 and 6, whereas in all the other groups, the PTH-induced increase in serum NTX was significantly greater at wk, 6 compared with wk 0. The same pattern emerged for CTX, although the difference in group 3 (-T,+E) was not significant (P = 0.12). Serum OC and P1NP levels fell during PTH infusions in all groups and at all time points (P < 0.001), but no significant differences were observed between wk 0 and 6 in any group. CONCLUSIONS: These results demonstrate that the selective suppression of testosterone, estradiol, or both hormones increases the skeletal responsiveness to the bone-resorbing effects of PTH in men. These findings underscore the importance of both androgens and estrogens in male skeletal homeostasis and suggest that changes in skeletal sensitivity to PTH may play an important role in the pathogenesis of hypogonadal bone loss in men.
Hang Lee; Joel S Finkelstein; Megan Miller; Sarah J Comeaux; Rachel I Cohen; Benjamin Z Leder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-12-13
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  91     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-08     Completed Date:  2006-06-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1069-75     Citation Subset:  AIM; IM    
Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
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MeSH Terms
Aromatase / blood*
Bone Development / drug effects
Bone Resorption
Collagen / blood
Collagen Type I
Estradiol / blood*
Middle Aged
Osteocalcin / blood
Parathyroid Hormone / pharmacology*
Peptide Fragments / blood
Peptides / blood
Procollagen / blood
Testosterone / blood*
Grant Support
Reg. No./Substance:
0/Collagen Type I; 0/Parathyroid Hormone; 0/Peptide Fragments; 0/Peptides; 0/Procollagen; 0/collagen type I trimeric cross-linked peptide; 0/procollagen Type I N-terminal peptide; 104982-03-8/Osteocalcin; 50-28-2/Estradiol; 58-22-0/Testosterone; 9007-34-5/Collagen; EC

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