Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men.
OBJECTIVE
To explore effects on serum lipids, pituitary-gonadal axis, prostate and bone turnover of the administration of the mixed oestrogen agonist/antagonist raloxifene in healthy elderly men.


METHODS
Thirty healthy men aged 60-70 years randomly received raloxifene 120 mg/day (n=15) or placebo (n=15) for 3 months.


METHODS
In this double-blind, placebo-controlled study, serum gonadotrophins, sex hormones, prostate specific antigen (PSA), a marker of bone turnover, urinary hydroxyproline (OHPro) and cholesterol were measured at baseline and after 3 months.


RESULTS
Raloxifene significantly increased serum concentrations of LH and FSH (by 29% and 21%), total testosterone (20%), free testosterone (16%) and bioavailable testosterone (not bound to sex hormone-binding globulin (SHBG; 20%). In parallel with testosterone, 17 beta-oestradiol also increased by 21%. SHBG increased by 7%. Total cholesterol (TChol) decreased significantly, from 5.7 to 5.5 mmol/l (P=0.03). Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) showed a trend to decrease. Overall, there was no change in urinary OHPro/creatinine ratio as a marker for bone resorption. However, the raloxifene-induced increases in both serum testosterone and 17 beta-oestradiol were significantly related to a lower OHPro/creatinine ratio. Total PSA increased by 17% without significant changes in free PSA or free/total PSA ratio. Participants reported no side effects and raloxifene was well tolerated.


CONCLUSIONS
In healthy elderly man, raloxifene 120 mg/day for 3 months increased LH, FSH and sex steroid hormones. Potentially beneficial effects were the small but significant decrease in TChol and the trend towards a decrease in LDL-c. Negative effects were the trend towards a decrease in HDL-c and the significant increase in serum PSA. A decrease in markers of bone resorption during raloxifene treatment was found only in men with relatively high increases in serum testosterone and 17 beta-oestradiol. Overall, there were no clear beneficial effects of administration of raloxifene to ageing men in this preliminary investigation.
Duschek
Erik J J
EJ
Department of Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. e.duschek@vumc.nl
Gooren
Louis J
LJ
Netelenbos
Coen
C
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006062:Gonadotropins / Q000097:blood*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*
D004965:Estrogen Antagonists; D006062:Gonadotropins; D008055:Lipids; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D017430:Prostate-Specific Antigen