Serum androgen levels and insulin resistance in postmenopausal women: association with hormone therapy, tibolone and raloxifene.
OBJECTIVE
To assess endogenous androgen and insulin resistance status in postmenopausal women receiving continuous combined hormone therapy (HT), tibolone, raloxifene or no therapy.


METHODS
A total of 427 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Among them 84 were taking HT (46 women conjugated equine estrogens 0.625 mg; medroxyprogesterone acetate, 5 mg, CEE/MPA; and 38 women 17beta-estradiol 2 mg; norethisterone acetate 1 mg, E2/NETA); 83 were taking tibolone 2.5 mg; 50 were taking raloxifene HCl 60 mg; and 210 women were not receiving any therapy. Main outcome measures were FSH, LH, estradiol, total testosterone, SHBG, free androgen index (FAI), Delta4-Androstendione (Delta4-A), Dehydroepiandrosterone sulphate (DHEAS) and HOMA insulin resistance index (HOMA-IR).


RESULTS
In women not on hormone therapy smoking and older age was associated with lower DHEAS levels. FAI values increased linearly with increasing BMI. Age and BMI were positive determinants of HOMA-IR, while no association was identified between endogenous sex steroids and insulin resistance. CEE/MPA therapy was associated with higher SHBG, lower FAI and lower HOMA-IR values compared to women not on therapy (age and BMI-adjusted SHBG: CEE/MPA 148.8 nmol/l, controls 58.7 nmol/l, p < 0.01; age-adjusted FAI: CEE/MPA 0.8, controls 3.2, p < 0.05; age-adjusted HOMA-IR: CEE/MPA 1.3, controls 2.6, p < 0.05). On the contrary, E2/NETA treatment had no effect on these parameters. Women on tibolone had lower SHBG, higher FAI and similar HOMA-IR values compared to controls (age and BMI-adjusted SHBG: 24.1 nmol/l, p < 0.01; FAI: 6.0, p < 0.05; HOMA-IR: 2.3, p = NS). Raloxifene users did not exhibit any difference with respect to sex steroids and HOMA-IR levels.


CONCLUSIONS
CEE/MPA users had lower free testosterone and improved insulin sensitivity. Tibolone on the other hand associated with higher free testosterone, while raloxifene did not relate to any of these parameters.
Christodoulakos
G
G
2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, V. Sofias 76, GR-11528, Athens, Greece.
Lambrinoudaki
I
I
Panoulis
C
C
Sioulas
V
V
Rizos
D
D
Caramalis
G
G
Botsis
D
D
Creatsas
G
G
D000328:Adult; D000368:Aged; D000728:Androgens / Q000097:blood*; D003430:Cross-Sectional Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000494:pharmacology*; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000728:Androgens; D004966:Estrogens, Conjugated (USP); D007328:Insulin; D009652:Norpregnenes; D020845:Selective Estrogen Receptor Modulators; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; C027385:tibolone; D009640:Norethindrone