Serum androgen levels and insulin resistance in postmenopausal women: association with hormone therapy, tibolone and raloxifene

• Published in: Maturitas 2005-04, Vol.50 (4), p.321-330
• Main Authors: Christodoulakos, G., Lambrinoudaki, I., Panoulis, C., Sioulas, V., Rizos, D., Caramalis, G., Botsis, D., Creatsas, G.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Androgen; Androgens - blood; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate - blood; Estradiol - blood; Estradiol - pharmacology; Estrogen; Estrogen Replacement Therapy; Estrogens, Conjugated (USP) - pharmacology; Female; Humans; Insulin; Insulin - blood; Insulin Resistance; Medroxyprogesterone Acetate - pharmacology; Middle Aged; Norethindrone - analogs & derivatives; Norethindrone - pharmacology; Norpregnenes - pharmacology; Postmenopausal; Postmenopause; Raloxifene; Raloxifene Hydrochloride - pharmacology; Selective Estrogen Receptor Modulators - pharmacology; Sex Hormone-Binding Globulin - metabolism; Testosterone - blood; Tibolone
• ISSN: 0378-5122; 1873-4111
• DOI: 10.1016/j.maturitas.2004.08.002

To assess endogenous androgen and insulin resistance status in postmenopausal women receiving continuous combined hormone therapy (HT), tibolone, raloxifene or no therapy. 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 17β-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), Δ 4-Androstendione (Δ 4-A), Dehydroepiandrosterone sulphate (DHEAS) and HOMA insulin resistance index (HOMA-IR). 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. 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.