Testosterone addition to estrogen therapy - effects on inflammatory markers for cardiovascular disease.
OBJECTIVE
To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women.


METHODS
Fifty surgically postmenopausal women were included in this double-blind, placebo-controlled and randomized study to receive daily oral treatment with estradiol valerate 2 mg + placebo (E/P) or estradiol valerate 2 mg + testosterone undecanoate 40 mg (E/T) for 24 weeks and then switched to the other regimen for another 24 weeks. Sex hormones, High sensitivity CRP (hsCRP), Interleukin-6 (IL-6), Tissue necrosis factor (TNF)-alpha, Insulin-like growth factor binding globulin (IGFBP-1), vascular cell adhesion molecule (VCAM)- 1, and homocysteine were analyzed at baseline and after 6 and 12 months.


RESULTS
Estradiol and androgens increased as expected during the treatments. After 6 months of E/P, increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded, whereas IL-6, TNF-alpha, and homocysteine were unchanged. When testosterone was added to estrogen, the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone. However, testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6, TNF-alpha, and homocysteine.


CONCLUSIONS
Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects. On the contrary, the estrogen-induced increase in hsCRP was suppressed.
Kocoska-Maras
Ljiljana
L
Department of Woman and Child Health, Division of Obstetrics and Gynecology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. ljiljana.kocoska-maras@karolinska.se
Hirschberg
Angelica Lindén
AL
Byström
Birgitta
B
Schoultz
Bo Von
BV
Rådestad
Angelique Flöter
AF
D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D001835:Body Weight; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D013196:Dihydrotestosterone / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008163:Luminescent Measurements; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D018579:Patient Selection; D017698:Postmenopause; D011863:Radioimmunoassay; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D018970:Insulin-Like Growth Factor Binding Protein 1; D015850:Interleukin-6; D012738:Sex Hormone-Binding Globulin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D013196:Dihydrotestosterone; D006710:Homocysteine; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002097:C-Reactive Protein