Testosterone addition to estrogen therapy – Effects on inflammatory markers for cardiovascular disease

Abstract

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)-α, 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-α, 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-α, and homocysteine.

Conclusion. 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.

Keywords:

• Testosterone
• estrogen therapy, hsCRP
• IL-6
• TNF-α
• IGFBP-1
• VCAM-1
• homocysteine

Acknowledgements

This study was supported by grants from the Swedish Medical Research Council (No. 20324) and the Karolinska Institutet. Skilful technical assistance was provided by Yvonne Pierre and Mo Pourian at the Research Laboratory for Reproductive Health.