The Effects of Hormone Replacement Therapy and Raloxifene on C-Reactive Protein and Homocysteine in Healthy Postmenopausal Women: A Randomized, Controlled Trial

Abstract

C-Reactive protein and homocysteine are independent risk factors for the development of cardiovascular disease. This study compared the effects of hormone replacement therapy (HRT) and raloxifene on serum C-reactive protein and homocysteine levels as markers of cardiovascular risk in healthy postmenopausal women. Healthy postmenopausal women (n = 390) were enrolled in a double blind, randomized, placebo-controlled, 6-month trial at eight out-patient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), raloxifene (60 or 120 mg/day), or placebo for 6 months. C-Reactive protein and homocysteine were measured in baseline and 6-month serum samples. HRT increased C-reactive protein levels by 84% (P<0.001), whereas raloxifene (60 and 120 mg/day) had no significant effect (-6% and -4%;, respectively; P>0.2). Raloxifene (60 and 120 mg/day) significantly lowered serum levels ofhomocysteine by 8% (P = 0.014) and 6% (P = 0.024), respectively, similar to the 7% (P = 0.014) reduction obtained with HRT. We conclude that HRT and raloxifene lower serum homocysteine levels to a comparable extent in postmenopausal women. Whereas cardiovascular risk predicted by C-reactive protein in healthy postmenopausal women is not influenced by raloxifene, the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.

Is Visceral Adiposity the “Enemy Within”?

“…[37][38][39][40] On the basis of observational studies, estrogen has traditionally been considered an influence for the better with regard to CVD risk. The recent results from the HERS trial, identifying a significant CVD risk for some women in the first year or so after the start of estrogen therapy, 41 however, raise the question of whether drugs that raise CRP may carry an unwanted risk based on their effects on inflammation.…”

Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women

“…Estrogen replacement therapy and the selective estrogen receptor modulator (SERM) raloxifene lower plasma Hcy (Walsh et al, 2000;Yildirir et al, 2002). Estrogen, but not raloxifene, increases circulating CRP concentration (de Valk-de Roo et al, 1999;Walsh et al, 2000;Yildirir et al, 2002) by increasing hepatic production of CRP (Walsh et al, 2001;Skouby et al, 2002).…”

“…Estrogen replacement therapy and the selective estrogen receptor modulator (SERM) raloxifene lower plasma Hcy (Walsh et al, 2000;Yildirir et al, 2002). Estrogen, but not raloxifene, increases circulating CRP concentration (de Valk-de Roo et al, 1999;Walsh et al, 2000;Yildirir et al, 2002) by increasing hepatic production of CRP (Walsh et al, 2001;Skouby et al, 2002). Both estrogen and raloxifene have been reported to decrease vascular adhesion molecules (Koh et al, 1999;Blum et al, 2000) by binding to estrogen receptors on the vascular endothelium and modulating transcription of these adhesion molecules (Caulin-Glaser et al, 1996).…”

Increased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response

“…7,8 CRP is an independent marker for the risk of cardiovascular disease in men with and without coronary artery disease and in postmenopausal women without clinically evident coronary artery disease. 9 It is important to note, however, that the cutoff value above which individuals without known disease should be considered at elevated risk and below which level patients with coronary artery disease should be considered at low risk requires additional evaluation in population studies and a consensus. Also, it must be acknowledged that in some vascular disorders, CRP levels may remain elevated for years without ever leading to an acute cardiovascular event.…”