Effects of high dose oestrogen therapy on circulating inflammatory markers

Whilst initial studies suggested HRT reduced the incidence of coronary heart disease, recent studies have suggested HRT increases cardiovascular risk. The route of HRT administration appears important with oral oestrogen significantly increasing levels of inflammatory markers and transdermal oestrogen causing no such changes. As the effects of the very high levels of oestrogen taken by male to female transsexuals are poorly understood this study has compared the changes occurring in circulating inflammatory markers following 6 months oral or transdermal oestrogen therapy.

23 patients (mean age 36+/-10 years) about to commence oral oestrogen were enrolled into Group 1. Group 2 comprised 7 patients (mean age 47+/-6 years) about to commence transdermal oestrogen. Plasma lipids (total cholesterol, triglyceride and HDL cholesterol); cytokines (IL-1, IL-6, IL-8, TNFalpha); antioxidants (superoxide dismutase, total nitric oxide, glutathione) and clotting factors (Factor V11, Factor V111, Factor 1X, fibrinogen) were measured after 0, 2, 4 and 6 months treatment.

No significant differences were found in plasma lipid levels. Group 1 patients showed significantly raised levels of IL-6, IL-1 and IL-8 during the first 2-4 months of treatment. Thereafter levels fell. Levels of SOD, FV11 and FV1X in Group 1 also increased over the study period. Patients receiving transdermal oestrogen showed elevated levels of GSH in the second month of treatment, but no significant changes in any of the other parameters measured. The rise in levels of IL-1 and Factor IX in the second month of treatment was significantly higher in the oral group than in the transdermal group. No other significant differences between the treatment groups were found.

Transsexual patients receiving oral oestrogen showed significant changes in inflammatory markers involved in the pathogenesis of vascular disease. No such changes were associated with transdermal oestrogen. Changes in two inflammatory markers were significantly greater than among patients receiving transdermal oestrogen.