Type and route of estrogen administration.
Hormone replacement therapy (HRT) can be administered orally and non-orally. Providing equivalent doses are given, all forms of HRT can equally relieve menopausal symptoms and prevent bone loss and osteoporosis. Different routes of administration will have differing metabolic effects, with oral HRT producing a hepatic first-pass effect not seen with non-oral HRT. The first-pass effect can produce benefits including larger reductions in low density lipoprotein cholesterol, lipoprotein(a) and insulin resistance, and larger increases in high density lipoprotein cholesterol. Unwanted effects are seen in increases in triglycerides and in coagulation activation. Cardiovascular effects of oral and transdermal HRT appear to be fairly similar, with improvements in vascular endothelial function, angiotensin-converting-enzyme activity, and in most markers of inflammation. There is a paucity of studies on the effects of transdermal HRT on cardiovascular outcomes, but the few data available suggest similar effects to oral HRT, and dose rather than route of administration is probably more important in this respect. Oral HRT may be preferred in women with evidence of insulin resistance, such as in metabolic syndrome or maturity-onset diabetes mellitus. Transdermal HRT may be preferred in women with coagulation disturbances. But, for the majority of women, personal preference should determine their choice of HRT route.