HRT for the Primary Prevention of Coronary Heart Disease

Abstract

The incidence of coronary heart disease (CHD) in women increases significantly after the menopause and is a leading cause of death. Hence primary prevention of CHD is of paramount importance. Since loss of ovarian hormones leads to adverse metabolic and vascular changes, hormone replacement therapy (HRT) is a logical treatment to reverse these changes. Estrogen has beneficial effects on lipids and lipoproteins in lowering low-density lipoprotein (LDL) cholesterol and increasing high-density lipoprotein (HDL) cholesterol. Triglycerides may be increased or decreased, depending on the route of administration of the estrogen. These effects are dose-dependent and can be modified by the addition of a progestogen. Androgenic, rather than non-androgenic, progestogens have less favourable effects. Estrogens have mainly favourable effects on glucose and insulin metabolism, improving glucose tolerance and reducing insulin resistance. Again these beneficial changes are reduced by the addition of androgenic progestogens. HRT reduces central fat deposition. It has little or no adverse effect on blood pressure, and certain combinations of estrogen and progestogen may actually lower it. The effect of estrogen on haemostasis is to increase coagulation activation when given by the oral, but not the transdermal, route of administration, but this is also dose-dependent. Thus the types of hormones, doses and route of administration can be manipulated in the individual to give the most favourable metabolic cardiovascular risk profile. Estrogen has direct beneficial effects on arteries and arterial function. It is vasodilatory through its effects on nitric oxide (NO) production and on ion channels. It may also have favourable effects on vascular remodelling, but this again is dose-dependent. Observational studies have consistently shown an association between HRT use and reduction in CHD incidence and death. Furthermore, studies have also shown that cessation of HRT is associated with a transient increase in cardiovascular death. Animal studies have shown that intervention with HRT soon after menopause has the most favourable outcome on atheroma development, the so-called timing hypothesis, and human studies have confirmed this. Clinical trials looking at CHD endpoints now provide growing evidence that HRT is effective for the primary prevention of CHD. The type of hormones given, their route of administration and the dose given at initiation, which will depend on the chronological or menopausal age of the patient, are key to determining a beneficial cardiovascular outcome.