Endocrine control of plasma lipoprotein metabolism: effects of gonadal steroids.

Gonadal steroids are powerful modulators of plasma lipoprotein metabolism. In general, steroids with oestrogenic activity increase plasma levels of HDL, especially HDL2, and reduce levels of LDL. Steroids with androgenic activity have opposite effects, consistent with the sex difference in HDL and LDL levels. Triglyceride levels are lowered by exogenous administration of androgens and are raised by oral oestrogens, contrary to the observed sex difference in this lipid. The impact of administered gonadal steroids is modified by factors such as dosage and chemical structure, with synthetic steroids having a more pronounced effect than natural hormones. The effects of these steroids may depend on the pre-treatment lipoprotein pattern and endocrine status, and are modified by the route of administration, with oral hormones often having greater metabolic effects than those given parenterally. The net effects of oestrogen and progestagen combined preparations on lipoprotein metabolism depends on the balance between oestrogenic and androgenic activity. In contrast, endogenous changes in sex hormone levels, such as those accompanying puberty, the menstrual cycle and the menopause, have relatively little effect on plasma lipoproteins. Data concerning puberty and castration in males indicate that testosterone is a key factor in the sex difference in HDL levels. There is evidence that loss of ovarian function induces significant increases in LDL level, but endogenous changes in oestrogen levels have little effect on HDL metabolism in women. Changes in triglyceride levels are due mainly to alteration in VLDL secretion and catabolism. LDL levels are controlled by the activity of B100, E receptors and, to a lesser extent, changes in LCAT activity. Gonadal steroids affect HDL levels by altering apoAI synthesis and by controlling the activity of hepatic lipase. Lp(a) levels are increased during early pregnancy but may be decreased by anabolic steroids. The mechanisms behind such actions are unknown. Gonadal hormones influence all areas of plasma lipoprotein metabolism and therefore may affect cardiovascular risk by favourably affecting the plasma lipoprotein profile. In postmenopausal women, use of oestrogens has led to a 60% reduction in cardiovascular disease (Bush et al, 1987). Androgens and progestagens with androgenic properties induce changes in plasma lipoproteins which may increase risk. Further study of the mechanisms involved in these changes is obligatory given the widespread use of these hormones.