Metabolic effects of hormone replacement preparations

BMJ 1996; 312 doi: https://doi.org/10.1136/bmj.312.7046.1608 (Published 22 June 1996) Cite this as: BMJ 1996;312:1608
  1. Naveed Sattar,
  2. Chris J Packard,
  3. Alan J Jaap
  1. Registrar in clinical chemistry Professor in clinical biochemistry Senior registrar in medicine Glasgow Royal Infirmary, Glasgow G4 0SF

    EDITOR,—The recent article by the Medical Research Council's General Practice Research Framework examined the metabolic effects of an oestrogen only and a combined hormone replacement preparation (containing norgesterol) in women with hysterectomy and concluded that the possibly beneficial and adverse effects of the two regimens were fairly evenly balanced on lipids and coagulability.1 We believe that a greater emphasis should have been placed on the results for high density lipoprotein cholesterol, which is a potent independent risk factor for coronary heart disease in women of that age. In the lipid research clinics prevalence study, high density lipoprotein cholesterol was second only to age as a predictor of coronary heart disease in women, more so than low density lipoprotein cholesterol.2 From the Framingham data3 we calculated that for a similar group of women the difference in high density lipoprotein cholesterol concentration observed at 12 months between oestrogen only and the combined preparation would translate into a 33% lower risk of a non-fatal myocardial event with the oestrogen only preparation. In contrast, the significance of a moderate increase in factor VIIc (probably related to the increase in triglyceride) in terms of risk of coronary heart disease is not known as there have been no studies to date examining factor VIIc as a marker of cardiovascular risk in women. The observed rise in high density lipoprotein cholesterol may be more important as a marker and outweigh the concomitant increment in factor VIIc in terms of coronary heart disease risk.

    The difference in high density lipoprotein cholesterol concentrations between regimens is likely to be due to increased hepatic lipase mediated catabolism with the combined preparation. Oestrogens lower and progestogens increase hepatic lipase activity in proportion to their degree of androgenicity. The point here is that preparations containing androgenic progestogens may be associated with a more atherogenic lipoprotein profile, since it has recently been shown that in women hepatic lipase is also involved in perturbing the low density lipoprotein subfraction profile towards a smaller, denser, more atherogenic pattern.4

    Finally, this study did not incorporate measures of insulin sensitivity, nor was any comment made on the potential disparity in the effects of the two regimens on carbohydrate metabolism. Oestrogen only preparations have been shown to improve insulin sensitivity, whereas added progestogens seem to oppose this beneficial effect in proportion to their androgenicity.5 As a result, the choice of hormone replacement preparations may be an especially important consideration for women with abnormal glucose tolerance, and in these women the addition of a relatively non-androgenic progestogen may be advantageous.


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