L‐norgestrel and progesterone have different influences on plasma lipoproteins

Abstract

Twenty-six postmenopausal women who had been on cutaneous oestradiol treatment for 3-6 months were given either 120 micrograms of 1-norgestrel (n = 13) or 300 mg of progesterone (n = 13) sequentially for another 6 months. The concentrations of cholesterol, phospholipids and triglycerides were determined in plasma and in the HDL, HDL2, HDL3, LDL and VLDL fractions before and after one, three and six cycles of progestin treatment. Already after 11 days on 1-norgestrel, the mean HDL cholesterol and the mean HDL phospholipid concentrations were reduced by 15%. The reduction of the HDL-lipids was mainly confined to the HDL2 fraction which was decreased by 25-30%. L-norgestrel also reduced the mean TG concentration both in the VLDL and the combined LDL + HDL fractions. Progesterone gave only minor changes of the plasma lipids and lipoproteins. Reduced HDL, especially HDL2, concentration, as induced by 1-norgestrel, might increase the risk for ischaemic heart disease. Therefore, it seems that, as regards the effects on the lipoproteins, progesterone might be more suitable than the 19-nortestosterone derivative 1-norgestrel for postmenopausal sequential hormonal therapy.

Tamoxifen, serum lipoproteins and cardiovascular risk

“…The increase of the high density lipoprotein cholesterol,sex hormone binding globulin and, as demonstrated indirectly in this study, of thyroxine binding globulin in plasma suggests that tamoxifen stimulates liver protein synthesis, just like 17fl-oestradiol does, when given orally (Fahraeus et al, 1982;Fex et al, 1981). Although our findings could also be explained by decreased protein degradation, proteinspecific stimulation of production seems more likely.…”

Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits.

“…The influence of combined estrogen and progestogen therapy on accumulation of cholesterol in the arterial wall has not been investigated before, either in women or in rabbits. Earlier studies of women suggest that 19-nortestosterone derivatives, such as levonorgestrel and norethisterone acetate, reduce or even reverse the beneficial effect of estrogen on HDL cholesterol (8,(28)(29)(30), considered by some to be the most predictive lipoprotein for atherosclerosis in women (31). These studies suggest that the addition ofa progestogen, especially 19-nortestosterone derivatives, may reduce or even reverse the protective effects of estrogen on cardiovascular disease.…”

Relative Fatty Acid Composition of Lecithin during Postmenopausal Replacement Therapy – A Comparison between Ethinyl Estradiol and Estradiol Valerate

“…Synthetic alkylated estrogens like ethinyl estradiol and 'natural' non-alkylated estrogens like estradiol valerate have been reported to have different effects as regards lipid metabolism [1,2]. Both compounds in crease HDL cholesterol and reduce LDL cho lesterol [3,4], thus causing a pattern which may be associated with a reduced risk of ath erosclerosis and ischemic heart disease [5,6] During the first three cycles unopposed estrogens were given for 3 weeks followed by an interval o f 1 week. During the following three cycles progestogens, estriol or tamoxifen were added sequentially during the last 10 days of each treatment cycle.…”