Effects of dydrogesterone and norethisterone, in combination with oestradiol, on lipoproteins and inflammatory markers in postmenopausal women

Objective: The lack of cardiovascular benefit from postmenopausal hormone replacement therapy (HRT) in randomised controlled trials is not readily explained. The androgenic properties of progestogens could be crucial in understanding the results of these studies, all of which employed medroxyprogesterone. We have previously reported that medroxyprogesterone has some androgenic effects intermediate between those of the more androgenic norethisterone and the less androgenic desogestrel. To examine the androgenicity of progestogens further, we compared the effects of dydrogesterone (DGT) that is even less androgenic than desogestrel, and norethisterone (NET), on lipoproteins and inflammatory markers while maintaining the same oestrogen dose. Method: In a crossover trial, 25 non-hysterectomised postmenopausal women were randomised to two preparations of HRT each for three 28-day treatment cycles. Both HRT regimens comprised oestradiol (1 mg). One also included DGT (10 mg) and the other NET (1 mg). Oestradiol was taken continuously and the progestogens sequentially. Measurements were made at baseline and on the last day of the oestradiol phase and the last day of the progestogen phase in the third treatment cycle of each regimen. Results: NET was more effective than DGT in significantly reducing lipoprotein (a) (p <0.05). NET was, however, associated with significantly lower levels of high-density lipoprotein (HDL) cholesterol (p = 0.001) and triglycerides (p <0.05). NET was less effective in opposing the oestrogen-related increase in C-reactive protein (CRP). Interleukin-6 levels did not change with either progestogen. Conclusion: The effect of androgenic progestogens on cardiovascular risk factors may not be as deleterious as previously assumed, especially if the lower HDL levels result from more efficient reverse cholesterol transport. The hormone related rise in C-reactive protein, without a corresponding increase in interleukin-6, may not represent a systemic inflammatory response. © 2005 Elsevier Ireland Ltd. All rights reserved.