Randomised comparison of oestrogen versus oestrogen plus progestogen hormone replacement therapy in women with hysterectomy

Abstract

<h3>Abstract</h3> <b>Objective</b>: To compare the acceptability and symptomatic and metabolic effects of two regimens of hormone replacement therapy in women with hysterectomy. <b>Design</b>: Randomised, double blind comparison. <b>Setting</b>: Seven group practices in the Medical Research Council9s general practice research framework. <b>Subjects</b>: 321 women with hysterectomy aged 35-59. <b>Interventions</b>: Hormone replacement therapy with (a) conjugated equine oestrogen 625 µg daily alone or (b) conjugated equine oestrogen 625 µg daily plus the progestogen norgestrel 150 µg daily for the last 12 days of the “cycle.” <b>Main outcome measures</b>: Changes in blood pressure, weight, symptoms, and haemostatic and lipid values. <b>Results</b>: After two years 36% (57/158) of women randomly allocated to take oestrogen alone had discontinued treatment as compared with 30% (49/163) of women allocated to take oestrogen plus progestogen. Smokers were more likely to withdraw than non-smokers. There were no clear differences between the two groups in symptoms often attributed to hormone replacement therapy or in blood pressure or weight. At one year low density lipoprotein cholesterol concentrations had fallen substantially in both groups. High density lipoprotein cholesterol concentrations rose to significantly higher values in women taking oestrogen alone compared with those taking oestrogen plus progestogen, though triglyceride concentrations and factor VII activity were also significantly higher in this group. Fibrinogen concentration tended to fall, though not significantly, in both groups, possibly more in women taking oestrogen alone. <b>Conclusions</b>: Oestrogen plus progestogen was no less well tolerated than oestrogen alone. There was a fairly even balance between possibly beneficial and adverse effects of the two regimens on lipid concentrations and coagulability. Concern that the combined regimen may not have the cardioprotective effects ascribed to oestrogen alone can to some extent be allayed, with reassurance for the growing numbers of women with intact uteri using the combined regimen. Misgivings about the combined regimen in women with hysterectomy on the grounds of its acceptability and its effects on lipid values may also be unfounded. <h3>Key messages</h3> Key messages In fact, in hysterectomised women norgestrel containing hormone replacement preparations may be as well tolerated as unopposed oestrogen There may be little difference between norgestrel containing hormone replacement therapy and oestrogen only preparations in their lipid and haemostatic effects Pending the results of clinical end point trials, anxieties about the metabolic effects of norgestrel in hormone replacement therapy can largely be allayed