ABSTRACT
OBJECTIVES: 1. To determine the prevalence of endometrial hyperplasia in postmenopausal women taking standard proprietary regimens of sequential oestrogen/progestogen; 2. to determine the effects of nine months treatment with an oral continuous combined regimen of 2 mg 17beta-oestradiol and 1 mg norethisterone acetate (Kliofem [Kliogest outside the UK]; Novo Nordisk, Denmark) on endometrial histology in postmenopausal women. DESIGN: An open, prospective study in postmenopausal women. SETTING: Fifty-four menopause clinics in the UK. PARTICIPANTS: 2028 postmenopausal women: 1312 (Group A) taking sequential oestrogen-progestogen hormone replacement therapy (HRT), and 716 (Group B) not taking HRT, were recruited. In Group A, 388 women took preparations containing 10 days of progestogen, 921 had 12 days, and 3 had 13 days per cycle. METHODS: Endometrial aspiration biopsies were taken towards the end of a three-month run-in period (Group A) or at study entry (Group B), before administration of the continuous combined HRT regimen. Biopsies were repeated at the end of the nine month treatment period. MAIN OUTCOME MEASURE: Endometrial histology. RESULTS: Initial endometrial biopsy data were available for 1106 women in Group A, who by the time of endometrial investigation had been taking HRT for a median duration of 2.56 years (5th to 95th centiles: 0.77 to 8.49 years). Data were available for 661 untreated women, who had no bleeding and had not taken HRT within the last year (Group B). Complex hyperplasia was found in 59 women (5.3%), and atypical hyperplasia in a further eight (0.7%) in Group A. In Group B there were no cases with complex hyperplasia, but one woman showed atypical hyperplasia (0.2%). At the end of the nine months of continuous combined therapy there was no case of hyperplasia among 1196 biopsies (upper 95% confidence limit of risk 0.31%) in women completing the study. Within this Group all of the women with complex hyperplasia arising during previous sequential HRT and who completed the study (n = 38) reverted to normal endometrial patterns. There was no case of endometrial carcinoma during the study. CONCLUSIONS: Despite taking standard regimens of sequential HRT containing at least 10 days of progestogen, there was a 5.3% prevalence of complex endometrial hyperplasia, and a 0.7% prevalence of atypical hyperplasia. However, continuous combined HRT (Kliofem) containing daily progestogen is not associated with an increased risk of hyperplasia and will convert the endometrium to normal in those with complex hyperplasia arising during previous sequential HRT.
Subject(s)
Endometrial Hyperplasia/chemically induced , Estradiol Congeners/adverse effects , Estradiol/adverse effects , Norethindrone/adverse effects , Progesterone Congeners/adverse effects , Administration, Oral , Adult , Aged , Drug Combinations , Endometrial Hyperplasia/pathology , Estradiol/administration & dosage , Estradiol Congeners/administration & dosage , Estrogen Replacement Therapy/adverse effects , Estrogen Replacement Therapy/methods , Female , Humans , Middle Aged , Norethindrone/administration & dosage , Norethindrone/analogs & derivatives , Norethindrone Acetate , Prevalence , Progesterone Congeners/administration & dosage , Prospective Studies , Treatment OutcomeABSTRACT
Hormone replacement therapy (HRT) must be taken for many years to attain the long-term benefits on osteoporosis and cardiovascular disease. However, this level of compliance with HRT is rarely achieved. This analysis documents the effect of continuous combined HRT with Kliogest on the relief of menopausal symptoms, and the patient preference for HRT over a 9-month treatment period. A total of 2151 postmenopausal women, of whom 1435 were currently on sequential therapy and 716 had not been previously treated, were enrolled from 55 centers in the UK. Women received a daily tablet of Kliogest for 9 months. Quality of life was assessed using the Greene Climacteric Scale, and the women completed patient preference questionnaires. Treatment with continuous combined therapy was at least as effective as previous sequential regimens in alleviating menopausal symptoms. By the study conclusion, patient preference was strongly in favor of Kliogest with 91% of completers preferring it to their previous sequential therapy. Improved quality of life and patient preference for continuous combined therapy may encourage long-term compliance with treatment, allowing more women to experience the long-term beneficial effects of HRT on osteoporosis and cardiovascular disease.
