ArticleBMJ (Clinical research ed.)2002
Effect on endometrium of long term treatment with continuous combined oestrogen-progestogen replacement therapy: follow up study.
Article in BMJ (Clinical research ed.), 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Hormone therapy in postmenopausal women and risk of endometrial hyperplasia.The Cochrane database of systematic reviews · 2012Pooled it
- Management of Patients Diagnosed with Endometrial Hyperplasia: Comparison of Guidelines.Cancers · 2026Review
- Review
- Combined estrogen-progestin pill is a safe and effective option for endometrial hyperplasia without atypia: a three-year single center experience.Journal of gynecologic oncology · 2019Article
- Effects of vitamin d plus calcium supplements on pharmacokinetics of isoflavones in thai postmenopausal women.Evidence-based complementary and alternative medicine : eCAM · 2011Article
- Endometrial hyperplasia risk in relation to recent use of oral contraceptives and hormone therapy.Annals of epidemiology · 2009Article
- Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence.Clinical interventions in aging · 2008Review
- HT update: spotlight on estradiol/norethindrone acetate combination therapy.Clinical interventions in aging · 2008Review
- Making decisions about hormone replacement therapy.BMJ (Clinical research ed.) · 2003Review
- Continuous combined hormone replacement therapy and endometrial hyperplasia.BMJ (Clinical research ed.) · 2002Article
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8 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo determine effects of five years of treatment with an oral continuous combined regimen of 2 mg 17beta-oestradiol and 1 mg norethisterone acetate on endometrial histology in postmenopausal women.
designFollow up study in postmenopausal women.
setting31 menopause clinics in the United Kingdom.
participants534 postmenopausal women, all with an intact uterus, who had completed nine months of treatment with oral continuous combined 2 mg 17beta-oestradiol and 1 mg norethisterone acetate agreed to take part in a long term follow up study. Women were assigned to different groups on the basis of the treatment status immediately before entering the original study: 360 women had taken sequential oestrogen-progestogen hormone replacement therapy, 164 had taken no hormone replacement therapy, and 10 had taken unopposed oestrogen therapy.
methodsEndometrial aspiration specimens were taken before the women started the continuous combined regimen, after 9 and 24-36 months, and at the end of the five year treatment period or on withdrawal from the study.
main outcome measureResults of endometrial histology.
resultsThe duration of treatment with continuous combined hormone replacement therapy was 4.4 (range 1.1-5.9) years. Data on endometrial specimens were available for 526 women after nine months of treatment, 465 women after 24-36 months of treatment, and 398 women who completed the five years treatment (345 women) or were withdrawn between the two latter visits for biopsies (53 women). No cases of endometrial hyperplasia or malignancy were detected at biopsy; 69% of women had an endometrium classified as atrophic or unassessable on completion of the study or withdrawal from it. Before the continuous combined therapy was started, complex hyperplasia was detected in 21 women who had taken sequential hormone replacement therapy before the study and in one who had taken unopposed oestrogen. All of these women had normal results on histological examination of endometrial tissue after nine months of treatment with continuous combined hormone replacement therapy, and hyperplasia did not recur after up to five years of treatment.
conclusionsLong term treatment (for up to five years) with continuous combined hormone replacement therapy containing oestradiol 2 mg and norethisterone 1 mg daily was associated with neither endometrial hyperplasia nor malignancy. In women who had complex hyperplasia during previous sequential or unopposed regimens, the endometrium returned to normal during treatment with continuous combined hormone replacement therapy. These findings provide reassurance about the long term safety of this continuous combined regimen in terms of the endometrium.
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