Endometrial status in post-menopausal women on long-term continuous combined hormone replacement therapy (Kliofem®) a comparative study of endometrial biopsy, outpatient hysteroscopy and transvaginal ultrasound

Piegsa, K; Calder, Ann; Davis, Jamaine; McKay-Hart, David; Wells, Michael; Bryden, F.

doi:10.1016/s0301-2115(96)02670-x

Cited by 31 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The histopathologist can therefore be reassured that where the endometrial cavity has been entered and little or no endometrial tissue obtained, there is very little likelihood of important endometrial pathology being present. 19 Other diYculties that may be encountered with Pipelle sampling include the interpretation of focal changes of glandular tortuosity and crowding in disrupted endometrial fragments that are subject to considerable biopsy artifact. This is particularly true in the context of a secretory endometrium.…”

Section: "Pipelle" Samples and Diagnostic Diyculties With Endometrialmentioning

confidence: 99%

“…42 Endometrial polyps are less common in women on continuous combined HRT, but have been reported. 19 Rarely, women reporting breakthrough bleeding after having achieved prolonged amenorrhoea on continuous combined HRT will be found to have an endometrial polyp. 44 Such cases always warrant biopsy and histological evaluation, however, because adenocarcinoma can also occur.…”

Section: Hrt and Endometrial Polypsmentioning

confidence: 99%

See 1 more Smart Citation

Hormone replacement therapy and the endometrium

Feeley

Wells²

2001

Journal of Clinical Pathology

View full text Add to dashboard Cite

Modern hormone replacement therapy (HRT) regimens contain oestrogen and progestogen, given either in a cyclical or continuous combined manner. Most endometrial biopsies from women on sequential HRT show weak secretory features. Approximately 15% show proliferative activity, although this figure may be less if more than nine days of progestogen is given in each cycle. A small proportion will show an inactive or atrophic endometrium. Up to 50% of biopsies from women on continuous combined HRT contain minimal endometrial tissue for histopathological analysis: this correlates well with an atrophic endometrium with no appreciable pathology. Of the 50% with more substantial material, approximately one half will show endometrial atrophy, and one half will show weak secretory features. Proliferative, menstrual, and pseudodecidual changes are rare. Approximately 20% of women given unopposed oestrogen for one year develop endometrial hyperplasia. The relative risk of endometrial carcinoma is two to three. This is dramatically reduced by the addition of progestogen to the regimen, but cyclical progestogen as part of a sequential HRT regimen does not completely eliminate the risk of carcinoma. The prevalence of endometrial hyperplasia associated with sequential HRT is 5.4%, and that of atypical hyperplasia (endometrial intraepithelial neoplasia) is 0.7%. Continuous combined HRT is not associated with the development of hyperplasia or carcinoma, and may normalise the endometrium of women who have developed complex hyperplasia on sequential HRT. The probability of a histopathologist finding clinically relevant pathology in an endometrial biopsy specimen of a patient on HRT is low and is more likely to be a manifestation of pre-existing disease. (J Clin Pathol 2001;54:435-440)

show abstract

Section: "Pipelle" Samples and Diagnostic Diyculties With Endometrialmentioning

confidence: 99%

Section: Hrt and Endometrial Polypsmentioning

confidence: 99%

Hormone replacement therapy and the endometrium

Feeley

Wells²

2001

Journal of Clinical Pathology

View full text Add to dashboard Cite

show abstract

“…16 17 24 25 A separate study of 40 postmenopausal women treated with the same drug at one of the participating sites confirmed that the Pipelle method of sampling was effective and that an unassessable specimen was associated with endometrial atrophy 26…”

Section: Discussionmentioning

confidence: 92%

Effect on endometrium of long term treatment with continuous combined oestrogen-progestogen replacement therapy: follow up study

Wells

Sturdee²,

Barlow³

et al. 2002

BMJ

View full text Add to dashboard Cite

Objective To determine effects of five years of treatment with an oral continuous combined regimen of 2 mg 17 -oestradiol and 1 mg norethisterone acetate on endometrial histology in postmenopausal women. Design Follow up study in postmenopausal women. Setting 31 menopause clinics in the United Kingdom. Participants 534 postmenopausal women, all with an intact uterus, who had completed nine months of treatment with oral continuous combined 2 mg 17 -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. Methods Endometrial 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 measure Results of endometrial histology. Results The 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. Conclusions Long 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.

show abstract

“…4 Four women receiving Kliofem with ET values ranging from 9 to 15 mm showed either pseudodecidual change or atrophy with polyps or a fibroid. 3 Of further note is the report that the SERM agent idoxifene induced an ET of 5 mm or greater in 16% of subjects over the course of 12 weeks, but histologic features were unremarkable. 16 Most previous investigations have studied women as a group within 10 years of menopause.…”

Section: Discussionmentioning

confidence: 98%

“…The endometrium does not appear to change with time on treatment with opposed therapy. Histologically the endometrium did not show a tendency toward hyperplasia with time in younger women taking 2 mg 17 β-estradiol plus 1 mg norethindrone (norethisterone), 3 although a suggestion of increasing thickness with time was noted with sequential therapy 4 ; however, the effect of low dose CCT, e.g., 300 µg conjugated equine estrogens or 25 µg Estraderm patch (Ciba Consumer Pharmaceuticals, Woodbridge, NJ), on ET over the long term remains to be studied. The effect of age as a factor in determining endometrial response has been investigated infrequently, but one study of ET found no relation between ET and either weight or age.…”

Section: Ilona Wanda Chantler Mb Chb Michael William John Davie Mmentioning

confidence: 94%

Low dose continuous combined hormone replacement therapy: early and late postmenopausal effect on endometrium.

Chantler

Davie

2000

Journal of Ultrasound in Medicine

View full text Add to dashboard Cite

We investigated endometrial response to low (25 microg through the skin estradiol plus 700 microg norethindrone) and standard dose (2 mg oral estradiol plus 1 mg norethindrone acetate or 700 microg norethindrone) continuous combined therapy in postmenopausal women with time and bone mineral density response. Endometrial thickness was distributed logarithmically, with the means after use of 25 microg estradiol (4.3 mm) and 2 mg estradiol (3.8 mm) being similar. Subjects studied 15.4 +/‐ 7.0 months apart showed a difference of endometrial thickness of ‐0.55 +/‐ 1.3 mm. Neither pretreatment bone mineral density nor change correlated with endometrial thickness. Age, estrogen dose, bone mineral density, weight, and time on treatment do not relate to endometrial thickness. A commonly regarded cutoff point for biopsy, an endometrial thickness of 8 mm, is about 1 SD greater than the mean.

show abstract

Endometrial status in post-menopausal women on long-term continuous combined hormone replacement therapy (Kliofem®) a comparative study of endometrial biopsy, outpatient hysteroscopy and transvaginal ultrasound

Cited by 31 publications

References 23 publications

Hormone replacement therapy and the endometrium

Hormone replacement therapy and the endometrium

Effect on endometrium of long term treatment with continuous combined oestrogen-progestogen replacement therapy: follow up study

Low dose continuous combined hormone replacement therapy: early and late postmenopausal effect on endometrium.

Contact Info

Product

Resources

About