Preliminary report on the use of tamoxifen in the treatment of endometriosis

Haber, Gillian; Behelak, Youssef

doi:10.1016/0002-9378(87)90057-3

Cited by 23 publications

(7 citation statements)

References 21 publications

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“…Overall it would appear that tamoxifen may enhance endometrial proliferation in 30-40% of postmenopausal women, but it is unclear which patients will respond to tamoxifen as a weak estrogen and which will not. This paradox is paralleled by contradictory reports that tamoxifen worsens the symptoms of endometriosis [28,29] or treats it successfully [30]. Interestingly tamoxifen also has been associated with an endometrial carcinoma arising from an ovarian endometriotic focus [3 11.…”

Section: Tamoxifen the Vagina And The Uterusmentioning

confidence: 99%

Gynecologic effects of tamoxifen and the association with endometrial carcinoma

Assikis

Jordan

1995

Intl J Gynecology & Obste

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Tamoxifen has been used as an adjuvant therapy for breast cancer for nearly two decades. The benefits of adjuvant tamoxifen therapy in prolonging disease-free and overall survival have been shown in randomized clinical trials. Despite this, some developing evidence suggests that tamoxifen causes a 2- to 3-fold increase in endometrial cancer. This paper reviews the reports of endometrial carcinoma in tamoxifen-treated patients. Two hundred fifty cases of endometrial carcinoma are reported, but only one case is identified in a premenopausal woman. When documented, 77% (n=127) of the cases are good-grade (grade 1 or 2) and 80% (n=125) are stage-I disease. Since the distribution of good grade (79%) and stage I (74%) from the Surveillance, Epidemiology and End Results (SEER) data are comparable, concerns about more aggressive or late-stage disease appear to be unwarranted. The modest increase in the incidence of early-stage, good-grade endometrial carcinoma described during tamoxifen therapy suggests that it would be unreasonable to institute an aggressive detection strategy of endometrial biopsies. This approach would only lead to further detection bias and would not be cost-effective. Physicians should ensure that patients do not have pre-existing endometrial cancer prior to adjuvant tamoxifen therapy for breast cancer and, furthermore, they should educate patients about signs and symptoms of early endometrial carcinoma and when reported these should be followed up with a gynecologic examination.

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Section: Tamoxifen the Vagina And The Uterusmentioning

confidence: 99%

Gynecologic effects of tamoxifen and the association with endometrial carcinoma

Assikis

Jordan

1995

Intl J Gynecology & Obste

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“…Endometriosis is associated with severely painful menstruation, chronic pelvic pain, and infertility [1,2]. Although the etiology and exact mechanism for the development of endometriosis is unclear, there is a large body of laboratory and circumstantial evidence that suggests a crucial role for estrogen in the establishment and maintenance of this disease [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis1

Xue

Lin²,

Cheng³

et al. 2007

Biology of Reproduction

293

234

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Steroid receptors in the stromal cells of endometrium and its disease counterpart tissue endometriosis play critical physiologic roles. We found that mRNA and protein levels of estrogen receptor 2 (ESR2) were strikingly higher, whereas levels of estrogen receptor 1 (ESR1), total progesterone receptor (PGR), and progesterone receptor B (PGR B) were significantly lower in endometriotic versus endometrial stromal cells. Because ESR2 displayed the most striking levels of differential expression between endometriotic and endometrial cells, and the mechanisms for this difference are unknown, we tested the hypothesis that alteration in DNA methylation is a mechanism responsible for severely increased ESR2 mRNA levels in endometriotic cells. We identified a CpG island occupying the promoter region (À197/þ359) of the ESR2 gene. Bisulfite sequencing of this region showed significantly higher methylation in primary endometrial cells (n ¼ 8 subjects) versus endometriotic cells (n ¼ 8 subjects). The demethylating agent 5-aza-2 0 -deoxycytidine significantly increased ESR2 mRNA levels in endometrial cells. Mechanistically, we employed serial deletion mutants of the ESR2 promoter fused to the luciferase reporter gene and transiently transfected into both endometriotic and endometrial cells. We demonstrated that the critical region (À197/þ372) that confers promoter activity also bears the CpG island, and the activity of the ESR2 promoter was strongly inactivated by in vitro methylation. Taken together, methylation of a CpG island at the ESR2 promoter region is a primary mechanism responsible for differential expression of ESR2 in endometriosis and endometrium. These findings may be applied to a number of areas ranging from diagnosis to the treatment of endometriosis.

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“…Conditions of oestrogen excess have been reported to exacerbate endometriosis, while medical interventions that inhibit oestrogen production or action, i.e. down-regulating doses of gonadotrophin-releasing hormone (GnRH) analogues (Schriock et al, 1985), progestins (Vercellini et al, 1997), androgens (Barbieri et al, 1982) and anti-oestrogens (Haber and Behelak, 1987), ameliorate its symptoms.…”

Section: Introductionmentioning

confidence: 99%

Oestrogen receptor (ER)-alpha and ER- isoforms in normal endometrial and endometriosis-derived stromal cells

Brandenberger

Lebovic

Tee

et al. 1999

Molecular Human Reproduction

155

108

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Several investigators have noted that hormone-dependent development of endometriosis implants lags behind that of simultaneously analysed eutopic endometrium. With the recent discovery of the oestrogen receptor-β (ER-β) isoform, the aim of this study was to investigate whether differences in the expression of ER-α and ER-β might explain this observation. mRNA transcripts from endometrial stromal cells isolated from normal endometrium (NE) and from endometriomas (EI) were analysed using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. RT-PCR and Southern blot analyses of the two ER isoforms indicated that NE and EI stromal cells predominantly express ER-α mRNA, however the relative concentrations of ER isoform mRNA transcripts differed between the two cell types. Steady-state ER-α:ER-β mRNA ratios were 15.5 ⍨ 2.8 and 5.2 ⍨ 0.9 respectively for NE and EI cells (P ⍧ 0.02). NE and EI stromal cells expressed ER proteins with similar K d (~0.9 nM) and densities (~24 500 binding sites/cell) respectively. Functional ER expression was indicated by an increase in progesterone receptor concentrations of~60% (P ⍧ 0.03) after incubation with 10 nM oestradiol. We postulate that differential transcript processing, ligand specificity and biological actions of the ER-α and -β isoforms may influence differential growth responses in normal and ectopic endometrium.

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Preliminary report on the use of tamoxifen in the treatment of endometriosis

Cited by 23 publications

References 21 publications

Gynecologic effects of tamoxifen and the association with endometrial carcinoma

Gynecologic effects of tamoxifen and the association with endometrial carcinoma

Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis1

Oestrogen receptor (ER)-alpha and ER- isoforms in normal endometrial and endometriosis-derived stromal cells

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