Effects of Estrogens and Progestins on the Biochemistry and Morphology of the Postmenopausal Endometrium

Whitehead, MI; Townsend, P. T.; Pryse‐Davies, J.; Ryder, T. A.; King, R. J. B.

doi:10.1056/nejm198112313052701

Cited by 387 publications

(95 citation statements)

References 29 publications

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“…The commonly used estrogen preparations are conjugated equine estrogen and natural estradiol in micronized form, and the most commonly used progesterone is medroxyprogesterone acetate (MPA). Combined estrogen/progesterone HRT is widely prescribed to millions of women (17)(18)(19). It is used in either cyclic or continuous fashion.…”

Section: Hormone Replacement Therapymentioning

confidence: 99%

“…The effect of combined HRT on the endometrium includes a wide spectrum of morphologic features (18,20). Various combinations of weakly to intensely proliferative glands and/or secretory glands, with sub-and supranuclear vacuoles and luminal secretion, often surrounded by stromal edema, stromal hyperplasia, and decidual reaction, are seen.…”

Section: Hormone Replacement Therapymentioning

confidence: 99%

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Hormonal Pathology of the Endometrium

2000

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The endometrial tissue is a sensitive target for steroid sex hormones and is able to modify its structural characteristics with promptness and versatility. This article discusses briefly endogenous hormonal effects (cyclic changes, luteal phase defect, unopposed estrogen effect) and describes the histologic patterns encountered in the most commonly used hormone therapies: oral contraceptives, ovulation stimulation, hormone replacement therapy, and antitumoral hormone therapy.Oral contraceptives exert a predominant progestational effect on the endometriun, inducing an arrest of glandular proliferation, pseudosecretion, and stromal edema followed by decidualized stroma with granulocytes and thin sinusoidal blood vessels. Prolonged use results in progressive endometrial atrophy.Ovulation induction therapy accelerates the maturation of the stroma and is often associated with a discrepancy between early secretory glands and an edematous or decidualized stroma with spiral arterioles.Hormone replacement therapy with estrogen alone may result in continuous endometrial proliferation, hyperplasia, and neoplasia. The use of both estrogen and progesterone elicits a wide range of histologic patterns, seen in various combinations: proliferative and secretory changes, often mixed in the same tissue sample; glandular hyperplasia (in polyps or diffuse) ranging from simple to complex atypical; stromal hyperplasia and/or decidual transformation; epithelial metaplasia (eosinophilic, ciliated, mucinous); and inactive and atrophic endometrium.Progesterone therapy for endometrial hyperplasia and neoplasia induces glandular secretory changes, decidual reaction, and spiral arterioles. Glandular proliferation is usually arrested, but neoplastic changes may persist and coexist with secretory changes.Lupron therapy produces a shrinking of uterine leiomyomas by accelerating their hyaline degeneration, similar to that in postmenopausal involution. It generally produces endometrial atrophy.Tamoxifen for breast carcinoma has an estrogenagonist effect on the uterus in approximately 20% of patients, who develop endometrial polyps, glandular hyperplasia, adenomyosis, and/or leiomyomata. Both endometrioid and nonendometrioid carcinomas are seen, often in polyps. Their causal relationship to tamoxifen therapy is debatable. Mod Pathol 2000;13(3):285-294Hormone therapy is widely used throughout the world by women of all ages for a variety of reasons, ranging from oral contraception and ovulation stimulation for family planning to hormone replacement therapy in menopause, to adjuvant therapy of tumors of the breast and uterus. The histopathologic changes of the uterus, and particularly of the endometrium, associated with these therapies encompass a variety of morphologic features that are often difficult to interpret. The endometrium is a sensitive target tissue for steroid sex hormones and is able to modify its structural characteristics with promptness and versatility. The physiologic changes of the endometrium during reproductive life and after men...

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Section: Hormone Replacement Therapymentioning

confidence: 99%

Section: Hormone Replacement Therapymentioning

confidence: 99%

Hormonal Pathology of the Endometrium

2000

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“…2,3 Progestin was added to counteract unopposed estrogen's proliferative effects on postmenopausal endometrium. 4,5 Estrogen-plus-progestin regimens that included progestin for 7 to 9 days per 28-day cycle did not appear to produce endometrial cancer risks that were lower than the risks in women who had taken unopposed estrogen. 6 Estrogen-plus-progestin regimens that included !10 days of progestin per 28-day cycle appeared to generate no increases in endometrial cancer risk.…”

mentioning

confidence: 95%

Endometrial cancer and menopausal hormone therapy in the National Institutes of Health‐AARP Diet and Health Study cohort

Lacey

Leitzmann

Chang

et al. 2007

Cancer

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BACKGROUND.Menopausal hormone therapy formulations for women without hysterectomy have included estrogen plus progestin for years, but endometrial cancer risks associated with the use of sequential and continuous estrogen‐plus‐progestin regimens remain unclear.METHODS.The National Institutes of Health‐AARP Diet and Health Study included 73,211 women who were ages 50 years to 71 years at baseline and who completed 2 questionnaires (1995–1996 and 1996–1997). Linkage to state cancer registries and mortality indices identified 433 incident endometrial cancers through 2000. Using proportional hazards regression, the authors estimated relative risks (RRs) and 95% confidence intervals (95% CIs) relative to never‐use of hormone therapy.RESULTS.In 51,312 women who never used hormones or only used estrogen‐plus‐progestin regimens at doses consistent with current practice, neither sequential estrogen plus progestin (daily estrogen plus progestin for 10–14 days per cycle: RR, 0.74; 95% CI, 0.39–1.40) nor continuous estrogen plus progestin (daily estrogen plus progestin for ≥20 days per cycle: RR, 0.80; 95% CI, 0.55–1.15) had any statistically significant association with endometrial cancer. Long durations (≥5 years) of sequential regimen use (RR, 0.79; 95% CI, 0.38–1.66) and of continuous regimen use (RR, 0.85; 95% CI, 0.53–1.36) were not associated with endometrial cancer.CONCLUSIONS.Confirmation that these estrogen‐plus‐progestin regimens neither increase nor decrease the risk of endometrial cancer could influence menopausal symptom management for women who are considering estrogen‐plus‐progestin therapy. Cancer 2007. Published 2007 by The American Cancer Society.

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“…HRT increases proliferation of the endometrium. which is also an oestrogen-responsive tissue (Whitehead et al 1981). The use of HRT (E, or E,+ P) by our patients did not increase their breast epithelial proliferation index.…”

Section: Ki67 Labellingmentioning

confidence: 42%

Epithelial proliferation and hormone receptor status in the normal post-menopausal breast and the effects of hormone replacement therapy

Hargreaves

Knox²,

Swindell³

et al. 1998

Br J Cancer

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Summary The proliferation rate (as assessed by Ki67 expression) and expression of oestrogen-regulated progesterone receptor (PR) was studied in normal post-menopausal breast epithelium. Normal breast epithelium from patients receiving hormone replacement therapy (HRT) at the time of surgery containing either oestrogen alone (E2) or oestrogen and progesterone combined activities (E2 + P) was also studied, as HRT has been linked to an increased breast cancer risk. Samples of breast tissue. containing normal epithelium. from 185 patients undergoing surgery for benign or malignant disease were immunocytochemically stained for PR and Ki67. The percentage of labelled cells was expressed as the labelling index (LI). The median Ki67 Li in normal post-menopausal breast epithelium was 0.19 and median PR LI was 4.75, and both were unaffected by patient age, duration of menopause or if the tissue sample originated from a breast with benign or malignant disease. Proliferation did not alter significantly in patients taking HRT (P = 0.61); however, PR expression was up-regulated in both E2 and E2 + P users (P = 0.01). The dose and duration of HRT had no effect on either parameter. A possible attenuation of sensitivity to oestradiol-induced proliferation but not to PR expression occurs in the post-menopausal breast.

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Effects of Estrogens and Progestins on the Biochemistry and Morphology of the Postmenopausal Endometrium

Cited by 387 publications

References 29 publications

Hormonal Pathology of the Endometrium

Hormonal Pathology of the Endometrium

Endometrial cancer and menopausal hormone therapy in the National Institutes of Health‐AARP Diet and Health Study cohort

Epithelial proliferation and hormone receptor status in the normal post-menopausal breast and the effects of hormone replacement therapy

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