Increased Incidence of Endometrial Cancer Following the Women's Health Initiative: An Assessment of Risk Factors

Constantine, Ginger D.; Kessler, Grant; Graham, Shelli; Goldstein, Steven R.

doi:10.1089/jwh.2018.6956

Cited by 131 publications

(95 citation statements)

References 73 publications

(62 reference statements)

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“…A recent study on the world-wide assessment of endometrial cancer and its risk factors revealed endometrial cancer as the sixth most common neoplasm in women [100]. This study documents remarkable increase in endometrial cancer (EC) in 26 of the 43 populations studied during 1978-2013.…”

Section: Endometriosis-associated Extra-ovarian Cancersmentioning

confidence: 58%

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

Ghosh

Anupa

et al. 2019

COGO

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Endometriosis is an inflammatory disease characterized by the presence of endometrium-like tissue outside the uterus primarily on pelvic organs and tissues. It affects up to 15% of women in the reproductive age group and is often associated with pelvic pain and subfertility. Different theories explain how retrograde menstruation gives rise to endometrial deposits at ectopic sites, and how several other factors are involved in the progression of the disease. Its final diagnosis is established through direct visualization at laparoscopy or surgery followed by histological confirmation. Available epidemiological reports along with histopathological observations and molecular studies shed interesting light on the pathogenetic basis of different variants of the disease like deep infiltrating endometriosis and ovarian endometriosis. Evidence also suggests that endometriosis is a neoplastic condition which serves as a precursor of ovarian and endometrial cancers. In the present review, we have attempted to take a stock of the current epidemiological and molecular knowledge regarding endometriosis associated cancers and develop a model of functional network with interactions among critical genomic factors regulating cellular processes leading to fibrotic reaction. It is being conjectured that cyclic bleeding associated with inflammatory and oxidative stress followed by repeated tissue injury and repair along with recurrent estrogenic stimulation and ovulatory events in the pelvic environment bring about the complex phenotype of atypical endometriosis and associated neoplasm with a trade-off malignant transformation in high risk population. Finally, we have presented an algorithm for pre-emptive monitoring and management of endometriosis-associated cancers.

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Section: Endometriosis-associated Extra-ovarian Cancersmentioning

confidence: 58%

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

Ghosh

Anupa

et al. 2019

COGO

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“…Although diabetes has long been known to be an independent risk factor for EC, little is known about the relationships between IR and EC [213]. Literature data were unable to indicate clear associations between insulin, IGFs, and sex steroid hormones with EC incidence because of the multitude of dysregulated pathways that lead to EC progression.…”

Section: Perspective and Future Directionsmentioning

confidence: 99%

Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA

Sidorkiewicz

Jóźwik

Niemira

et al. 2020

Cancers

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Endometrial cancer (EC) remains one of the most common cancers of the female reproductive system. Epidemiological and clinical data implicate insulin resistance (IR) and its accompanying hyperinsulinemia as key factors in the development of EC. MicroRNAs (miRNAs) are short molecules of non-coding endogenous RNA that function as post-transcriptional regulators. Accumulating evidence has shown that the miRNA expression pattern is also likely to be associated with EC risk factors. The aim of this work was the verification of the relationships between IR, EC, and miRNA, and, as based on the literature data, elucidation of miRNA’s potential utility for EC prevention in IR patients. The pathways affected in IR relate to the insulin receptors, insulin-like growth factors and their receptors, insulin-like growth factor binding proteins, sex hormone-binding globulin, and estrogens. Herein, we present and discuss arguments for miRNAs as a plausible molecular link between IR and EC development. Specifically, our careful literature search indicated that dysregulation of at least 13 miRNAs has been ascribed to both conditions. We conclude that there is a reasonable possibility for miRNAs to become a predictive factor of future EC in IR patients.

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“…The post-WHI analysis [54] discovered a high incidence of endometrial cancer [55], specially an increase over time in women aged 50-74 years (with an annual percentage change, in 2004-2009: 2.8%; in 2005-2009: 3.3%; and 2006-2009: 4.2%) [56], parallel to the decrease in the use of FDA-approved estrogen plus progestogen HT and parallel to the increase of endometrial hyperplasia [57], and after the increasing usage of compounded bioidentical HT (CBHT) instead of pharmacological products [58,59], even if CBHT are not approved by the FDA, because both hormone compounds lack of standard [type (estrogen: is E2 or E3), dosage, (under dosage), and underpotency (for progesterone)] [60].…”

Section: Endometrial Safety On Mht: History Regimens Endometrial Asmentioning

confidence: 99%

Endometrial Histology and Safety on Non-Oral Routes of Hormone Therapy for Perimenopausal/Early Menopausal Women: Transdermal Estrogens and Vaginal Micronized Progesterone

Russu¹

2020

Hormone Therapy and Replacement in Cancer and Aging-Related Diseases

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The Women's Health Initiative issues, confusions, and misunderstandings regarding women's and medical staff 's fears about coronary heart disease; stroke; venous thromboembolism; breast cancer; metabolic, cognitive and mood disorders; and general mortality have driven many attempts to promote other safe regimens for perimenopause/early menopause and midlife health. Perimenopause/early menopause climacteric syndrome may be safely treated with sequential transdermal/percutaneous estrogens and progestogens/vaginal progesterone or continuous transdermal estrogen plus intrauterine system medicated with progestogen/progesterone or with continuous combined transdermal estrogen-vaginal progesterone regimen, when menopause since 3 years. Endometrial safety is assessed in terms of endometrial hyperplasia and carcinoma prevention. Transvaginal sonography, hysteroscopy, and endometrial biopsy at 6/12 months ensure about secretory and atrophy/inactive endometrial aspects as markers for endometrial safety. The majority of endometrial carcinomas depicted after MHT are high grade, not estrogen dependent, developed on an atrophic endometrium. The histologic, genomic, and transcriptomic assessments with immunohistochemistry are diagnoses adjunct for cell proliferation/mitosis and apoptosis presence. Proteins, growth factors, cytokines as PAX2, PTEN and its genetic aberrations, microRNA-binding protein family (IMP, IGF-BP, progesterone dependent), bcl 2, Ki-67, K-ras, p53, p16, and steroid (estrogen and progesterone) receptors are markers for differentiation between benign hyperplasia/ endometrial intraepithelial neoplasia, type 1/type 2 endometrial carcinomas, and long-term outcome.

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Increased Incidence of Endometrial Cancer Following the Women's Health Initiative: An Assessment of Risk Factors

Cited by 131 publications

References 73 publications

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA

Endometrial Histology and Safety on Non-Oral Routes of Hormone Therapy for Perimenopausal/Early Menopausal Women: Transdermal Estrogens and Vaginal Micronized Progesterone

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