Is there an altered steroid profile in patients with endometrial carcinoma?

Möllerström, Gunnar; Carlström, Kjell; Lagrelius, A.; Einhorn, Nina

doi:10.1002/1097-0142(19930701)72:1<173::aid-cncr2820720132>3.0.co;2-x

Cited by 14 publications

(6 citation statements)

References 48 publications

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“…Carcinogenesis hormonal mechanisms may be operating in cancer in addition to, or along with, the potential AC excess during 6 h of 15,000 ppm CE daily exposure. The presence of uterine carcinomas and the associated presence of many ovarian metastasized uterine cancers both suggest the possibility of adrenal-promoted cancer mechanism occurred in FM that has been already reported in humans (Mollerstrom, et al, 1993;Lucas, 1974). Only FM were positive in the NTP bioassay, and only FM showed hyperkinetic stereotypic running (stress) in their cages but only during exposure and two other independent studies exhibited the same type of hyperkinesis of recursive running in their cages (Griesemer and Eustis, 1994;Pottenger, et al, 1993;US EPA, 2008).…”

Section: Metastasismentioning

confidence: 74%

Analysis of chloroethane toxicity and carcinogenicity including a comparison with bromoethane

2008

Toxicol Ind Health

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Chloroethane (CE) gas carcinogenicity is analyzed and determined from a National Toxicology Program (NTP) bioassay where an inhalation concentration of 15,000 ppm CE gas in air produced the highest incidence of an uncommon-to-rare tumor ever observed by the NTP. Persistently inhaled CE produces endometrial cancers in female mice. The first-tumor-corrected uterine endometrial incidence (I) in B6C3F1 mice is 90%, but no significant tumors occurred in F344 rats. The endometrial cancers dispersed by 1) migrating locally to the adjacent myometrium, 2) then migrating to the bloodstream by intravasation, 3) entering 17 distal organs by extravasation and adapting to the new tissue environment. Distal cancers retained sufficient endometrial cell features to be recognized at each metastatic site. CE produced one of the highest metastasis rates ever observed by NTP of 79%. Comparing CE with bromoethane (BE), a structural analogue, it was found that BE too produced rare murine endometrial cancers yielding the second highest NTP incidence rate of I = 58% with a similar high malignancy rate of 56%. Because of the historical rarity of endometrial tumors in the B6C3F1 mouse, both of these SAR haloethanes seem to be evoking a strong, related carcinogenic potential in B6C3F1 mice, but not in F344 rats. The question of whether humans are similar to mice or to rats is addressed here and in Gargas, et al., 2008. The powerful carcinogenesis caused by these halohydrocarbons may have been caused by excessive and metabolically unresolved acetaldehyde (AC) which is directly generated by Cyp2E1 in the oxidative elimination of CE. With >95% AC metabolic production, as predicted from pharmacokinetic (PK) studies depending on CE exposure, AC is the main elimination intermediate. AC is a known animal carcinogen and a strongly suspected human carcinogen. Also, CE causes incipient decreases of tissue essential glutathione pools [GSH] by Phase II conjugation metabolic elimination of CE (and BE), by glutantione transferase (GST), in most organs (except brain) exposed to high circulating CE and it metabolites. In three laboratories, an excessive stress reaction of hyperkinesis was observed only during 15,000 ppm gas exposure but not when the exposure ceased or when exposure was presented at 150 ppm. Test rodents other than the female mice did not exhibit a pattern of visible stress nor did they have a carcinogenic response to CE gas. Unremitting stress has been documented to contribute a feedback to the hypothalamus which stimulates the hypothalamic-pituitary-axis (HPA), which in turn, induces the adrenal glands. Because estrus and estrogen and progesterone levels were unaltered by CE gas, the adrenal over stimulation, causing high steroid output, may be the penultimate step in this extraordinary carcinogenic response. High adrenal production of corticosteroids could adversely promote endometrial cells to cancers in mice - a mechanism that has already been observed in humans.

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Section: Metastasismentioning

confidence: 74%

Analysis of chloroethane toxicity and carcinogenicity including a comparison with bromoethane

2008

Toxicol Ind Health

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“…Few prospective studies have shown no statistical association between the levels of testosterone and endometrial cancer in premenopausal women 16 whereas positive association between testosterone levels and endometrial cancer risk was observed in post menopausal women in many studies. 16,17 Many case control studies have shown that endometrial cancer risk is also increased in both pre and postmenopausal women with elevated plasma levels of androstenedione 18,19 and testosterone [20] and few did not show the association. 21,22 Androgens do not appear to have any direct stimulatory effect on endometrial cell proliferation and the results from in vitro studies suggest a reduction in proliferation rates.…”

Section: Resultsmentioning

confidence: 99%

Study of endogenous hormones in endometrial cancer patients of premenopausal women

2020

IJCBR

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Introduction: Several studies were conducted worldwide to estimate various endogenous hormone levels in endometrial cancer patients of post-menopausal women and very few studies were done in premenopausal women. In India, our study is the first study conducted to estimate the endogenous hormones in endometrial cancer patients of premenopausal age group. Materials and Methods: 25 number of endometrial cancer patients were taken as cases and 50 number of age matched healthy subjects were selected as controls for this study. Total testosterone, follicular estrogen, mid luteal estrogen, luteal estrogen, and follicular progesterone, mid luteal progesterone, luteal progesterone and fasting insulin were estimated for all the subjects. Results: Statistical significant increase were observed in the levels of testosterone, follicular progesterone, mid luteal progesterone and luteal progesterone in cases when compared to controls. No statistical significant difference were observed in follicular estrogen, mid luteal estrogen, luteal estrogen and fasting insulin levels between cases and controls. Conclusion: From our study we conclude that endogenous hormones play a major role in the development of endometrial cancer in pre menopausal women as Testosterone is increased and progesterone is decreased in cases when compared to controls. Extensive studies are required to diagnose endometrial cancer in early stages for better prognosis.

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“…This is because the level of sex-hormone-binding globulin is decreased in obese postmenopausal women 16 30–36. It is worth mentioning that although all postmenopausal women are capable of converting androgens to oestrogens under ‘physiological’ conditions,37 only those that have a high efficiency in doing so are at risk of developing endometrial cancer38 39; indeed, extrafollicular oestrogen concentrations are significantly higher in women with endometrial carcinomas relative to healthy controls 22 26 34. It is possible that some of the conversion occurs in the endometrium, through endometrial aromatase cytochrome P450, thus increasing oestrogen concentrations at the endometrial level 21 40…”

Section: Pathogenetic Mechanism In Endometrial Carcinomas At Menopausmentioning

confidence: 99%

The pathogenesis of endometrial carcinomas at menopause: facts and figures

Sivridis

Giatromanolaki

2011

J Clin Pathol

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Almost a third of the life of a woman is now postmenopausal, and during this period over 80% of endometrial carcinomas develop. This is by far the most common gynaecological malignancy in the industrialised world and, probably, the less completely understood with regard to its pathogenesis after the menopause. For while it is generally thought that these neoplasms are non-oestrogen-induced, we are, at the same time, informed that oestrogenic stimulation is continuous during menopause through increases to oestrone formation in the adipose tissue from androgens of adrenal and ovarian origin. Furthermore, the postmenopausal endometrium has been typified as atrophic, which is indeed true, but is also implied as being inactive, which in fact it is not; in most cases, the postmenopausal endometrium appears to be weakly proliferative with potential to give rise to an endometrial carcinoma. It is also assumed that postmenopausal endometrial tumours are predominantly of serous papillary and clear cell type, and, in general, they are not well-differentiated endometrioid carcinomas; in reality, no more than 15% are serous papillary and clear cell carcinomas, and no less than 55% are well-differentiated endometrioid neoplasms. The overall prognosis is presumed to be poor, yet postmenopausal patients harbouring well-differentiated endometrioid carcinomas have the same excellent prognosis as those premenopausal women having endometrioid tumours of similar grade and stage. This brief account of endometrial carcinogenesis at menopause re-evaluates these issues and, in the light of new and old evidence, proposes the separation of G1 endometrioid adenocarcinomas (low-grade tumours) from all others (high-grade tumours).

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Is there an altered steroid profile in patients with endometrial carcinoma?

Cited by 14 publications

References 48 publications

Analysis of chloroethane toxicity and carcinogenicity including a comparison with bromoethane

Analysis of chloroethane toxicity and carcinogenicity including a comparison with bromoethane

Study of endogenous hormones in endometrial cancer patients of premenopausal women

The pathogenesis of endometrial carcinomas at menopause: facts and figures

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