Pathologic Effects of Oral Contraceptives

Hilliard, George D.; Norris, Henry J.

doi:10.1007/978-3-642-81267-5_2

Cited by 6 publications

(3 citation statements)

References 78 publications

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“…Estrogens are well established as important etiological agents for uterine carcinogenesis in humans (32)(33)(34)(35). Although exact roles remain to be detailed, tumor-promoting effects involving up-regulation of cell proliferation have long been suggested.…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive Effects of Hydroxymatairesinol on Uterine Carcinogenesis in Donryu Rats

Katsuda

Yoshida

Saarinen

et al. 2004

Exp Biol Med (Maywood)

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Hydroxymatairesinol (HMR), obtained from the heartwood of spruce (Picea abies), has been demonstrated to exert chemo-preventive effects on the development of mammary tumors in rats. To examine the influence of HMR on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at 11 weeks of age and fed thereafter 0, 200, or 600 ppm HMR mixed in the soy-containing diet until 15 months of age. Incidences of uterine adenocarcinoma in both 200 and 600 ppm HMR-dosed groups were significantly reduced to 11% and 15%, respectively, less than 50% of 0 ppm, at the end of the experiment (P < 0.05). A delay in the start of persistent estrus by HMR was observed at 8 months of age compared with controls given carcinogen alone. From urinalysis, HMR was metabolized mainly to enterolactone and hydroxyenterolactone. These findings suggest that HMR or its metabolites exert chemo-preventive effects in the rat ENNG-uterine carcinogenesis model.

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Section: Discussionmentioning

confidence: 99%

Chemopreventive Effects of Hydroxymatairesinol on Uterine Carcinogenesis in Donryu Rats

Katsuda

Yoshida

Saarinen

et al. 2004

Exp Biol Med (Maywood)

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“…Estrogens are well established to be important etiological agents for uterine carcinogenesis in humans. [12][13][14][15] Although the exact roles still remain to be detailed, the tumor-promotive effects of up-regulation of cell proliferation have long been suggested. Natural and synthetic estrogenic hormones express their effects mainly by binding to estrogen receptors.…”

Section: Discussionmentioning

confidence: 99%

“…11) While its etiology remains largely unclear, it has been pointed out that hormones such as estrogen may play essential roles. [12][13][14][15] Menoxenia, polycystic ovary syndrome, chronic anovulation, estrogen replacement therapy, obesity, hypertension, diabetes, and the nulliparous state have been listed as risk factors. [16][17][18][19][20] Recently, epidemiological evidence has accumulated with regard to endometrial cancers as second primaries after the use of tamoxifen, an anti-estrogen, for the treatment of breast cancer.…”

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confidence: 99%

Uterine Adenocarcinoma in N‐Ethyl‐N‐nitro‐N‐nitrosoguanidine‐treated Rats with High‐dose Exposure to p‐tert‐Octylphenol during Adulthood

Katsuda

Yoshida

Kuroda

et al. 2002

Japanese Journal of Cancer Research

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Since many risk factors are associated with the development of uterine adenocarcinomas in humans, the etiology is unclear in most cases, although it has been pointed out that estrogen may play essential roles. To clarify the effects of exposure to p-tert-octylphenol (OP), an environmental xenoestrogen, on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N-ethyl-N′ ′ ′ ′-nitro-N-nitrosoguanidine (ENNG) at 11 weeks of age and exposed thereafter to 100 mg/kg OP by s.c. injection until 15 months of age. Adult ovariectomized (OVX) rats were also treated in a similar way. OP had no effect on occurrence of persistent estrus in middle age, although uterotrophic effects were obvious in OVX rats. At the termination, development of uterine adenocarcinomas was significantly increased in animals exposed to OP during adulthood. No tumors, but a few focal hyperplasias, developed in OVX rats. These findings suggest that OP has tumor-promoting effects on ENNG-treated endometrium of rats, possibly due to direct action on the uterus, as indicated by the uterotrophic effect when a high dose of OP was given. The results provide clues to the mechanisms of influence of hormonal disrupters on uterine carcinogenesis. Key words: Octylphenol -Rat -Uterine adenocarcinoma -AdulthoodRecently, the possible adverse consequences arising from the release of man-made substances with estrogenic, anti-estrogenic or androgenic properties, so-called endocrine disrupting chemicals (EDCs), into the environment have become an important social issue. p-tert-Octylphenol [OP;1,3,phenol, Fig. 1], one of the alkylphenols (APs), is listed as an EDC with estrogenic activity in vitro 1,2) and in vivo. 3,4) Environmental OP is thought to be derived from biodegradation of non-ionic surfactants, alkylphenol polyethoxylates (APEOs), 5) and is found in the sludge of sewage-treatment plants as well as in the river and sea sediments.1, 6) It has been pointed out that human exposure to OP may occur not only through drinking water extracted from polluted rivers and foods from fields contaminated with sewage sludge, but also by contact with manufactured and/or breakdown products, such as absorption through skin from shampoos and cosmetics, or inhalation and ingestion from pesticide sprays. 7)While APs, including OP, exist at only very low concentrations in the environment (below 1 µg/liter in water in Europe) 8) and are markedly less estrogenic than estradiol-17β (E2), this does not rule out potential toxicity of chronic exposure to animals and human beings, taking into account the evidence of bioaccumulation in fish. 9)Carcinogenicity is the most important possible adverse consequence of chemicals including EDCs. In fact, it has been hypothesized that environmental estrogens, including APs, may be causative agents for breast cancer in humans.10) The uterine adenocarcinoma is one of the most common malignant tumors in women.11) While its etiology remains largely unclear, it has been pointed out that hormones such as estroge...

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Spontaneous uterine adenocarcinomas in aged rats and their relation to endocrine imbalance

Nagaoka

Oda

Matsushima

et al. 1990

J Cancer Res Clin Oncol

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In addition to spontaneous uterine endometrial adenocarcinomas at a high incidence (35.1%), development of endometrial hyperplasia/adenoma was also frequently detected in rats of the Donryu strain. The total yield of all observed proliferative endometrial lesions was very high (60.6%). The tumors arose commonly in the uterine horn of aged rats. Histologically, most demonstrated glandular structures, consisting of cuboidal or columnar cells with weak eosinophilic or basophilic cytoplasm and large nuclei. In about half of the animals with adenocarcinomas, metastasis to remote organs such as the lung was observed. Histological examination of the ovary and vaginal epithelium revealed ovarian cysts, atrophy of the ovary and cornification of the vaginal epithelium more frequently in rats with endometrial carcinomas than in animals without tumors. These findings indicate that adenocarcinoma development in Donryu rats is associated with endocrine imbalance [increased serum estrogen: progesterone (E2:P)ratios]. By comparative investigation of strain differences, it was confirmed that irregular estrous cycles began earlier with higher incidence in Donryu rats than in F344 rats, a low-incidence strain. Histological findings of the ovary and vaginal epithelium also suggested relatively increased estrogen levels in Donryu rats compared to F344 rats. Estimated plasma values of gonad steroids showed that the E2:P ratio in Donryu rats at 12 months of age was about five times that in F344 rats. These results therefore indicate that hormone imbalance, particularly an increased E2:P ratio, may play an important role in the spontaneous occurrence of endometrial adenocarcinoma in Donryu rats.

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Pathologic Effects of Oral Contraceptives

Cited by 6 publications

References 78 publications

Chemopreventive Effects of Hydroxymatairesinol on Uterine Carcinogenesis in Donryu Rats

Chemopreventive Effects of Hydroxymatairesinol on Uterine Carcinogenesis in Donryu Rats

Uterine Adenocarcinoma in N‐Ethyl‐N‐nitro‐N‐nitrosoguanidine‐treated Rats with High‐dose Exposure to p‐tert‐Octylphenol during Adulthood

Spontaneous uterine adenocarcinomas in aged rats and their relation to endocrine imbalance

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