Intimal Vascular Lesions Associated With Female Reproductive Steroids

Irey, Nelson S.; Norris, Henry J.

doi:10.1097/00006254-197403000-00002

Cited by 30 publications

(34 citation statements)

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“…At times occlusive thrombosis is present within these tumors. Similar changes have been observed in experimental animals given large doses of contraceptive steroids (10) and have been reported in the portal vessels of patients with reproductive steroid exposure (29). There is also some experimental evidence that exogenous estrogen may alter vascular integrity (30).…”

Section: Methodssupporting

confidence: 77%

Human Liver Neoplasia and Steroid Exposure

1982

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This study examines experience with over 250 liver tumors in young women. Most were oral contraceptive related. There were two distinct benign liver tumor types: focal nodular hyperplasia and liver cell adenoma. Six benign liver tumors were examined for estrogen receptors. They did not contain significant quantities of estrogen receptor, supporting experimental studies of an epigenetic origin. Multiple tumors occurred in about 20% of cases but did not change the favorable prognosis associated with benign tumors. The most significant source of morbidity and mortality was spontaneous hemorrhage or rupture. Twenty-three women in this series had hepatocellular carcinoma and the majority of these were associated with prolonged steroid usage. These malignant liver tumors occurred in young females without cirrhosis or other factors known to be associated with hepatic malignancy. Unlike "hepatocellular carcinomas" reported in males taking anabolic androgenic steroids, the tumors in females had a high rate of metastasis t o a variety of organs. The risk of liver tumors in oral contraceptive users remains unknown, but must be very small since an estimated 150 million women worldwide and 40 million in the U.S.A. have used oral contraceptives.

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Section: Methodssupporting

confidence: 77%

Human Liver Neoplasia and Steroid Exposure

1982

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“…While there is no proof that these are primary, they are similar to lesions appearing in experimental animals receiving steroids. These vascular lesions also bear a striking resemblance to lesions reported in patients with reproductive steroid exposure (23).…”

Section: Resultssupporting

confidence: 57%

Human liver tumors in relation to steroidal usage.

Barrows¹,

Christopherson²

1983

Environ Health Perspect

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Since 1973 a number of investigators have reported an association between liver neoplasia and steroid usage. Through referral material we have examined the histology of over 250 cases of hepatic neoplasia, most in patients receiving steroid medications. The majority have been benign, predominantly focal nodular hyperplasia (55%) and hepatocellular adenoma (39%). The average age was 31.4 years; 83% had significant steroid exposure with an average duration of 71 months for focal nodular hyperplasia and 79.6 months for hepatocellular adenoma. The type of estrogenic agent was predominantly mestranol; however, during the period mestranol was the most frequently used synthetic steroid. A distinct clinical entity of life threatening hemorrhage from the lesion occurred in 31% of patients with hepatocellular adenoma and 9% of patients with focal nodular hyperplasia. Recurrence of benign tumors has occurred in some patients who continued using steroids and regression has been observed in patients who had incomplete tumor removal but discontinued steroid medication. Medial and intimal vascular changes have been present in a large number of the benign tumors. The relationship of these vascular changes to oncogenesis is unclear, but similar lesions have been described in the peripheral vasculature associated with steroid administration. A number of hepatocellular carcinomas have also been seen. Of significance is the young age of these patients and lack of abnormal histology in adjacent nonneoplastic liver. A striking number of the malignant hepatocellular tumors have been of the uncommon type described as "eosinophillic hepatocellular carcinoma with lamellar fibrosis." The epidemiology of liver lesions within this series is difficult to assess, since the material has been referred from very diverse locations.

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“…In this regard, the sex difference in the incidence and pathogenesis of pulmonary hypertension has encouraged research that is focused on the mechanisms involved. The change in female hormones was put forth as one possible explanation, based on studies showing that PAH was more prevalent in women who had taken oral contraceptives (16,23) or received hormone replacement therapy (43). Nonetheless, some controversial findings refuted such an association (1) and a female-favorable advantage in IPAH survival has even been documented (18).…”

mentioning

confidence: 99%

EET-dependent potentiation of pulmonary arterial pressure: sex-different regulation of soluble epoxide hydrolase

Kandhi

Qin

Froogh

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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We tested the hypothesis that suppression of epoxyeicosatrienoic acid (EET) metabolism via genetic knockout of the gene for soluble epoxide hydrolase (sEH-KO), or female-specific downregulation of sEH expression, plays a role in the potentiation of pulmonary hypertension. We used male (M) and female (F) wild-type (WT) and sEH-KO mice; the latter have high pulmonary EETs. Right ventricular systolic pressure (RVSP) and mean arterial blood pressure (MABP) in control and in response to in vivo administration of U46619 (thromboxane analog), 14,15-EET, and 14,15-EEZE [14,15-epoxyeicosa-5(z)-enoic acid; antagonist of EETs] were recorded. Basal RVSP was comparable among all groups of mice, whereas MABP was significantly lower in F-WT than M-WT mice and further reduced predominantly in F-KO compared with M-KO mice. U46619 dose dependently increased RVSP and MABP in all groups of mice. The increase in RVSP was significantly greater and coincided with smaller increases in MABP in M-KO and F-WT mice compared with M-WT mice. In F-KO mice, the elevation of RVSP by U46619 was even higher than in M-KO and F-WT mice, associated with the least increase in MABP. 14,15-EEZE prevented the augmentation of U46619-induced elevation of RVSP in sEH-KO mice, whereas 14,15-EET-induced pulmonary vasoconstriction was comparable in all groups of mice. sEH expression in the lungs was reduced, paralleled with higher levels of EETs in F-WT compared with M-WT mice. In summary, EETs initiate pulmonary vasoconstriction but act as vasodilators systemically. High pulmonary EETs, as a function of downregulation or deletion of sEH, potentiate U46619-induced increases in RVSP in a female-susceptible manner. pulmonary hypertension; soluble epoxide hydrolase; epoxyeicosatrienoic acids; right ventricular systolic pressure; sex difference PULMONARY ARTERIAL HYPERTENSION (PAH) is a progressive disease with different etiologies that primarily affects small pulmonary arteries (28) and is associated with elevated pulmonary vasoconstriction, smooth muscle proliferation, endothelial dysfunction, and pulmonary remodeling (32). The two major factors that specifically contribute to the increase in pulmonary vascular resistance are vasoconstriction and vascular remodeling (9). Acute vasodilation resulting from the inhibition of Rho-kinase, an enzyme that causes sustained pulmonary vasoconstriction to generate pulmonary hypertension (33), significantly ameliorates pulmonary arterial pressure in patients with severe pulmonary hypertension (PH) (14, 17). Based on this evidence, recent studies arose to address the concern that specific roles of vasoconstriction in late stages of PH was underappreciated (39). The findings address an important issue that pulmonary artery tone and consequentially pulmonary resistance are controlled by factors released from the pulmonary vasculature. In this regard, any lung-sourced vasoconstrictors merit consideration as an endogenous trigger for PAH. For instance, endothelium-derived metabolites of arachidonic acid (AA) by lipoxygenase to ...

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Intimal Vascular Lesions Associated With Female Reproductive Steroids

Cited by 30 publications

References 0 publications

Human Liver Neoplasia and Steroid Exposure

Human Liver Neoplasia and Steroid Exposure

Human liver tumors in relation to steroidal usage.

EET-dependent potentiation of pulmonary arterial pressure: sex-different regulation of soluble epoxide hydrolase

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