Transdermal estrogen replacement therapy in postmenopausal women previously treated for porphyria cutanea tarda

Bulaj, Zaneta J.; Franklin, Michael R.; Phillips, John D.; Miller, Karen; Bergonia, Hector A.; Ajioka, Richard S.; Griffen, Linda M.; Guinee, Donald J.; Edwards, Corwin Q.; Kushner, James P.

doi:10.1067/mlc.2000.111024

Cited by 42 publications

(27 citation statements)

References 19 publications

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“…In contrast, most (but not all) of the uroporphyrinogen III generated would be decarboxylated and ultimately converted to heme. This scenario is supported by the observation that hepatic heme production is not deficient in PCT or in animal models of PCT as functional hemoproteins, such as cytochrome P450s, can be induced (34,35).…”

Section: Discussionsupporting

confidence: 59%

“…Most heterozygotes for URO-D mutations do not express a phenotype unless additional genetic or environmental factors are present. These include homozygosity for mutant hemochromatosis alleles, hepatitis C, alcohol abuse, and the use of medicinal estrogens (2). No mutations in the URO-D gene have been identified in the remaining two-thirds of patients (designated sporadic PCT, or S-PCT).…”

mentioning

confidence: 99%

“…The fluorescent property of uroporphyrin is responsible for the photodermatitis that occurs on sunexposed areas. Porphyric disorders are usually due to mutations affecting enzymes in the heme biosynthetic pathway, but only approximately one-third of patients with PCT are heterozygous for a mutant allele of URO-D (designated familial PCT, or F-PCT) (1,2). Most heterozygotes for URO-D mutations do not express a phenotype unless additional genetic or environmental factors are present.…”

mentioning

confidence: 99%

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A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda

Phillips¹,

Bergonia²,

Reilly

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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131

102

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Porphyria cutanea tarda (PCT), the most common form of porphyria in humans, is due to reduced activity of uroporphyrinogen decarboxylase (URO-D) in the liver. Previous studies have demonstrated that protein levels of URO-D do not change when catalytic activity is reduced, suggesting that an inhibitor of URO-D is generated in hepatocytes. Here, we describe the identification and characterization of an inhibitor of URO-D in liver cytosolic extracts from two murine models of PCT: wild-type mice treated with iron, ␦-aminolevulinic acid, and polychlorinated biphenyls; and mice with one null allele of Uro-d and two null alleles of the hemochromatosis gene (Uro-d ؉/؊ , Hfe ؊/؊ ) that develop PCT with no treatments. In both models, we identified an inhibitor of recombinant human URO-D (rhURO-D). The inhibitor was characterized by solid-phase extraction, chromatography, UV-visible spectroscopy, and mass spectroscopy and proved to be uroporphomethene, a compound in which one bridge carbon in the uroporphyrinogen macrocycle is oxidized. We synthesized uroporphomethene by photooxidation of enzymatically generated uroporphyrinogen I or III. Both uroporphomethenes inhibited rhURO-D, but the III isomer porphomethene was a more potent inhibitor. Finally, we detected an inhibitor of rhURO-D in cytosolic extracts of liver biopsy samples of patients with PCT. These studies define the mechanism underlying clinical expression of the PCT phenotype, namely oxidation of uroporphyrinogen to uroporphomethene, a competitive inhibitor of URO-D. The oxidation reaction is iron-dependent.heme ͉ porphyrins ͉ iron ͉ oxidation

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda

Phillips¹,

Bergonia²,

Reilly

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

131

102

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“…42 Down-regulation of HAMP by alcohol in a rat model was also reported by Bridle et al 43 Oral estrogen use is an independent risk factor for the development of PCT. 44 Estrogens may have a variety of adverse effects on the liver, including steatosis and steatohepatitis. 45,46 Evidence in humans and in animal models of nonalcoholic fatty liver disease suggests that oxidative cellular damage plays an important role in disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of hepcidin in porphyria cutanea tarda

Ajioka¹,

Phillips²,

Weiss

et al. 2008

Blood

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“…Os estrogênios tradicionalmente têm sido evitados em pacientes com LES pela possibilidade de maior ativação da doença. O estudo que melhor avaliou os efeitos do uso da TH em pacientes com LES foi o SELENA Trial (24). As pacientes incluídas receberam, por um ano, placebo ou estrogênio conjugados (0,625 mg diários) associados a medroxiprogesterona (5 mg por 12 dias ao mês), ambos por via oral.…”

Section: Porfiria Doença Hepatobiliar E Lupus Eritematoso Sistêmicounclassified

Terapia hormonal na menopausa: quando não usar

Spritzer

Wender

2007

Arq Bras Endocrinol Metab

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RESUMOA menopausa corresponde à cessação permanente da menstruação, conseqüente à perda da função folicular ovariana ou à remoção cirúrgica dos ovários. A idade média para ocorrência da menopausa natural gira em torno de 50 anos. A deficiência estrogênica decorrente da menopausa está associada com sintomas vasomotores, atrofia urogenital, declínio cognitivo, assim como a um aumento no risco de doenças crônico-degenerativas, aterosclerose e doença cardiovascular, osteoporose e doença de Alzheimer. A estrogenioterapia permanece sendo o tratamento mais efetivo para o manejo dos sintomas vasomotores e atrofia urogenital. Em mulheres com útero presente, a progesterona natural ou os progestogênios devem ser associados ao tratamento com estradiol para antagonizar os efeitos proliferativos deste hormônio sobre o endométrio e anular o risco de hiperplasia/carcinoma endometrial. Por outro lado, em determinadas condições clínicas, a terapia hormonal não é recomendada ou é mesmo contra-indicada. Neste artigo, focalizamos criticamente essas situações clínicas em que não se deve indicar a terapia hormonal na menopausa. Menopause is defined as the permanent cessation of menses, as a result of the loss of ovarian follicular function or of surgical removal of ovaries. The mean age for occurrence of natural menopause is around 50 years. Estrogen deficiency has been associated with vasomotor symptoms, urogenital atrophy, and cognitive impairment, as well as increased risk of chronic degenerative diseases such as osteoporosis and Alzheimer's disease. Estrogen therapy remains the most effective treatment for the management of vasomotor symptoms and urogenital atrophy. Progesterone or progestins should be added to estrogen treatment in women with uterus, in order to antagonize the estrogen-induced endometrial proliferation. In turn, in specific clinical conditions hormone therapy is not recommended. In the present article, the authors critically focus these clinical conditions in which hormone therapy should not be used.

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Transdermal estrogen replacement therapy in postmenopausal women previously treated for porphyria cutanea tarda

Cited by 42 publications

References 19 publications

A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda

A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda

Down-regulation of hepcidin in porphyria cutanea tarda

Terapia hormonal na menopausa: quando não usar

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