Enhancement of the Anti-inflammatory Action of Hydrocortisone by Estrogen

Spangler, Arthur S.; Antoniades, Harry N.; Sotman, S L; Inderbitizin, Theodor M.

doi:10.1210/jcem-29-5-650

Cited by 54 publications

(18 citation statements)

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“…Postmenopausal females may be particularly predisposed to sarcopenia due to the absence of the anabolic effects of circulating testosterone in addition to losing the anti-inflammatory effects of estrogen. Estrogen has been shown to have anti-inflammatory properties and men continue to aromatize estrogen so long as they have circulating testosterone (50)(51)(52)(53)(54)(55)(56)(57)(58)(59). In our study, we did not have data on whether our post-menopausal patients were on estrogen replacement therapy (ERT) and future studies are needed to compare the rate of sarcopenia and complications in this patient group.…”

Section: Discussionmentioning

confidence: 96%

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

Jin¹,

Mellon²,

Frakes³

et al. 2018

J. Gastrointest. Oncol.

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Background: Total psoas area (TPA), a marker of sarcopenia, has been used as an independent predictor of clinical outcomes in gastrointestinal (GI) cancers as a proxy for frailty and nutritional status. Our study aimed to evaluate whether TPA, in contrast to traditional measurements of nutrition like body mass index (BMI) and body surface area (BSA), was predictive of outcomes in borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients receiving stereotactic body radiation therapy (SBRT). Methods: Retrospective analysis of an institutional review board approved database of 222 BRPC and LAPC treated with SBRT from 2009-2016 yielded 183 patients that met our selection criteria of pre-SBRT computed tomography (CT) imaging with an identifiable L4 vertebra. Once the L4 vertebral level was identified, the bilateral psoas muscles were manually contoured. This area was normalized by patient height, with units described in mm 2 /m 2 . Receiver operating characteristic (ROC) curves were generated for TPA, BMI, and BSA to elicit clinically relevant cutoffs. Regression and Kaplan-Meier analyses were used to correlate toxicity with survival functions.Results: Low TPA (OR =1.903, P=0.036) was predictive of acute toxicities, and only TPA was predictive of Grade 3 or higher acute toxicities (OR =10.24, P=0.007). Both findings were independent of tumor resectability. Pain (P=0.003), fatigue (P=0.040), and nausea (P=0.039) were significantly associated with low TPA. No association was identified between any measurement of nutritional status and the development of late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median =21.98 months) than their LAPC (median =16.2 months) counterparts (P=0.002), independent of nutritional status. Conclusions: TPA measurement is readily available and more specific than BMI or BSA as a predictor of acute radiotoxic complications following SBRT in BRPC/LAPC patients. A TPA of <500 mm 2 /m 2 is a clinically relevant cutoff that can direct physicians to address expected complications of pain, fatigue, and nausea. However, tumor resectability remains as the only predictor of overall survival in this cohort.

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Section: Discussionmentioning

confidence: 96%

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

Jin¹,

Mellon²,

Frakes³

et al. 2018

J. Gastrointest. Oncol.

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“…Taken together, E2 may be therapeutically useful for the treatment of macrophage-involving in£ammatory skin diseases like psoriasis. Only one study reported that combinational use of estrogen with cor-ticosteroid reduced the dose of the latter drug required for a psoriatic patient, indicating the synergistic e¡ect of estrogen (Spangler et al, 1969). The e¡ects of estrogen on skin in vivo have recently been studied; topical or systemic estrogen treatment is known to prevent skin aging whereas it may cause skin hyperpigmentation (Sator et al, 2001;Shah and Maibach, 2001).…”

Section: Discussionmentioning

confidence: 99%

17beta-Estradiol Inhibits MCP-1 Production in Human Keratinocytes

Kanda¹,

Watanabe²

2003

J Invest Dermatol

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A chemokine, monocyte chemoattractant protein 1 (MCP-1), attracts macrophages. The production of MCP-1 is enhanced in keratinocytes of psoriatic lesions, which may contribute to macrophage infiltration into the lesions. It is known that estrogen regulates the course of psoriasis. We examined in vitro effects of 17beta-estradiol (E2) on MCP-1 production by human keratinocytes. E2 inhibited constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced MCP-1 secretion, mRNA expression, and promoter activity in keratinocytes, and these effects of E2 were counteracted by estrogen receptor antagonist ICI 182 780. GC-rich Sp1 element and activator protein 1 (AP-1) element on MCP-1 promoter were required for constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced transcription, respectively, and involved in transrepression by E2. E2 inhibited constitutive Sp1 and 12-O-tetradecanoylphorbol-13-acetate-induced AP-1 transcriptional activities whereas it did not inhibit DNA binding of Sp1 or AP-1 c-Fos/c-Jun. E2 inhibited Sp1 and AP-1 transcriptional activities and MCP-1 promoter activity in estrogen receptor beta (ERbeta) transfected SKBR3 cells. Deletion of the A/B region or mutation of activation function 2 in ERbeta abrogated E2-dependent transcriptional inhibition by ERbeta whereas mutation of DNA-binding domain retained the inhibitory effects. Transfection of ERbeta enhanced the inhibitory effects of E2 on Sp1 and AP-1 transcriptional activities and MCP-1 promoter activities in nontransfected keratinocytes. Coimmunoprecipitation studies showed an E2-dependent association of ERbeta with Sp1 or AP-1 in ERbeta-transfected keratinocytes. These results suggest that E2-bound ERbeta may inhibit MCP-1 gene expression by inhibiting Sp1 and AP-1 transcriptional activities in keratinocytes. A/B region and intact activation function 2 of ERbeta may be responsible for the effects of E2.

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“…Also, addition of estrogens to corticosteroid therapy resulted in a threefold to twentyfold reduction in the corticosteroid requirement for control of inflammatory skin diseases. 34 Neither of these two human studies separated possible metabolic versus pharmacodynamic interactions. In our study, no clear relationship was observed between the female hormone levels and the methylprednisolone IC 50 values for cortisol suppression.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

Lew

Ludwig

Milad

et al. 1993

Clin Pharmacol Ther

155

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The pharmacokinetics and selected pharmacodynamic responses to methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC 50 ) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC 50 values for effects of methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response.Male subjects typically have been used in most drug studies. However, the findings of these studies are applied clinically to both male and female patients, despite their physiologic differences. Of the studies that have enrolled both men and women, most fail to analyze their findings by gender and instead treat all the subjects as one homogeneous group. 1 This bias in clinical research has been of concern within the health professions. [2][3][4] The literature currently lacks guidelines regarding dosing regimens based on gender.Copyright © 1993 by Mosby-Year Book, Inc.Reprint requests: William J. Jusko, PhD, Hochstetter 565, School of Pharmacy, State University or New York at Buffalo, Buffalo, NY 14260. Presented at the Ninety-fourth Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, March 24-26, 1993, Honolulu, Hawaii (Abstract: Clin Pharmacol Ther 1993;53:183). NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2014 October 23. Published in final edited form as:Clin Pharmacol Ther. 1993 October ; 54(4): 402-414. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptGender-related differences in disposition have been observed for numerous drugs. The total and unbound clearance of diazepam, which undergoes oxidative metabolism, was found to be greater in women. 5 Clearance of oxazepam (total and unbound) 6 and acetaminophen, 7 both of which undergo glucuronide conjugation, is significantly greater ...

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Enhancement of the Anti-inflammatory Action of Hydrocortisone by Estrogen

Cited by 54 publications

References 0 publications

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

17beta-Estradiol Inhibits MCP-1 Production in Human Keratinocytes

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

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