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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical observations and experimental data suggest that sex hormones influence the development of systemic lupus erythematosus (SLE). An imbalance between androgen and estrogen plasma levels may suggest an abnormality in the aromatase activity involved in estradiol synthesis. Aromatase activity in skin and subcutaneous tissue and plasma sex-hormone levels (testosterone, androstenedione, estrone, estradiol, dehydrosterone sulfate, cortisol) were measured in 15 SLE patients (nine female, six male) who had never received corticosteroid treatment and in eight (four female, four male) healthy control subjects. There was a tendency toward an increase in aromatase activity in SLE patients when compared to control subjects. Among SLE patients the aromatase activity varied inversely with disease activity. Patients with SLE had decreased androgen and increased estrogen levels. Aromatase activity in SLE patients had significant direct correlation with estrogen levels. These data suggest that abnormal regulation of aromatase activity may partially explain the abnormalities of estrogen synthesis in SLE.
Lupus 1992 May
PMID:Plasma sex hormones and aromatase activity in tissues of patients with systemic lupus erythematosus. 130 81

The numerous clinical and experimental data suggesting a lupus-induced modulation of sex hormones prompted the study of sex hormone metabolism in these patients. Some hormonal abnormalities were reported in female patients: a) over production of 16-alpha-hydroxylated estradiol derivatives with potent peripheral estrogenic activities; b) under production of the following androgens: testosterone, dihydrotestosterone, dihydroandrosterone, dihydroandrosterone sulfate, delta 4-androstenedione. Moreover, some observations suggest an excessive transformation of androgens into estrogens: increased oxidation of testosterone on C17, skin lesions, abnormal skin, aromatase activity responsible for estradiol synthesis.
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PMID:[Sex hormone metabolism in acute systemic lupus erythematosus]. 236 14

The effects of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), which blocks oestrogen formation, have been studied in female MRL/MP-lpr/lpr mice which are a model of SLE. At 11.5 weeks, mice were implanted subcutaneously either with empty Silastic implants or with implants containing 25 mg 4-OHA. At 15 weeks, they were sacrificed by decapitation and liver, thymus, kidneys and uterus taken for wet weight, histology and measurement of cytosolic and nuclear oestrogen receptors. Thymus weights were significantly lower in 4-OHA-treated mice although uterus weights were similar in both groups. Also, whereas thymuses from control-treated mice were packed with plasma cells with abundant cytoplasm, those from 4-OHA-treated mice contained T cells with large nuclei. Relative oestrogen receptor abundances were: uterus > liver > thymus, although cytosolic receptors could not be detected in thymus cytosols of MRL mice unless they were treated with the aromatase inhibitor. In kidney, there was histological evidence that inflammation was limited to mesangium in 4-OHA-treated mice. These results support the hypothesis that oestrogens may be involved in the aetiology of murine SLE and provide data suggesting that substances which block oestrogen production in vivo may be useful to treat certain forms of SLE.
Lupus 1993 Aug
PMID:Effects of an aromatase inhibitor on thymus and kidney and on oestrogen receptors in female MRL/MP-lpr/lpr mice. 826 69

Although osteoporosis has traditionally been considered a disease of women, men also incur substantial bone loss with aging, and elderly men have age-specific hip fracture incidence rates and vertebral fracture prevalence rates that are at least half those in women. Early postmenopausal bone loss (which results in the syndrome of type I osteoporosis) is due to the direct skeletal consequences of estrogen deficiency, manifested by an increase in bone resorption without an adequate increase in bone formation. Recent evidence indicates that even late postmenopausal bone loss (type II or 'smile' osteoporosis) in women may be due to estrogen deficiency. In particular, the late consequences of estrogen deficiency in elderly women result in abnormalities in calcium homeostasis and increases in parathyroid hormone secretion, leading to increased bone resorption and bone loss. The etiology of bone loss in aging men has remained relatively unclear. Recent evidence from a male deficient in estrogen receptor-alpha and in two males with aromatase deficiency indicate that estrogen may play a significant role in bone metabolism in men. Moreover, several large epidemiologic studies have found that bone mineral density correlates better with serum estrogen than testosterone in aging men. Thus estrogen deficiency may lead to bone loss in men.
Lupus 1999
PMID:Osteoporosis: gender differences and similarities. 1045 20

Sex hormones seem to play an important role as modulators of the autoimmune disease onset/perpetuation. Generally, steroid hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immunosuppressors. Synovial fluid levels (SF) of proinflammatory estrogens relative to androgens are significantly elevated in both male and female rheumatoid arthritis (RA) patients, as compared to controls, which is most probably due to increase of local enzymatic aromatase activity. Serum levels of estrogens have been found altered in RA patients, particularly estradiol in man. Thus, available steroid prehormones are rapidly converted to proinflammatory estrogens in the synovial tissue in the presence of inflammatory cytokines (i.e., TNFalpha, IL-1, IL-6). The increased estrogen concentrations observed in RA SF of both sexes are characterized mainly by the hydroxylated forms, in particular, 16alpha-hydroxyestrone, showing a mitogenic tumor growth stimulating role. Altered serum hydroxylated estrogens have been found also in serum of systemic lupus erythematosus (SLE) patients. As a matter of fact, our recent studies indicate that 17-beta estradiol (E2) clearly enhanced the expression of markers of cell growth and proliferation, whereas testosterone (T) induced an increase of markers indicating DNA damage and apoptosis. In particular, our data further shows that the enhancing role of estrogens on immune/inflammatory response is exerted by activating the NFkB complex pathway. In conclusion, locally increased estrogens (i.e., synovial tissue in RA or skin in SLE) might exert activating effects on cell proliferation, including macrophages and fibroblasts, suggesting new roles for estrogens in autoimmunity.
Lupus 2004
PMID:Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. 1548 92

Secondary osteoporosis is common among patients being evaluated for osteoporosis. All men and premenopausal women with unexplained bone loss or a history of a fragility fracture should undergo a work-up for secondary osteoporosis. Also, postmenopausal women with risk factors for secondary osteoporosis should be carefully evaluated. The evaluation should include a thorough history, physical examination, bone mineral density testing, and laboratory testing. While there is no consensus for a cost-effective laboratory evaluation, some recommendations include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium, phosphate, creatinine, liver function tests, a complete blood count, testosterone in men, and thyroid-stimulating hormone. After a thorough review of the evaluation for secondary osteoporosis, this chapter reviews the pathophysiology and treatment of secondary osteoporotic disorders, including vitamin D insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis, ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for breast cancer. Physicians have a significant responsibility to evaluate and treat the underlying medical problem that is the cause of secondary osteoporosis and to optimize bone health in the individual patient.
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PMID:The management of secondary osteoporosis. 1630 Nov 95

Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients.
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PMID:Estrogens and autoimmune diseases. 1726 96

Autoantibodies and lupus-like syndromes can develop following the use of certain medications; however, although many patients develop autoantibodies, only a minority develop clinical features. Although these autoantibodies primarily consist of antinuclear and antihistone antibodies, additional types of antibody, such as antineutrophil cytoplasmic antibodies and anti-double-stranded DNA antibodies, have been reported in association with minocycline and tumor necrosis factor inhibitor therapy. Clinical features of drug-related lupus usually consist of constitutional symptoms, arthralgias, arthritis, myalgias and serositis, although cutaneous manifestations have been reported in association with the use of tumor necrosis factor inhibitors. Typically, clinical features resolve with discontinuation of the medication, although antibodies can persist for months or years. Arthralgias and inflammatory arthritis have also been reported in association with the use of aromatase inhibitors and other biologic agents such as interleukins and interferons.
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PMID:Drug insight: autoimmune effects of medications-what's new? 1820 8

Experimental and animal studies suggested that estrogens play an important role in the development of systemic lupus erythematosus (SLE) through a variety of mechanisms involved in the regulation of the immune system. The objective of this study was to investigate the association between genetic variations in estrogen metabolic pathway genes, including estrogen receptor alpha (ESR1), estrogen receptor beta (ESR2), and aromatase (CYP19A1), and risk of SLE. We performed a genetic study of SLE among 46 medical record-confirmed female SLE cases and 102 female controls participating in an Internet-based case-control study of SLE. Polymorphisms analysed included: ESR1 PvuII, XbaI, and GT repeat; ESR2 RsaI, AluI, and CA repeat; and CYP19A1 RsaI, SfaN1, and TTTA repeat. We found significant association of the ESR1 PvuII (PP vs. pp, odds ratio (OR): 3.1, 95% confidence interval (CI): 1.1-9.3) and XbaI (XX vs. xx, adjusted OR: 3.4, 95% CI: 1.1-10.5) with SLE. Carrying the PPXX genotype conferred the highest risk (PPXX vs. ppxx, OR: 4.6, 95% CI: 1.3-15.9). We also found an association of SLE with the ESR2 CA repeat (SS vs. LL, OR: 2.8, 95% CI: 1.0-8.0). Our results support a role of estrogen in pathogenesis of SLE and suggested that genetic variants in the estrogen receptor genes might influence susceptibility.
Lupus 2010 May
PMID:Association of estrogen and aromatase gene polymorphisms with systemic lupus erythematosus. 2030 46

Epidemiological and experimental immunological evidence suggest that estrogens enhance the humoral immune response, and at the same time, seem to play important roles in pathophysiology of autoimmune rheumatic diseases. Estrogens in human subjects are generally considered as enhancers of cell proliferation (anti-apoptotic), however, rather than through their serum levels (that may exert opposite dose-related effects), they play important roles through their peripheral metabolites especially in autoimmune rheumatic diseases. Several investigations strongly support an accelerated aromatase-mediated peripheral metabolic conversion of upstream androgen precursors to estrogen metabolites in peripheral tissues affected by immune/inflammatory reactions, both, in male and female patients. In RA synovial tissue, biological effects of these metabolites as a consequence of altered peripheral sex hormone synthesis (intracrine, e.g., at the level of macrophages and fibroblasts) mainly results in stimulation of cell proliferation and cytokine production (i.e. TNF). It was shown that RA synovial cells mainly produce the cell proproliferative 16alpha-hydroxyestrone which, in addition to 16alpha-hydroxy-17beta-estradiol, is the downstream estrogen metabolite that interferes with monocyte proliferation. Therefore, a preponderance of 16alpha-hydroxylated estrogens is an unfavorable sign, at least, in synovial inflammation and possibly related synovial tissue hyperplasia. Interestingly, urinary concentration and total urinary loss of 2-hydroxyestrogens was found 10 times higher in healthy subjects compared to RA or SLE patients irrespective of prior prednisolone treatment or sex. The intracrine synthesis of active estrogen metabolites at the level of cells involved in the immune response (e.g. macrophages and fibroblasts) represents a common pathway that characterizes a similar final immune reactivity in both male and female patients.
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PMID:Estrogen metabolism and autoimmunity. 2215 98


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