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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medical treatment of endometriosis is a critical aspect of the therapeutic approach to this disease. This review will present an overview of current literature about the medical treatment of endometriosis, without referring to the surgical treatment or a combination of both. The main purpose of the current medical treatment of endometriosis is to create an amenorrheic state, in other words, to create a hypoestrogenic environment by suppressing estrogen secretion of the ovary. Current research has focused upon medications designed to attack specific aspects of the development and maintenance of endometriosis. This includes progesterone receptor modulators, gonadotropin releasing hormone (GnRH) analogs, aromatase inhibitors and, tumor necrosis factor alpha (TNFalpha) inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors and estrogen receptor beta agonists like inmunomodulators. These drugs show decreased spreading of lesions and reduced disease related symptoms. Medical treatment is moderately effective in reducing pain but ineffective in improving fertility; a combination of medical treatment with assisted reproductive technology may be beneficial in improving fertility.
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PMID:Medical treatment of endometriosis. 1616 34

The current case report describes the development and medical treatment of an aggressive pelvic endometrioma in a post-menopausal patient, who had undergone abdominal hysterectomy and salpingo-oophorectomy a decade earlier. The patient was referred to the authors' centre because of right-sided sciatic pain. Three months before her admission she was hospitalized elsewhere due to subacute bowel obstruction. She was operated on and a resection of a part of sigmoid colon and an endometrioma, which was the cause of the subobstruction, was carried out. During the clinical investigation for the right-sided sciatic pain, an intrapelvic mass was found, which was compressing the lumbo-sacral plexus mimicking sciatica. The diagnosis of recurrent endometrioma was confirmed by a computerized tomography-guided biopsy and the decision was made to treat it with an aromatase inhibitor (letrozole). Eighteen months later, the endometrioma was almost completely regressed and the patient was free of symptoms. Medical management of recurrent post-menopausal endometriosis with aromatase inhibitors seems to be an effective alternative treatment to surgery.
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PMID:Successful treatment of an aggressive recurrent post-menopausal endometriosis with an aromatase inhibitor. 1627 8

Endometriosis is an estrogen-dependent gynaecological disease associated with pain and infertility, which occurs in humans and menstruating primates. In this study, the marmoset monkey (Callithrix jacchus), which is a non-menstruating primate with high circulating estrogen levels, was used to test firstly the hypothesis that endometriosis is based on uterine shedding into the peritoneal cavity, secondly to study the pathogenesis of endometriosis due to its estrogenic situation. Female marmoset monkeys (n = 29) were exposed to two different experimental procedures (non-invasive versus invasive) for intrapelvic placement of endometrial cells by uterine flushing over an experimental period of 2-3 years. First endometriotic foci were detected by colour Doppler ultrasound at the bladder, the uterus and the ovaries at the earliest after 4 months of either treatments. However, invasive induction was more effective in terms of the time-course of induction and the number of resulting endometriotic foci. The analysis of the endometriotic foci by histology, immunohistochemistry and molecular techniques allowed a division into two distinct groups: an initial developing stage occurred, which under further treatment led to the second stage of established endometriosis. Both procedures showed a treatment-dependent increase of vascular supply to the endometriotic foci over the experimental period. The invasive method induced the final established stage of endometriosis more rapidly, with the expression of steroid receptors, aromatase, 17betaHSD1 and CD10. Altogether, 72% of the treated marmoset monkeys developed endometriosis under our endometrial reflux protocols. Our data support the theory that endometriosis can be induced artificially in a non-menstruating primate (C. jacchus) by endometrial shedding into the peritoneal cavity. Because the marmoset is a primate with very high peripheral estrogen levels, this offers an interesting model for studying the pathogenesis of this estrogen-dependent disease, as well as for therapeutic impacts on enzymes involved in steroid metabolism.
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PMID:Induction of endometriosis in the marmoset monkey (Callithrix jacchus). 1660 6

The data summarized here suggest the existence of a new central pathway for the hormonal regulation of pain. These data mainly collected in quail, a useful model in neuroendocrinology, demonstrate that numerous neurons in the superficial laminae of the spinal cord express aromatase (estrogen-synthase). Chronic and systemic blockade of this enzyme in quail alters nociception within days, indicating that the slow genomic effects of sex steroids on nociception classically observed in mammals also occur in birds and require aromatization of androgens into estrogens. However, by contrast with these slow effects, acute intrathecal inhibition of aromatase in restricted spinal cord segments reveals that estrogens can also control nociception much faster, within 1 min, presumably through the activation of a nongenomic pathway and in a manner that depends on an immediate response to fast activation/deactivation of local aromatase activity. This emergent central and rapid paracrine mechanism might permit instantaneous and segment-specific changes in pain sensitivity; it draws new interesting perspectives for the study of the estrogenic control of pain, thus far limited to the classical view of slow genomic changes in pain, depending on peripheral estrogens. The expression of aromatase in the spinal cord in other species and in other central nociception-related areas is also briefly discussed.
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PMID:Estrogen synthesis in the spinal dorsal horn: a new central mechanism for the hormonal regulation of pain. 1691 20

Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and a high risk of fractures due to tumor-driven bone loss (osteolysis), which is caused by increased osteoclast activity. Osteolysis releases bone-bound growth factors including transforming growth factor beta (TGF-beta). The widely accepted model of osteolytic bone metastasis in breast cancer is based on the hypothesis that the TGF-beta released during osteolytic lesion development stimulates tumor cell parathyroid hormone related protein (PTHrP), causing stromal cells to secrete receptor activator of NFkappaB ligand (RANKL), thus increasing osteoclast differentiation. Elevated osteoclast numbers results in increased bone resorption, leading to more TGF-beta being released from bone. This interaction between tumor cells and the bone microenvironment results in a vicious cycle of bone destruction and tumor growth. Bisphosphonates are commonly prescribed small molecule therapeutics that target tumor-driven osteoclastic activity in osteolytic breast cancers. In addition to bisphosphonate therapies, steroidal and non-steroidal antiestrogen and adjuvant therapies with aromatase inhibitors are additional small molecule therapies that may add to the arsenal for treatment of osteolytic breast cancer. This review focuses on a brief discussion of tumor-driven osteolysis and the effects of small molecule therapies in reducing osteolytic tumor progression.
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PMID:Breast cancer bone metastasis and current small therapeutics. 1716 Jul 9

Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. Clinical trials have assessed 5 years of AI therapy, either as an alternative to tamoxifen for primary adjuvant therapy of breast cancer, or after 5 years of adjuvant tamoxifen. Treatment of 2-3 years' duration after 2-3 years of tamoxifen has also been studied. AI therapy brings side effects related to estrogen deprivation, and this side effect profile differs in clinically relevant ways from that seen with tamoxifen. In particular, the selective estrogen receptor modulatory effects of tamoxifen contribute to menopausal symptoms, vaginal discharge, and the rare but worrisome risks of thromboembolism and uterine carcinoma. By contrast, the low levels of estrogen achieved with aromatase inhibition contribute to menopausal symptoms, vaginal dryness and sexual dysfunction, and accelerated bone demineralization with risk of osteoporosis and osteoporotic fracture. Clinical experience also suggests that AI therapy is associated with a novel musculoskeletal side effect consisting of an arthralgia syndrome. The actual incidence of AI-associated arthralgias or musculoskeletal symptoms is not known, though such symptoms are quite prevalent and appear more commonly with AI use than with tamoxifen. Arthralgias can be a reason for discontinuation of AI treatment. The possible mechanisms of AI-associated arthralgia are unclear. Estrogen deficiency causes bone loss, which in turn contributes to arthralgia. Less well-studied functions of estrogen include regulating immune cells and cytokines involved in bone remodeling, and modulating pain sensitivity at the level of the central nervous system. Arthralgia and arthritis have seldom been rigorously differentiated in clinical trials of AIs. Assessment of inflammatory and rheumatologic markers, as well as detailed evaluation of patient symptoms using appropriate quality-of-life instruments, may be warranted in order to understand both the symptoms and the etiology of the arthralgia syndrome. Treatment options for arthralgia (primarily non-steroidal anti-inflammatory drugs) are currently inadequate, but areas of active research include high-dose vitamin D and new-targeted therapies to inhibit bone loss.
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PMID:Aromatase inhibitor-associated arthralgia syndrome. 1736 3

Aromatase inhibitors are recommended for use by postmenopausal women who have estrogen receptor-positive early-stage breast cancer. They reduce local and distant recurrence more effectively than tamoxifen. Anastrozole (Arimidex, AstraZeneca Pharmaceuticals LP), letrozole (Femara, Novartis Pharmaceuticals Corporation), and exemestane (Aromasin, Pfizer Inc.) inhibit aromatase activity, thus significantly decreasing estrogen production in tissues such as liver, muscle, and fat. Very low levels of estrogen may be one cause of musculoskeletal pain, a common side effect associated with the drugs. In the major adjuvant aromatase inhibitor clinical trials, 25%-30% of the patients enrolled experienced musculoskeletal pain. Although quality-of-life studies demonstrate that aromatase inhibitors are well tolerated overall, some women discontinue this treatment because of musculoskeletal pain. Little is known about how to predict, measure, or manage musculoskeletal pain caused by aromatase inhibition. Oncology nurses play an important role in the assessment and management of side effects related to cancer. This article provides an overview of the current knowledge about musculoskeletal pain in patients with breast cancer receiving aromatase inhibitor therapy.
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PMID:Aromatase inhibitors and musculoskeletal pain in patients with breast cancer. 1762 27

The use of combined oral contraceptives (COCs) is associated with a reduced risk of developing endometriosis, myomas, and endometrial and ovarian carcinoma. The mechanisms involved are multiple; next to ovulation suppression, a reduction in inflammation in the genital tract is involved. This is accomplished through inhibition of the endometrial expression of enzymes related to the biosynthesis of prostaglandin and oestrogen, particularly cyclooxygenase type II (Cox-2) and aromatase. The blockade of these enzymatic systems by COCs explains the beneficial effects of these compounds in treating the symptoms, and halting the progression of myomas, endometriosis and adenomyosis, all of which are characterized by increased inflammation. Inhibition of aromatase and Cox-2 expression in the endometrium by COCs may explain their efficacy in controlling the pain and excessive uterine bleeding caused by these pathologies. The reduction of inflammation in the endometrium may also be the mechanism behind the lower incidence of endometrial carcinoma in COC users. The blockade of ovulation and ovarian steroidogenesis, on the other hand, may explain the lesser incidence of ovarian cancer and the improvement of acne in users. In conclusion, inflammation appears to play a pivotal role in the development of various benign and malignant gynecological diseases. COCs reduce inflammation in the female genital tract by blocking enzymes such as Cox-2 and aromatase.
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PMID:Non-contraceptive health benefits of oral contraceptives. 1796 79

Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2-3 years of tamoxifen, or as an extended treatment after 5 years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available.
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PMID:Tolerance of adjuvant letrozole outside of clinical trials. 1845 95

A case of a menopausal woman known for a chronic diffuse pain syndrome and breast cancer positive for estrogen receptors is presented. She developed an increase of her diffuse pain syndrome and joint aches after the introduction of an aromatase inhibitor. Soreness quickly improved after the interruption of the drug. We emphasize some etiological hypotheses concerning the painful symptoms, especially the role of aromatase and estrogens.
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PMID:[Intensification of a diffuse chronic pain syndrome by the introduction of an aromatase inhibitor]. 1854 14


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