9,205 research outputs found

    Do aromatase inhibitors have adverse effects on cognitive function?

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    Aromatase inhibitors are an important component of treatment for most postmenopausal women with hormone receptor-positive, early-stage breast cancer. Women taking aromatase inhibitors experience very low levels of circulating estrogen. This might be expected to result in cognitive dysfunction given the important relationship between estrogen and cognition in the basic science literature. Several studies have examined the cognitive effects of aromatase inhibitors, including two within large randomized trials which were adequately powered to detect moderate (but not small) effects. With this caveat, the available data do not support the hypothesis that aromatase inhibitors adversely affect cognitive function or that aromatase inhibitors might have a more adverse effect on cognitive function in comparison with tamoxifen. Further research is needed for confirmation

    Role of aromatase inhibitors in breast cancer

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    Primarily, the role of the aromatase inhibitors has been investigated in postmenopausal women with breast cancer, although it is also now being assessed in premenopausal patients following ovarian ablation/suppression. Aromatase inhibitors markedly suppress endogenous oestrogens without directly interacting with oestrogen receptors, and thus have a different mechanism of action to the antioestrogen, tamoxifen. The inhibitors may be divided into subgroups according to their structure (steroidal and nonsteroidal), and there appears to be a lack of cross-resistance between the classes of aromatase inhibitors enabling them to be used sequentially and potentially to prolong endocrine hormone therapy. In addition, with increased efficacy and favourable safety and tolerability profiles, the aromatase inhibitors are starting to challenge tamoxifen as first choice endocrine treatment in a number of settings. Potential differences in side-effect profiles may appear between the steroidal and nonsteroidal aromatase inhibitors when used in long-term settings. Thus, it has been suggested that the steroidal agents have favourable end organ effects; for example, the steroidal inhibitor, exemestane, has minimal negative effects on bone and lipid metabolism in animal and clinical studies. This paper provides an overview of the current and future roles of aromatase inhibitors for breast cancer treatment

    Aromatase inhibitors in men: effects and therapeutic options

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    Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended

    Treatment of endometriosis by aromatase inhibitors: efficacy and side effects

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    The recent demonstration that aromatase is expressed at higher levels in endometriosis implants than in normal endometrium has led to pilot studies using inhibitor aromatasis in patients with endometriosis. We conducted a systematic review of the literature and studied the efficacy of aromatase inhibitors on endometriosis. There were seventeen studies (case reports/series) evaluating outcomes of aromatase inhibitors. Studies suggest that aromatase inhibitors alone or co-administered with progestins, oral contraceptives or gonadotrophin releasing hormone (GnRH) agonist could reduce pain and endometriosis. There is only one randomized controlled trial comparing aromatase inhibitor+GnRH agonist and GnRH agonist and one study with eighty patients. Side-effects profiles of aromatase inhibitor regimens are favorable; it does not appear a significant bone loss. Aromatase inhibitors seem to have a promising effect on endometriosis but randomized controlled trials are needed to prove their effects and their safety

    Aromatase inhibitor therapy for endometrial stromal sarcoma — two-centre experience

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    Objectives: Endocrine therapy is the recommended systemic treatment for steroid receptor positive endometrial stromalsarcoma (ESS). There is no current consensus on the optimal hormonal therapy for ESS. The literature offers several reports on advanced/recurrent/metastatic ESS patients treated with progestins, whereas data on the efficacy of aromatase inhibitors are scarce.Material and methods: We retrospectively identified cases treated for ESS with aromatase inhibitors at our institutions. There were five patients with advanced or unresectable recurrent estrogen, progesterone and androgen receptor-positive ESS, treated with aromatase inhibitors: letrozole or anastrozole (at a daily dose of 2.5 mg and 1 mg, respectively), as first-line endocrine therapy in all but one case treated following progression with megestrol acetate.Results: Disease stabilization was achieved in four cases (80%), including two with long-term progression-free survivalfor up to 10 years attained under letrozole treatment, and one case after prior progestin treatment. During therapy, nosubstantial toxicity was observed.Conclusions: Aromatase inhibitors as first- or second-line endocrine treatment achieve disease control in most steroidreceptor positive ESS. Our series of cases is evidence of aromatase inhibitors efficacy as long-term endocrine treatmentoption for ESS patients

    Current medical treatment of estrogen receptor-positive breast cancer

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    Approximately 80% of breast cancers (BC) are estrogen receptor (ER)-positive and thus endocrine therapy (ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of (i) ovarian function suppression (OFS), usually obtained using gonadotropin-releasing hormone agonists (GnRHa), (ii) selective estrogen receptor modulators or down-regulators (SERMs or SERDs), (iii) aromatase inhibitors (AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs (i.e. tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs (i.e. fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type I are permanent steroidal inhibitors of aromatase, while type II are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs (i.e. anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors (palbociclib) and mammalian target of rapamycin (mTOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness

    Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs).

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    Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed
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