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[Display omitted] • The uncontrolled release and poor targeted action of the ASZ cause its low efficacy. • The ALI hydrogel enhanced the sustainability and permeation of ASZ. • Transdermal ALI hydrogel reduced tumor volume by 99.19% and mortality by 10.93%. • ALI hydrogel enhanced the ASZ's accumulation in the tumor and its anti-tumor action. Anastrazole (ASZ) is an effective aromatase inhibitor that is used for breast cancer treatment. Nevertheless, ASZ's effectiveness is diminished due to its low water solubility, unregulated release, absence of targeting, and inadequate patient compliance. The goal of the research was to create a hydrogel formulation of ASZ-loaded invasomes (ALI) to enhance the solubility, permeability, targeting, and efficacy of ASZ while also sustaining its release for treatment of breast cancer. The optimized ALI formulation was determined to be 3%w/v phospholipid, 0.15%w/v cholesterol, 3%v/v ethanol, and 1 %v/v cineole based on the results of the pre-formulation study. After conducting in vitro characterization of the optimum formulation, it was combined with carbopol for in vivo examination of its anti-tumor efficacy in a rat model of 7, 12-dimethylbenzanthracene. Compared to free ASZ, ALI hydrogel increased its penetration by 10.67 times and prolonged its release by 64.02%. Compared to the control positive group, ALI hydrogel reduced tumor volume by 99.19% and mortality by 10.93%. The anti-tumor effect of the ALI hydrogel was demonstrated by its ability to accumulate more ASZ in tumors and reduce hypercellular tumors. Overall, transdermal ALI hydrogel shows potential as a promising approach for treating breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Inferior overall response rate with abemaciclib plus endocrine therapy was observed in patients with hormone receptor-positive/HER2-negative advanced breast cancer (BC) and BMI ≥ 25. We assessed the impact of baseline BMI on KI67% changes, achievement of complete cell cycle arrest (CCCA), clinical, and radiological responses in patients included in the NEOMONARCH trial. Methods: Exploratory post hoc analysis of the NEOMONARCH trial was performed. Patients were classified according to baseline BMI into underweight/normal weight (BMI < 25 kg/m2) and overweight/obese (BMI ≥ 25 kg/m2). Results: 222 patients (84.4%) had baseline BMI information available. In the overall cohort, mean Ki67% changes at 2 weeks were similar between the two BMI groups: − 19 (IQR − 27.8 to − 10.4) for patients with BMI < 25 and − 17.2 (IQR − 26.8 to − 11) for patients with BMI ≥ 25 (p = 0.760). There was no statistical difference in patients achieving CCCA after 2 weeks of treatment according to BMI (p = 0.096). Mean Ki67% reduction at 2 weeks was significantly higher for patients receiving abemaciclib plus anastrozole when compared to either anastrozole or abemaciclib alone, regardless of BMI. At the end of treatment, there was no significant difference regarding radiological (p = 0.366) or clinical response (p = 0.261). Conclusion: BMI categorized by the threshold of 25 did not significantly impact KI67% changes or clinical and radiological response. Although limited by the small sample size, these results are reassuring that the combination of abemaciclib plus anastrazole appears to be active in the early setting regardless of baseline BMI. Trial registration: ClinicalTrials.gov identifier: NCT02441946. [ABSTRACT FROM AUTHOR]

Anastrazole has recently been approved for the prevention of breast cancer in high-risk women in the UK. When given to high-risk women anastrazole halves the risk of developing breast cancer but doesn't reduce the risk of breast cancer death and is associated with significant harms. Women need to be counselled about both the benefits and risks associated with anastrazole use to enable an informed treatment choice. [ABSTRACT FROM AUTHOR]

Radiation-induced pulmonary fibrosis (RIPF) is a known complication in cancer patients after getting thoracic radiotherapy. Aromatase inhibitors (AIs) as anastrozole have been used instead of tamoxifen for adjuvant endocrine treatment of postmenopausal women with hormone sensitive breast cancer. This study is to evaluate the concurrent treatment of anastrozole and RIPF in rats. Twenty four female Wistar rats were distributed into 4 groups: Control (C), Radiation group (R) (total dose 30 Gy in 10 fractions, 5 fractions/week), anastrozole group (A) (0.003 mg/200 g body weight) orally for 14 consecutive days, and Radiation + anastrozole group (R + A). Radiation exposure resulted in a significant increase (p < 0.05) in pulmonary Transforming growth factor-beta 1 (TGF-β), SMAD family member 3 (Smad3), Platelet-derived growth factor (PDGF), malondialdehyde (MDA), Total nitrate/nitrite (NO), interleukin 1β (IL-1β) and interleukin 6 (IL-6) compared to the control group. While, significant decreases (p < 0.05) in superoxide dismutase (SOD) activity, reduced glutathione (GSH) and connective tissue growth factor (CTGF) were observed in lung tissue. These alterations were minimized by anastrozole intervention. Also, anastrozole markedly hindered the lung histopathological changes observed after radiation. Concomitant use of anastrozole with radiation seems to attenuate radiation-induced pulmonary toxicity via TGF-β/Smad 3 and TGF-β/PDGF pathways in rats. [ABSTRACT FROM AUTHOR]

Aromatase inhibitors are standard of care for low-grade endometrial stromal sarcomas (LGESS), based on very high response rates reported in retrospective studies. We evaluated the activity of anastrozole in recurrent/metastatic LGESS patients enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER±)/progesterone receptor (PR+) gynecological cancers. An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER ± PR + ve LGESS with measurable disease, treated until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. 15 eligible patients were enrolled. CBR at 3 months was 73% (95% CI: 48–89.1%); unchanged at 6 months. Best response was 26.7%, including complete response in one (6.7%; 95% CI 1.2–29.8%), partial response in three (20%, 95% CI 7.1–45.2%) and stable disease in seven (46.7%). Four patients ceased treatment by 3 months due to progression. Median PFS was not reached (25th percentile: 2.9 months (95% CI: 1.2–NR)). PFS was 73.3%, 73.3% and 66% at 6, 12, and 18 months, respectively. Six patients remained on treatment for an average of 44.2 months (range 34.5–63.6) up until data cut. Toxicity was as expected, with 3 patients stopping due to adverse effects. The 26.7% objective response rate with anastrozole is lower than reported in retrospective series, but the CBR was high and durable. The results underscore the importance of prospective trials in rare cancers. • Hormonal therapy is standard of care for recurrent or metastatic low-grade endometrial stromal sarcomas (LGESS). • LGESS are rare and there are no prior prospective trials of hormonal therapy. • Retrospective studies report high response rates to aromatase inhibitors in LGESS. • The response rate of 26.7% with anastrozole is much lower than reported in retrospective case studies. [ABSTRACT FROM AUTHOR]

A unified stability‐indicating method has been proposed using standardized ultra‐fast liquid chromatography conditions applicable to quantification of both anastrozole and letrozole in low dose pharmaceutical tablets. The drugs were subjected to chromatography one at a time following forced degradation at accelerated stress conditions. Separation of the main analyte from the possible degradation products was achieved on a Waters Acquity BEH C18 (50 × 2.1 mm; 1.7 µm) column maintained at 40°C with gradient elution of mobile phase comprising solvent A (0.1% orthophosphoric acid and acetonitrile [70:30 v/v]) and solvent‐B (0.1% orthophosphoric acid and acetonitrile [30:70 v/v]) at a flow rate of 0.35 mL/min. Photo diode array detection of anastrozole and letrozole was made at 215 and 236 nm, respectively. The stress testing demonstrated that both the drugs are susceptible to degrade by base hydrolysis and oxidation. The method was also applied for cleaning validation (residue analysis) at 0.5 µg with a limit of quantification > 10 S/N for 0.1 µg of both drugs. The recovery assessed on two different surfaces of cGMP area (Stainless steel and Class‐A Glass) was satisfactory. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most frequent cancer in the world. Anastrazole is an aromatase inhibitor which used for treating females with breast cancer by decreasing the level of estrogen. Aim of study: To study the effect of anastrazole on serum levels of estradiol and tumor marker CA15.3 in Iraqi breast cancer females recruited from oncology center at Imam AL-Hussein Medical city. Method: The study included 85 females with breast cancer treated with anastrazole. Estrogen (E2) and tumor marker cancer antigen (CA) 15-3 level was measured by already made kits. Result: The serum CA 15.3 concentrations are within the normal range in about 88.23%, while the remaining are above the normal limit. In case of serum estrogen levels, all patients are within the normal value. Conclusion: The Serum levels of CA 15.3 in most women treated with anastrazole are within the normal value with only small percentage are above the normal limit. But at the same time the serum estrogen levels are within the normal range in all females. [ABSTRACT FROM AUTHOR]

Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET). We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs). Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2–4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2–24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62–84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86–3.30) and OS (HR 2.66, 95% CI 1.65–4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77–3.30). High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer. • Meta-analysis of Ki-67 prognostic value after neoadjuvant endocrine therapy. • Twelve studies reporting data from 7897 women with ER+/HER2− early breast cancer. • High Ki-67 was associated with worse recurrence-free survival and overall survival. • Ki-67 index after neoadjuvant endocrine therapy is a strong prognostic biomarker. • These findings will better inform clinical trials design and future clinical practice. [ABSTRACT FROM AUTHOR]

Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators (clomiphene), estrogen conversion blockers (anastrozole), and hormone replacement.

Increasing numbers of women are being identified at ‘high-risk’ of breast cancer, defined by The National Institute of Health and Care Excellence (NICE) as a 10-year risk of ≥8%. Classically women have been so identified through family history based risk algorithms or genetic testing of high-risk genes. Recent research has shown that assessment of mammographic density and single nucleotide polymorphisms (SNPs), when combined with established risk factors, trebles the number of women reaching the high risk threshold. The options for risk reduction in such women include endocrine chemoprevention with the selective estrogen receptor modulators tamoxifen and raloxifene or the aromatase inhibitors anastrozole or exemestane. NICE recommends offering anastrozole to postmenopausal women at high-risk of breast cancer as cost effectiveness analysis showed this to be cost saving to the National Health Service. Overall uptake to chemoprevention has been disappointingly low but this may improve with the improved efficacy of aromatase inhibitors, particularly the lack of toxicity to the endometrium and thrombogenic risks. Novel approaches to chemoprevention under investigation include lower dose and topical tamoxifen, denosumab, anti-progestins and metformin. Although oophorectomy is usually only recommended to women at increased risk of ovarian cancer it has been shown in numerous studies to reduce breast cancer risks in the general population and in those with mutations in BRCA1/2 . However, recent evidence from studies that have confined analysis to true prospective follow up have cast doubt on the efficacy of oophorectomy to reduce breast cancer risk in BRCA1 mutation carriers, at least in the short-term. [ABSTRACT FROM AUTHOR]

Introduction: The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers. Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators (clomiphene), estrogen conversion blockers (anastrozole), and hormone replacement. [ABSTRACT FROM AUTHOR]

An otherwise asymptomatic 66-year-old British Caucasian female with a history of breast cancer was referred by the oncologists due to progressively abnormal liver function tests (LFTs). After undergoing wide local excision and axillary dissection she was started on the anti-oestrogen drug Arimidex (anastrozole) as the tumour cells were oestrogen receptor positive. With a background of normal LFTs, an absence of risk factors for chronic liver disease and otherwise good health, 6 months after starting Arimidex the oncology team noted deranged LFTs. Her hepatitis screening including hepatitis A-C, HSV, HIV, CMV and EBV serology and metabolic screening was negative. Liver ultrasound was essentially normal.The autoimmune screening was positive for ANA (1:160) and weakly positive for anti-smooth muscle antibody (1:80). A liver biopsy demonstrated heavy portal tract inflammation, associated interface hepatitis, and numerous necroinflammatory foci throughout the liver parenchyma. There was also a moderate to marked mixed inflammatory infiltrate of mainly plasma cells and lymphocytes with scattered eosinophils and neutrophils, which best reflects drug-induced liver injury (DILI), although potentially could also correspond with autoimmune hepatitis.The exact mechanism of liver injury from anastrazole is not very clear, but metabolic and immune-mediated damage and individual susceptibility are likely involved in what are often idiosyncratic reactions. The type of cellular immune recruitment (e.g., T-helper cells) reflects the chronicity of injury, with the potential to prolonged liver derangement months or years beyond the period of drug exposure such that DILI may mimic and/or cause drug-induced autoimmune hepatitis. [ABSTRACT FROM AUTHOR]

Background: Statutory State-based cancer registries are considered the 'gold standard' for researchers identifying cancer cases in Australia, but research using self-report or administrative health datasets (e.g. hospital records) may not have linkage to a Cancer Registry and need to identify cases. This study investigated the validity of administrative and self-reported data compared with records in a State-wide Cancer Registry in identifying invasive breast cancer cases. Methods: Cases of invasive breast cancer recorded on the New South Wales (NSW) Cancer Registry between July 2004 and December 2008 (the study period) were identified for women in the 45 and Up Study. Registry cases were separately compared with suspected cases ascertained from: i) administrative hospital separations records; ii) outpatient medical service claims; iii) prescription medicines claims; and iv) the 45 and Up Study baseline survey. Ascertainment flags included diagnosis codes, surgeries (e.g. lumpectomy), services (e.g. radiotherapy), and medicines used for breast cancer, as well as self-reported diagnosis. Positive predictive value (PPV), sensitivity and specificity were calculated for flags within individual datasets, and for combinations of flags across multiple datasets. Results: Of 143,010 women in the 45 and Up Study, 2039 (1.4%) had an invasive breast tumour recorded on the NSW Cancer Registry during the study period. All of the breast cancer flags examined had high specificity (>97.5%). Of the flags from individual datasets, hospital-derived 'lumpectomy and diagnosis of invasive breast cancer' and '(lumpectomy or mastectomy) and diagnosis of invasive breast cancer' had the greatest PPV (89% and 88%, respectively); the later having greater sensitivity (59% and 82%, respectively). The flag with the highest sensitivity and PPV = 85% was 'diagnosis of invasive breast cancer' (both 86%). Self-reported breast cancer diagnosis had a PPV of 50% and sensitivity of 85%, and breast radiotherapy had a PPV of 73% and a sensitivity of 58% compared with Cancer Registry records. The combination of flags with the greatest PPV and sensitivity was '(lumpectomy or mastectomy) and (diagnosis of invasive breast cancer or breast radiotherapy)' (PPV and sensitivity 83%). Conclusions: In the absence of Cancer Registry data, administrative and self-reported data can be used to accurately identify cases of invasive breast cancer for sample identification, removing cases from a sample, or risk adjustment. Invasive breast cancer can be accurately identified using hospital-derived diagnosis alone or in combination with surgeries and breast radiotherapy. [ABSTRACT FROM AUTHOR]

Background Aromatase inhibitors are frequently used as an adjuvant therapy in the treatment of breast cancer. We observed that several patients taking aromatase inhibitors presented with severe dry eye symptoms, and we investigated whether there is a relationship between aromatase inhibitors and dry eyes in these patients. Design Retrospective chart review. Participants Forty-one women. Methods A computerized search of health records was performed to identify patients using anastrazole, letrozole and exemestane seen by the Cornea Service from August 2008 to March 2011. The results were compared with age-matched controls. Main Outcome Measures Ocular surface changes among aromatase inhibitors users. Results Of the 41 women, 39 were Caucasians. Thirty-nine patients had breast cancer (95%), one patient had ovarian cancer (2.5%) and one had an unknown primary cancer. Mean age was 68 ± 11.3 years (range 47-95). Most common presenting symptoms were blurred vision in 28 (68%) patients, irritation/foreign body sensation in 12 (29%) patients, redness in 9 (22%) patients, tearing in 6 (22%) patients and photosensitivity in 2 (5%) patients. Mean Schirmer's test measurement was 11 ± 5.8 mm (range 0.5-20 mm). Blepharitis was noted in 68 of 82 eyes (73%), decreased or poor tear function in 24 eyes (29%), conjunctival injection in 18 eyes (22%) and superficial punctate keratitis in 12 eyes (29%). Among an age-matched population (45-95 years), dry eye syndrome was found in only 9.5% of patients. Conclusions Because the prevalence of ocular surface disease signs and symptoms appears to be higher in study group than control patients, aromatase inhibitors might be a contributing factor to the dry eye symptoms. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of 2.5 mg letrozole with those of 1 mg anastrazole daily on the hormonal and semen profiles of a subset of infertile men with low T/E2 ratios. Design: Prospective, nonrandomized study. Setting: Reproductive medicine clinic. Patient(s): The study group consisted of 29 infertile men with a low serum T/E2 ratio (<10). Intervention(s): Patients were divided into two groups. Group A included 15 patients treated with 2.5 mg letrozole orally once daily for 6 months, and Group B consisted of 14 patients treated with 1 mg anastrazole orally every day for 6 months. Main Outcome Measure(s): Hormonal evaluation included measurement of serum FSH, LH, PRL, T, and E2. In all sperm analyses pretreatment and posttreatment total motile sperm counts (ejaculate volume × concentration × motile fraction) were evaluated. Result(s): The use of aromatase inhibitors (either letrozole or anastrazole) in cases of infertile men with low T/E2 ratios improved both hormonal and semen parameters. Conclusion(s): This study suggests that some men with severe oligospermia, low T levels, and normal gonadotropin concentration may have a treatable endocrinopathy. [ABSTRACT FROM AUTHOR]

Tamoxifen (TAM) is a selective estrogen-receptor modulator that is widely used in the prevention and treatment of estrogen-receptor–positive breast cancer. Its use has significantly contributed to a decline in breast cancer mortality, since breast cancer patients treated with TAM for 5 years exhibit a 30–50% reduction in both the rate of disease recurrence after 10 years of patient follow-up and in the occurrence of contralateral breast cancer. However, in patients treated with TAM, there is substantial interindividual variability in the development of resistance to TAM therapy and in the incidence of TAM-induced adverse events, including deep-vein thrombosis, hot flashes, and the development of endometrial cancer. Aromatase inhibitors (AIs) have emerged as a viable alternative to TAM, working by inhibiting aromatase activity and blocking estrone/estrodiol biosynthesis in postmenopausal women. The current third-generation AIs, anastrozole, exemestane, and letrozole, were used initially for the treatment of metastatic breast cancer, demonstrating similar or greater benefit but less toxicity, compared with TAM, and are now being employed as adjuvant treatment for early breast cancer in postmenopausal women. This article will focus on the UDP-glucuronosyltransferases, a family of metabolizing enzymes that play an important role in the deactivation and clearance of TAM, anastrazole, and exemestane, and how interindividual differences in these enzymes may play a role in patient response to these agents. [ABSTRACT FROM AUTHOR]

Abstract: MEDLINE, EMBASE, Scopus, and Web of Science databases literature search from inception to March 2009 was performed to identify published clinical trials and cohort, observational, and in vitro studies that evaluated the use of aromatase inhibitors in reproductive medicine for indications other than ovulation induction. Aromatase inhibitors are currently being investigated for breast cancer prevention in women at high risk. Aromatase inhibitors may be used for treatment of symptomatic myomas and endometriosis as an alternative to surgical intervention. Current evidence does not support the routine use of aromatase inhibitors for these conditions without prospective controlled trials. Aromatase inhibitor cotreatment can be used to prevent the initial estrogen flare effect of gonadotropin-releasing hormone agonist treatment to offer flexibility in initiating this therapy. [Copyright &y& Elsevier]

Lung cancer has become increasingly common in women, and gender differences in the physiology and pathogenesis of the disease have suggested a role for estrogens. In the lung recent data have shown local production of estrogens from androgens via the action of aromatase enzyme and higher levels of estrogen in tumor tissue as compared with surrounding normal lung tissue. High levels of aromatase expression are also maintained in metastases as compared with primary tumors. Consistent with these findings, clinical studies suggest that aromatase expression may be a useful predictive biomarker for prognosis in the management of non-small cell lung cancer (NSCLC), the most common form of lung malignancy. Low levels of aromatase associate with a higher probability of long-term survival in older women with early stage NSCLC. Treatment of lung NSCLC xenografts in vivo with an aromatase inhibitor (exemestane) alone or combined with standard cisplatin chemotherapy elicits a significant reduction in tumor progression as compared to paired controls. Further, lung cancer progression is also governed by complex interactions between estrogen and growth factor signaling pathways to stimulate the growth of NSCLC as well as tumor-associated angiogenesis. We find that combination therapy with the multitargeted growth factor receptor inhibitor vandetanib and the estrogen receptor antagonist fulvestrant inhibit tumor growth more effectively than either treatment administered alone. Thus, incorporation of antiestrogen treatment strategies in standard antitumor therapies for NSCLC may contribute to improved patient outcome, an approach that deserves to be tested in clinical trials. [ABSTRACT FROM AUTHOR]

Objective To assess the effects of aromatase inhibitors in women symptomatic of pain with endometriosis. Design A systematic review of published literature. Material and methods We conducted a comprehensive literature search to identify all the published observational and randomised studies evaluating the efficacy of aromatase inhibitors on pain associated with endometriosis. A combination of keywords was used to identify the maximum number of relevant citations in MEDLINE, EMBASE, CINAHL and the Cochrane Database. Outcome Pain relief, lesion size and quality of life. Results There were eight studies (137 women) evaluating outcomes of aromatase inhibitors. In case series/reports (seven studies, 40 women), aromatase inhibitors combined with progestogens or oral contraceptive pill or gonadotrophin-releasing hormone (GnRH) analogues reduced mean pain scores and lesion size and improved quality of life. An RCT (97 women) demonstrated that aromatase inhibitors in combination with GnRH analogues significantly improved pain ( P < 0.0001) compared with GnRH analogues alone together with significant improvement in multidimensional patient scores ( P < 0.0001). There was no significant reduction in spine or hip-bone densities. Conclusion Aromatase inhibitors appear to have a promising effect on pain associated with endometriosis, but the strength of this inference is limited due to a dearth of the evidence available. [ABSTRACT FROM AUTHOR]

Aim. The present study was designed to investigate the effects of two aromatase inhibitors on steroid hormone levels, bone mineral density (BMD) and bone turnover markers in intact female rats. Methods. Letrozole and anastrazole at two different dose levels were investigated for their effect on serum levels of estradiol, androstenedione, testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate, BMD of femur and dorsal spine, and osteocalcin and pyridinoline levels as bone turnover markers. Fifty intact female rats were randomly divided in five groups (group 1 (n = 10): control, 2 ml saline; group 2 (n = 10): letrozole 1 mg/kg; group 3 (n = 10): letrozole 2 mg/kg; group 4 (n = 10): anastrazole 0.1 mg/kg; group 5 (n = 10): anastrazole 0.2 mg/kg), and oral gavages were applied for a period of 16 weeks. Results. Both doses of letrozole and anastrazole did not change femoral and vertebral BMD. Serum estradiol levels were reduced significantly at all dose levels by both agents (p < 0.001); all androgen levels were significantly elevated by letrozole (p < 0.05), although anastrazole increased only androstenedione (p < 0.05). The higher dose of letrozole increased osteocalcin levels (p < 0.05), while pyridinoline levels were increased (p < 0.05) by the higher dose of anastrazole. Conclusion. Our results indicate that short-term use of letrozole and anastrazole had no clear effects on BMD in intact rats. Further investigations are needed to understand their effects on bone metabolism in intact females. [ABSTRACT FROM AUTHOR]

Abstract: A rapid, sensitive and specific method for quantifying the aromatase inhibitor (anastrozole) in human plasma using dexchlorpheniramine as the internal standard (I.S.) is described herein. The analyte and the I.S. were extracted from 200μl of human plasma by liquid–liquid extraction using a mixture of diethyl ether:dichloromethane (70:30, v/v) solution. Extracts were removed and dried in the organic phase then reconstituted with 200μl of acetonitrile:water (50:50; v/v). The extracts were analyzed by high performance liquid chromatography coupled with photospray tandem mass spectrometry (HPLC–MS–MS). Chromatography was performed isocratically on a Genesis, C18 4μm analytical column (100mm×2.1mm i.d.). The method had a chromatographic run time of 2.5min and a linear calibration curve ranging from 0.05–10ngml−1. The limit of quantification (LOQ) was 0.05ngml−1. This HPLC–MS–MS procedure was used to assess pharmacokinetic studies. [Copyright &y& Elsevier]

Aromatase inhibitors have the potential to treat a wide spectrum of diseases where estradiol is required to manifest clinical symptoms. Their use was initially indicated for the treatment of hormone-dependent advanced postmenopausal breast cancer, but little is known regarding their role in gynecology. This review will address the current use of aromatase inhibitors in the treatment of ovulation induction, endometriosis and uterine myomata. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of aromatase inhibitors in ovulation induction, superovulation, and IVF. Design: A literature search was conducted with the key words “aromatase inhibitor,” “letrozole,” “anastrazole,” “ovulation induction,” “ovulation,” and “superovulation” in MEDLINE, EMBASE, and the Cochrane Database of systematic reviews. Result(s): Ovulation induction with letrozole is associated with an ovulation rate of 70%–84% and a pregnancy rate of 20%–27% per cycle. In one study, ovulation and pregnancy rates with letrozole seemed to be higher than those of anastrazole. In superovulation, letrozole is associated with few developing follicles and thick endometrium. The use of letrozole for superovulation is associated with a pregnancy rate higher than with the use of clomiphene citrate (CC) (16.7% vs. 5.6%). The addition of letrozole to FSH treatment leads to a decreased FSH requirement. The pregnancy rate for treatment with letrozole and FSH was similar to that for FSH alone. Conclusion(s): Aromatase inhibitors are as effective as or superior to CC in ovulation induction and in superovulation. Unlike CC, they do not carry an antiestrogenic effect on the endometrium. Given the advantages of aromatase inhibitors, they can be used to replace CC as ovulation-inducing drugs. Their role in IVF remains to be determined. [Copyright &y& Elsevier]

We report a long-term follow-up on the use of anastrozole in the treatment of peripheral precocious puberty (PP) in McCune-Albright syndrome (MAS). A girl, age 3 years and 9 months, was diagnosed with MAS due to PP, café-au-lait spots, and polyostotic fibrous dysplasia. Serum estradiol was elevated, and gonadotropins were suppressed. Pelvic ultrasound showed an enlarged uterus and a follicle cyst (13 mm) in the left ovary. Bone scintigraphy showed osteogenic lesions on the skull, humerus, tibia, and acetabulum. Bone age was 3 years and 5 months at the chronological age of 3 years. After 36 months of treatment with anastrozole (1 mg/day), there was suppression of breast growth, normalization of growth velocity and serum estradiol, and disappearance of ovarian cysts. However, there was increase in uterine volume, advancement of bone age, and two episodes of vaginal bleeding (18th and 24th months). This report shows the partial benefit of anastrozole in the treatment of peripheral PP of girls with MAS. [ABSTRACT FROM AUTHOR]

Uterine tumour resembling ovarian sex cord tumour (UTROSCT) are a histological variant of endometrial stromal sarcomas (ESS). There is no established medical management of metastatic UTROSCT or ESS, although there is evidence supporting the use of hormonal therapy. Given the success of aromatase inhibitors in breast cancer, their potential role in ESS and UTROSCT is of current interest. We report the first case of response to second-line, single agent anastrazole in a patient with metastatic UTROSCT. [ABSTRACT FROM AUTHOR]

Background. Hormonal therapy for endometrial cancer is occasionally warranted in the premenopausal woman who is interested in maintaining fertility. Combining progesterone with an agent that eliminates the adipose production of estrogen will theoretically be more effective than progesterone alone.Cases. Two cases of reproductive-aged women with grade 1 endometrial cancer who were treated with medroxyprogesterone acetate and anastrozole daily for 3 and 6 months subsequently reverted to normal endometrium.Conclusion. Progesterone combined with the elimination of adipose production of estrogen may be an effective therapy in well-differentiated endometrial cancer in the obese premenopausal woman. [Copyright &y& Elsevier]