Objective:Breast cancer is the second most prevalent cause of mortality in women and the predominant malignancy type.However,breast cancer treatment faces challenges in managing aromatase inhibitor-induced arthralgia....Objective:Breast cancer is the second most prevalent cause of mortality in women and the predominant malignancy type.However,breast cancer treatment faces challenges in managing aromatase inhibitor-induced arthralgia.Aromatase inhibitors have been shown to decrease recurrence risk in hormone receptor-positive cases;however,joint discomfort remains the primary adverse effect.Randomized clinical trials have evaluated the therapeutic outcomes of acupuncture for medication-related musculoskeletal complications.This comprehensive analysis sought to elucidate both the therapeutic efficacy and placebo responses associated with acupuncture intervention.Methods:Two reviewers searched for randomized controlled trials(RCTs)in four English(PubMed,Embase,Web of Science,and the Cochrane Library)and four Chinese databases(CNKI,Wanfang Database,VIP,and SinoMed)from their inception to May 31,2024.Methodological quality was assessed using the Cochrane risk of bias tool.Data were synthesized using random effects models and presented with forest plots.Results:Seven trials involving 604 patients were included.The primary outcome and Brief Pain Inventory(BPI)score differed between the acupuncture and control groups(sham acupuncture or usual medication)in three subscales over the course of 6 weeks:worst pain:standardized mean difference(SMD)=-1.18,95%confidence interval(CI):-1.74,-0.63,P<0.001;painrelated interference:SMD=-0.87,95%CI:-1.70,-0.05,P=0.038;pain severity:SMD=-0.63,95%CI:-1.22,-0.04,P=0.036.No severe adverse events were reported in any study.Conclusions:This meta-analysis showed that acupuncture is a safe and effective treatment for patients with breast cancer with aromatase inhibitor-induced arthralgia during the course of 6 weeks.Improvements in the blinding method and clarification of the total treatment recommendations and intervals need to be explored further.展开更多
Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particula...Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particularly in those with hypogonadism,elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic–pituitary–testicular axis by suppressing follicle-stimulating hormone(FSH)and luteinizing hormone(LH)production and impaired spermatogenesis.Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment.We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males.Overall,eight original articles were included and critically evaluated.Either steroidal(Testolactone)or nonsteroidal(Anastrozole and Letrozole)aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile.While the evidence is promising,future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.展开更多
To investigate the effect of Yikun Neiyi Wan （益坤内异丸YKNYW） and gestrinone on the expression of aromatase P450 （P450arom）, cyclo-oxygenase-2 （COX-2） and estrogen receptor （ER） in isolated ectopic and normal...To investigate the effect of Yikun Neiyi Wan （益坤内异丸YKNYW） and gestrinone on the expression of aromatase P450 （P450arom）, cyclo-oxygenase-2 （COX-2） and estrogen receptor （ER） in isolated ectopic and normal endometriat stroma cells in vitro. Methods： Digestion and serial filtration were used to isolate and culture the ectopic and eutopic endometrial cells from patients with chocolate cyst in virto Transformation of the cell morphology was observed in a inverted microscope. The effect of YKNYW on the expression of aromatase P450, cyclo-oxygenase-2, estrogen receptor in cultured endometriosis cells were detected by immunohistochemical method. Results： The expression levels of P450arom, COX-2 in glandular epithelium cells in vitro were decreased significantly by YKNYW compared with gestrinone （P〈0.05）. ER expression in mesenchymal cells of endometriosis was increased by YKNYW in the large and medium dosage groups compared with gestrinone. Conclusion： The mechanism by which YKNYW alleviates endometriosis pain is possibly related to the decrease in ectopic endometrial P450 arom and COX-2 expression in glandular epithelium, contrary to gestrinone, and the increase in ER expression in mesenchymalis, consistent with gestrione in patients with endometriosis.展开更多
OBJECTIVE: To investigate the effect of Jianpi Bushen(JPBS) formula on aromatase inhibitor(AI)-associated bone loss after menopause.METHODS: Six-month-old female rats were randomly divided into 6 groups: a sham group,...OBJECTIVE: To investigate the effect of Jianpi Bushen(JPBS) formula on aromatase inhibitor(AI)-associated bone loss after menopause.METHODS: Six-month-old female rats were randomly divided into 6 groups: a sham group, an ovariectomized(OVX) group, an OVX treated with exemestane and 3 OVX groups each treated with a different dose of JPBS formula. Bone mineral density(BMD) at the lumbar vertebrae, histology, bone markers and serum levels of estrogen were assessed. Furthermore, a cohort study was conducted in 130 postmenopausal women with breast cancer that had undergone treatment with AIs. The subjects were given JPBS + caltrate D or caltrate D only, administered orally. BMD at the lumbar vertebrae and femoral neck and bone markers were evaluated in both control and herbal treatment groups at baseline and 12 months.RESULTS: Experimental results indicated that a high dose of JPBS significantly increased the trabecular bone area percentage(Tb.Ar %) and broadened the trabecular thickness(Tb.Th). The JPBS formula enriched the carboxyterrninal propeptide of type ipmcollagen and increased serum estrogen level significantly. The clinical investigation revealed that bone loss was decreased in the group treated with JPBS vs control(BMD T score at lumbar vertebrae, 3.9% increased vs 14.58% decreased, respectively, P = 0.004 and BMD T score on femoral neck, 1.8% decreased vs 22.45% decreased, respectively, P = 0.008). Besides, JPBS formula elevated Nmiddle osteocalcin and decreased type Ⅰ collagen cross-linked C-terminal telopeptide.CONCLUSION: JPBS formula prevented aromatase-inhibitor-associated bone loss after menopause by inhibiting bone resorption and promoting bone formation.展开更多
Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid ...Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid peroxidation and on the expression of testicular aromatase and estrogen receptors （ER）. Methods： CR was initiated in 1-month-old rats and carried on until the age of 18 months. Results： In control and CR2 rats an age-related decrease of the aromatase and of ER （α and β） gene expression was observed; in parallel a diminution of testicular weights, and of the total number and motility of epididymal spermatozo was recorded. In addition, aging in control and CR2 rats was accompartied by a significant decrease in testicular superoxide dismutase, catalase activities, and an increase in lipid peroxidation level （thiobarbituric acid reactive substance）, associated with alterations of spermatogenesis. Conversely, caloric restriction-treatment exerted a protective effect and all the parameters were less affected by aging. Conclusion： These results indicate that during aging, a low caloric diet （not undernutrition） is beneficial for spermatogenesis and likely improves the protection of the cells via an increase of the cellular antioxidant defense system in which aromatase/ ER could play a role. （Asian J Andro12008 Mar; 10： 177-187）展开更多
AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to ...AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale. RESULTS: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed. CONCLUSION: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.展开更多
Objective：Estradiol （E2） plays an important role in the development of breast cancer.In postmenopausal women,the estrogen can be synthesized via aromatase （CYP19） pathway and steroid-sulfatase （STS） pathway in ...Objective：Estradiol （E2） plays an important role in the development of breast cancer.In postmenopausal women,the estrogen can be synthesized via aromatase （CYP19） pathway and steroid-sulfatase （STS） pathway in peripheral tissues,when the production in ovary has ceased.The objective of our study was to explore the effects of Shu-Gan-Liang-Xue Decoction （SGLXD） on the expressions of CYP19 and STS in estrogen receptor positive breast cancer MCF-7 and T47D cells.Methods：The effects of SGLXD on the cell viability of MCF-7 and T47D were analyzed by MTT assay.By quantitative real-time RT-PCR and Western blot,we evaluated the mRNA and protein expressions of CYP19 and STS in MCF-7 and T47D cells after SGLXD treatment.Results：By MTT assay,the cell viability rates of MCF-7 and T47D were significantly inhibited by SGLXD in a dose-dependent manner,the IC50 values were 40.07 mg/ml for MCF-7 cells and 25.62 mg/ml for T47D cells,respectively.As evidenced by real-time PCR and Western blot,the high concentrations of SGLXD significantly down-regulated the expressions of CYP19 and STS both in the transcript level and the protein level.Conclusion：The results suggest that SGLXD is a potential dual aromatase-sulfatase inhibitor by simultaneously down-regulating the expressions of CYP19 and STS in MCF-7 and T47D cells.展开更多
Hormone Receptor positive (HR+) breast cancer is the most common malignancy in women. New strategies in the treatments have targeted the estrogen biosynthesis pathways including the inhibition of the aromatase and 17...Hormone Receptor positive (HR+) breast cancer is the most common malignancy in women. New strategies in the treatments have targeted the estrogen biosynthesis pathways including the inhibition of the aromatase and 17β-HSD1 enzymes. The present work, describes the study of a new family of 9 hybrid compounds derived from estrone attached to a coumarin fragment, linked through different lengths of hydrocarbon chains. The activity of these compounds was evaluated by molecular docking with two relevant enzymes in breast cancer (HR+). It has been proposed nine compounds as 17β-HSD1 inhibitors and six as aromatase inhibitors. We found important interactions with key amino acids at the orthosteric site of each enzyme and their score values compared to the crystallographic ligand. The in silico analysis showed good score values in the proposed compounds, where the steroidal portion presented important interactions with Met374 and Tyr155 in aromatase and in 17β-HSD1 respectively. Highlighting Compounds 2, 5 and 8 with an aromatic ring at the C4 position of the coumarin moiety, which favored arene-H type interactions essential for protein-ligand recognition. In addition, the results related to the 17β-HSD1 enzyme demonstrated how the length of the linker influences the interaction;the best score was found for derivative 8 with a chain of 8 methylenes.展开更多
Testicular function is regulated by pituitary hormones and also by paracrine and autocrine factors. A number of reports have pointed out the importance of estrogens and progesterone in male reproductive tract. Recentl...Testicular function is regulated by pituitary hormones and also by paracrine and autocrine factors. A number of reports have pointed out the importance of estrogens and progesterone in male reproductive tract. Recently, we have reported in testicular biopsies from men with Sertoli Cell Only Syndrome (SCO) or Hypospermatogenesis (H) with Leydig cell hyperplasia (LCH) an increase in the expression of the TGFB1 and its receptors ALK1 and endoglin, which are involved in the proliferation of Leydig cells. The aim of the present work was to analyze the expression of aromatase, estrogen and progesterone receptors (ERs, PR) in pathological testicular biopsies with SCO or H with and without LCH. The ERs and CYP19 proteins were detected in the Leydig cells from all pathological biopsies analyzed. Biopsies with SCO or H with LCH showed an increment in the immunostaining of CYP19 and ERs in the Leydig cells respect to biopsies without LCH. The gene expression of CYP19 was increased in SCO or H biopsies with LCH respect to SCO and H biopsies without LCH. PR was localized in Leydig cells and showed a significant increment in biopsies with LCH respect from biopsies without LCH. The gene expression of both PRA and PRB was increased in biopsies with LCH respect to biopsies without LCH. In concussion, alterations in the gene expression of aromatase, ERs, and PR and the likely interactions of these systems with locally produced factors such as growth factors and cytokines, might lead to Leydig cell proliferation in testicular pathology.展开更多
The aim of this study was to evaluate the polymorphism in a portion of the gene regulatory region for ovarian aromatase （CYP19a） in three strains of Tilapia, Oreochomis niloticus （Linnaeus） （GIFT--Genetically Imp...The aim of this study was to evaluate the polymorphism in a portion of the gene regulatory region for ovarian aromatase （CYP19a） in three strains of Tilapia, Oreochomis niloticus （Linnaeus） （GIFT--Genetically Improved Farmed Tilapia, Chitralada and Supreme）. A total of 90 animals per strain of Tilapia, Oreochromis niloticus （Linnaeus） were analysed. After DNA extraction, samples were subjected to PCR using primers designed to flank the region of interest encompassing the sites of transcription （WT1-KTS and SRY）. Samples were analyzed by PCR-SSCP and subsequently sequenced. Three polymorphisms were identified in this region, resulting in two different sequences, in the GIFT strain while no polymorphism was found in both Supreme and Chitralada strains. At the position - 1178 the substitution of a guanine for a cytosine, at the - 1081 the exchange of guanine for adenine and at the position -1 138 we found a SNP, possible site of heterozygosity. Even with polymorphisms in the target study area, when taking the three strains into account, one can assume that the portion of the regulatory region of the ovarian aromatase gene in the Supreme strain and Chitralada does not show polymorphism.展开更多
The work was carried out by microinjections of an aromatase inhibitor letrozole, an estrogen receptor modulator tamoxifen in incubated eggs Gallus g. domesticus, the first day of incubation. It also used 5-azacytidine...The work was carried out by microinjections of an aromatase inhibitor letrozole, an estrogen receptor modulator tamoxifen in incubated eggs Gallus g. domesticus, the first day of incubation. It also used 5-azacytidine (5-AC) at the same time. Injection of progesterone was carried out before the onset of meiosis prophase 1 on 16 h of incubation. Morphologically and histologically and by PCR, sex of the 17-day embryos was controlled. According to information received microinjection of letrozole caused almost a 100% inversion of genetic males to females, which is manifested in the morphology of the gonads. In other experiments, sex reversal is not revealed. The results are obtained in this study, and the data suggest that the presence of gonadogenesis in female chickens makes earlier emergence of aromatase in the beginning of incubation, than that according to the classical scheme of sex determination in birds. Presumably this kind of synthesis is triggered by some W-chromosomal factors. It failed to detect the phenomenon of gender inversion—the transformation of males into females after exposure to demethylating agent 5-AC that casts doubt on the participation of male hypermethylated (MHM)-RNA-segment in regulating the activity of sex determining genes.展开更多
Aim: To identify the correlation between mRNA expression of aromatase, 17β-HSD2 level of TGF-β1 and stage of endometriosis. Methods: Case control study was done on 80 patients divided by 40 endometriosis patients an...Aim: To identify the correlation between mRNA expression of aromatase, 17β-HSD2 level of TGF-β1 and stage of endometriosis. Methods: Case control study was done on 80 patients divided by 40 endometriosis patients and 40 patients as control. mRNA expression of aromatase, mRNA 17β-SD2, was checked using reverse-transcriptase polymerase chain reaction (RT-PCR) and TGF-β1 serum and peritoneal fluid was checked using ELISA. Result: Level of mRNA aromatase from ectopic and eutopic endometrium increased significantly compared to control group (p < 0.001). mRNA 17β-HSD2 expression is significantly lower compared to control (p TGF-β1 on endometriosis group was significantly higher compared to control group (p < 0.05). Level of peritoneal fluid TGF-β1 on endometriosis group was higher than control group (p < 0.001). There are no correlations between mRNA aromatase, type 2 17β-HSD, TGF-β1 serum level to endometriosis stage. There are significant correlations between peritoneal fluid TGF-β1 levels to endometriosis stage.展开更多
The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvan...The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvant therapy drugs for early stages of breast cancer. In this paper,we employed the FDA-approved aromatase inhibitor aminoglutethimide (AG) to design and prepare a new class of multi-targeting Pt(IV) prodrugs (aminoplatins 1–3) by utilizing the targeting,estrogen-manipulating,and chemo-sensitizing effects of the aromatase inhibitor. Aminoplatin 3,as a representative,exhibited an enhanced anticancer activity up to 190-fold greater than the parent Pt(Ⅱ) drug cisplatin,and 3 had less toxicity to normal cells,displaying higher anticancer efficacy and a superior therapeutic index compared to those of cisplatin. Moreover,aminoplatin 3 could enhance intracellular accumulation,induce remarkable DNA damage,inhibit migration and metastasis,and result in S phase cell cycle arrest and apoptosis in ER-positive MCF-7 cells. Besides,molecular docking results showed that 3 simultaneously occupies the heme iron-binding domain and the ASD-binding site of aromatase by a highly efficient dual-binding pattern to aromatase,which further displayed a striking anti-estrogenic effect by significant downregulation of CPY19A1 and ERα in ER-positive MCF-7 cells. Most strikingly,our in vivo anticancer evaluation data also provided evidence that 3 effectively inhibited tumor growth and attenuated kidney toxicity compared to cisplatin in MCF-7 xenografted BALB/c nude mice. Our results suggest that the anticancer activity of aminoplatins is mechanistically distinct from that of the conventional platinum drugs,and modifying platinum drugs with aromatase inhibitors may represent an improved modality for the treatment of advanced postmenopausal breast cancer.展开更多
Monocrotophos(MCP)and Glyphosate(GLY)are used as an insecticide and herbicide respectively in agricultural fields in India and other developed countries.Since agricultural fields are located close to water bodies,ther...Monocrotophos(MCP)and Glyphosate(GLY)are used as an insecticide and herbicide respectively in agricultural fields in India and other developed countries.Since agricultural fields are located close to water bodies,there is a high risk of water contamination by these chemicals with consequent residue accumulation in aquatic biota including fish.The 48 h LC50 was found to be 106 mg/L and 78 mg/L for MCP and GLY respectively.To investigate the effects of these two agrochemicals,the adult climbing perch,Anabas testudineus female fish were treated with 3 concentrations of MCP and GLY for 30 days.The MCP concentrations were 3.5×10^(-4)%(T1),5.3×10^(-4)%(T2),and 10.6×10^(-4)%(T3)and GLY concentrations were 2.6×10^(-4)%(T1),3.9×10^(-4)%(T2),and 7.8×10^(-4)%(T3).One group was kept as control.Molecular docking analysis showed that GLY interacted with brain aromatase protein at residues MET424,THR423,PRO479 with a binding energy of -10.685 and with a docking score of -4.769.In the case of MCP,the binding residues were MET424,THR423,and PHE422 ofbrain aromatase with a binding energy of -10.436 with a docking score of -2.824.Similarly,GLYinteracted with ovary aromatase at residues ASN 479,THR477,ASN 230,GLU 226,GLN 483,PRO 484,and GLU 486 with a binding energy of -10.685 and with a docking score of5.177.In the case of MCP,the binding residues were ASP 312,THR 313,SER 481,and TRP 228 of ovary aromatase with a binding energy of -2.405 and with a docking score of -3.372.These agrochemicals caused ovarian damage and alteration in gonadosomatic index and cytochrome P450 aromatase gene expression.展开更多
Background:Aromatase inhibitors(AIs)are associated with improved cancer-related survival in breast cancer,but also higher risks of adverse cardiovascular outcomes.This study compared cardiovascular outcomes between so...Background:Aromatase inhibitors(AIs)are associated with improved cancer-related survival in breast cancer,but also higher risks of adverse cardiovascular outcomes.This study compared cardiovascular outcomes between sodium-glucose cotransporter-2 inhibitor(SGLT2i)and dipeptidyl peptidase-4 inhibitor(DPP4i)among breast cancer patients receiving AIs.Methods:This was a retrospective,territory-wide study enrolling female patients≥45 years old with diabetes mellitus and breast cancer who received SGLT2i or DPP4i on the date of AIs initiation,between 2015 and 2020 in Hong Kong.The primary outcome was major adverse cardiovascular events(MACE).The secondary outcomes included components of MACE[stroke/transient ischemic attack(TIA),nonfatal myocardial infarction(MI),and cardiovascular death],heart failure,and all-cause mortality.Multivariable Cox regression was applied to evaluate the association between SGLT2i versus DPP4i with outcomes.Results:Initially,a total of 76147 diabetes patients treated with SGLT2i or DPP4i were identified.After matching,226 patients(mean age,65.5±7.6 years)were included(113 SGLT2i users versus 113 DPP4i users).During a median follow-up of 5.51 years,43(19.02%)patients developed composite MACE.Compared with DPP4i users,SGLT2i was not significantly associated with MACE[hazard ratio(HR):0.54;95%confidence interval(CI):0.27-1.10]in the adjusted model.For the secondary outcomes,breast cancer patients treated with SGLT2i presented with an 84%lower risk of stroke/TIA(HR:0.16;95%CI:0.04-0.61)than DPP4i users after adjustments.No significant associations were observed between SGLT2i with MI(HR:0.41;95%CI:0.10-1.69),cardiovascular mortality(HR:0.86;95%CI:0.20-3.70),all-cause mortality(0.51;95%CI:0.17-1.58),and heart failure(0.47;95%CI:0.12-1.89),in relation to DPP4i.Conclusion:SGLT2i was associated with lower risks of stroke/TIA in diabetic patients with breast cancer receiving AIs compared with DPP4i.展开更多
Aromatase inhibitor-induced musculoskeletal symptoms(AIMSS),especially joint pain,have been widely reported in postmenopausal women undergoing endocrine therapy for hormone receptor-positive breast cancer and are a ma...Aromatase inhibitor-induced musculoskeletal symptoms(AIMSS),especially joint pain,have been widely reported in postmenopausal women undergoing endocrine therapy for hormone receptor-positive breast cancer and are a major cause of treatment termination.Aerobic exercise has emerged as a promising nonpharmacological intervention to counteract AIMSS in this population.This study aimed to perform a systematic review and meta-analysis to assess the effect of aerobic exercise on aromatase inhibitor-induced worst joint pain in postmenopausal breast cancer.A systematic literature search was performed using ClinicalTrials.gov,PubMed,and the Cochrane Library that yielded 1415 records.Studies comparing the effect of aerobic exercise with usual care on the worst joint pain through brief pain inventory(BPI)scoring in postmenopausal women with breast cancer receiving aromatase inhibitor therapy were included.For each group,the mean change from baseline and standard deviation(SD)of worst joint pain(BPI score)were calculated.Mean differences(MDs)with 95%confidence intervals(CIs)were pooled using a random-effects model.Subgroup analyses were conducted to explore heterogeneity based on exercise intervention.Three randomized controlled trials(n=297)were included.Pooled analysis showed no significant overall effect of exercise compared with control(standardized mean difference[SMD]=−0.16;95%CI[−1.45,1.14];p=0.65;I^(2)=74%).Subgroup analysis indicated a significant difference by exercise type(p=0.003),suggesting exercise modality influenced outcomes.Aerobic exercise,evaluated in two RCTs,significantly reduced worst joint pain(SMD=−0.41;95%CI[−0.50,−0.32];p=0.01;I^(2)=0%),indicating consistent benefit across studies.In contrast,the single study assessing Nordic walking showed no significant improvement(SMD=0.56;95%CI[−0.08,1.19];p=0.08).Risk-of-bias assessment revealed variability across studies,with one trial rated low risk,one with some concerns,and one at high risk,which may partly explain the observed heterogeneity(I^(2)=74%).Aerobic exercise interventions did not show an overall significant effect on the worst joint pain.However,subgroup analysis revealed that multi-component aerobic exercise programs were associated with significant pain reduction,while the study with only Nordic walking intervention was not.Considering the clinical burden of aromatase inhibitorinduced musculoskeletal symptoms,aerobic exercise can be a potentially useful non-pharmacologic adjunct to endocrine therapy.However,given the variation in the assessed risk of bias among the included studies,these outcomes should be interpreted with due caution.To confirm these results and determine the optimal exercise type and duration for managing aromatase inhibitor–associated musculoskeletal symptoms in breast cancer survivors,further large-scale trials are necessary.展开更多
Objective： To assess the effectiveness of Yishen Jiangu Granules（益肾健骨颗粒, YSJGG） on aromatase inhibitor-associated musculoskeletal symptoms（AIMSS）. Methods： A single-arm, open-label study was conducted in 3...Objective： To assess the effectiveness of Yishen Jiangu Granules（益肾健骨颗粒, YSJGG） on aromatase inhibitor-associated musculoskeletal symptoms（AIMSS）. Methods： A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks（12.4 g orally twice daily）. The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form（BPI-SF） over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index（WOMAC）, Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands（M-SACRAH）, the Functional Assessment of Cancer Therapy-Breast（FACT-B）, bone mineral density（BMD） and blood indices such as calcium（Ca）, phosphate（P）, and alkaline phosphatase（ALP）. Results： Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome（BPI-SF worst pain scores） achieved a 2.17-point reduction compared with baseline（5.75±1.87 vs 3.58±2.15, P〈0.01）. There were reductions in pain severity（decreased 1.65, P〈0.01） and pain-related interference（decreased 2.55, P〈0.01）. The changes in WOMAC and M-SACRAH scores were similar to BPI-SF（P〈0.05）. In the FACT-B, only physical wel-being and functional wel-being were improved compared with baseline（P〈0.05）. No clinical differences were found in BMD, Ca, P and ALP. Conclusion： YSJGG is an effective and wel-tolerated agent to reduce AIMSS.展开更多
Certain aspects of social behavior help animals make adaptive decisions during encounters with other animals.When mice choose to approach another conspecific,the motivation and preference behind the interaction is not...Certain aspects of social behavior help animals make adaptive decisions during encounters with other animals.When mice choose to approach another conspecific,the motivation and preference behind the interaction is not well understood.Estrogen and oxytocin are known to influence a wide array of social behaviors,including social motivation and social preference.The present study investigated the effects of estrogen and oxytocin on social preference using aromatase(ArKO),estrogen receptor(ER)α(αERKO),ERβ(βERKO),oxytocin(OTKO),oxytocin receptor(OTRKO)knockout and their respective wild-type(WT)male mice.Mice were presented with gonadally-intact versus castrated male(IC),intact male versus ovariectomized female(IF),or intact male versus empty cage(IE)stimuli sets for 5 days.ArWT showed no preference for either stimuli in IC and IF and intact male preference in IE,but ArKO mice preferred a castrated male or an ovariectomized female,or had no preference for either stimulus in IC,IF and IE stimuli sets,respectively,suggesting reduced intact male preference.αandβWT mice preferred a castrated male,showed no preference,and preferred an intact male in IC,IF and IE,respectively.αERKO mice displayed similar modified social preference patterns as ArKO,whereas the social preference ofβERKO mice remained similar toβWT.OTWT preferred a castrated male whereas OTKO,OTRWT and OTRKO mice failed to show any preference in IC and none showed preference for either stimuli in IF.Collectively,these findings suggest that estrogen regulates social preference in male mice and that impaired social preference in oxytocin-deficient mice may be due to severe deficits in social recognition.展开更多
Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the po...Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the possibility of sperm retrieval during micro-TESE and even lead to the presence of sperm in the ejaculate in some cases,thereby obviating the need for micro-TESE.However,their routine use before micro-TESE in cases of nonobstructive azoospermia(NOA)being associated with hypergonadotropic hypogonadism and eugonadism(normogonadotropic condition)has not been supported with robust evidence.In this review,we discuss different types of medical therapy used before micro-TESE for NOA,their risks and benefits,and the available evidence surrounding their use in this setting.展开更多
基金supported by the National Key R&D Program of China(2019YFC1712200-2019YFC1712204)the National Natural Science Foundation of China(82004467,82030125)the Youth Project of Traditional Chinese Medicine-Integration of Traditional and Western Medicine Projects of Tianjin Health Commission(No.2025027).
文摘Objective:Breast cancer is the second most prevalent cause of mortality in women and the predominant malignancy type.However,breast cancer treatment faces challenges in managing aromatase inhibitor-induced arthralgia.Aromatase inhibitors have been shown to decrease recurrence risk in hormone receptor-positive cases;however,joint discomfort remains the primary adverse effect.Randomized clinical trials have evaluated the therapeutic outcomes of acupuncture for medication-related musculoskeletal complications.This comprehensive analysis sought to elucidate both the therapeutic efficacy and placebo responses associated with acupuncture intervention.Methods:Two reviewers searched for randomized controlled trials(RCTs)in four English(PubMed,Embase,Web of Science,and the Cochrane Library)and four Chinese databases(CNKI,Wanfang Database,VIP,and SinoMed)from their inception to May 31,2024.Methodological quality was assessed using the Cochrane risk of bias tool.Data were synthesized using random effects models and presented with forest plots.Results:Seven trials involving 604 patients were included.The primary outcome and Brief Pain Inventory(BPI)score differed between the acupuncture and control groups(sham acupuncture or usual medication)in three subscales over the course of 6 weeks:worst pain:standardized mean difference(SMD)=-1.18,95%confidence interval(CI):-1.74,-0.63,P<0.001;painrelated interference:SMD=-0.87,95%CI:-1.70,-0.05,P=0.038;pain severity:SMD=-0.63,95%CI:-1.22,-0.04,P=0.036.No severe adverse events were reported in any study.Conclusions:This meta-analysis showed that acupuncture is a safe and effective treatment for patients with breast cancer with aromatase inhibitor-induced arthralgia during the course of 6 weeks.Improvements in the blinding method and clarification of the total treatment recommendations and intervals need to be explored further.
文摘Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particularly in those with hypogonadism,elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic–pituitary–testicular axis by suppressing follicle-stimulating hormone(FSH)and luteinizing hormone(LH)production and impaired spermatogenesis.Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment.We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males.Overall,eight original articles were included and critically evaluated.Either steroidal(Testolactone)or nonsteroidal(Anastrozole and Letrozole)aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile.While the evidence is promising,future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.
文摘To investigate the effect of Yikun Neiyi Wan （益坤内异丸YKNYW） and gestrinone on the expression of aromatase P450 （P450arom）, cyclo-oxygenase-2 （COX-2） and estrogen receptor （ER） in isolated ectopic and normal endometriat stroma cells in vitro. Methods： Digestion and serial filtration were used to isolate and culture the ectopic and eutopic endometrial cells from patients with chocolate cyst in virto Transformation of the cell morphology was observed in a inverted microscope. The effect of YKNYW on the expression of aromatase P450, cyclo-oxygenase-2, estrogen receptor in cultured endometriosis cells were detected by immunohistochemical method. Results： The expression levels of P450arom, COX-2 in glandular epithelium cells in vitro were decreased significantly by YKNYW compared with gestrinone （P〈0.05）. ER expression in mesenchymal cells of endometriosis was increased by YKNYW in the large and medium dosage groups compared with gestrinone. Conclusion： The mechanism by which YKNYW alleviates endometriosis pain is possibly related to the decrease in ectopic endometrial P450 arom and COX-2 expression in glandular epithelium, contrary to gestrinone, and the increase in ER expression in mesenchymalis, consistent with gestrione in patients with endometriosis.
基金Supported by a TCM Scientific and Technological Research Fund of Guangdong Provincial Hospital of Chinese Medicine,People's Republic of China(No.2011KT371)
文摘OBJECTIVE: To investigate the effect of Jianpi Bushen(JPBS) formula on aromatase inhibitor(AI)-associated bone loss after menopause.METHODS: Six-month-old female rats were randomly divided into 6 groups: a sham group, an ovariectomized(OVX) group, an OVX treated with exemestane and 3 OVX groups each treated with a different dose of JPBS formula. Bone mineral density(BMD) at the lumbar vertebrae, histology, bone markers and serum levels of estrogen were assessed. Furthermore, a cohort study was conducted in 130 postmenopausal women with breast cancer that had undergone treatment with AIs. The subjects were given JPBS + caltrate D or caltrate D only, administered orally. BMD at the lumbar vertebrae and femoral neck and bone markers were evaluated in both control and herbal treatment groups at baseline and 12 months.RESULTS: Experimental results indicated that a high dose of JPBS significantly increased the trabecular bone area percentage(Tb.Ar %) and broadened the trabecular thickness(Tb.Th). The JPBS formula enriched the carboxyterrninal propeptide of type ipmcollagen and increased serum estrogen level significantly. The clinical investigation revealed that bone loss was decreased in the group treated with JPBS vs control(BMD T score at lumbar vertebrae, 3.9% increased vs 14.58% decreased, respectively, P = 0.004 and BMD T score on femoral neck, 1.8% decreased vs 22.45% decreased, respectively, P = 0.008). Besides, JPBS formula elevated Nmiddle osteocalcin and decreased type Ⅰ collagen cross-linked C-terminal telopeptide.CONCLUSION: JPBS formula prevented aromatase-inhibitor-associated bone loss after menopause by inhibiting bone resorption and promoting bone formation.
文摘Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid peroxidation and on the expression of testicular aromatase and estrogen receptors （ER）. Methods： CR was initiated in 1-month-old rats and carried on until the age of 18 months. Results： In control and CR2 rats an age-related decrease of the aromatase and of ER （α and β） gene expression was observed; in parallel a diminution of testicular weights, and of the total number and motility of epididymal spermatozo was recorded. In addition, aging in control and CR2 rats was accompartied by a significant decrease in testicular superoxide dismutase, catalase activities, and an increase in lipid peroxidation level （thiobarbituric acid reactive substance）, associated with alterations of spermatogenesis. Conversely, caloric restriction-treatment exerted a protective effect and all the parameters were less affected by aging. Conclusion： These results indicate that during aging, a low caloric diet （not undernutrition） is beneficial for spermatogenesis and likely improves the protection of the cells via an increase of the cellular antioxidant defense system in which aromatase/ ER could play a role. （Asian J Andro12008 Mar; 10： 177-187）
文摘AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale. RESULTS: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed. CONCLUSION: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.
基金supported by the National Natural Science Foundation of China (No. 200930973906)
文摘Objective：Estradiol （E2） plays an important role in the development of breast cancer.In postmenopausal women,the estrogen can be synthesized via aromatase （CYP19） pathway and steroid-sulfatase （STS） pathway in peripheral tissues,when the production in ovary has ceased.The objective of our study was to explore the effects of Shu-Gan-Liang-Xue Decoction （SGLXD） on the expressions of CYP19 and STS in estrogen receptor positive breast cancer MCF-7 and T47D cells.Methods：The effects of SGLXD on the cell viability of MCF-7 and T47D were analyzed by MTT assay.By quantitative real-time RT-PCR and Western blot,we evaluated the mRNA and protein expressions of CYP19 and STS in MCF-7 and T47D cells after SGLXD treatment.Results：By MTT assay,the cell viability rates of MCF-7 and T47D were significantly inhibited by SGLXD in a dose-dependent manner,the IC50 values were 40.07 mg/ml for MCF-7 cells and 25.62 mg/ml for T47D cells,respectively.As evidenced by real-time PCR and Western blot,the high concentrations of SGLXD significantly down-regulated the expressions of CYP19 and STS both in the transcript level and the protein level.Conclusion：The results suggest that SGLXD is a potential dual aromatase-sulfatase inhibitor by simultaneously down-regulating the expressions of CYP19 and STS in MCF-7 and T47D cells.
文摘Hormone Receptor positive (HR+) breast cancer is the most common malignancy in women. New strategies in the treatments have targeted the estrogen biosynthesis pathways including the inhibition of the aromatase and 17β-HSD1 enzymes. The present work, describes the study of a new family of 9 hybrid compounds derived from estrone attached to a coumarin fragment, linked through different lengths of hydrocarbon chains. The activity of these compounds was evaluated by molecular docking with two relevant enzymes in breast cancer (HR+). It has been proposed nine compounds as 17β-HSD1 inhibitors and six as aromatase inhibitors. We found important interactions with key amino acids at the orthosteric site of each enzyme and their score values compared to the crystallographic ligand. The in silico analysis showed good score values in the proposed compounds, where the steroidal portion presented important interactions with Met374 and Tyr155 in aromatase and in 17β-HSD1 respectively. Highlighting Compounds 2, 5 and 8 with an aromatic ring at the C4 position of the coumarin moiety, which favored arene-H type interactions essential for protein-ligand recognition. In addition, the results related to the 17β-HSD1 enzyme demonstrated how the length of the linker influences the interaction;the best score was found for derivative 8 with a chain of 8 methylenes.
文摘Testicular function is regulated by pituitary hormones and also by paracrine and autocrine factors. A number of reports have pointed out the importance of estrogens and progesterone in male reproductive tract. Recently, we have reported in testicular biopsies from men with Sertoli Cell Only Syndrome (SCO) or Hypospermatogenesis (H) with Leydig cell hyperplasia (LCH) an increase in the expression of the TGFB1 and its receptors ALK1 and endoglin, which are involved in the proliferation of Leydig cells. The aim of the present work was to analyze the expression of aromatase, estrogen and progesterone receptors (ERs, PR) in pathological testicular biopsies with SCO or H with and without LCH. The ERs and CYP19 proteins were detected in the Leydig cells from all pathological biopsies analyzed. Biopsies with SCO or H with LCH showed an increment in the immunostaining of CYP19 and ERs in the Leydig cells respect to biopsies without LCH. The gene expression of CYP19 was increased in SCO or H biopsies with LCH respect to SCO and H biopsies without LCH. PR was localized in Leydig cells and showed a significant increment in biopsies with LCH respect from biopsies without LCH. The gene expression of both PRA and PRB was increased in biopsies with LCH respect to biopsies without LCH. In concussion, alterations in the gene expression of aromatase, ERs, and PR and the likely interactions of these systems with locally produced factors such as growth factors and cytokines, might lead to Leydig cell proliferation in testicular pathology.
文摘The aim of this study was to evaluate the polymorphism in a portion of the gene regulatory region for ovarian aromatase （CYP19a） in three strains of Tilapia, Oreochomis niloticus （Linnaeus） （GIFT--Genetically Improved Farmed Tilapia, Chitralada and Supreme）. A total of 90 animals per strain of Tilapia, Oreochromis niloticus （Linnaeus） were analysed. After DNA extraction, samples were subjected to PCR using primers designed to flank the region of interest encompassing the sites of transcription （WT1-KTS and SRY）. Samples were analyzed by PCR-SSCP and subsequently sequenced. Three polymorphisms were identified in this region, resulting in two different sequences, in the GIFT strain while no polymorphism was found in both Supreme and Chitralada strains. At the position - 1178 the substitution of a guanine for a cytosine, at the - 1081 the exchange of guanine for adenine and at the position -1 138 we found a SNP, possible site of heterozygosity. Even with polymorphisms in the target study area, when taking the three strains into account, one can assume that the portion of the regulatory region of the ovarian aromatase gene in the Supreme strain and Chitralada does not show polymorphism.
文摘The work was carried out by microinjections of an aromatase inhibitor letrozole, an estrogen receptor modulator tamoxifen in incubated eggs Gallus g. domesticus, the first day of incubation. It also used 5-azacytidine (5-AC) at the same time. Injection of progesterone was carried out before the onset of meiosis prophase 1 on 16 h of incubation. Morphologically and histologically and by PCR, sex of the 17-day embryos was controlled. According to information received microinjection of letrozole caused almost a 100% inversion of genetic males to females, which is manifested in the morphology of the gonads. In other experiments, sex reversal is not revealed. The results are obtained in this study, and the data suggest that the presence of gonadogenesis in female chickens makes earlier emergence of aromatase in the beginning of incubation, than that according to the classical scheme of sex determination in birds. Presumably this kind of synthesis is triggered by some W-chromosomal factors. It failed to detect the phenomenon of gender inversion—the transformation of males into females after exposure to demethylating agent 5-AC that casts doubt on the participation of male hypermethylated (MHM)-RNA-segment in regulating the activity of sex determining genes.
文摘Aim: To identify the correlation between mRNA expression of aromatase, 17β-HSD2 level of TGF-β1 and stage of endometriosis. Methods: Case control study was done on 80 patients divided by 40 endometriosis patients and 40 patients as control. mRNA expression of aromatase, mRNA 17β-SD2, was checked using reverse-transcriptase polymerase chain reaction (RT-PCR) and TGF-β1 serum and peritoneal fluid was checked using ELISA. Result: Level of mRNA aromatase from ectopic and eutopic endometrium increased significantly compared to control group (p < 0.001). mRNA 17β-HSD2 expression is significantly lower compared to control (p TGF-β1 on endometriosis group was significantly higher compared to control group (p < 0.05). Level of peritoneal fluid TGF-β1 on endometriosis group was higher than control group (p < 0.001). There are no correlations between mRNA aromatase, type 2 17β-HSD, TGF-β1 serum level to endometriosis stage. There are significant correlations between peritoneal fluid TGF-β1 levels to endometriosis stage.
基金supported by the National Natural Science Foundation of China(21977080,21371135,and 21772146)Tianjin Municipal Natural Science Foundation(17JCZDJC33100).
文摘The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvant therapy drugs for early stages of breast cancer. In this paper,we employed the FDA-approved aromatase inhibitor aminoglutethimide (AG) to design and prepare a new class of multi-targeting Pt(IV) prodrugs (aminoplatins 1–3) by utilizing the targeting,estrogen-manipulating,and chemo-sensitizing effects of the aromatase inhibitor. Aminoplatin 3,as a representative,exhibited an enhanced anticancer activity up to 190-fold greater than the parent Pt(Ⅱ) drug cisplatin,and 3 had less toxicity to normal cells,displaying higher anticancer efficacy and a superior therapeutic index compared to those of cisplatin. Moreover,aminoplatin 3 could enhance intracellular accumulation,induce remarkable DNA damage,inhibit migration and metastasis,and result in S phase cell cycle arrest and apoptosis in ER-positive MCF-7 cells. Besides,molecular docking results showed that 3 simultaneously occupies the heme iron-binding domain and the ASD-binding site of aromatase by a highly efficient dual-binding pattern to aromatase,which further displayed a striking anti-estrogenic effect by significant downregulation of CPY19A1 and ERα in ER-positive MCF-7 cells. Most strikingly,our in vivo anticancer evaluation data also provided evidence that 3 effectively inhibited tumor growth and attenuated kidney toxicity compared to cisplatin in MCF-7 xenografted BALB/c nude mice. Our results suggest that the anticancer activity of aminoplatins is mechanistically distinct from that of the conventional platinum drugs,and modifying platinum drugs with aromatase inhibitors may represent an improved modality for the treatment of advanced postmenopausal breast cancer.
基金financial support from Department of Biotechnology,Govt of India(BT/PR28560/AAQ/3/919/2018).
文摘Monocrotophos(MCP)and Glyphosate(GLY)are used as an insecticide and herbicide respectively in agricultural fields in India and other developed countries.Since agricultural fields are located close to water bodies,there is a high risk of water contamination by these chemicals with consequent residue accumulation in aquatic biota including fish.The 48 h LC50 was found to be 106 mg/L and 78 mg/L for MCP and GLY respectively.To investigate the effects of these two agrochemicals,the adult climbing perch,Anabas testudineus female fish were treated with 3 concentrations of MCP and GLY for 30 days.The MCP concentrations were 3.5×10^(-4)%(T1),5.3×10^(-4)%(T2),and 10.6×10^(-4)%(T3)and GLY concentrations were 2.6×10^(-4)%(T1),3.9×10^(-4)%(T2),and 7.8×10^(-4)%(T3).One group was kept as control.Molecular docking analysis showed that GLY interacted with brain aromatase protein at residues MET424,THR423,PRO479 with a binding energy of -10.685 and with a docking score of -4.769.In the case of MCP,the binding residues were MET424,THR423,and PHE422 ofbrain aromatase with a binding energy of -10.436 with a docking score of -2.824.Similarly,GLYinteracted with ovary aromatase at residues ASN 479,THR477,ASN 230,GLU 226,GLN 483,PRO 484,and GLU 486 with a binding energy of -10.685 and with a docking score of5.177.In the case of MCP,the binding residues were ASP 312,THR 313,SER 481,and TRP 228 of ovary aromatase with a binding energy of -2.405 and with a docking score of -3.372.These agrochemicals caused ovarian damage and alteration in gonadosomatic index and cytochrome P450 aromatase gene expression.
基金supported by grants from the National Natural Science Foundation of China(82370332,82570390)the Tianjin Key Medical Discipline Construction Project(TJYXZDXK-3-006B)
文摘Background:Aromatase inhibitors(AIs)are associated with improved cancer-related survival in breast cancer,but also higher risks of adverse cardiovascular outcomes.This study compared cardiovascular outcomes between sodium-glucose cotransporter-2 inhibitor(SGLT2i)and dipeptidyl peptidase-4 inhibitor(DPP4i)among breast cancer patients receiving AIs.Methods:This was a retrospective,territory-wide study enrolling female patients≥45 years old with diabetes mellitus and breast cancer who received SGLT2i or DPP4i on the date of AIs initiation,between 2015 and 2020 in Hong Kong.The primary outcome was major adverse cardiovascular events(MACE).The secondary outcomes included components of MACE[stroke/transient ischemic attack(TIA),nonfatal myocardial infarction(MI),and cardiovascular death],heart failure,and all-cause mortality.Multivariable Cox regression was applied to evaluate the association between SGLT2i versus DPP4i with outcomes.Results:Initially,a total of 76147 diabetes patients treated with SGLT2i or DPP4i were identified.After matching,226 patients(mean age,65.5±7.6 years)were included(113 SGLT2i users versus 113 DPP4i users).During a median follow-up of 5.51 years,43(19.02%)patients developed composite MACE.Compared with DPP4i users,SGLT2i was not significantly associated with MACE[hazard ratio(HR):0.54;95%confidence interval(CI):0.27-1.10]in the adjusted model.For the secondary outcomes,breast cancer patients treated with SGLT2i presented with an 84%lower risk of stroke/TIA(HR:0.16;95%CI:0.04-0.61)than DPP4i users after adjustments.No significant associations were observed between SGLT2i with MI(HR:0.41;95%CI:0.10-1.69),cardiovascular mortality(HR:0.86;95%CI:0.20-3.70),all-cause mortality(0.51;95%CI:0.17-1.58),and heart failure(0.47;95%CI:0.12-1.89),in relation to DPP4i.Conclusion:SGLT2i was associated with lower risks of stroke/TIA in diabetic patients with breast cancer receiving AIs compared with DPP4i.
文摘Aromatase inhibitor-induced musculoskeletal symptoms(AIMSS),especially joint pain,have been widely reported in postmenopausal women undergoing endocrine therapy for hormone receptor-positive breast cancer and are a major cause of treatment termination.Aerobic exercise has emerged as a promising nonpharmacological intervention to counteract AIMSS in this population.This study aimed to perform a systematic review and meta-analysis to assess the effect of aerobic exercise on aromatase inhibitor-induced worst joint pain in postmenopausal breast cancer.A systematic literature search was performed using ClinicalTrials.gov,PubMed,and the Cochrane Library that yielded 1415 records.Studies comparing the effect of aerobic exercise with usual care on the worst joint pain through brief pain inventory(BPI)scoring in postmenopausal women with breast cancer receiving aromatase inhibitor therapy were included.For each group,the mean change from baseline and standard deviation(SD)of worst joint pain(BPI score)were calculated.Mean differences(MDs)with 95%confidence intervals(CIs)were pooled using a random-effects model.Subgroup analyses were conducted to explore heterogeneity based on exercise intervention.Three randomized controlled trials(n=297)were included.Pooled analysis showed no significant overall effect of exercise compared with control(standardized mean difference[SMD]=−0.16;95%CI[−1.45,1.14];p=0.65;I^(2)=74%).Subgroup analysis indicated a significant difference by exercise type(p=0.003),suggesting exercise modality influenced outcomes.Aerobic exercise,evaluated in two RCTs,significantly reduced worst joint pain(SMD=−0.41;95%CI[−0.50,−0.32];p=0.01;I^(2)=0%),indicating consistent benefit across studies.In contrast,the single study assessing Nordic walking showed no significant improvement(SMD=0.56;95%CI[−0.08,1.19];p=0.08).Risk-of-bias assessment revealed variability across studies,with one trial rated low risk,one with some concerns,and one at high risk,which may partly explain the observed heterogeneity(I^(2)=74%).Aerobic exercise interventions did not show an overall significant effect on the worst joint pain.However,subgroup analysis revealed that multi-component aerobic exercise programs were associated with significant pain reduction,while the study with only Nordic walking intervention was not.Considering the clinical burden of aromatase inhibitorinduced musculoskeletal symptoms,aerobic exercise can be a potentially useful non-pharmacologic adjunct to endocrine therapy.However,given the variation in the assessed risk of bias among the included studies,these outcomes should be interpreted with due caution.To confirm these results and determine the optimal exercise type and duration for managing aromatase inhibitor–associated musculoskeletal symptoms in breast cancer survivors,further large-scale trials are necessary.
基金Supported by Beijing Municipal Science and Technology Commission,China(No.D131100002213001,D161100005116005)Beijing Municipal Administration of Hospitals,China(No.QML20150903)
文摘Objective： To assess the effectiveness of Yishen Jiangu Granules（益肾健骨颗粒, YSJGG） on aromatase inhibitor-associated musculoskeletal symptoms（AIMSS）. Methods： A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks（12.4 g orally twice daily）. The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form（BPI-SF） over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index（WOMAC）, Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands（M-SACRAH）, the Functional Assessment of Cancer Therapy-Breast（FACT-B）, bone mineral density（BMD） and blood indices such as calcium（Ca）, phosphate（P）, and alkaline phosphatase（ALP）. Results： Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome（BPI-SF worst pain scores） achieved a 2.17-point reduction compared with baseline（5.75±1.87 vs 3.58±2.15, P〈0.01）. There were reductions in pain severity（decreased 1.65, P〈0.01） and pain-related interference（decreased 2.55, P〈0.01）. The changes in WOMAC and M-SACRAH scores were similar to BPI-SF（P〈0.05）. In the FACT-B, only physical wel-being and functional wel-being were improved compared with baseline（P〈0.05）. No clinical differences were found in BMD, Ca, P and ALP. Conclusion： YSJGG is an effective and wel-tolerated agent to reduce AIMSS.
基金This work was supported by Grants-in-Aid for Scientific Research(23240057 and 15H05724)the University of Tsukuba Research Project(to S.O.).
文摘Certain aspects of social behavior help animals make adaptive decisions during encounters with other animals.When mice choose to approach another conspecific,the motivation and preference behind the interaction is not well understood.Estrogen and oxytocin are known to influence a wide array of social behaviors,including social motivation and social preference.The present study investigated the effects of estrogen and oxytocin on social preference using aromatase(ArKO),estrogen receptor(ER)α(αERKO),ERβ(βERKO),oxytocin(OTKO),oxytocin receptor(OTRKO)knockout and their respective wild-type(WT)male mice.Mice were presented with gonadally-intact versus castrated male(IC),intact male versus ovariectomized female(IF),or intact male versus empty cage(IE)stimuli sets for 5 days.ArWT showed no preference for either stimuli in IC and IF and intact male preference in IE,but ArKO mice preferred a castrated male or an ovariectomized female,or had no preference for either stimulus in IC,IF and IE stimuli sets,respectively,suggesting reduced intact male preference.αandβWT mice preferred a castrated male,showed no preference,and preferred an intact male in IC,IF and IE,respectively.αERKO mice displayed similar modified social preference patterns as ArKO,whereas the social preference ofβERKO mice remained similar toβWT.OTWT preferred a castrated male whereas OTKO,OTRWT and OTRKO mice failed to show any preference in IC and none showed preference for either stimuli in IF.Collectively,these findings suggest that estrogen regulates social preference in male mice and that impaired social preference in oxytocin-deficient mice may be due to severe deficits in social recognition.
文摘Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the possibility of sperm retrieval during micro-TESE and even lead to the presence of sperm in the ejaculate in some cases,thereby obviating the need for micro-TESE.However,their routine use before micro-TESE in cases of nonobstructive azoospermia(NOA)being associated with hypergonadotropic hypogonadism and eugonadism(normogonadotropic condition)has not been supported with robust evidence.In this review,we discuss different types of medical therapy used before micro-TESE for NOA,their risks and benefits,and the available evidence surrounding their use in this setting.
