-
Frontiers in Neuroendocrinology Oct 2020Epidemiological, clinical, and basic research over the past thirty years have described the benefits of estrogen on cognition, mood, and brain health. Less is known... (Review)
Review
Epidemiological, clinical, and basic research over the past thirty years have described the benefits of estrogen on cognition, mood, and brain health. Less is known about tamoxifen, a selective estrogen receptor modifier (SERM) commonly used in breast cancer which is able to cross the blood-brain barrier. In this article, we review the basic pharmacology of tamoxifenas well as its effects on cognition and mood. The literature reveals an overall impairing effect of tamoxifen on cognition in breast cancer patients, hinting at central antiestrogen activity. On the other hand, tamoxifen demonstrates promising effects in psychiatric disorders, like bipolar disorder, where its therapeutic action may be independent of interaction with estrogen receptors. Understanding the neuropsychiatric properties of SERMs like tamoxifen can guide future research to ameliorate unwanted side-effects and provide novel options for difficult to treat disorders.
Topics: Affect; Animals; Antineoplastic Agents, Hormonal; Cognition; Estrogen Antagonists; Humans; Tamoxifen
PubMed: 32822707
DOI: 10.1016/j.yfrne.2020.100869 -
British Journal of Cancer Feb 2023
Review
Topics: Humans; Female; Tamoxifen; Antineoplastic Agents, Hormonal; Breast Neoplasms
PubMed: 36765172
DOI: 10.1038/s41416-023-02158-5 -
The Oncologist 2011For premenopausal patients with receptor-positive early breast cancer, administration of tamoxifen for 5 years constitutes the main adjuvant endocrine therapy. During... (Review)
Review
For premenopausal patients with receptor-positive early breast cancer, administration of tamoxifen for 5 years constitutes the main adjuvant endocrine therapy. During pregnancy, tamoxifen and its metabolites interact with rapidly growing and developing embryonic or fetal tissues. Information about tamoxifen and pregnancy was gathered by searching PubMed. In addition, we had access to the records of the pharmaceutical company AstraZeneca. Because these observations are retrospective and other therapies and diagnostic measures are possible confounders, a causal relationship was not established between tamoxifen treatment and pregnancy outcome. The records from AstraZeneca documented three live births with congenital anomalies and four live births without congenital anomalies related to tamoxifen treatment before pregnancy. Tamoxifen therapy during pregnancy resulted in 16 live births with congenital malformations and a total of 122 live births without malformations. The 122 live births without malformations included 85 patients from a prevention trial that did not record a single anomaly, whereas the AstraZeneca Safety Database alone reported 11 babies with congenital malformations of 44 live births. Additionally, there were: 12 spontaneous abortions, 17 terminations of pregnancy without known fetal defects, six terminations of pregnancy with fetal defects, one stillbirth without fetal defects, two stillbirths with fetal defects, and 57 unknown outcomes. The relatively high frequency of severe congenital abnormalities indicates that reliable birth control during tamoxifen treatment is mandatory. After tamoxifen use, a washout period of 2 months is advisable based on the known half-life of tamoxifen. In case of an inadvertent pregnancy, risks and options should be discussed.
Topics: Abnormalities, Drug-Induced; Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Humans; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Tamoxifen
PubMed: 22020212
DOI: 10.1634/theoncologist.2011-0121 -
Clinical Pharmacokinetics Aug 2015The antiestrogenic drug tamoxifen is widely used in the treatment of estrogen receptor-α-positive breast cancer and substantially decreases recurrence and mortality... (Review)
Review
The antiestrogenic drug tamoxifen is widely used in the treatment of estrogen receptor-α-positive breast cancer and substantially decreases recurrence and mortality rates. However, high interindividual variability in response is observed, calling for a personalized approach to tamoxifen treatment. Tamoxifen is bioactivated by cytochrome P450 (CYP) enzymes such as CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5, resulting in the formation of active metabolites, including 4-hydroxy-tamoxifen and endoxifen. Therefore, polymorphisms in the genes encoding these enzymes are proposed to influence tamoxifen and active tamoxifen metabolites in the serum and consequently affect patient response rates. To tailor tamoxifen treatment, multiple studies have been performed to clarify the influence of polymorphisms on its pharmacokinetics and pharmacodynamics. Nevertheless, personalized treatment of tamoxifen based on genotyping has not yet met consensus. This article critically reviews the published data on the effect of various genetic polymorphisms on the pharmacokinetics and pharmacodynamics of tamoxifen, and reviews the clinical implications of its findings. For each CYP enzyme, the influence of polymorphisms on pharmacokinetic and pharmacodynamic outcome measures is described throughout this review. No clear effects on pharmacokinetics and pharmacodynamics were seen for various polymorphisms in the CYP encoding genes CYP2B6, CYP2C9, CYP2C19 and CYP3A4/5. For CYP2D6, there was a clear gene-exposure effect that was able to partially explain the interindividual variability in plasma concentrations of the pharmacologically most active metabolite endoxifen; however, a clear exposure-response effect remained controversial. These controversial findings and the partial contribution of genotype in explaining interindividual variability in plasma concentrations of, in particular, endoxifen, imply that tailored tamoxifen treatment may not be fully realized through pharmacogenetics of metabolizing enzymes alone.
Topics: Breast Neoplasms; Estrogen Antagonists; Female; Humans; Precision Medicine; Tamoxifen
PubMed: 25940823
DOI: 10.1007/s40262-015-0273-3 -
The Oncologist 2012Tamoxifen is an effective antiestrogen used in the treatment of hormone receptor-positive breast cancer. Bioconversion of tamoxifen to endoxifen, its most abundant... (Review)
Review
Tamoxifen is an effective antiestrogen used in the treatment of hormone receptor-positive breast cancer. Bioconversion of tamoxifen to endoxifen, its most abundant active metabolite, is primarily dependent on the activity of cytochrome P450 2D6 (CYP2D6), which is highly polymorphic. Over 20 published studies have reported on the potential association between CYP2D6 polymorphism and tamoxifen treatment outcome, with highly inconsistent results. The purpose of this review is to explore differences among 17 independent studies to identify factors that may have contributed to the discrepant findings. This report discusses six putative factors that are grouped into two categories: (a) clinical management criteria: hormone receptor classification, menopausal status, and tamoxifen combination therapy; (b) pharmacologic criteria: genotyping comprehensiveness, CYP2D6 inhibitor coadministration, and tamoxifen adherence. Comparison of these factors between the positive and negative studies suggests that tamoxifen combination therapy, genotyping comprehensiveness, and CYP2D6 inhibitor coadministration may account for some of the contradictory results. Future association studies on the link between CYP2D6 genotype and tamoxifen treatment efficacy should account for combination therapy and CYP2D6 inhibition, and interrogate as many CYP2D6 alleles as possible.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Cytochrome P-450 CYP2D6; Estrogen Receptor Modulators; Female; Humans; Pharmacogenetics; Polymorphism, Genetic; Tamoxifen; Treatment Outcome
PubMed: 22531359
DOI: 10.1634/theoncologist.2011-0418 -
Asian Journal of Andrology Mar 2006Idiopathic oligoasthenoteratozoospermia (iOAT) affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age,... (Review)
Review
Idiopathic oligoasthenoteratozoospermia (iOAT) affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age, non-inflammatory functional alterations in post-testicular organs, infective agents (Chlamydia trachomatis, herpes virus and adeno-associated viruses), alterations in gamete genome, mitochondrial alterations, environmental pollutants and "subtle" hormonal alterations are all considered possible causes of iOAT. Increase of reactive oxygen species in tubules and in seminal plasma and of apoptosis are reputed to affect sperm concentration, motility and morphology. iOAT is commonly diagnosed by exclusion, nevertheless spectral traces of the main testicular artery may be used as a diagnostic tool for iOAT. The following can be considered therapies for iOAT: 1) tamoxifen citrate (20 mg/d) + testosterone undecanoate (120 mg/d) (pregnancy rate per couple/month [prcm]: 3.8%); 2) folic acid (66 mg/d) + zinc sulfate (5 mg/d); 3) L-carnitine (2 g/d) alone or in combination with acetyl-L-carnitine (1 g/d) (prcm: 2.3%); and 4) both carnitines = one 30 mg cinnoxicam suppository every 4 days (prcm: 8.5%). Alpha-blocking drugs improved sperm concentration but not morphology, motility or pregnancy rate. Tranilast (300 mg/d) increased sperm parameters and pregnancy rates in an initial uncontrolled study. Its efficacy on sperm concentration (but not on sperm motility, morphology or prcm) was confirmed in subsequent published reports. The efficacy of tamoxifen + testosterone undecanoate, tamoxifen alone, and recombinant follicle-stimulating hormone is still a matter for discussion.
Topics: Acetylcarnitine; Animals; Antioxidants; Apoptosis; Autoimmunity; Chlamydia Infections; Chlamydia trachomatis; Chromosome Deletion; Chromosomes, Human, Y; Diagnosis, Differential; Environmental Pollutants; Folic Acid; Follicle Stimulating Hormone, Human; Genitalia, Male; Humans; Inflammation; Male; Oligospermia; Reactive Oxygen Species; Recombinant Proteins; Sperm Count; Spermatozoa; Tamoxifen; Zinc Sulfate
PubMed: 16491265
DOI: 10.1111/j.1745-7262.2006.00123.x -
Nutrients Dec 2022Tamoxifen is commonly used to treat estrogen receptor-positive breast cancer and hepatocellular carcinoma. Phytoconstituents are considered candidates for...
Tamoxifen is commonly used to treat estrogen receptor-positive breast cancer and hepatocellular carcinoma. Phytoconstituents are considered candidates for chemopreventive drugs in cancer treatment. However, it remains unknown what would happen if tamoxifen and phytoconstituents were administrated simultaneously. We aimed to observe the synergistic antitumor effects of tamoxifen and naringenin/quercetin on human hepatic carcinoma and to explore the potential underlying molecular mechanisms. The HepG2 cell line was used as an in vitro model. Cell proliferation, invasion, migration, cycle progression and apoptosis were investigated along with reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) repression. The signaling pathways involved were identified using real-time quantitative polymerase chain reaction analysis. As the results show, tamoxifen in combination with higher concentrations of naringenin or quercetin significantly inhibited cell growth compared to either agent alone. These antiproliferative effects were accompanied by the inhibition of cell migration and invasion but the stimulation of cell apoptosis and loss of ΔΨm, which depended on the ROS-regulated p53 signaling cascades. Conversely, lower concentrations of naringenin and quercetin inhibited the tamoxifen-induced cell antiproliferative effects by regulating cell migration, invasion, cycle and apoptosis. Taken together, our findings revealed that phytoconstituents exerted contradictory cytoprotective and cytotoxic effects induced by tamoxifen in human hepatic cancer.
Topics: Humans; Tamoxifen; Quercetin; Hep G2 Cells; Reactive Oxygen Species; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor
PubMed: 36558554
DOI: 10.3390/nu14245394 -
Biomedicine & Pharmacotherapy =... Sep 2023Gene knockout is a technique routinely used in basic experimental research, particularly in mouse skeletal and developmental studies. Tamoxifen-induced Cre/loxp system... (Review)
Review
Gene knockout is a technique routinely used in basic experimental research, particularly in mouse skeletal and developmental studies. Tamoxifen-induced Cre/loxp system is known for its temporal and spatial precision and commonly utilized by researchers. However, tamoxifen has been shown its side effects on affecting the phenotype of mouse bone directly. This review aimed to optimize tamoxifen administration regimens including its dosage and duration, to identify an optimal induction strategy that minimizes potential side effects while maintaining recombination efficacy. This study will help researchers in designing gene knockout experiments in bone when using tamoxifen.
Topics: Mice; Animals; Tamoxifen; Mice, Transgenic; Integrases; Gene Knockout Techniques
PubMed: 37379643
DOI: 10.1016/j.biopha.2023.115045 -
Internal Medicine (Tokyo, Japan) Nov 2017Cases of drug-induced lung injury caused by tamoxifen are rare. A 74-year-old man underwent surgery for the treatment of right breast cancer; tamoxifen was administered...
Cases of drug-induced lung injury caused by tamoxifen are rare. A 74-year-old man underwent surgery for the treatment of right breast cancer; tamoxifen was administered as an adjuvant therapy after surgery. The patient developed cough and dyspnea and chest computed tomography showed ground glass opacification in the lower lobe of the right lung. He was diagnosed with tamoxifen-induced lung injury. The diagnosis was made based on the exclusion of other causes and recurrence with the re-administration of tamoxifen. Physicians should therefore be aware of the potential for the development of tamoxifen-induced lung injury.
Topics: Aged; Antineoplastic Agents, Hormonal; Breast Neoplasms, Male; Chemotherapy, Adjuvant; Humans; Lung Injury; Male; Tamoxifen; Tomography, X-Ray Computed
PubMed: 28943550
DOI: 10.2169/internalmedicine.8649-16 -
IARC Monographs on the Evaluation of... 1996
Review
Topics: Animals; Antineoplastic Agents, Hormonal; Carcinogenicity Tests; Carcinogens; Estrogen Antagonists; Humans; Tamoxifen
PubMed: 9097127
DOI: No ID Found