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Journal of Clinical Medicine Feb 2023dopamine agonists are the recommended treatment for male prolactinomas, but some patients may develop dopamine-agonist-resistant hyperprolactinemia, leading to... (Review)
Review
BACKGROUND
dopamine agonists are the recommended treatment for male prolactinomas, but some patients may develop dopamine-agonist-resistant hyperprolactinemia, leading to persistent hypogonadism that requires treatment with testosterone. However, testosterone replacement therapy may be associated with a decrease in the efficacy of dopamine agonists due to the aromatization of testosterone to estradiol, which can stimulate the proliferation and hyperplasia of lactotroph cells in the pituitary, inducing resistance to dopamine agonists.
OBJECTIVE
this paper systematically reviewed the role of aromatase inhibitors for men with prolactinoma and dopamine-agonist-resistant or persistent hypogonadism following treatment.
METHOD
we performed a systematic review of all studies (according to PRISMA guidelines), assessing the role of aromatase inhibitors, including anastrozole and letrozole, for male prolactinoma. An English-language search for relevant studies was conducted on PubMed from its inception to 1 December 2022. The reference lists of the relevant studies were also reviewed.
RESULTS
our systematic review identified six articles (nine patients), including five case reports and a single case series, on the use of aromatase inhibitors for male prolactinomas. Reducing estrogen levels with an aromatase inhibitor improved sensitivity to dopamine agonists, as the addition of anastrozole or letrozole improves the control of prolactin levels and may lead to the shrinkage of tumors.
CONCLUSION
aromatase inhibitors are of potential value to patients with dopamine-agonist-resistant prolactinoma, or when hypogonadism persists while using high-dose dopamine agonists.
PubMed: 36835974
DOI: 10.3390/jcm12041437 -
Journal of Neuroendocrinology Feb 2023Steroid hormones are often synthesized in multiple tissues, affect several different targets, and modulate numerous physiological endpoints. The mechanisms by which this... (Review)
Review
Steroid hormones are often synthesized in multiple tissues, affect several different targets, and modulate numerous physiological endpoints. The mechanisms by which this modulation is achieved with temporal and spatial specificity remain unclear. 17β-estradiol for example, is made in several peripheral tissues and in the brain, where it affects a diverse set of behaviors. How is estradiol delivered to the right target, at the right time, and at the right concentration? In the last two decades, we have learned that aromatase (estrogen-synthase) can be induced in astrocytes following damage to the brain and is expressed at central synapses. Both mechanisms of estrogen provision confer spatial and temporal specificity on a lipophilic neurohormone with potential access to all cells and tissues. In this review, I trace the progress in our understanding of astrocytic and synaptic aromatization. I discuss the incidence, regulation, and functions of neuroestradiol provision by aromatization, first in astrocytes and then at synapses. Finally, I focus on a relatively novel hypothesis about the role of neuroestradiol in the orchestration of species-specific behaviors.
Topics: Animals; Songbirds; Brain; Estradiol; Estrogens; Synapses; Aromatase
PubMed: 35983989
DOI: 10.1111/jne.13192 -
European Journal of Histochemistry : EJH Aug 2023This study aimed at exploring the expression and clinical significance of aromatase P450, adhesion molecule CD24 and HER2/neu in endometrial cancer. The expression of...
This study aimed at exploring the expression and clinical significance of aromatase P450, adhesion molecule CD24 and HER2/neu in endometrial cancer. The expression of aromatase P450, adhesion molecule CD24 and HER2/neu was detected by immunohistochemistry in 15 cases of endometrial hyperplasia group, 50 cases of endometrial adenocarcinoma and 3 cases of uterine papillary adenocarcinoma, with 15 cases of normal endometrium as control group. We detected no expression of aromatase P450, adhesion molecule CD24 or HER2/neu in control group. Aromatase P450 positive expression rate was 66.7% in endometrial hyperplasia group and 70.3% in endometrial carcinoma group, without significant difference (p>0.05). There was no significant difference (p>0.05) in the positive expression rate of aromatase P450 between different myometrial invasion groups of endometrial adenocarcinomas. CD24 positive expression rate was 40.0% in endometrial hyperplasia group and 79.6% in endometrial carcinoma group, with significant difference (p<0.05). HER2/neu positive expression rate was 26.7% in the endometrial hyperplasia group and 57% in endometrial carcinoma group, with significant difference (p<0.05). In conclusion, aromatase P450 may be one factor associated with endometrial cancer cell proliferation, while CD24 and HER2/neu may be important factors associated with the invasion and metastasis of endometrial cancer.
Topics: Female; Humans; Endometrial Hyperplasia; Aromatase; Clinical Relevance; Endometrial Neoplasms; Immunohistochemistry; Endometrium; CD24 Antigen
PubMed: 37565251
DOI: 10.4081/ejh.2023.3655 -
International Journal of Molecular... May 2021Ovarian granulosa cells (GCs) are the most important source of estrogen. Therefore, aromatase (estrogen synthase), which is the key enzyme in estrogen synthesis, is not... (Review)
Review
Ovarian granulosa cells (GCs) are the most important source of estrogen. Therefore, aromatase (estrogen synthase), which is the key enzyme in estrogen synthesis, is not only an important factor of ovarian development, but also the key to estrogen secretion by GCs. Disorders of the ovarian estrogen secretion are more likely to induce female estrogen‑dependent diseases and fertility issues, such as ovarian cancer and polycystic ovary syndrome. Hence, aromatase is an important drug target; treatment with its inhibitors in estrogen‑dependent diseases has attracted increasing attention. The present review article focuses on the regulation and mechanism of the aromatase activity in the GCs, as well as the specific regulation of aromatase promoters. In GCs, follicle‑stimulating hormone (FSH) is dependent on the cyclic adenosine monophosphate (cAMP) pathway to regulate the aromatase activity, and the regulation of this enzyme is related to the activation of signaling pathways, such as phosphatidylinositol 3‑kinase (PI3K) and extracellular signal‑regulated kinase (ERK). In addition, endocrine‑disrupting substance and other related factors affect the expression of aromatase, which eventually create an imbalance in the estrogen secretion by the target tissues. The present review highlights these useful factors as potential inhibitors for target therapy.
Topics: Aromatase; Estrogens; Female; Granulosa Cells; Humans; Neoplasm Proteins; Ovarian Neoplasms; Polycystic Ovary Syndrome
PubMed: 33693952
DOI: 10.3892/ijmm.2021.4906 -
Seminars in Oncology Nursing Oct 2023The objective of this systematic review was to establish an overview of aromatase inhibitor-related symptoms reported by postmenopausal women with nonmetastatic,... (Review)
Review
PURPOSE
The objective of this systematic review was to establish an overview of aromatase inhibitor-related symptoms reported by postmenopausal women with nonmetastatic, estrogen receptor-positive breast cancer.
DATA SOURCES
Eight databases (PubMed, Cochrane, Cumulative Index to Nursing and Allied Health Literature [CINAHL], Ovid EMBASE, Ovid MEDLINE, PsycINFO, Scopus, and Web of Science) were searched for trials published between January 2004 and November 2021. Inclusion criteria were studies exploring patient-reported aromatase inhibitor-related symptoms in postmenopausal women with nonmetastatic estrogen receptor-positive breast cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Mixed Method Appraisal Tool were used to rate the quality of the trials included. Of 325 full-text papers, 10 were included. Patient-reported symptoms were clustered by using the European Organization for Research and Treatment of Cancer Quality of Life C30 questionnaire domains. Additional domains were used to cluster other symptoms mentioned: menopausal, sex-related, body alteration, and eye-related. The following clusters were the most frequently presented: sex-related (14 symptoms), pain (9 symptoms), insomnia (5 symptoms), and menopausal (5 symptoms).
CONCLUSION
The target group reported a variety of symptoms related to aromatase inhibitors. No tools are currently available to measure all the symptoms reported, indicating a need to revise the tools to acknowledge additional symptoms. Prospective studies are needed to investigate the prevalence of aromatase inhibitor-related symptoms in women with breast cancer.
IMPLICATION FOR NURSING PRACTICE
Identification of patient-reported clinically relevant symptoms can enable targeted symptom assessment and management strategies for women with breast cancer undergoing aromatase inhibitor treatment.
Topics: Female; Humans; Aromatase Inhibitors; Receptors, Estrogen; Postmenopause; Quality of Life; Breast Neoplasms
PubMed: 37612223
DOI: 10.1016/j.soncn.2023.151487 -
Frontiers in Endocrinology 2020Traumatic brain injury (TBI) is responsible for various neuronal and cognitive deficits as well as psychosocial dysfunction. Characterized by damage inducing... (Review)
Review
Traumatic brain injury (TBI) is responsible for various neuronal and cognitive deficits as well as psychosocial dysfunction. Characterized by damage inducing neuroinflammation, this response can cause an acute secondary injury that leads to widespread neurodegeneration and loss of neurological function. Estrogens decrease injury induced neuroinflammation and increase cell survival and neuroprotection and thus are a potential target for use following TBI. While much is known about the role of estrogens as a neuroprotective agent following TBI, less is known regarding their formation and inactivation following damage to the brain. Specifically, very little is known surrounding the majority of enzymes responsible for the production of estrogens. These estrogen metabolizing enzymes (EME) include aromatase, steroid sulfatase (STS), estrogen sulfotransferase (EST/SULT1E1), and some forms of 17β-hydroxysteroid dehydrogenase (HSD17B) and are involved in both the initial conversion and interconversion of estrogens from precursors. This article will review and offer new prospective and ideas on the expression of EMEs following TBI.
Topics: Animals; Aromatase; Brain Injuries, Traumatic; Encephalitis; Estradiol Dehydrogenases; Estrogens; Humans; Neuroprotective Agents; Steryl-Sulfatase; Sulfotransferases
PubMed: 32547495
DOI: 10.3389/fendo.2020.00345 -
Andrology Nov 2020Functional hypogonadism increases in prevalence due to aging as well as an overall increase of obesity. Aromatase inhibitors (AIs) and selective estrogen receptor... (Review)
Review
INTRODUCTION
Functional hypogonadism increases in prevalence due to aging as well as an overall increase of obesity. Aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs) could be an alternative for testosterone replacement therapy (TRT), but have not yet been established as common clinical practice.
METHODS
We conducted a thorough search of the literature published between 2009 and 2018. Only RCTs published in English were included. We assessed the impact of AIs and SERMs on gonadal steroids, sexual function and semen parameters, body composition and glucose homeostasis, physical function, bone mineral density (BMD), anemia, as well as potential adverse effects.
RESULTS
Twelve RCTs were included, with a total number of 645 patients. A total of 145 men were included in RCTs comparing AIs versus placebo or TRT and 476 men in RCTs with SERMs versus placebo or TRT. One RCT compared AIs versus SERMs in 24 men. Inclusion criteria were heterogenic. Most studies only included a small number of patients (range 11-256) and follow-up time was relatively short (6 weeks to 12 months). AIs as well as SERMs increased serum testosterone levels. Overall, there was no effect on sexual symptoms nor on semen parameters. Following aromatase inhibition, only minimal improvement of body composition and physical function was observed in some of the trials, but spinal BMD decreased. SERMs only induced a small improvement in body composition. The effect of SERMs on physical function and on BMD was not assessed. No major adverse effects occurred.
CONCLUSION
AIs are not recommended as treatment for functional hypogonadism because of insufficient efficacy as well as a decrease in BMD. SERMs might be an alternative for TRT, but more research is needed to evaluate their effect on hypogonadal signs and symptoms, as well as on their long-term safety profile.
Topics: Aromatase Inhibitors; Biomarkers; Eunuchism; Hormone Replacement Therapy; Humans; Male; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Testosterone; Treatment Outcome
PubMed: 31696669
DOI: 10.1111/andr.12725 -
Biomedicine & Pharmacotherapy =... Dec 2023Documented male-female differences in the risk of cardiovascular and chronic kidney diseases have been largely attributed to estrogens. The cardiovascular and renal... (Meta-Analysis)
Meta-Analysis Review
Documented male-female differences in the risk of cardiovascular and chronic kidney diseases have been largely attributed to estrogens. The cardiovascular and renal protective effects of estrogens are mediated via the activation of estrogen receptors (ERα and ERβ) and G protein-coupled estrogen receptor, and involve interactions with the renin-angiotensin-aldosterone system. Aromatase, also called estrogen synthase, is a cytochrome P-450 enzyme that plays a pivotal role in the conversion of androgens into estrogens. Estrogens are biosynthesized in gonadal and extra-gonadal sites by the action of aromatase. Evidence suggests that aromatase inhibitors, which are used to treat high estrogen-related pathologies, are associated with the development of cardiovascular events. We review the potential role of aromatization in providing cardio-renal protection and highlight several meta-analysis studies on cardiovascular events associated with aromatase inhibitors. Overall, we present the potential of aromatase enzyme as a fundamental contributor to cardio-renal protection.
Topics: Male; Female; Humans; Aromatase; Aromatase Inhibitors; Androgens; Estrogens; Receptors, Estrogen; Cardiovascular Diseases
PubMed: 37931519
DOI: 10.1016/j.biopha.2023.115832 -
Drug Design, Development and Therapy 2023Endometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain,... (Review)
Review
Endometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain, dysmenorrhea, dyspareunia, and infertility which are the most often presenting symptoms. Aromatase P450 is the key enzyme for ovarian estrogen biosynthesis and there is evidence that endometriotic lesions express aromatase and are able to synthesize their own estrogens. Aromatase inhibitors (AIs) are potent drugs that suppress the estrogen synthesis via suppression of aromatase. We performed a systematic review of systematic reviews and narrative reviews on the use of aromatase inhibitors in the medical management of endometriosis. We searched: PubMed (1950-2022), Google Scholar (2004-2022), Cochrane Library (2010-2022) and Researchgate (2010-2022). The search included the following medical subject headings (MeSH) or keywords: "Aromatase Inhibitors" AND "Endometriosis" AND "Systematic reviews" OR "Systematic review" AND "Reviews" OR "Reviews" AND "Endometriosis". The electronic database search yielded initially 12,106 studies from the different databases. Further assessment of the studies resulted in exclusion of (n = 12,015) studies due to duplicates and irrelevance; Finally, 24 studies were selected for inclusion, 5 were Systematic reviews and 19 were Narrative reviews. The 5 systematic reviews were assessed by AMSTAR-2 criteria and were found to have low quality. Narrative reviews were assessed with SANRA criteria and were found to have high-quality aromatase inhibitors are potent drugs that can manage the endometriosis-related symptoms in cases where initial medical management has failed to show positive results. However, their use is limited by the adverse effects that are linked with menopausal symptoms. aromatase inhibitors can be administered as an alternative treatment in patients. Future studies with randomized design are required to reach safer conclusions and further investigation. These studies should define the therapeutic dose, new add-back therapy modalities. Future directions should examine the most-appropriate way of administration and the duration of therapy.
Topics: Female; Humans; Aromatase; Aromatase Inhibitors; Endometriosis; Estrogens; Systematic Reviews as Topic
PubMed: 37168488
DOI: 10.2147/DDDT.S315726 -
Molecular Pharmacology Aug 2022Exemestane (EXE) is an aromatase inhibitor used to treat hormone-dependent breast cancer. EXE is extensively metabolized, with unchanged EXE and its active metabolite...
Exemestane (EXE) is an aromatase inhibitor used to treat hormone-dependent breast cancer. EXE is extensively metabolized, with unchanged EXE and its active metabolite 17-dihydroexemestane (17-DHE) accounting for 17 and 12%, respectively, of total plasma EXE The major circulating EXE metabolites are the cysteine conjugates of EXE and 17-DHE, and the 17-DHE glucuronide, which together account for 70% of total plasma EXE The goal of the present study was to examine the inhibition potential of major metabolites of EXE through inhibition assays using aromatase-overexpressing cells and pooled ovarian tissues. Estrone formation was used as a measure of aromatase activity and was detected and quantified using UPLC-MS. EXE-cys, 17β-DHE, and 17β-DHE-cys all exhibited inhibition of estrone formation at both 1 µM and 10 µM concentrations, with 17β-DHE and EXE-cys showing significant inhibition of estrone formation (63% each) at 10 µM. In contrast, 17β-DHE-Gluc displayed minimal inhibition (5-8%) at both concentrations. In ovarian tissue, EXE-cys and 17β-DHE showed similar patterns of inhibition, with 49% and 47% inhibition, respectively, at 10 µM. The value for EXE-cys (16 {plus minus} 10 µM) was similar to 17β-DHE (9.2 {plus minus} 2.7 µM) and higher than EXE (1.3 {plus minus} 0.28 µM), and all three compounds showed time-dependent inhibition with shifts of 13 {plus minus} 10, 5.0 {plus minus} 2.5 and 36 {plus minus} 12-fold, respectively. Given its high circulating levels in patients taking EXE, these results suggest that EXE-cys may contribute to the pharmacologic effect of EXE The current study is the first to examine the major phase II metabolites of EXE (EXE-cys, 17β-DHE-cys, and 17β-DHE-Gluc) for inhibition potential against the target enzyme, aromatase (CYP19A1). EXE-cys was found to significantly inhibit aromatase in a time dependent manner. Given its high circulating levels in patients taking EXE, this phase II metabolite may play an important role in reducing circulating estrogen levels
PubMed: 35953090
DOI: 10.1124/molpharm.122.000545