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Current Oncology (Toronto, Ont.) Feb 2023Cardiovascular disease (CVD) is one of the most common comorbidities in breast cancer survivors. Recently, the target population and treatment period for aromatase... (Meta-Analysis)
Meta-Analysis
Cardiovascular disease (CVD) is one of the most common comorbidities in breast cancer survivors. Recently, the target population and treatment period for aromatase inhibitor (AI) treatment in breast cancer patients has been expanding. However, information on adverse CVD events from the long-term use of AI is still lacking. The aim of this study was to investigate the CVD side effects of AI treatment and to evaluate the changes in lipid profile during AI treatment. A systematic search of PubMed (Medline), EMBASE, and Cochrane Library databases reporting on cardiovascular outcomes or lipid profiles change in adult female breast cancer patients (>19 years old) with AI was performed. The pooled analysis of 25 studies showed that the prevalence rate of any type of cardiovascular disease was 6.08 per 100 persons (95% CI 2.91-10.31). Angina was the most common type of heart-related cardiovascular event accounting for 3.85 per 100 persons, followed by any type of stroke (3.34) and venous thromboembolism (2.95). Ischemic stroke (OR 1.39, 95% CI 1.07-1.81) and myocardial infarction (OR 1.30, 95% CI 0.88-1.93) were more common in AI compared with tamoxifen, whereas the prevalence of venous thromboembolism (OR 0.61, 95% CI 0.37-1) was significantly lower in the AI group. In addition, treatment with AI for 6-12 months showed a decrease in HDL-cholesterol and an increase in LDL-cholesterol and total cholesterol. Various CVDs can occur when using AI, and in particular, the risk of MI and ischemic stroke increases in comparison with the adverse effect of tamoxifen. The occurrence of CVD might be related to the deterioration of the lipid profile after AI treatment. Therefore, a customized individualization strategy considering each patient's CV risk factors is needed during AI treatment.
Topics: Adult; Humans; Female; Young Adult; Breast Neoplasms; Aromatase Inhibitors; Cardiovascular Diseases; Venous Thromboembolism; Tamoxifen; Cholesterol; Lipids; Ischemic Stroke
PubMed: 36826103
DOI: 10.3390/curroncol30020142 -
Human Reproduction Update Aug 2022The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.
OBJECTIVE AND RATIONALE
The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.
SEARCH METHODS
A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.
OUTCOMES
A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias.
WIDER IMPLICATIONS
This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.
Topics: Azoospermia; Hormones; Humans; Klinefelter Syndrome; Male; Prospective Studies; Retrospective Studies; Semen; Sperm Retrieval; Spermatozoa; Testis
PubMed: 35526153
DOI: 10.1093/humupd/dmac016 -
Asian Journal of Andrology 2020Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to... (Meta-Analysis)
Meta-Analysis
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.
Topics: Anastrozole; Aromatase Inhibitors; Clinical Trials as Topic; Estradiol; Humans; Hypogonadism; Infertility, Male; Letrozole; Male; Semen Analysis; Spermatogenesis; Testolactone; Testosterone; Treatment Outcome
PubMed: 31621654
DOI: 10.4103/aja.aja_101_19 -
Handbook of Experimental Pharmacology 2020Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone...
Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate - DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.
Topics: Bone Density; Bone and Bones; Fractures, Bone; Humans; Medroxyprogesterone Acetate; Pharmaceutical Preparations
PubMed: 31889220
DOI: 10.1007/164_2019_340 -
Journal of Clinical Pharmacy and... May 2022Breast cancer is one of the leading causes of morbidity and mortality in women worldwide. In order to reduce the risks of its recurrence, endocrine therapies, such as... (Meta-Analysis)
Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Breast cancer is one of the leading causes of morbidity and mortality in women worldwide. In order to reduce the risks of its recurrence, endocrine therapies, such as tamoxifen and aromatase inhibitors are commonly administered. Despite having a similar efficacy in preventing breast cancer recurrence, these drugs differ in terms of instigating cardiovascular morbidities. Recent randomized controlled trials and cohort studies provide inconclusive evidence of the cardiovascular risks associated with the administration of these endocrine therapies. This present review and meta-analysis evaluates the comparative cardiovascular adverse event outcomes in breast cancer patients receiving tamoxifen and aromatase inhibitors. To evaluate the comparative cardiovascular adverse outcomes, such as venous thromboembolism, heart failure, angina, myocardial infarction and stroke in patients with breast cancer receiving tamoxifen and aromatase inhibitors.
METHODS
A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases, including Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE. A random-effect meta-analysis was conducted to compare the cardiovascular adverse events (i.e. venous thromboembolism, heart failure, angina, myocardial infarction, stroke) in breast cancer patients treated with tamoxifen and aromatase inhibitors.
RESULTS AND DISCUSSION
From 993 studies, 20 eligible studies were identified, with 174,142 female breast cancer patients (mean age: 67.4 ± 3.8 years). A meta-analysis revealed insignificantly (p > 0.05) higher risks of venous thromboembolism (Odds ratio, 95% CI: 1.70, 0.91-3.18) in patients treated with tamoxifen as compared to aromatase inhibitors. We also observed insignificantly higher risks of stroke (0.93, 0.45-1.91), angina (0.77, 0.12-4.59), myocardial infarction (0.74, 0.30-1.79), and heart failure (0.81, 0.22-2.91) in patients receiving aromatase inhibitors as compared to tamoxifen.
WHAT IS NEW AND CONCLUSIONS
The study provides evidence regarding the comparative cardiovascular adverse outcomes between breast cancer patients consuming tamoxifen and aromatase inhibitors. The study reports an insignificant increase in the events of stroke, angina, myocardial infarction, and heart failure in breast cancer patients treated with aromatase inhibitors as compared to tamoxifen. The study also reports that tamoxifen treatment is associated with an insignificant increase in the events of venous thromboembolism as compared to treatment with aromatase inhibitors.
Topics: Aged; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Cardiovascular Diseases; Female; Heart Failure; Humans; Middle Aged; Myocardial Infarction; Neoplasm Recurrence, Local; Stroke; Tamoxifen; Venous Thromboembolism
PubMed: 34984740
DOI: 10.1111/jcpt.13598 -
Archives of Osteoporosis Jan 2023This systematic review (SR) assessed the use of denosumab (Prolia®) to treat osteoporosis in cancer patients receiving endocrine therapy. Denosumab was found to prevent... (Meta-Analysis)
Meta-Analysis Review
The clinical effectiveness of denosumab (Prolia®) in patients with hormone-sensitive cancer receiving endocrine therapy, compared to bisphosphonates, selective estrogen receptor modulators (SERM), and placebo: a systematic review and network meta-analysis.
UNLABELLED
This systematic review (SR) assessed the use of denosumab (Prolia®) to treat osteoporosis in cancer patients receiving endocrine therapy. Denosumab was found to prevent vertebral fractures and improve bone mineral density in cancer patients with osteoporosis. This is the first SR to assess treating osteoporotic cancer patients with denosumab.
PURPOSE
This study assessed the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs) (bazedoxifene, raloxifene) and placebo for the treatment of osteoporosis in hormone-sensitive cancer patients receiving endocrine therapy (men with prostate cancer [MPC] on hormone ablation therapy [HAT], and women with breast cancer [WBC] on adjuvant aromatase inhibitor therapy [AAIT]).
METHODS
Systematic literature searches were conducted in three biomedical databases to identify randomized controlled trials (RCTs). Frequentist network meta-analyses and/or pairwise meta-analyses were performed on predetermined outcomes (i.e., vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, treatment-related adverse events [AEs], serious AEs [SAEs], withdrawal due to treatment-related AEs).
RESULTS
A total of 14 RCTs (15 publications) were included. Denosumab was found to prevent vertebral fractures in cancer patients receiving endocrine therapy, relative to placebo. Similarly, denosumab, zoledronate, and alendronate improved BMD at the femoral neck (FN) and lumbar spine (LS) in MPC on HAT, relative to placebo. Denosumab, ibandronate and risedronate improved BMD at the LS and total hip (TH) in WBC on AAIT, relative to placebo. Denosumab and risedronate improved trochanteric (TRO) BMD in WBC on AAIT, relative to placebo. Similarly, denosumab improved FN BMD in WBC on AAIT.
CONCLUSION
In MPC on HAT, denosumab (relative to placebo) was effective at preventing vertebral fractures and improving BMD at the FN and LS. Moreover, in WBC on AAIT, denosumab (relative to placebo) improved BMD at the FN, LS, TH, and TRO, as well as prevent vertebral fracture.
Topics: Female; Humans; Male; Alendronate; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Hormones; Ibandronic Acid; Neoplasms; Network Meta-Analysis; Osteoporosis; Risedronic Acid; Selective Estrogen Receptor Modulators; Spinal Fractures; Treatment Outcome; Zoledronic Acid; Randomized Controlled Trials as Topic
PubMed: 36624318
DOI: 10.1007/s11657-023-01211-3 -
The Breast Journal 2023Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a... (Review)
Review
BACKGROUND
Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a well-tolerated therapy, AI-induced musculoskeletal symptoms are common and may be accused for treatment discontinuation. Recently, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors changed the therapeutic setting, and currently, ribociclib, palbociclib, and abemaciclib are all approved in combination with nonsteroidal AIs in patients with ER-positive, HER2-negative advanced or metastatic breast cancer. This systematic review aims to identify the frequency of aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) in the adjuvant setting in patients under AI monotherapy compared to patients under combination therapy with AIs and CDK4/6 inhibitors and demonstrate the underlying mechanism of action.
METHODS
This study was performed in accordance with PRISMA guidelines. The literature search and data extraction from all randomized clinical trials (RCTs) were done by two independent investigators. Eligible articles were identified by a search of MEDLINE and ClinicalTrial.gov database concerning the period 2000/01/01-2021/05/01.
RESULTS
Arthralgia was reported in 13.2 to 68.7% of patients receiving AIs for early-stage breast cancer, while arthralgia induced by CDK4/6 inhibitors occurred in a much lower rate [20.5-41.2%]. Bone pain (5-28.7% vs. 2.2-17.2%), back pain (2-13.4% vs. 8-11.2%), and arthritis (3.6-33.6% vs. 0.32%) were reported less frequently in patients receiving the combination of CDK4/6 inhibitors with ET.
CONCLUSIONS
CDK4/6 inhibitors might have a protective effect against joint inflammation and arthralgia occurrence. Further studies are warranted to investigate arthralgia incidence in this population.
Topics: Humans; Female; Aromatase Inhibitors; Breast Neoplasms; Arthralgia; Cyclin-Dependent Kinase 4
PubMed: 37293258
DOI: 10.1155/2023/3614296 -
Clinical Breast Cancer Dec 2023Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing... (Meta-Analysis)
Meta-Analysis Review
Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67 pg/mL (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < .001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but 1 study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.
Topics: Female; Humans; Breast Neoplasms; Cancer Survivors; Neoplasm Recurrence, Local; Vaginal Diseases; Vagina; Estradiol; Survivors; Testosterone; Estrogens; Atrophy; Estriol
PubMed: 37806915
DOI: 10.1016/j.clbc.2023.08.003 -
Frontiers in Endocrinology 2023To investigate the efficacy of monotherapy with AIs or GnRHa in improving the height of boys with idiopathic short stature (ISS). (Meta-Analysis)
Meta-Analysis
Comparative efficacy of aromatase inhibitors and gonadotropin-releasing hormone analogue in increasing final height of idiopathic short stature boys: a network meta-analysis.
OBJECTIVE
To investigate the efficacy of monotherapy with AIs or GnRHa in improving the height of boys with idiopathic short stature (ISS).
METHOD
We performed a systematic search in Pubmed, The Cochrane Library, Chinese National Knowledge Infrastructure databases, and Wanfang Database for eligible studies. The network meta-analysis was conducted using STATA software.
RESULTS
We identified a total of four studies that included 136 individuals. We used FAH/PAH as the main outcome of final height. The results revealed a statistically higher final height after treatment with AI or GnRHa in idiopathic short stature children(MD= 4.63, 95% CI[3.29,5.96]). In network meta-analysis, the direct and indirect comparison between AI and GnRHa was presented in the forest plot. Compared with control group, both AI and GnRHa were effective in increasing the final height, with the mean effect of 4.91(95%CI:1.10,8.17) and 5.55(95%CI:1.12,9.98) respectively. However, there was no statistical difference between the GnRHa and AI treatment, of which the mean effect was 0.65(95%CI: -4.30,5.60).
CONCLUSION
Both AIs and GnRHa monotherapy were effective in augmenting the final height of boys with idiopathic short stature when compared to placebo groups. However, there was no statistical difference between the GnRHa and AI treatments.
Topics: Male; Child; Humans; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; Network Meta-Analysis; Body Height; Human Growth Hormone; Dwarfism
PubMed: 37124748
DOI: 10.3389/fendo.2023.1167351 -
Clinical Nuclear Medicine Sep 2023[ 18 F]fluoroestradiol (FES) can be used for the noninvasive visualization and quantification of tumor estrogen receptor (ER) expression and activity and was...
INTRODUCTION
[ 18 F]fluoroestradiol (FES) can be used for the noninvasive visualization and quantification of tumor estrogen receptor (ER) expression and activity and was FDA-approved as a diagnostic agent in May 2022 for detecting ER-positive lesions in patients with recurrent or metastatic breast cancer. PET imaging was also used to detect ER-positive lesions and malignancy among patients with uterine, ovarian, and other ER-positive solid tumors. We conducted a systemic review of the studies on FES PET imaging used among patients with cancer not limited to breast cancer to better understand the application of FES PET imaging.
METHODS
PubMed/MEDLINE and Cochrane Library databases were used to perform a comprehensive and systematic search and were updated until August 15, 2022. Two authors independently reviewed the titles and abstracts of the retrieved articles by using the search algorithm and selected the articles based on the inclusion and exclusion criteria. All statistical analyses were conducted using R statistical software.
RESULTS
Forty-three studies with 2352 patients were included in the qualitative synthesis, and 23 studies with 1388 patients were included in the quantitative analysis, which estimated the FES-positive detection rate. Thirty-two studies (77%) included breast cancer patients in 43 included studies. The FES SUV mean was higher in patients with endometrial cancer (3.4-5.3) than in those with breast cancer (2.05) and uterine sarcoma (1.1-2.6). The pooled detection rates of FES PET imaging were 0.80 for breast and 0.84 for ovarian cancer patients, both similar to that of 18 F-FDG. The FES uptake threshold of 1.1 to 1.82 could detect 11.1% to 45% ER heterogeneity, but the threshold of FES uptake did not have consistent predictive ability for prognosis among patients with breast cancer, unlike uterine cancer. However, FES uptake can effectively predict and monitor treatment response, especially endocrine therapy such as estradiol, ER-blocking agents (fulvestrant and tamifoxen), and aromatase inhibitors (such as letrozole and Z-endoxifen).
CONCLUSIONS
[ 18 F]fluoroestradiol PET is not only a convenient and accurate diagnostic imaging tool for detecting ER-expressing lesions in patients with breast and ovarian cancer but also among patients with uterine cancer. [ 18 F]fluoroestradiol PET is a noninvasive predictive and monitoring tool for treatment response and prognosis.
Topics: Humans; Female; Breast Neoplasms; Estradiol; Positron-Emission Tomography; Receptors, Estrogen; Uterine Neoplasms; Ovarian Neoplasms
PubMed: 37482660
DOI: 10.1097/RLU.0000000000004760