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Andrology Feb 2024Selective oestrogen receptor modulators and aromatase inhibitors stimulate endogenous gonadotrophins and testosterone in men with hypogonadism. There are no systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Selective oestrogen receptor modulators and aromatase inhibitors stimulate endogenous gonadotrophins and testosterone in men with hypogonadism. There are no systematic reviews/meta-analyses assessing the effects of selective oestrogen receptor modulators/aromatase inhibitors on semen parameters in men with secondary hypogonadism.
OBJECTIVES
To assess the effect of monotherapy or a combination of selective oestrogen receptor modulators/aromatase inhibitors on sperm parameters and/or fertility in men with secondary hypogonadism.
MATERIALS AND METHODS
A systematic search was conducted in PubMed, MEDLINE, Cochrane Library and ClinicalTrials.gov. Study selection and data extraction were performed by two reviewers independently. Randomised controlled trials and non-randomised studies of interventions reporting effects of selective oestrogen receptor modulators and/or aromatase inhibitors on semen parameters or fertility in men with low testosterone with low/normal gonadotrophins were selected. The risk of bias was assessed using ROB-2 and ROBINS-I tools. The results of randomised controlled trials were summarised using vote counting while summarising effect estimates where available. Non-randomised studies of intervention meta-analysis were conducted using the random-effect model. The certainty of evidence was assessed using GRADE.
RESULTS
Five non-randomised studies of interventions (n = 105) of selective oestrogen receptor modulators showed an increase in sperm concentration (pooled mean difference 6.64 million/mL; 95% confidence interval 1.54, 11.74, I = 0%) and three non-randomised studies of interventions (n = 83) of selective oestrogen receptor modulators showed an increase in total motile sperm count (pooled mean difference 10.52; 95% confidence interval 1.46-19.59, I = 0%), with very low certainty of evidence. The mean body mass index of participants was >30 kg/m . Four randomised controlled trials (n = 591) comparing selective oestrogen receptor modulators to placebo showed a heterogeneous effect on sperm concentration. Three included men with overweight or obesity. The results were of very low certainty of evidence. Limited pregnancy or live birth data were available. No studies comparing aromatase inhibitors with placebo or testosterone were found.
DISCUSSION AND CONCLUSION
Current studies are of limited size and quality but suggest that selective oestrogen receptor modulators may improve semen parameters in those patients, particularly when associated with obesity.
Topics: Pregnancy; Female; Humans; Male; Aromatase Inhibitors; Semen; Selective Estrogen Receptor Modulators; Testosterone; Estrogens; Hypogonadism; Obesity
PubMed: 37306109
DOI: 10.1111/andr.13480 -
Gynecological Endocrinology : the... 2015The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs)... (Comparative Study)
Comparative Study Meta-Analysis Review
The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR) = 1.55 (95% confidence interval (CI): 1.26-1.90; I(2) = 0%) and RR = 1.38 (95% CI: 1.05-1.83; I(2) = 61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.
Topics: Aromatase Inhibitors; Clomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Live Birth; MEDLINE; Nitriles; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Prospective Studies; Randomized Controlled Trials as Topic; Triazoles
PubMed: 26479460
DOI: 10.3109/09513590.2015.1096337 -
Clinical Endocrinology Dec 2020Aromatase deficiency (AD) caused by cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1) variants is characterized by a deficiency in androgen-to-oestrogen...
BACKGROUND
Aromatase deficiency (AD) caused by cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1) variants is characterized by a deficiency in androgen-to-oestrogen conversion.
OBJECTIVE
To investigate the clinical characteristics and accurate management of aromatase-deficient children.
PATIENTS AND METHODS
We described three 46, XX aromatase-deficient children, searched PubMed with "(aromatase deficiency) AND (46, XX OR ovaries)" and manually searched citations in identified studies for the literature review.
RESULTS
Two girls and one boy (3.4-9.2 years) with the 46, XX karyotype presented ambiguous genitalia and maternal antenatal virilization, normal-low height, delayed bone age, normal glucose and lipid profiles, markedly elevated follicle-stimulating hormone (FSH) levels and poor oestradiol responses to human menopausal gonadotropin stimulation. Ultrasound revealed normal-sized uterus and ovaries with undetectable follicles. Histopathology revealed primordial follicles and few primary follicles in ovaries. One patient presented granulosa and follicular membrane cell proliferation and interstitial sclerosis. We identified four CYP19A1 variants; c.146_158del and c.344G >A were unreported. We reviewed available data from thirty 46, XX patients (0.2-32 years). Some patients were not diagnosed until puberty/adulthood; three were initially misdiagnosed with congenital adrenocortical hyperplasia. The main characteristics were maternal antenatal virilization (21/29), ambiguous genitalia (mainly Prader IV or III, 19/23), delayed bone age (16/17), low bone mass (5/8), markedly elevated FSH levels and ovarian cysts (13/30).
CONCLUSIONS
46, XX AD is easily neglected or misdiagnosed. Ambiguous genitalia, maternal antenatal virilization and markedly elevated FSH levels are important diagnostic indicators. We described two novel variants, new histopathological features of ovaries and an early management strategy.
Topics: 46, XX Disorders of Sex Development; Adult; Aromatase; Child; China; Female; Follicle Stimulating Hormone; Gynecomastia; Humans; Infertility, Male; Male; Metabolism, Inborn Errors; Pregnancy
PubMed: 32623730
DOI: 10.1111/cen.14277 -
Oncology Nursing Forum May 2017Women taking aromatase inhibitors (AIs) as part of the management of hormone receptor-positive breast cancer experience more symptoms of sexual dysfunction, including... (Review)
Review
PROBLEM IDENTIFICATION
Women taking aromatase inhibitors (AIs) as part of the management of hormone receptor-positive breast cancer experience more symptoms of sexual dysfunction, including vaginal atrophy, as opposed to postmenopausal women and women treated with tamoxifen (Nolvadex®). Vaginal testosterone could be an alternative to estrogen, which is contraindicated in this population. .
LITERATURE SEARCH
A systematic review was completed by searching PubMed and Scopus databases. .
DATA EVALUATION
64 search results were reduced to a final sample of 3 articles after applying inclusion and exclusion criteria. .
SYNTHESIS
Published results suggest that vaginally applied testosterone doses of 150 mcg and 300 mcg improve symptoms of sexual dysfunction in women taking AIs. Minimal side effects are observed, and estradiol levels are not affected by vaginally applied testosterone. Additional research is needed to evaluate vaginal testosterone in women taking AIs. .
CONCLUSIONS
Vaginal testosterone shows preliminary promise as an option to manage sexual side effects of AI therapy in postmenopausal cancer survivors; however, available data are too limited to draw practice-changing conclusions. .
IMPLICATIONS FOR RESEARCH
Large-scale randomized, controlled trials need to be completed to evaluate the efficacy and safety of vaginal testosterone in women taking AIs.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Middle Aged; Neoplasms, Hormone-Dependent; Sexual Dysfunction, Physiological; Testosterone
PubMed: 28635978
DOI: 10.1188/17.ONF.296-301 -
Frontiers in Pharmacology 2022To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients. We conducted a...
Efficacy and Safety of Initial 5 Years of Adjuvant Endocrine Therapy in Postmenopausal Hormone Receptor-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.
To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients. We conducted a systematic search of the PubMed, Web of Science, and EMBASE to obtain relevant studies published between January 2000 and January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival and overall survival and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the value of surface under the cumulative ranking curve (SUCRA) was used to obtain rankings. Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) [hazard ratio (HR) 0.91, 95% confidence interval (95%CI) 0.87-0.96], anastrozole (ANA) (0.94, 0.90-0.97), letrozole (LET) (0.93, 0.89-0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87-0.96), and TAM followed by ANA (0.92, 0.87-0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86-0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04-2.98), ANA (1.58, 1.03-2.43), and LET (1.63, 1.02-2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons. The sequential use of aromatase inhibitors, which has the best curative effects and relatively mild side effects, may be the optimal treatment mode for hormone receptor-positive postmenopausal EBC patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs. [website], identifier [registration number].
PubMed: 35721183
DOI: 10.3389/fphar.2022.886954 -
ESMO Open Apr 2021Approximately 50% of human epidermal growth factor receptor 2 (HER2)-positive breast cancer lesions express hormone receptors. These tumors present a unique therapeutic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 50% of human epidermal growth factor receptor 2 (HER2)-positive breast cancer lesions express hormone receptors. These tumors present a unique therapeutic challenge, and the optimal endocrine therapeutic approach remains controversial. We aimed to study the optimal adjuvant endocrine therapy in this setting, to better establish the basis for clinical recommendations in HER2-positive disease.
METHODS
We conducted a literature search up to May 2020, in which we identified randomized controlled trials (RCTs) that investigated the efficacy of various adjuvant hormonal therapies among premenopausal and postmenopausal patients with hormone receptor (HR)-positive, HER2-positive early breast cancer. Disease-free survival (DFS) was calculated with the random effect model and hazard ratios (HRs) with 95% confidence intervals (CI).
RESULTS
Six RCTs (N = 5390 patients) were included in the final analysis. There was no significant difference in DFS between adjuvant treatment with aromatase inhibitors and tamoxifen (HR 0.99, 95% CI 0.68-1.44, P = 0.96). Furthermore, after omitting the ALTTO trial, as it did not randomize patients to hormonal therapy, no significant difference was observed between the two protocols (HR 1.06, 95% CI 0.65-1.73, P = 0.81).
CONCLUSION
Our study demonstrates similar DFS with tamoxifen and aromatase inhibitors as adjuvant endocrine treatment in HER2-positive HR-positive early-stage breast cancer patients. Future larger prospective studies focusing on the various contemporary endocrine regimens are warranted to validate our findings.
Topics: Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Tamoxifen
PubMed: 33735801
DOI: 10.1016/j.esmoop.2021.100088 -
Heliyon Mar 2020The cytochrome P450 enzyme functions as the rate-limiting enzyme in changing androgens to estrogens. Inhibition of aromatase is one of the significant objectives of... (Review)
Review
The cytochrome P450 enzyme functions as the rate-limiting enzyme in changing androgens to estrogens. Inhibition of aromatase is one of the significant objectives of treatment of hormone-dependent diseases such as breast cancer, especially in post-menopausal women. Natural compounds like chrysin, as a flavor that has a high concentration in honey and propolis, are rich sources of them can be useful in inhibiting aromatase for chemoprevention following treatment or in women at risk of acquiring breast cancer. This study intended to summarize the existing evidence on the effect of chrysin on aromatase activity. We systematically searched Science Direct, PubMed and Google Scholar and hand searched the reference lists of identified relevant articles, up to 5 February, 2019. Articles with English abstracts that reported the effect of chrysin on aromatase inhibition and without publication date restriction were investigated. Twenty relevant articles were chosen from a total of 1721 articles. Only one study was performed on humans and two studies were assayed on rats, while other studies were evaluated in vitro. All the studies except one showed that chrysin had the potency of aromatase inhibition; however, only one study performed on endometrial stromal cells showed that chrysin and naringenin did not indicate aromatase inhibitory properties. Various assay methods and experimental conditions were the important aspects leading to different results between the studies. Chrysin has potency in inhibition of the aromatase enzyme and thus can be useful in preventing and treating the hormone-dependent breast cancer and as an adjuvant therapy for estrogen-dependent diseases.
PubMed: 32181408
DOI: 10.1016/j.heliyon.2020.e03557 -
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 -
Integrative Cancer Therapies 2021Aromatase inhibitor-induced arthralgia (AIA) is the most common side effect of aromatase inhibitors (AIs) used in breast cancer patients and is related to the rate of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aromatase inhibitor-induced arthralgia (AIA) is the most common side effect of aromatase inhibitors (AIs) used in breast cancer patients and is related to the rate of adherence to AIs. The clinical effects of acupuncture on AIA have been assessed by some randomized controlled trials (RCTs). However, some studies reported that acupuncture was effective, while others claimed that it was ineffective. To clarify the clinical and placebo effects of acupuncture in treating AIA, we conducted this meta-analysis.
METHODS
Two reviewers (XL and GW) independently searched for RCTs in 5 English databases (PubMed, Web of Science, Embase, Springer, Cochrane Library) and 4 Chinese databases (China National Knowledge Infrastructure Database (CNKI), SinoMed, VIP and Wanfang Database) from their inception to 30 November 2019. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this meta-analysis was performed by fixed or random-effects models, and data were pooled with mean differences (MDs).
RESULTS
Seven trials involving 603 patients were reviewed. The primary outcome, the Brief Pain Inventory (BPI) score, significantly differed between the acupuncture and control groups [pain-related interference: MD = -1.89, 95% confidence interval (CI) [-2.99, -0.79], = 3.36 ( = .008 < .05), pain severity: MD = -1.57, 95% CI [-2.46, -0.68], = 3.45 ( = .0006 < .05), worst pain: MD = -2.31, 95% CI [-3.15, -1.48], = 5.47 ( < .0001 < .05)]. No severe adverse events were reported in any study.
CONCLUSION
This meta-analysis showed that acupuncture is a safe and effective treatment for breast cancer patients with AIA. Additional research with improved blinding methods is warranted to further explore the nature of non-specific and placebo effects in true and sham acupuncture.
Topics: Acupuncture Therapy; Aromatase Inhibitors; Arthralgia; Breast Neoplasms; Female; Humans; Treatment Outcome
PubMed: 33586504
DOI: 10.1177/1534735420980811 -
Actas Urologicas Espanolas Mar 2024This systematic review aims to evaluate the optimal treatment for male infertility resulting from Anabolic Androgenic Steroids (AAS) abuse. (Review)
Review
OBJECTIVE
This systematic review aims to evaluate the optimal treatment for male infertility resulting from Anabolic Androgenic Steroids (AAS) abuse.
METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies that compared different protocols for the recovery of spermatogenesis in patients after AAS use were included.
RESULTS
13 studies investigating different protocols to restore spermatogenesis in patients with AAS abuse met the inclusion criteria. The available agents that showed restoration of spermatogenesis include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their use is still poorly described in the literature.
CONCLUSIONS
Clinicians need to be aware of the detrimental effects of AAS on spermatogenesis. AAS-associated infertility may be reversible, but sperm production may take over a year to normalize. Both conservative and aggressive treatment can boost spermatogenesis with positive results. Further understanding of male reproductive endocrinology and high-quality data on the field of restoration of spermatogenesis after AAS abuse are warranted.
Topics: Humans; Male; Androgens; Anabolic Androgenic Steroids; Anabolic Agents; Semen; Testosterone Congeners; Spermatogenesis
PubMed: 37567343
DOI: 10.1016/j.acuroe.2023.07.007