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Indian Journal of Pediatrics Oct 2023Enlargement of breasts among boys is termed gynecomastia. This could be due to an alteration in the androgen-estrogen ratio along with the effects of other hormones... (Review)
Review
Enlargement of breasts among boys is termed gynecomastia. This could be due to an alteration in the androgen-estrogen ratio along with the effects of other hormones including growth hormone, insulin like growth factor 1, prolactin, and other factors affecting aromatase enzyme. The common causes of gynecomastia are pubertal gynecomastia, obesity, drugs and hypogonadism. Several other diseases including liver or renal failure, thyrotoxicosis, Klinefelter syndrome, tumors and environmental pollutants can cause gynecomastia. History and clinical examination will help formulate targeted investigations and management. The factors to be evaluated in these include examination of breasts and testes, in addition to other parts of systemic examination. Treatment of underlying disorders can improve gynecomastia, such as use of testosterone in hypogonadism. Some boys may not need any intervention as gynecomastia may resolve on its own. Medical management is useful in simple gynecomastia. Tamoxifen has been tried successfully in adolescents with gynecomastia. Other drugs including clomiphene, danazol, letrozole and anastrozole have not been consistently useful in this age group. In severe chronic gynecomastia, surgery is the treatment of choice.
Topics: Adolescent; Male; Humans; Gynecomastia; Hypertrophy; Tamoxifen; Growth Hormone; Hypogonadism
PubMed: 37592101
DOI: 10.1007/s12098-023-04810-7 -
The World Allergy Organization Journal Aug 2023I have read the article titled "" by Wang et al (2022) with great interest. This study examined the change in throat microbiota and its association with laryngeal edema...
I have read the article titled "" by Wang et al (2022) with great interest. This study examined the change in throat microbiota and its association with laryngeal edema (LE) attacks and attack severity in hereditary angioedema (HAE) patients. This study demonstrated the comparative richness of Bacteroidetes and Prevotellaceae in recent LE attacks and detected positive association between the attack severity scores and Bacteroidetes richness. Nevertheless, I have some questions and concerns about the methodological design of their study. For instance, in the article, the description of HAE and HAE patients is not exactly correct. I do not also agree with the authors on the effect of long-term prophylactic danazol use in HAE patients of this study. It is very important when or how the swab was obtained after the LE attack. The last, not the least, point now is what the authors suggest to improve this dysbiosis in these HAE patients. The discussion to elaborate these points in the study could be helpful and enlightening for readers and future research in this area.
PubMed: 37577027
DOI: 10.1016/j.waojou.2023.100806 -
Medicine Aug 2023Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.
METHODS
We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.
RESULT
Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.
CONCLUSION
For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.
Topics: Female; Humans; Endometriosis; Danazol; Gestrinone; Leuprolide; Mifepristone; Network Meta-Analysis; Levonorgestrel
PubMed: 37543781
DOI: 10.1097/MD.0000000000034496 -
The Lancet. Haematology Sep 2023The MOMENTUM study met all key endpoints at week 24, demonstrating symptom, spleen, and anaemia benefits with momelotinib versus danazol in patients with myelofibrosis.... (Randomized Controlled Trial)
Randomized Controlled Trial
Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM): an updated analysis of an international, double-blind, randomised phase 3 study.
BACKGROUND
The MOMENTUM study met all key endpoints at week 24, demonstrating symptom, spleen, and anaemia benefits with momelotinib versus danazol in patients with myelofibrosis. In this updated analysis, we report duration of week 24 responses and new responses with momelotinib through week 48.
METHODS
MOMENTUM is an international, double-blind, randomised, phase 3 study done at 107 sites across 21 countries. Patients were 18 years or older with primary, post-polycythaemia vera, or post-essential thrombocythaemia myelofibrosis, previously treated with an approved Janus kinase (JAK) inhibitor for 90 days or more (≥28 days with haematological complications), and had an Eastern Cooperative Oncology Group performance status of 2 or less. Patients were randomly assigned (2:1) to either the momelotinib group (200 mg orally once per day) or danazol group (300 mg orally twice per day) through week 24 via non-deterministic biased coin minimisation and an interactive response system. Stratification factors were Total Symptom Score (TSS; <22 vs ≥22), spleen size (<12 cm vs ≥12 cm), transfusion burden (0 units vs 1-4 units vs ≥5 units), and study site. After week 24, all patients initially randomly assigned to either group who remained on the study received open-label momelotinib. The primary endpoint, which has already been reported, was Myelofibrosis Symptom Assessment Form TSS response rate at week 24. Predefined secondary endpoints were duration of week 24 TSS and transfusion independence responses, safety, and survival, which are summarised post hoc at the week 48 data cutoff (May 17, 2022). TSS, transfusion independence, and splenic responses at week 48 were defined post hoc and assessed in all evaluable patients who entered the open-label period and provided sufficient data. The timing of this updated analysis was defined post hoc after all patients had the opportunity to complete their week 48 assessments, as most patients entered an extended access study (NCT03441113) after week 48. This study is registered with ClinicalTrials.gov, number NCT04173494, and is now complete.
FINDINGS
Between April 24, 2020, and Dec 3, 2021, a total of 195 patients were randomised (130 [67%] in the momelotinib group and 65 [33%] in the danazol group). 93 (72%) of 130 patients in the momelotinib group and 41 (63%) of 65 in the danazol group entered the momelotinib open-label extension period. Median follow-up was 48·4 weeks (IQR 40·6-55·7). Among TSS-evaluable patients at week 48, 30 (45%) of 67 patients in the momelotinib group who continued treatment and 15 (50%) of 30 in the danazol group who crossed over were responders. TSS responders at any time during the open-label period by week 48 were 46 (61%) of 75 evaluable patients in the momelotinib group who continued and 19 (59%) of 32 in the danazol group who crossed over, including most week 24 responders plus new responders after week 24. No new safety signals emerged with long-term follow-up. The most common non-haematological treatment-emergent adverse events in momelotinib-treated patients over the entire study period as of the data cutoff were diarrhoea (45 [26%] of 171) and asthenia (28 [16%]); the most common grades 3-4 treatment-emergent adverse events were thrombocytopenia (33 [19%]) and anaemia (19 [11%]). Serious treatment-emergent adverse events were reported in 79 (46%) of 171 patients, and fatal treatment-emergent adverse events were reported in 30 (18%); two fatal treatment-emergent adverse events were considered possibly related to momelotinib (rotaviral enteritis and Staphylococcus pneumonia).
INTERPRETATION
Momelotinib was associated with durable symptom, spleen, and anaemia benefits, late responses after week 24, and favourable safety through week 48. These results highlight the potential benefits of treatment with momelotinib in patients with myelofibrosis, particularly those with anaemia.
FUNDING
Sierra Oncology, a GSK company.
Topics: Humans; Anemia; Antineoplastic Combined Chemotherapy Protocols; Danazol; Double-Blind Method; Janus Kinase Inhibitors; Primary Myelofibrosis; Adolescent; Adult
PubMed: 37517413
DOI: 10.1016/S2352-3026(23)00174-6 -
Women's Health Reports (New Rochelle,... 2023Most women who are treated at fertilization (IVF) clinics have trouble conceiving due to ovarian failure (OF), which seems to be associated to short telomeres and...
BACKGROUND
Most women who are treated at fertilization (IVF) clinics have trouble conceiving due to ovarian failure (OF), which seems to be associated to short telomeres and reduced or absent telomerase activity in their granulosa cells. Indeed, telomere pathways are involved in organ dysfunction. However, sexual steroids can stimulate the expression of the telomerase gene and have been successfully used to prevent telomere attrition. Thus, a strategy to improve IVF outcomes in women with OF could be telomerase reactivation using sexual steroids.
METHODS
We conducted a double-blind, placebo-controlled study. Patients with diminished ovarian reserve were randomized to Danazol or placebo for 3 months. We included patients with normal ovarian reserve in the study as untreated controls. Patients and controls underwent several ovarian stimulations (OSs). Telomere and IVF parameters were assessed.
RESULTS
We found that the mean telomere length in blood and the percentage of short and long telomeres were similar throughout the 3 months of treatment with Danazol. Remarkably, while the number of cells with one telomeric repeat-containing RNA (TERRA) focus decreased ( = 0.04) after the first month of Danazol treatment, the number of cells with 2 to 4 TERRA foci increased ( = 0.02). Regarding fertility, no differences were found in the antral follicle count. Interestingly, in OS performed after the trial, all Danazol-treated patients had a better MII oocyte rate compared to OS performed before the pilot study.EudraCT number: 2018-004400-19.
CONCLUSIONS
Danazol treatment seemed to affect telomere maintenance, since both the number of TERRA foci and the ratio of MII oocytes changed. However, further research is needed to confirm these results.
PubMed: 37476605
DOI: 10.1089/whr.2023.0013 -
Asia Pacific Allergy Jun 2023Hereditary angioedema (HAE) is an uncommon disorder characterized clinically by recurrent episodes of nonitchy subcutaneous and/or submucosal swellings. The estimated...
Hereditary angioedema (HAE) is an uncommon disorder characterized clinically by recurrent episodes of nonitchy subcutaneous and/or submucosal swellings. The estimated prevalence of HAE is ~ 1: 10,000 to 1: 50,000. There are no prevalence data from India, however, estimates suggest that there are 27,000 to 135,000 patients with HAE in India at present. The majority of these, however, remain undiagnosed. Replacement of plasma-derived or recombinant C1-esterase inhibitor (C1-INH) protein, administered intravenously, is the treatment of choice during the management of acute episodes of angioedema (i.e., "on-demand treatment") and is also useful for short-term prophylaxis (STP) and long-term prophylaxis (LTP). This has been found to be effective and safe even in young children and during pregnancy. Until recently, none of the first-line treatment options were available for "on-demand treatment," STP or LTP in India. As a result, physicians had to use fresh frozen plasma for both "on-demand treatment" and STP. For LTP, attenuated androgens (danazol or stanozolol) and/or tranexamic acid were commonly used. These drugs have been reported to be useful for LTP but are associated with a significant risk of adverse effects. Intravenous pd-C1-INH, the first-line treatment option, is now available in India. However, because there is no universal health insurance, access to pd-C1-INH is a significant challenge. HAE Society of India has developed these consensus guidelines for India and other resource-constrained settings where plasma-derived C1-INH therapy is the only available first-line treatment option for the management of HAE and diagnostic facilities are limited. These guidelines have been developed because it may not be possible for all patients to access the recommended therapy and at the recommended doses as suggested by the international guidelines. Moreover, it may not be feasible to follow the evaluation algorithm suggested by the international guidelines.
PubMed: 37388810
DOI: 10.5415/apallergy.0000000000000100 -
The American Journal of Cardiology Aug 2023End-stage heart failure is a prevalent and fatal cardiovascular disease. Almost 1 in 4 cases of mortality in the United States is attributed to heart failure. Left... (Review)
Review
End-stage heart failure is a prevalent and fatal cardiovascular disease. Almost 1 in 4 cases of mortality in the United States is attributed to heart failure. Left ventricular assist devices (LVADs) have emerged as a safe destination therapy or bridge to transplant. Despite remarkable results, LVAD is associated with significant adverse events, such as gastrointestinal bleeding (GIB). In this review, we aimed to understand the incidence and prevalence, pathophysiologic mechanisms, predictors, diagnostic mechanisms, management, and preventative measures of GIB in patients with an LVAD. GIB is a common adverse event in patients with an LVAD with an incidence of 15% to 25%. The exact pathogenesis of GIB is poorly understood. However, different mechanisms of bleeding have been described, such as arteriovenous malformations, acquired von Willebrand syndrome, coagulopathy, and treatment with antithrombotic therapy. Upper GIB is the most common site of GIB in patients with an LVAD. The management of GIB in patients with LVAD includes ensuring hemodynamic stability, holding or reversing antithrombotic therapy, and investigating and controlling the source of GIB through diagnostic and interventional endoscopic and radiologic means. Prophylactic medication use (e.g., danazol, octreotide, and bevacizumab) can decrease the risk of GIB in patients with an LVAD by decreasing arteriovenous malformations. Despite that the overall risk of GIB has decreased with new advancements in LVAD technology, further studies are needed regarding predictors, risk stratification, and optimal antithrombotic therapy to minimize the morbidity and mortality in patients with an LVAD. In conclusion, prompt diagnosis and management in a multidisciplinary team approach are crucial and lifesaving in such a life-threatening condition.
Topics: Humans; United States; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Incidence; Heart Failure; Heart-Assist Devices; Arteriovenous Malformations; Retrospective Studies
PubMed: 37352668
DOI: 10.1016/j.amjcard.2023.05.059 -
The Cochrane Database of Systematic... Jun 2023Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment... (Review)
Review
BACKGROUND
Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment strategy is medical therapy with gonadotrophin-releasing hormone analogues (GnRHas) to reduce pain due to endometriosis. One of the adverse effects of GnRHas is a decreased bone mineral density. In addition to assessing the effect on pain, quality of life, most troublesome symptom and patients' satisfaction, the current review also evaluated the effect on bone mineral density and risk of adverse effects in women with endometriosis who use GnRHas versus other treatment options.
OBJECTIVES
To assess the effectiveness and safety of GnRH analogues (GnRHas) in the treatment of painful symptoms associated with endometriosis and to determine the effects of GnRHas on bone mineral density of women with endometriosis.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and the trial registries in May 2022 together with reference checking and contact with study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) which compared GnRHas with other hormonal treatment options, including analgesics, danazol, intra-uterine progestogens, oral or injectable progestogens, gestrinone and also GnRHas compared with no treatment or placebo. Trials comparing GnRHas versus GnRHas in conjunction with add-back therapy (hormonal or non-hormonal) or calcium-regulation agents were also included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodology as recommended by Cochrane. Primary outcomes are relief of overall pain and the objective measurement of bone mineral density. Secondary outcomes include adverse effects, quality of life, improvement in the most troublesome symptoms and patient satisfaction. Due to high risk of bias associated with some of the studies, primary analyses of all review outcomes were restricted to studies at low risk of selection bias. Sensitivity analysis including all studies was then performed.
MAIN RESULTS
Seventy-two studies involving 7355 patients were included. The evidence was very low to low quality: the main limitations of all studies were serious risk of bias due to poor reporting of study methods, and serious imprecision. Trials comparing GnRHas versus no treatment We did not identify any studies. Trials comparing GnRHas versus placebo There may be a decrease in overall pain, reported as pelvic pain scores (RR 2.14; 95% CI 1.41 to 3.24, 1 RCT, n = 87, low-certainty evidence), dysmenorrhoea scores (RR 2.25; 95% CI 1.59 to 3.16, 1 RCT, n = 85, low-certainty evidence), dyspareunia scores (RR 2.21; 95% CI 1.39 to 3.54, 1 RCT, n = 59, low-certainty evidence), and pelvic tenderness scores (RR 2.28; 95% CI 1.48 to 3.50, 1 RCT, n = 85, low-certainty evidence) after three months of treatment. We are uncertain of the effect for pelvic induration, based on the results found after three months of treatment (RR 1.07; 95% CI 0.64 to 1.79, 1 RCT, n = 81, low-certainty evidence). Besides, treatment with GnRHas may be associated with a greater incidence of hot flushes at three months of treatment (RR 3.08; 95% CI 1.89 to 5.01, 1 RCT, n = 100, low-certainty evidence). Trials comparing GnRHas versus danazol For overall pain, for women treated with either GnRHas or danazol, a subdivision was made between pelvic tenderness, partly resolved and completely resolved. We are uncertain about the effect on relief of overall pain, when a subdivision was made for overall pain (MD -0.30; 95% CI -1.66 to 1.06, 1 RCT, n = 41, very low-certainty evidence), pelvic pain (MD 0.20; 95% CI -0.26 to 0.66, 1 RCT, n = 41, very low-certainty evidence), dysmenorrhoea (MD 0.10; 95% CI -0.49 to 0.69, 1 RCT, n = 41, very low-certainty evidence), dyspareunia (MD -0.20; 95% CI -0.77 to 0.37, 1 RCT, n = 41, very low-certainty evidence), pelvic induration (MD -0.10; 95% CI -0.59 to 0.39, 1 RCT, n = 41, very low-certainty evidence), and pelvic tenderness (MD -0.20; 95% CI -0.78 to 0.38, 1 RCT, n = 41, very low-certainty evidence) after three months of treatment. For pelvic pain (MD 0.50; 95% CI 0.10 to 0.90, 1 RCT, n = 41, very low-certainty evidence) and pelvic induration (MD 0.70; 95% CI 0.21 to 1.19, 1 RCT, n = 41, very low-certainty evidence), the complaints may decrease slightly after treatment with GnRHas, compared to danazol, for six months of treatment. Trials comparing GnRHas versus analgesics We did not identify any studies. Trials comparing GnRHas versus intra-uterine progestogens We did not identify any low risk of bias studies. Trials comparing GnRHas versus GnRHas in conjunction with calcium-regulating agents There may be a slight decrease in bone mineral density (BMD) after 12 months treatment with GnRHas, compared to GnRHas in conjunction with calcium-regulating agents for anterior-posterior spine (MD -7.00; 95% CI -7.53 to -6.47, 1 RCT, n = 41, very low-certainty evidence) and lateral spine (MD -12.40; 95% CI -13.31 to -11.49, 1 RCT, n = 41, very low-certainty evidence). AUTHORS' CONCLUSIONS: For relief of overall pain, there may be a slight decrease in favour of treatment with GnRHas compared to placebo or oral or injectable progestogens. We are uncertain about the effect when comparing GnRHas with danazol, intra-uterine progestogens or gestrinone. For BMD, there may be a slight decrease when women are treated with GnRHas, compared to gestrinone. There was a bigger decrease of BMD in favour of GnRHas, compared to GnRHas in conjunction with calcium-regulating agents. However, there may be a slight increase in adverse effects when women are treated with GnRHas, compared to placebo or gestrinone. Due to a very low to low certainty of the evidence, a wide range of outcome measures and a wide range of outcome measurement instruments, the results should be interpreted with caution.
Topics: Female; Humans; Endometriosis; Danazol; Progestins; Gestrinone; Dysmenorrhea; Calcium; Dyspareunia; Pelvic Pain; Calcium, Dietary; Drug-Related Side Effects and Adverse Reactions; Gonadotropin-Releasing Hormone
PubMed: 37341141
DOI: 10.1002/14651858.CD014788.pub2 -
European Review For Medical and... Jun 2023The aim of this study is to investigate the temporal relationship between the first occurrence of thromboembolic events (TEE) and the timing of myeloproliferative...
OBJECTIVE
The aim of this study is to investigate the temporal relationship between the first occurrence of thromboembolic events (TEE) and the timing of myeloproliferative neoplasm (MPN) diagnosis and to determine risk factors for TEE-related mortality in MPN.
PATIENTS AND METHODS
A total of 138 BCR-ABL-negative MPN patients with TEE, diagnosed from January 2010 to December 2019, were included in this retrospective cohort. Patients were compared according to mortality and subjects were classified into three groups with respect to having suffered index TEE before, during, or after MPN diagnosis.
RESULTS
The mean age of surviving patients was 57.5±13.8, while those who had died had a mean age of 72.0±9.0 (p<0.001). Males represented 56.5% of patients with mortality and 60.9% of those without mortality (p=0.876). TEE was detected in 26.0% of MPN patients, and TEE-related mortality rate was 16.7%. There was no relationship between mortality and the classification of patients according to index TEE (p =0.884). High age (p<0.001) and danazol use (p=0.014) were independently associated with TEE-related mortality.
CONCLUSIONS
The temporal relationship between TEE and MPN diagnosis was not found to influence mortality. Older patients and danazol recipients should be considered to have a higher risk of TEE-related mortality.
Topics: Male; Humans; Middle Aged; Aged; Aged, 80 and over; Retrospective Studies; Danazol; Neoplasms; Myeloproliferative Disorders; Thromboembolism
PubMed: 37318468
DOI: 10.26355/eurrev_202306_32611