danazol vaginal cream / FemmePharma, Azurity Pharma - LARVOL DELTA

Preventive Effects of Eclipta prostrata and Hordeum vulgare Extract Complex on Precocious Puberty in Danazol- and High-Fat Diet-Induced Rat Models. (PubMed, Int J Mol Sci) - "Furthermore, EHEC attenuated the elevation in hypothalamic GnRH mRNA expression observed in both models, without affecting body weight. These findings suggest that EHEC modulates the hypothalamic-pituitary-gonadal axis and may serve as a potential natural therapeutic agent for the prevention of precocious puberty."

Journal • Preclinical

Therapeutic potential of luteolin in central precocious puberty: insights from a danazol-induced rat model. (PubMed, Front Endocrinol (Lausanne)) - "This study is the first to determine that luteolin ameliorates CPP via the Toll-like receptor signaling pathway. These findings enhance our understanding of luteolin's pharmacological actions and support its potential role in CPP treatment."

IO biomarker • Journal • Preclinical • Endocrine Disorders • Oncology • CXCL10 • CXCL11 • IL17A • IRF7 • STAT1 • TLR3 • TNFA

Zhibai dihuang pill (ZBDH) exhibits therapeutic effects on idiopathic central sexual precocity in rats by modulating the gut microflora. (PubMed, Heliyon) - "ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats."

Journal • Preclinical • Endocrine Disorders

Modulating the RFamide-related peptide-3/G protein-coupled receptor 147 signaling pathway with nourishing Yin-removing fire herbal mixture to alleviate precocious puberty in female rats: An experimental study. (PubMed, Int J Reprod Biomed) - "PP was induced in the model, normal saline, and NYRF groups by subcutaneous injection of danazol at PD5. Serum luteinizing hormone levels were reduced, reproductive organ coefficients were reduced, and the vaginal opening was delayed compared to the model and normal saline groups. The NYRF herbal mixture delayed sexual development in rats with PP by hypothalamic upregulating RFRP3 and downregulating GnRH and kisspeptin."

Journal • Preclinical

Therapeutic Effects of Melatonin in Female Mice with Central Precocious Puberty by Regulating the Hypothalamic Kiss-1/Kiss1R System. (PubMed, Behav Brain Res) - "A CPP model was established by subcutaneous injection of 300 micrograms of danazol into 5-day-old female mice, followed by treatment with melatonin and leuprolide. Melatonin suppressed the expressions of Kiss-1, Kiss1R and GnRH in the hypothalamus, and the expression of GnRHR in the pituitary of the female CPP mice. Our results suggest that melatonin can inhibit the hypothalamic-pituitary-gonadal (HPG) axis by down-regulating the Kiss-1/Kiss1R system, thereby treating CPP in female mice."

Journal • Preclinical • Endocrine Disorders

Endometriosis: Evaluation and Treatment. (PubMed, Am Fam Physician) - "Second-line treatments include gonadotropin-releasing hormone (GnRH) receptor agonists with add-back therapy, GnRH receptor antagonists, and danazol. Referral to gynecology for surgical management is indicated if empiric therapy is ineffective, immediate diagnosis and treatment are necessary, or patients desire pregnancy. Alternative treatments have limited benefit in alleviating pain symptoms but may warrant further investigation."

Journal • Endometriosis • Gastrointestinal Disorder • Gynecology • Infertility • Musculoskeletal Pain • Pain • Sexual Disorders • Women's Health

Interventions for heavy menstrual bleeding; overview of Cochrane reviews and network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "Evidence suggests LNG-IUS is the best first-line treatment for reducing menstrual blood loss (MBL); antifibrinolytics are probably the second best, and long-cycle progestogens are likely the third best. We cannot make conclusions about the effect of first-line treatments on perception of improvement and satisfaction, as evidence was rated as very low certainty. For second-line treatments, evidence suggests hysterectomy is the best treatment for reducing bleeding, followed by REA and NREA. We are uncertain of the effect on amenorrhoea, as evidence was rated as very low certainty. Minimally invasive hysterectomy may result in a large increase in satisfaction, and NREA also increases satisfaction, but we are uncertain of the true effect of the remaining second-line interventions, as evidence was rated as very low certainty."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Gynecology

Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds. (PubMed, Plants (Basel)) - "Gene set enrichment analysis revealed that the targets of APE were significantly associated with GnRH signaling and ovarian steroidogenesis pathways. In conclusion, APE may be used as a therapeutic remedy to inhibit the activation of the hypothalamic-pituitary-gonadal axis."

Journal • Preclinical • NTN1

Successful perioperative management of a pregnant patient with Hereditary Angioedema: a case report (Euroanaesthesia 2021) - "8mg dexamethasone, 4mg ondansetron and antibiotic were administered. Combined spinalepidural anesthesia (CSEA) was induced (7,5 mg levobupivacaine, 2.5mcg sufentanil and 100mcg morphine)...Danazol was discontinued prior to pregnancy... In conclusion, although rare, anesthesiologists should be familiar with the pathophysiology of HAE, as planning is essential. 1Moellman JJ et al. Diagnosis and management of hereditary angioedema."

Clinical • Allergy • Anesthesia • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Immunology • Obesity • Obstetrics

[VIRTUAL] Effect of tamoxifen on linear growth of precocious female SD rats (ESPE 2021) - " At 16-22 day of age, 16 precocious pubertal female rats(induced by 300 μg danazol s.c. at 5-day old), were randomized blocks (brood) to 2 groups( n = 8). Tamoxifen inhibited growth, especially weight gain and fat accumulation. Besides, tamoxifen has dual effects of anti-estrogen and estrogen-like on the growth plate. So tamoxifen is inapplicable for central precocious puberty treatment."

Preclinical • Endocrine Disorders • Genetic Disorders • IGF1 • IGFBP3

Effects of estrogen inhibition formula herbal mixture for danazol-induced precocious puberty in female rats: an experimental study with network pharmacology. (PubMed, Integr Med Res) - "The gene set enrichment analysis showed that the targets of EIF are mainly associated with the GnRH signaling and ovarian steroidogenesis pathways. EIF could be used in preclinical research for the treatment of precocious puberty by the inhibition of HPGA pre-maturation."

Journal

The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus. (PubMed, Front Pharmacol) - "Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15...We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway."

Journal

A Comparative, Open-Label, Controlled, monocentric study to determine the serum and Intraperitoneal fluids concentrations of vaginal applications of danazol (100mg/die) in comparison to administration of danazol oral capsules (600mg/die) in groups of women with suspected or confirmed endometriosis and scheduled for laparoscopy. ¿Studio comparativo, in aperto, controllato, monocentrico volto a... (clinicaltrialsregister.eu) - P2; N=24; Terminated; Sponsor: VIRAMAL LIMITED

Clinical • New P2 trial • Endometriosis • Gynecology

Study on the Mechanism of Sarsasapogenin in Treating Precocious Puberty by Regulating the HPG Axis. (PubMed, Evid Based Complement Alternat Med) - "Rats at 5 days of age were given a single subcutaneous injection of 300 micrograms of danazol to establish the precocious puberty model. Moreover, it can significantly downregulate the levels of serum hormones and reduce the expression of GnRH, GnRH-R, and kiss-1. In summary, our results indicate that sarsasapogenin can regulate the HPG axis through the kiss-1/GPR54 system for therapeutic precocious puberty."

Journal

Study to Determine Intraperitoneal,Tissue, Serum Concentrations of VML-0501 Following Five Days of Daily Vaginal Single Dose of VML-0501 (100 mg Danazol), in Comparison to Oral Danazol Capsules Daily 600 mg), in Women With Signs and Symptoms of Endometriosis Undergoing Laparoscopy (clinicaltrials.gov) - P2; N=30; Completed; Sponsor: Viramal Limited; Active, not recruiting ➔ Completed

Clinical • Trial completion • Endometriosis • Gynecology

MiR-664-2 impacts pubertal development in a precocious-puberty rat model through targeting the NMDA receptor-1. (PubMed, Biol Reprod) - "Consistently, the miR-664-2 expression in hypothalamus of the Danazol group was decreased compared to Vehicle. Our results suggested that attenuated miR-664-2 might participate in precocious puberty pathogenesis through enhancing the NMDAR1 signaling."

Journal • Preclinical

Study to Determine Intraperitoneal,Tissue, Serum Concentrations of VML-0501 Following Five Days of Daily Vaginal Single Dose of VML-0501 (100 mg Danazol), in Comparison to Oral Danazol Capsules Daily 600 mg), in Women With Signs and Symptoms of Endometriosis Undergoing Laparoscopy (clinicaltrials.gov) - P2; N=34; Active, not recruiting; Sponsor: Viramal Limited; Trial completion date: Feb 2020 ➔ Jun 2020

Clinical • Trial completion date • Endometriosis • Gynecology

Study to Determine Intraperitoneal,Tissue, Serum Concentrations of VML-0501 Following Five Days of Daily Vaginal Single Dose of VML-0501 (100 mg Danazol), in Comparison to Oral Danazol Capsules Daily 600 mg), in Women With Signs and Symptoms of Endometriosis Undergoing Laparoscopy (clinicaltrials.gov) - P2; N=34; Active, not recruiting; Sponsor: Viramal Limited; Trial completion date: Nov 2019 ➔ Feb 2020

Clinical • Trial completion date

Study to Determine Intraperitoneal,Tissue, Serum Concentrations of VML-0501 Following Five Days of Daily Vaginal Single Dose of VML-0501 (100 mg Danazol), in Comparison to Oral Danazol Capsules Daily 600 mg), in Women With Signs and Symptoms of Endometriosis Undergoing Laparoscopy (clinicaltrials.gov) - P2; N=34; Active, not recruiting; Sponsor: Viramal Limited; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Cyclical progestogens for heavy menstrual bleeding. (PubMed, Cochrane Database Syst Rev) - "Low- or very low-quality evidence suggests that short-course progestogen was inferior to other medical therapy, including tranexamic acid, danazol and the Pg-IUS with respect to reduction of menstrual blood loss. Long cycle progestogen therapy (medroxyprogesterone acetate or norethisterone) was also inferior to the LNG-IUS, tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss."

Journal • Review

Study to Determine Intraperitoneal,Tissue, Serum Concentrations of VML-0501 Following Five Days of Daily Vaginal Single Dose of VML-0501 (100 mg Danazol), in Comparison to Oral Danazol Capsules Daily 600 mg), in Women With Signs and Symptoms of Endometriosis Undergoing Laparoscopy (clinicaltrials.gov) - P2; N=34; Recruiting; Sponsor: Viramal Limited; Trial completion date: Jul 2019 ➔ Oct 2019

Trial completion date

"Per vaginam" topical use of hormonal drugs in women with symptomatic deep endometriosis: a narrative literature review. (PubMed, Arch Gynecol Obstet) - "The vaginal route represents a scarcely explored modality for drug administration. High local hormonal concentrations might achieve a greater effect on endometriotic lesions compared with alternative routes. Future studies should focus on the use of the vagina for delivering target therapies particularly in patients with deeply infiltrating rectovaginal lesions."

Clinical • Journal • Review

Endometriosis: A Rare Cause of Rectal Obstruction (ASCRS 2019) - "She was recommended to start on a gonadotropin-releasing hormone agonist (GnRHa) leuprolide (Lupron) however, this medication was too expensive and therefore transitioned to the GnRHa danazol. Medical treatment is least likely to resolve these deep infiltrating gastrointestinal lesions and require aggressive surgical resections. However, a combination approach of 3-6 months of GnRHa therapy prior to surgical resection can have the benefit of reducing the size of implants and local inflammation."

Study to Determine Intraperitoneal,Tissue, Serum Concentrations of VML-0501 Following Five Days of Daily Vaginal Single Dose of VML-0501 (100 mg Danazol), in Comparison to Oral Danazol Capsules Daily 600 mg), in Women With Signs and Symptoms of Endometriosis Undergoing Laparoscopy (clinicaltrials.gov) - P2; N=34; Recruiting; Sponsor: Viramal Limited; Trial completion date: Mar 2019 ➔ Jul 2019; Trial primary completion date: Mar 2019 ➔ Jul 2019

Clinical • Trial completion date • Trial primary completion date

Study to Determine Intraperitoneal,Tissue, Serum Concentrations of VML-0501 Following Five Days of Daily Vaginal Single Dose of VML-0501 (100 mg Danazol), in Comparison to Oral Danazol Capsules Daily 600 mg), in Women With Signs and Symptoms of Endometriosis Undergoing Laparoscopy (clinicaltrials.gov) - P2; N=34; Recruiting; Sponsor: Viramal Limited; Trial primary completion date: Dec 2018 ➔ Mar 2019

Clinical • Trial primary completion date