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ACTIVELY WORKING SUBSTANCE FROM THE GREEN TEA FOR THE TREATMENT OF ENDOMETRIOSIS AND UTERINE FIBROIDS. VIEW ON THE PROBLEM OF GERMAN AND RUSSIAN EXPERTS
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Introduction
Fibroid treatment with MR-guided focused ultrasound (MRgFUS; syn.: HIFU = high-intensity focused ultrasound) is a thermoablative method in which the tissue to be treated is heated by focused ultrasound in single small volume increments (sonifications, syn: sonications) under constant MRI control until complete denaturation of the planned fibroid volume is achieved. After thermoablation, imaging showed a lack of contrast enhancement of the treated tissue (NPV = non-perfused volume).
MRgFUS is organ-preserving and noninvasive and can be performed on an outpatient basis.
The treatment method is offered only by a few specialized centers.
The goal of MRgFUS treatment is to reduce or eliminate fibroid-related symptoms in affected women. A reduction in fibroid size can be achieved with ultrasound treatment. Complete fibroid regression is not to be expected and is also not the goal of the treatment.
The disciplines of gynecology and radiology agree that the indication for the treatment of uterine fibroids should be determined by a gynecologist following examination and counseling of the patient. Comprehensive patient counseling regarding the treatment options in symptomatic uterine fibroids should include medication, surgery, and the two non-surgical treatment options uterine artery embolization (UAE) and MRgFUS. The decision for or against a treatment alternative should be made under consideration of the patient's wishes and with knowledge of other treatment options, the chance of success, limitations, typical side effects, and possible complications (informed consent).
MRgFUS treatment provides a treatment method for patients with fibroid-related symptoms and allows further treatment individualization for uterine fibroids in Germany, Austria, and Switzerland.
* To be differentiated from non-MR-guided focused ultrasound.
Background:
This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis.
Objectives:
The objective of this overview was to summarise the evidence from Cochrane systematic reviews on treatment options for women with pain or subfertility associated with endometriosis.
Methods:
Published Cochrane systematic reviews reporting pain or fertility outcomes in women with clinically diagnosed endometriosis were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation (protocols and titles) for future inclusion. The reviews, protocols and titles were identified by searching the Cochrane Database of Systematic Reviews and Archie (the Cochrane information management system) in March 2014.Pain-related outcomes of the overview were pain relief, clinical improvement or resolution and pain recurrence. Fertility-related outcomes were live birth, clinical pregnancy, ongoing pregnancy, miscarriage and adverse events.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed using the AMSTAR tool. The quality of the evidence for each outcome was assessed using GRADE methods. Review findings were summarised in the text and the data for each outcome were reported in 'Additional tables'.
Main results:
Seventeen systematic reviews published in The Cochrane Library were included. All the reviews were high quality. The quality of the evidence for specific comparisons ranged from very low to moderate. Limitations in the evidence included risk of bias in the primary studies, inconsistency between the studies, and imprecision in effect estimates. Pain relief (14 reviews) Gonadotrophin-releasing hormone (GnRH) analogues One systematic review reported low quality evidence of an overall benefit for GnRH analogues compared with placebo or no treatment. Ovulation suppression Five systematic reviews reported on medical treatment using ovulation suppression. There was moderate quality evidence that the levonorgestrel-releasing intrauterine system (LNG-IUD) was more effective than expectant management, and very low quality evidence that danazol was more effective than placebo. There was no consistent evidence of a difference in effectiveness between oral contraceptives and goserelin, estrogen plus progestogen and placebo, or progestogens and placebo, though in all cases the relevant evidence was of low or very low quality. Non-steroidal anti-inflammatory drugs (NSAIDS)A review of NSAIDs reported inconclusive evidence of a benefit in symptom relief compared with placebo. Surgical interventions There were two reviews of surgical interventions. One reported moderate quality evidence of a benefit in pain relief following laparoscopic surgery compared to diagnostic laparoscopy only. The other reported very low quality evidence that recurrence rates of endometriomata were lower after excisional surgery than after ablative surgery. Post-surgical medical interventions Two reviews reported on post-surgical medical interventions. Neither found evidence of an effect on pain outcomes, though in both cases the evidence was of low or very low quality. Alternative medicine There were two systematic reviews of alternative medicine. One reported evidence of a benefit from auricular acupuncture compared to Chinese herbal medicine, and the other reported no evidence of a difference between Chinese herbal medicine and danazol. In both cases the evidence was of low or very low quality. Anti-TNF-α drugs One review found no evidence of a difference in effectiveness between anti-TNF-α drugs and placebo. However, the evidence was of low quality. Reviews reporting fertility outcomes (8 reviews) Medical interventions Four reviews reported on medical interventions for improving fertility in women with endometriosis. One compared three months of GnRH agonists with a control in women undergoing assisted reproduction and found very low quality evidence of an increase in clinical pregnancies in the treatment group. There was no evidence of a difference in effectiveness between the interventions in the other three reviews, which compared GnRH agonists versus antagonists, ovulation suppression versus placebo or no treatment, and pre-surgical medical therapy versus surgery alone. In all cases the evidence was of low or very low quality. Surgical interventions Three reviews reported on surgical interventions. There was moderate quality evidence that both live births or ongoing pregnancy rates and clinical pregnancy rates were higher after laparoscopic surgery than after diagnostic laparoscopy alone. There was low quality evidence of no difference in effectiveness between surgery and expectant management for endometrioma. One review found low quality evidence that excisional surgery resulted in higher clinical pregnancy rates than drainage or ablation of endometriomata. Post-surgical interventions Two reviews reported on post-surgical medical interventions. They found no evidence of an effect on clinical pregnancy rates. The evidence was of low or very low quality. Alternative medicine A review of Chinese herbal medicine in comparison with gestrinone found no evidence of a difference between the groups in clinical pregnancy rates. However, the evidence was of low quality. Adverse events Reviews of GnRH analogues and of danazol reported that the interventions were associated with higher rates of adverse effects than placebo; and depot progestagens were associated with higher rates of adverse events than other treatments. Chinese herbal medicine was associated with fewer side effects than gestrinone or danazol.Three reviews reported miscarriage as an outcome. No difference was found between surgical and diagnostic laparoscopy, between GnRH agonists and antagonists, or between aspiration of endometrioma and expectant management. However, in all cases the quality of the evidence was of low quality.
Authors' conclusions:
For women with pain and endometriosis, suppression of menstrual cycles with gonadotrophin-releasing hormone (GnRH) analogues, the levonorgestrel-releasing intrauterine system (LNG-IUD) and danazol were beneficial interventions. Laparoscopic treatment of endometriosis and excision of endometriomata were also associated with improvements in pain. The evidence on NSAIDs was inconclusive. There was no evidence of benefit with post-surgical medical treatment.In women with endometriosis undergoing assisted reproduction, three months of treatment with GnRH agonist improved pregnancy rates. Excisional surgery improved spontaneous pregnancy rates in the nine to 12 months after surgery compared to ablative surgery. Laparoscopic surgery improved live birth and pregnancy rates compared to diagnostic laparoscopy alone. There was no evidence that medical treatment improved clinical pregnancy rates.Evidence on harms was scanty, but GnRH analogues, danazol and depot progestagens were associated with higher rates than other interventions.
Objectives
In this review paper, the pros and cons of the available pharmacological options for the treatment of uterine fibroids are explored, including oral progestogens, levonorgestrel intra-uterine device, gonadotropin-releasing hormone analogs and progesterone receptor modulators with an emphasis on ulipristal acetate.
Study design
The choice of the appropriate therapeutic approach for uterine fibroids depends on several factors, including women's age, parity, childbearing aspirations and wish to preserve fertility, extent and severity of symptoms, size, number and location of myomas, risk of malignancy and proximity to menopause. Some treatment algorithms have been proposed for uterine fibroids, considering both efficacy and safety data from clinical trials, and women characteristics and choices. Therefore, we propose two optimized treatment algorithms for the treatment of uterine fibroids, one for the treatment of uterine fibroids in women of reproductive age with the desire to spare reproductive capacity, and another for the treatment of uterine fibroids in women >40 years with no desire for pregnancy.
Results
Symptoms associated with uterine fibroids may significantly impair a patient quality of life. Therapy includes surgery, which may range from a hysterectomy to several other uterus-sparing techniques and several different types of pharmacological therapies. Studies with ulipristal acetate have provided a change of paradigm in the treatment of uterine fibroids, demonstrating the efficacy and favorable tolerability profile, not only for the preoperative treatment of moderate to severe fibroid-associated symptoms, but also, and very importantly, for the long-term medical management of patients with symptomatic fibroids.
Purpose
There is significant discussion and uncertainty about the optimal management of symptomatic uterine leiomyomas (SULs). Nonsurgical procedures such as uterine artery embolization (UAE) have been developed. The goal of this study was to conduct a meta-analysis and an indirect treatment comparison to examine the comparative efficacy and safety of the surgical procedures to treat SULs compared with UAE.
Methods
MEDLINE, EMBASE, Lilacs, and the Cochrane Central Register of Controlled Trials databases were searched from inception to February 2016. Ten randomized controlled trials comparing UAE versus hysterectomy, myomectomy, and laparoscopic occlusion of the uterine arteries in patients with SUL published in a peer-reviewed journal were included. Two reviewers independently selected studies, assessed quality, and extracted data. Discrepancies were resolved through consensus.
Findings
Data from 986 patients submitted to UEA (n = 527) or surgery (n = 459) were analyzed. UAE had a lower risk of major complications (risk ratio [RR], 0.45 [95% CI, 0.22–0.95]; P = 0.04)and a higher risk of minor complications (RR, 1.65 [95% CI, 1.32–2.06]; P < 0.00001); UAE had a higher risk of re-intervention up to 2 years (RR, 3.74 [95% CI, 1.76–7.96]; P = 0.0006) and up to 5 years (RR, 5.01 [95% CI, 1.37–18.39]; P = 0.02); UAE had a similar risk of follicle-stimulating hormone levels >40 IU/L after 6 months (RR, 1.76 [95% CI, 0.24–12.95]; P = 0.58)and of recommending the procedure to another patient up to 5 years after treatment (RR, 1.00 [95% CI, 0.87–1.14]; P = 0.94). The indirect comparison between myomectomy and hysterectomy found that the 2 procedures were similar in the studied outcomes.
Implications
Compared with surgery, UAE had lower rates of major complications with an increased risk of re-intervention up to 2 and 5 years after the first procedure. UAE compared with surgery had a similar risk of ovarian failure and similar recommendation of the procedure to another patient. However, the number of trials was limited, and there was a high risk of bias in at least 2 domains. None of the trials blinded the participants and personnel or the outcome assessment. PROSPERO identifier: CRD42015026319.
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital “preconditioning”, whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment.
Purpose and objective:
Endometriosis is a gynaecological disease that is characterised by the presence of endometrium like tissue-epithelium and stroma that develops outside the uterine cavity, which is responsible for pelvic pain and infertility. Even though several medical therapies exist for the treatment of endometriosis, each of the drug class has its own limitations such as cost of treatment, side-effects and its short-term effect on the symptoms of endometriosis. In this review, we have attempted to summarize the current status and challenges of drug development for endometriosis.
Methods:
A systematic review was done and all the RCTs were selected from the identified hits. We included studies that explored the usage of therapeutic drugs on endometriosis patients from inception till November 2016. The search term used was 'Endometriosis' using PubMed and Clinicaltrials.gov. For the final analysis, 60 articles were analyzed and we identified the newly emerging drug therapies for endometriosis treatment and have briefed their current status and challenges in drug development for endometriosis. The quality of the selected studies was assessed based on the degree of bias.
Results:
The current classes of drugs that have shown promising therapeutic results include Gonadotropin- releasing hormone (GnRH) antagonists, aromatase inhibitors (AI), and selective progesterone and estrogen receptor modulators, dopamine receptor-2-agonists and statins. The drugs that failed midway during development include tanezumab, rosiglitazone, infliximab, pentoxifylline, telapristone acetate, asoprisnil and raloxifene.
Conclusion:
From the literature review, it appears that the most promising molecules for the treatment of endometriosis in the near future include elagolix, mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be seen if these molecules would succeed large phase 3 clinical trials and overcome the regulatory hurdles to become an essential tool in the gynaecologist's armamentarium against endometriosis.
Background:
Fibroids are the most common benign tumours of uterus. Heavy menstrual bleeding is the commonest concern for which medical attention is sought. Hysterectomies for leiomyoma constitute a third of all hysterectomies. Thus, healthcare cost to society due to uterine leiomyomas is of considerable importance.
Methods:
A prospective study was conducted at tertiary care hospital of armed forces. 120 women in pre-menopausal age group with complaints of menorrhagia, Pictorial Bleeding Assessment Chart (PBAC) scoring ≥100 and at least one fibroid ≥2.5 cm in size were recruited in the study. Patients in Group 1 were given Tab Tranexemic acid (500 mg) and Tab Mefenemic acid (500 mg) three times a day during menstrual bleeding for a period of 6 months. Patients in Group 2 were given Tab Mifepristone 50 mg twice a week. They were followed up at 1, 3 and 6 months of starting the medicine. Results were statistically analysed using Microsoft Excel sheet and paired t-test.
Results:
The average age was 40 years in the Group 2 and 45 years in Group 1. A size reduction of 36.99% in intramural and 39.39% in submucosal fibroids after six months of treatment with Mifepristone resulted in marked clinical improvement. 10% patients had side effects. In 30% of patients symptoms reappeared during the follow up period.
Conclusion:
Mifepristone when given in bi-weekly doses was found to be safe, efficacious, and cost effective as compared to treatment with tranexemic acid and mefenemic acid for management of fibroid uterus.
Objectives
To evaluate the fertility of women eligible for surgical multiple myomectomy, but who carefully elected a fertility-sparing uterine artery embolization (UAE). Methods
Non-comparative open-label trial, on women ≤40 years, presenting with multiple symptomatic fibroids (at least 3, ≥3 cm), immediate pregnancy wish, and no associated infertility factor.Women had a bilateral limited UAE using tris-acryl gelatin microspheres ≥500 μm.Fertility, ovarian reserve, uterus and fibroid sizes, and quality of life questionnaires (UFS-QoL) were prospectively followed. ResultsFifteen patients, aged 34.8 years (95%CI 32.2–37.5, median 36.0, q1–q3 29.4–39.5) were included from November 2008 to May 2012.During the year following UAE, 9 women actively attempting to conceive experienced 5 live-births (intention-to-treat fertility rate 33.3%, 95%CI 11.8%–61.6%). Markers of ovarian reserve remained stable. The symptoms score was reduced by 66% (95%CI 48%–85%) and the quality of life score was improved by 112% (95%CI 21%–204%). Uterine volume was reduced by 38% (95%CI 24%–52%).Women were followed for 43.1 months (95%CI 32.4–53.9), 10 live-births occurred in 8 patients, and 5 patients required secondary surgeries for fibroids. Conclusion
Women without associated infertility factors demonstrated an encouraging capacity to deliver after UAE. Further randomized controlled trials comparing UAE and myomectomy are warranted. Key points• Women without infertility factors showed an encouraging delivery rate after UAE.• For women choosing UAE over abdominal myomectomy, childbearing may not be impaired.• Data are insufficient to definitively recommend UAE as comparable to myomectomy.• Further randomized trials comparing fertility after UAE or myomectomy are warranted.
Objectives
To investigate the clinical factors predicting outcomes of leiomyoma treated with uterine artery embolization (UAE). MethodsA total of 183 uterine leiomyoma patients undergoing UAE were retrospectively analyzed. Patient age, characteristics of vascular supply in magnetic resonance imaging (MRI)/digital subtraction angiography (DSA), number, size and location of leiomyoma were recorded. Leiomyoma regrowth, new leiomyoma appearance and recurrence of any previously reported symptoms were carefully monitored over a mean follow-up of 30 months (median 32 months, range 12–80). Potential recurrence risk factors were analyzed by univariate and multivariate cox regression analysis. ResultsTwenty-three recurrences were recorded. The difference in the vascularity classification systems between MRI and DSA was not statistically significant (P = 0.059). High vascularity in MRI, high vascularity in DSA and multiple leiomyoma showed a significant risk of recurrence using univariate and multivariate analysis (P = 0.004, P < 0.001 and P = 0.023, respectively). The other factors were not significantly associated with leiomyoma recurrence (P > 0.05). Conclusion
Low vascularity and solitary leiomyoma indicated favourable outcomes in patients treated with UAE. Key Points• Low vascularity and solitary mass predicted favourable outcomes in UAE-treated patients.• MRI might provide information on vascularity in leiomyoma before UAE.• Variations in vascular supply, age, size, location were not associated with recurrence.
In this guideline, recommendations and standards for optimum diagnosis and treatment of endometriosis are presented. They are based on the analysis of the available scientific evidence as published in prospective randomized and retrospective studies as well as in systematic reviews. The guideline working group consisted of experts from Austria, Germany, Switzerland, and the Czech Republic.
Aim:
The objectives of this study were to evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRHa) treatment before surgery for women with uterine fibroids and to explore potential factors predicting the pooled effect sizes.
Methods:
A meta-analysis was performed from published randomized controlled trials using the random effects model. The efficacy of preoperative treatment with GnRHa was investigated according to volume measurements of fibroid tumors, postoperative complications, myoma recurrence, and changes in fertility. Metaregression and subgroup analysis were used to identify potential predictors of the effect sizes.
Results:
A total of 26 studies were selected for the meta-analysis. Preoperative GnRHa therapy for women with uterine fibroids was associated with a smaller preoperative volume of fibroid tumors, increased hemoglobin and hematocrit levels, reductions in preoperative pelvic symptoms and the vertical incision rate, and a higher proportion of patients undergoing a vaginal procedure. No differences were observed in postoperative complications, myoma recurrence, and changes in fertility in the GnRHa-treated patients compared with patients treated with placebo or alternative clinical agents. The metaregression suggested that age, the duration of GnRHa treatment, the type of control group, and the type of surgery were important predictors of the efficacy of preoperative GnRHa treatment.
Conclusions:
Preoperative GnRHa treatment for women with uterine fibroids reduces preoperative fibroid size and increases hemoglobin and hematocrit levels. Gonadotropin-releasing hormone agonist pretreatment reduces preoperative pelvic symptoms and the rate of vertical incision and results in a higher chance of patients to receive a vaginal procedure, without significant difference in postoperative complications when comparing with other preoperative treatments. The patients' age, duration of GnRHa treatment, agents selected as control, and types of surgical procedures serve as predictors of the efficacy of preoperative GnRHa treatment.
Background/aims:
To investigate the inhibitory effect of green tea extract, epigallocatechin gallate (EGCG), on wild-type human leiomyoma (WT-HuLM) cells and its potential action via catechol-o-methyltransferase (COMT) activity.
Methods:
Cell proliferation of WT-HuLM and COMT gene-silenced HuLM (COMT-shRNA-HuLM) cells treated with 0 or 100 µM EGCG for 7 days was measured using the MTT method. Total RNA and protein were extracted from cells treated with 0 or 100 µM of EGCG for 48 h. Gene expression profiling was performed using Human Signal Transduction PathwayFinder. Proliferation cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (Cdk4) and COMT protein levels were detected by Western blot analyses. COMT enzyme activity was evaluated by HPLC.
Results:
EGCG-treated WT-HuLM cells showed significantly decreased COMT expression (p < 0.001) and enzyme activity (p < 0.05) compared to untreated WT-HuLM cells, while COMT-shRNA-HuLM cells showed no significant change. At 100 μM of EGCG, survival of WT-HuLM cells was significantly lower (p < 0.05) compared to COMT-shRNA-HuLM cells. EGCG treatment modulated multiple signaling pathways in WT-HuLM compared to untreated control, while changes were minimal or reversed in COMT-shRNA-HuLM cells. EGCG significantly decreased PCNA, Cdk4 and soluble COMT protein levels (p < 0.001) in WT-HuLM, but not in COMT-shRNA-HuLM cells.
Conclusions:
The antiproliferative and gene-modulating effects of EGCG on HuLM cells are mediated, at least partially, via its effect on COMT expression and enzyme activity.
Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and development of an experimental endometriosis model in mice, but it suffers from poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized to enhance the stability and bioavailability of EGCG in vivo. In this study, the potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in mice was investigated. Homologous endometrium was subcutaneously transplanted into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4 weeks. The growth of the endometrial implants were monitored by IVIS(®) non-invasive in vivo imaging during the interventions. Angiogenesis of the endometriotic lesions was determined by Cellvizio(®) in vivo imaging and SCANCO(®) Microfil microtomography. The bioavailability, anti-oxidation and anti-angiogenesis capacities of the treatments were measured in plasma and lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle layers were collected for histological, microvessel and apoptosis examinations. The result showed that EGCG and pro-EGCG significantly decreased the growth of endometrial implants from the 2nd week to the 4th week of intervention. EGCG and pro-EGCG significantly reduced the lesion size and weight, inhibited functional and structural microvessels in the lesions, and enhanced lesion apoptosis at the end of interventions. The inhibition by pro-EGCG in all the angiogenesis parameters was significantly greater than that by EGCG, and pro-EGCG also had better bioavailability and greater anti-oxidation and anti-angiogenesis capacities than EGCG. Ovarian follicles and uterine endometrial glands were not affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In conclusion, pro-EGCG significantly inhibited the development, growth and angiogenesis of experimental endometriosis in mice with high efficacy, bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could be a potent anti-angiogenesis agent for endometriosis.
The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain.
We randomly assigned women with symptomatic fibroids, excessive uterine bleeding (a score of >100 on the pictorial blood-loss assessment chart [PBAC, an objective assessment of blood loss, in which monthly scores range from 0 to >500, with higher numbers indicating more bleeding]) and anemia (hemoglobin level of ≤10.2 g per deciliter) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day (96 women) or 10 mg per day (98 women) or to receive placebo (48 women). All patients received iron supplementation. The coprimary efficacy end points were control of uterine bleeding (PBAC score of <75) and reduction of fibroid volume at week 13, after which patients could undergo surgery.
At 13 weeks, uterine bleeding was controlled in 91% of the women receiving 5 mg of ulipristal acetate, 92% of those receiving 10 mg of ulipristal acetate, and 19% of those receiving placebo (P<0.001 for the comparison of each dose of ulipristal acetate with placebo). The rates of amenorrhea were 73%, 82%, and 6%, respectively, with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate. The median changes in total fibroid volume were -21%, -12%, and +3% (P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo, and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo). Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy. Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate (uterine hemorrhage) and in one patient during receipt of placebo (fibroid protruding through the cervix). Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo.
Treatment with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids. (Funded by PregLem; ClinicalTrials.gov number, NCT00755755.).
Endometriosis is a common, benign and chronic gynecological disorder. It is also an estrogen-dependent disorder that can result in substantial morbidity, including pelvic pain, pro gressive dysmenorrhea, dyspareunia, infertility and repeat surgeries. Endometriosis is often treated surgically upon diag nosis but with a higher rate of recurrence, suggesting that a combination of surgical and medical management might provide better outcomes. The primary goal of medical treatment for endometriosis is to halt the growth and activity of endometriosis lesions. The most widely utilized medical treat ment for endometriosis involves use of gonadotropin-releasing hormone (GnRH) agonists and oral contraceptives. Conventional agents also include androgen derivates and progestins. Due to the chronic nature of this disease, long-term or Dr. Hong-Yuan Huang repeated courses of medication may be required to control its related symptoms. Increasing knowledge about the pathogenesis of endometriosis at the cellular and molecular levels may give us the opportunity to use new, specific agents for treatment, including aromatase inhibitors, progesterone antagonists, selective progesterone receptor modulators, GnRH antagonists, intrauterine releasing systems with progestin and new pharmaceutical agents affecting inflammation, angiogenesis, and matrix metalloproteinase activity. Many of these promising new agents may prevent or inhibit the development of endometriosis. Further clinical trials may determine if these new therapies are superior to current medical treatment strategies for endometriosis.
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Клиника женского здоровья, гинекологии и акушерства проф. Эберта; адрес: Германия, 10787, г. Берлин, Нюрнбергер Штр. 67; тел
- Andreas D Ebert
Andreas D. Ebert, Клиника женского здоровья, гинекологии и акушерства проф.
Эберта; адрес: Германия, 10787, г. Берлин, Нюрнбергер Штр. 67; тел.: +7(923)2872131;
Phone: +7(923)2872131; e-mail: info@prof-ebert.d Vitaly B. Tskhai, Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str
- Andreas D Ebert
Andreas D. Ebert, Praxis of female health, gynecology and obstetrics; Address: Nürnberger Str.
67, Berlin, Germany, 10787; Phone: +7(923)2872131; e-mail: info@prof-ebert.d
Vitaly B. Tskhai, Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address:
1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation, 660022; Phone: +7 (39422)33467;
Phone: +49 3045050; webmaster(at)charite.de Islam Magalov
- David Matthias
David Matthias, University hospital charité Berlin; Address: Augustenburger Platz 1, Berlin,
Germany, 13353; Phone: +49 3045050; webmaster(at)charite.de
Islam Magalov, Azerbaijan Medical University; Address: 23, Bakixanov Str., Baku, Azerbaijan,
АZ1022; Phone: (+994 012) 4390858, e-mail: bsu@bsu.az
Russian Federation, 236016 ; Phone: +7 (4012)338217; post@kantiana.ru Tatyana A. Makarenko, Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str
- Alexander I Pashov
Alexander I. Pashov, Immanuel Kant Baltic Federal University; Address: 14, Alexander Nevsky
Str., Kaliningrad, Russian Federation, 236016 ; Phone: +7 (4012)338217; post@kantiana.ru
Tatyana A. Makarenko, Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical
University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation, 660022;
Phone: +7 (39422)33467; e-mail: makarenko7777@yandex.ru
Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str
- Daria E Nikiforova
- V F Professor
Daria E. Nikiforova, Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation, 660022;
Phone: +7 (39422)33467; e-mail: dashsemch@mail.ru
Поступила 12.09.2017 г.
Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice
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TH. Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice. Angiogenesis. 2013;(16):59-69. DOI:10.1007/
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