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      Clinical Efficacy of Dienogest versus Levonorgestrel-Releasing Intrauterine System for Adenomyosis

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          Abstract

          Objective

          The aim of this study is to evaluate the efficacy of dienogest versus levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis.

          Methods

          In this retrospective study, 85 patients with adenomyosis treated in The First Affiliated Hospital of Zhengzhou University from May 2019 to May 2021 were recruited and assigned, via the random number table method at a ratio of 1 : 1, to receive either dienogest (observation group, n = 41) or LNG-IUS (control group, n = 44). The patients presented with dysmenorrhea, menorrhagia, and infertility. The treatment outcome was evaluated using visual analogue scale (VAS) scores, menstrual volume, uterine volume, endometrial thickness, and adverse reactions.

          Results

          After treatment, the VAS score, menstrual volume, and endometrial thickness were significantly decreased in both groups ( P < 0.05). After 3, 6, and 12 months of treatment, patients receiving dienogest showed significantly lower VAS scores compared to those treated with LNG-IUS ( P < 0.05). After 6 and 12 months of treatment, patients receiving dienogest were also found to have a significantly better control of menstrual volume compared to those receiving LNG-IUS ( P < 0.05). Irregular vaginal bleeding was mainly seen in the first 3 months of treatment with dienogest. The incidence of irregular vaginal bleeding lasting more than 6 months was lower with LNG-IUS treatment than with dienogest ( P < 0.05), and it decreased in both groups as the duration of treatment increased.

          Conclusion

          Dienogest effectively alleviates dysmenorrhea, relieves pelvic pain, dyspareunia, and reduces menstrual flow in patients with adenomyosis, with few adverse effects and a high safety profile.

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          Most cited references16

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          Comparative responsiveness of verbal and numerical rating scales to measure pain intensity in patients with chronic pain.

          Verbal rating scale (VRS) and numerical rating scale (NRS) are regularly used to assess and monitor pain in chronic pain patients. Although the NRS has been generally preferred, limited comparative responsiveness evidence was reported. This study compared the responsiveness of VRS and NRS measuring current pain and investigated the influence of different references (ie, worst, least, average, and current pain or their composite) on the NRSs' responsiveness. Two hundred fifty-four chronic pain patients attended a 10-day pain self-management program and were assessed with two 6-point VRSs (assessing current pain) and four 11-point NRSs (assessing worst, least, average, and current pain) at pre- and posttreatment. A patient-reported rating of pain improvement was used as the criterion for standardized response mean and receiver operating characteristic curve analyses. Results showed that the VRSs and NRSs exhibited small responsiveness in all patients, but the magnitude of responsiveness became moderate to large in patients with improved pain. However, in patients with pain improvements, the NRS current pain item and composite score (made up of the 4 pain items) were found to have significantly larger responsiveness and greater discriminatory ability to detect the presence of improvement than other current pain VRSs and the NRSs assessing worst, least, and average pain. Potential implications for clinical practice are discussed.
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            Role of angiogenesis in adenomyosis-associated abnormal uterine bleeding and subfertility: a systematic review

            Abstract Background Adenomyosis commonly occurs with abnormal uterine bleeding (AUB) and is associated with subfertility and a higher miscarriage rate. Recent evidence showed abnormal vascularization in the endometrium in patients with adenomyosis, suggesting a role of angiogenesis in the pathophysiology of AUB and subfertility in adenomyosis and providing a possible treatment target. Objective and rationale We hypothesized that the level of abnormal vascularization and expression of angiogenic markers is increased in the ectopic and eutopic endometrium of adenomyosis patients in comparison with the endometrium of control patients. This was investigated through a search of the literature. Search methods A systematic search was performed in PubMed and Embase until February 2019. Combinations of terms for angiogenesis and adenomyosis were applied as well as AUB, subfertility or anti-angiogenic therapy. The main search was limited to clinical studies carried out on premenopausal women. Original research articles focusing on markers of angiogenesis in the endometrium of patients with adenomyosis were included. Studies in which no comparison was made to control patients or which were not published in a peer-reviewed journal were excluded. A second search was performed to explore the therapeutic potential of targeting angiogenesis in adenomyosis. This search also included preclinical studies. Outcomes A total of 20 articles out of 1669 hits met our selection criteria. The mean vascular density (MVD) was studied by quantification of CD31, CD34, von Willebrand Factor (vWF) or factor-VIII-antibody-stained microvessels in seven studies. All these studies reported a significantly increased MVD in ectopic endometrium, and out of the six articles that took it into account, four studies reported a significantly increased MVD in eutopic endometrium compared with control endometrium. Five articles showed a significantly higher vascular endothelial growth factor expression in ectopic endometrium and three articles in eutopic endometrium compared with control endometrium. The vascular and pro-angiogenic markers α-smooth muscle actin, endoglin, S100A13, vimentin, matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, tissue factor (TF), DJ-1, phosphorylated mammalian target of rapamycin, activin A, folli- and myostatin, CD41, SLIT, roundabout 1 (ROBO1), cyclooxygenase-2, lysophosphatidic acid (LPA) 1,4-5, phospho signal transducer and activator of transcription 3 (pSTAT3), interleukin (IL)-6, IL-22 and transforming growth factor-β1 were increased in ectopic endometrium, and the markers S100A13, MMP-2 and -9, TF, follistatin, myostatin, ROBO1, LPA1 and 4-5, pSTAT3, IL-6 and IL-22 were increased in eutopic endometrium, compared with control endometrium. The anti-angiogenic markers E-cadherin, eukaryotic translation initiation factor 3 subunit and gene associated with retinoic-interferon-induced mortality 19 were decreased in ectopic endometrium and IL-10 in eutopic endometrium, compared with control endometrium. The staining level of vWF and two pro-angiogenic markers (NF-κB nuclear p65 and TF) correlated with AUB in patients with adenomyosis. We found no studies that investigated the possible relationship between markers of angiogenesis and subfertility in adenomyosis patients. Nine articles reported on direct or indirect targeting of angiogenesis in adenomyosis—either by testing hormonal therapy or herbal compounds in clinical studies or by testing angiogenesis inhibitors in preclinical studies. However, there are no clinical studies on the effectiveness of such therapy for adenomyosis-related AUB or subfertility. Wider implications The results are in agreement with our hypothesis that increased angiogenesis is present in the endometrium of patients with adenomyosis compared with the endometrium of control patients. It is likely that increased angiogenesis leads to fragile and more permeable vessels resulting in adenomyosis-related AUB and possibly subfertility. While this association has not sufficiently been studied yet, our results encourage future studies to investigate the exact role of angiogenesis in the etiology of adenomyosis and related AUB or subfertility in women with adenomyosis in order to design curative or preventive therapeutic strategies.
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              Adenomyosis: a systematic review of medical treatment.

              Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however, patients can also be asymptomatic. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies, such as transvaginal ultrasound and magnetic resonance imaging. The aim of this review is to discuss the medical approach to the management of adenomyosis symptoms, including pain and abnormal uterine bleeding. The standard treatment of adenomyosis is hysterectomy, but there is no medical therapy to treat the symptoms of adenomyosis while still allowing patients to conceive. Medical therapies using suppressive hormonal treatments, such as continuous use of oral contraceptive pills, high-dose progestins, selective oestrogen receptor modulators, selective progesterone receptor modulators, the levonorgestrel-releasing intrauterine device, aromatase inhibitors, danazol, and gonadotrophin receptor hormone agonists can temporarily induce regression of adenomyosis and improve the symptoms.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2022
                15 July 2022
                15 July 2022
                : 2022
                : 1995472
                Affiliations
                Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                Author notes

                Academic Editor: Xiaonan Xi

                Author information
                https://orcid.org/0000-0001-8536-5735
                https://orcid.org/0000-0001-6474-4648
                Article
                10.1155/2022/1995472
                9307342
                35873621
                b29dd3e6-fb80-49ae-b598-af8d0bfc4294
                Copyright © 2022 Siyuan Yang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 April 2022
                : 30 May 2022
                : 6 June 2022
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81903114
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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