Efficacy of Estrogen Therapy in Patients With Intrauterine Adhesions: Systematic Review

Johary, Jolinda; Xue, Min; Zhu, Xiaogang; Xu, Dabao; Velu, Prasad Palani

doi:10.1016/j.jmig.2013.07.018

Cited by 169 publications

(112 citation statements)

References 61 publications

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“…21 In China, it has been reported that about 7% of cases of secondary amenorrhea and 40% of cases of infertility are caused by IUA, which remains a severe threat to reproductive women. 2 Over the decades, many experimental studies have focused on the regeneration of endometrium and on the prevention of scar reformation. One of the traditional therapeutic approaches for intrauterine adhesions is placing an IUD in the uterine cavity.…”

Section: Discussionmentioning

confidence: 99%

“…1 IUA increases the risk of menstrual abnormalities, secondary infertility, recurrent miscarriage, and pregnancy complications. 2 Common treatments include hysteroscopic adhesiolysis and administration of hormonal drugs to promote the regeneration of the endometrial tissue. However, readhesion and side effects frequently occur.…”

Section: Introductionmentioning

confidence: 99%

“…12 Evidence from many studies indicates that the application of estrogen therapy in patients with IUA results in satisfactory outcomes. 2 However, 17β-estradiol, by either oral delivery or systemic administration, imposes restrictions on its clinical use because of its limited half-life period in vivo, poor solubility in aqueous solutions, and low concentrations at the injured endometrium. Therefore, it may be important to enhance local concentrations to improve the efficacy of 17β-estradiol.…”

Section: Introductionmentioning

confidence: 99%

“…25 A recent systematic review provided sufficient evidence that the administration of estrogen could reduce reformation of IUA by promoting endometrial repair and covering the denuded endometrial layer. 2 Moreover, many studies revealed that using estrogen therapy alone as ancillary treatment was associated with satisfactory outcomes. The restoration of menstrual flow and pregnancy rate was substantially increased when compared with the group that did not receive any hormone therapy.…”

mentioning

confidence: 99%

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Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

Zhang¹,

Xia²,

Xu³

et al. 2017

IJN

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Intrauterine adhesions (IUA) frequently occur after infectious or mechanical injury to the endometrium, which may lead to infertility and/or pregnancy complications. There are few effective treatments due to the complex function of endometrium and shortage of native materials. 17β-estradiol (E 2 ) is commonly used as an ancillary treatment in IUA patients, but it is limited by its poor solubility in aqueous solutions and low concentrations at the injured sites. In this research, a mini-endometrial curette was used to injure the rat’s endometrium to form an IUA model. 17β-estradiol was encapsulated into the micelles of heparin-poloxamer and a thermosensitive hydrogel (E 2 -HP hydrogel) was formed. This sustained releasing system was applied to restore the structure and function of the injured uterus. E 2 -HP hydrogel was constructed and relevant characteristics including gelation temperature and micromorphology were evaluated. Sustained release of 17β-estradiol from HP hydrogel was performed both in vitro and in vivo. Ultrasonography measurement and pathologic characteristics on the IUA rats were performed to evaluate the therapeutic effect of E 2 -HP hydrogel. Endoplasmic reticulum (ER) stress-related apoptosis was analyzed to explore the possible mechanisms in IUA recovery. E 2 -HP hydrogel showed a prolonged release of E 2 at the targeting region and more effective endometrium regeneration in IUA rats. Significant improvements in both gland numbers and fibrosis area were observed in the E 2 -HP hydrogel group. We also demonstrated that E 2 -HP hydrogel in the recovery of IUA was closely related to the suppression of ER stress signals via the activation of downstream signals, PI3K/Akt and ERK1/2. HP hydrogel might be an effective approach to deliver E 2 into the injured endometrium. Therapeutic strategies targeting ER stress using E 2 -HP hydrogel might be a promising solution for the treatment of women with intrauterine adhesions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

Zhang¹,

Xia²,

Xu³

et al. 2017

IJN

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“…Estrogen is the most important female sex hormone, which serves pivotal functions in the regulation and development of the reproductive system of females and the formation of secondary sex characteristics. It has been reported that postoperative estrogen therapy may be used to prevent recurrent adhesions (6). However, the recurrence rate of IUA accounted for 62.5% in patients with severe IUAs (7).…”

Section: Introductionmentioning

confidence: 99%

Effects of endometrial stem cell transplantation combined with estrogen in the repair of endometrial injury

et al. 2018

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Abstract. The present study investigated the effects of endometrial stem cell (EnSCs) transplantation combined with estrogen in the repair of endometrial injury. A total of 30 patients with intrauterine adhesions (IUA) and 30 healthy individuals were selected. Expression of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-BB in endometrial tissue was assessed. Additionally, expression levels of epithelial membrane antigen (EMA), cytokeratin (CK), integrin α-6 (CD49f), Thy-1 membrane glycoprotein (THY-1), collagen type 1 (Col I), fibroblast (5B5) and vimentin in EnSCs were detected using western blot analysis and reverse transcription-quantitative polymerase chain reaction. A rat model of IUA was established and female rats were divided into the control, model, EnSCs, estrogen and estrogen plus EnSCs (E+EnSCs) groups. Blood was extracted at 1 and 5 weeks post-treatment, and serum levels of transforming growth factor (TGF)-β1, EGF, 17 β-estradiol (E2) and PDGF-BB were measured using ELISA. Hematoxylin and eosin staining was performed to observe the pathological changes of endometrial tissue in rats. Western blot analysis was used to detect the expression of estrogen receptor (ESR1) and matrix metalloproteinase (MMP)-9 in the endometrium. The results revealed that patients with IUA exhibited increased expression levels of EGF and PDGF-BB compared with those in control group. Additionally, EnSCs exhibited significantly increased expression levels of EMA, CD49f, CK, Col I, THY-1, 5B5 and vimentin compared with the remaining groups. An increased number of newly formed glands was observed in the E+EnSCs group compared with that in the EnSCs group.Increased levels of E2, but decreased levels of TGF-β1, EGF, PDGF-BB, ESR1 and MMP-9 were detected in EnSCs and estrogen groups compared with those in E+EnSCs group. These results suggest that EnSCs transplantation combined with estrogen could improve endometrial abnormalities. IntroductionIntrauterine adhesions (IUA) refer to the endometrial fibrosis caused by endometrial injury in operative hysteroscopy (1). Endometrial injuries may lead to recurrent miscarriages, infertility, amenorrhea, abnormal placentation, dysmenorrhea and abnormal uterine bleeding, thus being detrimental to the health of affected women (2). Expression levels of transforming growth factor (TGF)-β1, epidermal growth factor (EGF), basic fibroblast growth factor and platelet-derived growth factor (PDGF)-BB were found to be significantly increased in exudates in patients with IUA following surgery (3,4), which in turn promoted the growth of fibroblasts and the formation of adhesions. Despite advances in intraoperative techniques, including minimizing trauma of the healthy myometrium and endometrium, and reducing the usage of electrosurgery (5), the incidence of IUA caused by surgery remains high. Therefore, the development of novel approaches to inhibit the formation of post-surgical IUA is required.A variety of novel therapies for IUA have been developed. Estrogen is the most importa...

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Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility

Bosteels¹,

Weyers

Kasius

et al. 2015

Cochrane Database of Systematic Reviews

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Implications for clinical practiceThe quality of the evidence retrieved was low or very low for all outcomes. Clinical effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for researchAdditional studies are needed to assess the effectiveness of different anti-adhesion therapies for improving reproductive outcomes in subfertile women treated by operative hysteroscopy.

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Efficacy of Estrogen Therapy in Patients With Intrauterine Adhesions: Systematic Review

Cited by 169 publications

References 61 publications

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

Effects of endometrial stem cell transplantation combined with estrogen in the repair of endometrial injury

Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility

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Efficacy of Estrogen Therapy in Patients With Intrauterine Adhesions: Systematic Review

Cited by 169 publications

References 61 publications

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17&beta;-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17&beta;-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

Effects of endometrial stem cell transplantation combined with estrogen in the repair of endometrial injury

Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility

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Product

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Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model