Dienogest, a synthetic progestin, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a spheroid culture system

Shimizu, Yutaka; Mita, Shizuka; Takeuchi, Takashi; Notsu, Tatsuto; Mizuguchi, Kiyoshi; Kyo, Satoru

doi:10.1016/j.steroids.2010.08.010

Cited by 62 publications

(38 citation statements)

References 33 publications

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“…Although there was no statistically significant difference between the groups (p = 0.39), the highest resolution and regression rate (complete response) was in the DIE group. DIE not only behaves like a progesteron but also inhibits PGE2 production and aromatase expression in human endometrial epithelial cells [9]. Additionally, the proliferation of human immortalized endometrial epithelial cells was restricted by DIE with the help of the suppressing effect on levels of cyclin D1 [20].…”

Section: Discussionmentioning

confidence: 99%

“…Dienogest (DIE), which is a new generation (4th class) of oral progestins, is used in the treatment of endometriosis [8]. Shimizu et al [9] has also concluded that DIE may be considered effective treatment for gynecological diseases associated with abnormal endometrial proinflammatory and proliferative activities [10]. In another study, Kodama et al [11] investigated the efficacy of DIE in thinning the endometrium before hysteroscopic surgery.…”

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confidence: 99%

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The Efficacy of Dienogest in the Treatment of Simple Endometrial Hyperplasia without Atypia

Uysal

Açmaz²,

Madendağ³

et al. 2017

Gynecol Obstet Invest

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Aim: The aim of the study was to compare the effectiveness of dienogest (DIE), depo medroxyprogesterone 17-acetate (MPA), and micronized progesteron (MP) regimens for treatment of simple endometrial hyperplasia (EH) without atypia. Methods: One hundred and twenty premenopausal patients aged between 35 and 55, with simple EH without atypia, were offered 3 types of progestins (MPA, MP, and DIE) and were randomized to one of them. After 6 months of treatment, patients were reevaluated. The efficacy of different progestins in treatment of EH was compared with regard to resolution and regression rates. We classified the terms of resolution and regression as “complete response” and persistence as “no response”. Results: A total of 99 patients continued the study (31 in MP, 35 in MPA, and 33 in the DIE group). None of the results of endometrial pathology were progressed to atypia or complex hyperplasia. The complete response resolution rate was 93.5% in the MP, 88.5% in the MPA, and 96.9% in the DIE group. The highest complete response rate was in the DIE group, although there was no statistically significant difference between groups (p = 0.39). The efficacy of progestins was similar between the groups. Conclusion: DIE is an effective and convenient method for thinning the endometrium.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Efficacy of Dienogest in the Treatment of Simple Endometrial Hyperplasia without Atypia

Uysal

Açmaz²,

Madendağ³

et al. 2017

Gynecol Obstet Invest

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“…COX-1 and mPGES-1 are abundantly expressed in endometrial epithelial cells and epithelial cancer tissue, suggesting that PGE 2 serves as a major mediator involved in pathophysiology and pathogenesis of gynecologic diseases accompanied by abnormal growth or inflammation of endometrium. Shimizu et al, mentioned above, evaluated the influence of dienogest on PGE 2 formation, reporting that dienogest inhibited PGE 2 formation and this inhibitory action was lifted by PR antagonist RU-486 (49). In that report, dienogest was shown to inhibit the expression of PGE 2 synthase mRNA and protein as well as NF-κB activity, with such activity remaining to be seen 24 h after treatment.…”

Section: Applicability Of Dienogest To Treatment Of Endometrial Cancermentioning

confidence: 99%

Progestin therapy for endometrial cancer: The potential of fourth-generation progestin (Review)

et al. 2012

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Abstract. Progestin preparations are made of synthetic progesterone and have often been used for hormone therapy in gynecological patients with endometriosis or endometrial cancer. Hormone therapy using progestin is considered to be one of the effective means of treatment particularly when dealing with endometrial cancer (an estrogen-dependent tumor). Numerous reports have been published concerning its efficacy in advanced or recurrent cases of atypical endometrial hyperplasia or endometrial cancer. Dienogest has been developed as a fourth-generation progestin for hormone therapy for endometriosis that can be used with high safety for long periods of time. In Japan, dienogest has been recommended as a first-line drug for endometriosis-associated pain. However, its antitumor activity has also been attracting close attention following a report that this drug suppressed the proliferation in vitro of endometrial cancer-derived cell lines which failed to respond to other progestins such as medroxyprogesterine acetate (MPA). The mechanism for antitumor activity of dienogest is considered to differ from the mechanism for antitumor activity of conventional progestin preparations used for treatment of endometrial cancer. This drug is expected to be clinically applicable as a new drug for the treatment of endometrial cancer. Contents

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“…Вероятно, это связано с меньшими, по сравнению с НПВС ингибиторами ЦОГ-1 и ЦОГ-2, анальгетически-ми эффектами. К тому же появился ряд статей, указывающих, что длительное или неконтро-лируемое использование селективных НПВС может приводить к нелетальным инфарк там, тромбозам [9,10,20] [22]. В 2008 г. группа ис-следователей под руководством C. Olivares на основании рандомизированного исследования установила опти мальную дозировку целекок-сиба 100 мг [23].…”

Section: The Efficacy Of Selective Cyclooxygenase 2 Inhibitors In Theunclassified

The efficacy of selective cyclooxygenase 2 inhibitors in the treatment of genital endometriosis

et al. 2018

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External genital endometriosis is characterized by the processes of angiogenesis, neurogenesis, impaired apoptosis, local inflammation of the tissues, secretion of estradiol, and cell proliferation. In a similar manner, prostaglandin E2 affects tissues. The safest drugs that overwhelm COX-2 activity and inhibit the expression of prostaglandin E2 are selective COX-2 inhibitors. As a mediator of inflammation, prostaglandin E2 is involved in all inflammatory processes. It induces the expression of local P450 aromatase and the anti-apoptotic gene Bcl-2. E2 also possesses immunosuppressive-mediated activity and inhibits the synthesis of cytokines IFNγ, TNFα, and IL-12, IL-1β-mediated expression of chemokines, the proliferation of T- and B-cells and reduces the cytotoxic activity of NK cells, creating a background of the immunosuppressive characteristic of endometriosis [1–3]. This study included 100 patients of reproductive age (aged 22-35 years) with a confirmed diagnosis of external genital endometriosis of degree II–IV. Fifty patients received 100 mg of celecoxib in monotherapy and in combination with 2 mg of dienoguest. The control group included 50 people receiving monotherapy with 2 mg of dienogest. The effectiveness of therapy was assessed using the visual analog scale (VAS) and on the basis of the dynamics of algodismenorrhea, pain during coitus, clinical examination, and the patient’s subjective assessment of the degree of irritability and severity of depressive syndrome. The effectiveness of the treatment was evaluated according to MRI and ultrasound of the pelvic organs throughout the study. To control for possible complications of the therapy, the patients performed a comprehensive dynamic survey assessing the indicators of general blood analysis and the blood coagulation system. In the group with the combined application of celecoxib and dienoguest, a clinically significant reduction in pain syndrome and a decrease in the degree of irritability and depressive syndrome were noted relative to the control group. No side effects of celecoxib on the body systems were identified throughout the study. Thus, celecoxib can be recommended as a safe and effective combination therapy for endometriosis.

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Dienogest, a synthetic progestin, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a spheroid culture system

Cited by 62 publications

References 33 publications

The Efficacy of Dienogest in the Treatment of Simple Endometrial Hyperplasia without Atypia

The Efficacy of Dienogest in the Treatment of Simple Endometrial Hyperplasia without Atypia

Progestin therapy for endometrial cancer: The potential of fourth-generation progestin (Review)

The efficacy of selective cyclooxygenase 2 inhibitors in the treatment of genital endometriosis

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