Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management

Nwanodi, Oroma

doi:10.3390/healthcare5030030

Cited by 8 publications

(6 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been well established that metformin restrains EH via mTOR pathway modulation [ 110 ], as it activates AMPK, a significant negative regulator of mTOR signaling [ 111 ]. In PCOS, metformin can increase GLUT-4 and reduce androgen receptor (AR) levels in the endometrium, probably through the mTOR pathway [ 106 , 112 ].…”

Section: Mtor and Eif Signaling In Benign Endometrial Diseasesmentioning

confidence: 99%

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Driva

Schatz

Sobočan

et al. 2022

IJMS

View full text Add to dashboard Cite

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.

show abstract

Section: Mtor and Eif Signaling In Benign Endometrial Diseasesmentioning

confidence: 99%

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Driva

Schatz

Sobočan

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…In addition, for some patients with EC, surgical treatment appears to be unsuitable because of morbid obesity and other serious complications. Recently, several studies on the non-surgical treatment of EC have revealed new insights into this malignancy (12,13). Progestin and metformin are promising candidates as therapeutic agents for EC treatment (14).…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of metformin and medroxyprogesterone 17‑acetate on the development of endometrial cancer

Dong

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

Accumulating data indicate that insulin resistance and unopposed estrogen are important risk factors of endometrial cancer (EC). Medroxyprogesterone 17‑acetate (MPA) has been used in the treatment of EC for many years. However, the therapeutic effect of this agent on EC has not been satisfactory. 36 arMetformin was recently reported to be a promising agent for the treatment of malignant diseases including EC. However, information on the synergistic effect of the two agents in EC is limited. With the aim to evaluate the synergistic effect of metformin and MPA, we conducted the present study in vitro and in vivo. We found that the combined application of metformin and MPA significantly inhibited the proliferation of the Ishikawa cells and arrested the cells in the G0/G1 phase. Furthermore, the apoptosis rate of the Ishikawa cells was significantly increased. In the animal study, the development of the xenograft tumors was significantly suppressed by the combined application of the two agents. Further investigation revealed that the synergistic inhibitory effect of the two agents on EC can be at least partly, explained by the decreased expression of cyclin D1 and cyclin E. The results of the current study provide novel insights into the treatment of EC.

show abstract

“…The insulin-mediating effects of metformin have shown evidence of reducing the incidence of malignancies and improving patient survival ( 12 , 35 , 38 ). In addition, metformin has the potential to increase progestin-driven anti-proliferative mechanisms ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

A Prospective Cohort Study of Metformin as an Adjuvant Therapy for Infertile Women With Endometrial Complex Hyperplasia/Complex Atypical Hyperplasia and Their Subsequent Assisted Reproductive Technology Outcomes

Kong

Liu²,

Zhang

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

ObjectiveTo investigate the adjuvant efficacy of metformin treatment to achieve pathological complete response (CR) in patients with endometrial complex hyperplasia (CH) and complex atypical hyperplasia (CAH), and secondarily, to evaluate their pregnancy outcomes after following assisted reproductive technology (ART).Study DesignThis prospective cohort study analyzed 219 patients diagnosed with infertility and CH/CAH from January 2016 to December 2020. Among these patients, 138 were assigned to the control group (progesterone alone) and 81 were assigned to the study group (progesterone+metformin). After 8/12 weeks of therapy, the treatment responses were assessed by histological examination of curettage specimens obtained by hysteroscopy. Once the pathological results indicated CR, the patients were able to receive ART. The ART treatment and follow-up data of these patients were collected and analyzed.Results116 patients in the control group achieved CR, compared with 76 patients in the study group. The CR rate in the control group was significantly lower than that in the study group (P=0.034). We then divided the patients into subgroups to compare the treatment responses. In the subgroup analyses, patients with body mass index (BMI) ≥25 kg/m2 and patients with polycystic ovarian syndrome (PCOS) had higher CR rates in the metformin group compared with the control group (P=0.015, P=0.028 respectively). Subsequently, 68 patients in the control group and 47 patients in the study group received an ART cycle. We examined the pregnancy indications and found no significant differences in the clinical pregnancy rate and live birth rate between the two groups (P>0.05).ConclusionRegression of CH/CAH may be improved by progesterone+metformin compared with progesterone alone. The effect was particularly pronounced in patients with BMI ≥25 kg/m2 and patients with PCOS. Metformin had no obvious effect on subsequent ART outcomes. The trial is registered on the publicly accessible website:Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=15372, identifier ChiCTR-ONR-16009078.

show abstract

Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management

Cited by 8 publications

References 24 publications

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Synergistic effect of metformin and medroxyprogesterone 17‑acetate on the development of endometrial cancer

A Prospective Cohort Study of Metformin as an Adjuvant Therapy for Infertile Women With Endometrial Complex Hyperplasia/Complex Atypical Hyperplasia and Their Subsequent Assisted Reproductive Technology Outcomes

Contact Info

Product

Resources

About