Levonorgestrel-releasing intrauterine system for endometrial hyperplasia

Mittermeier, Theresa; Farrant, Charlotte; Wise, Michelle

doi:10.1002/14651858.cd012658.pub2

Cited by 44 publications

(47 citation statements)

References 45 publications

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“…Most experience is with oral progestin but its systemic side effects, including thromboembolic disease and weight gain [23,24], compromise its suitability for an obesity-driven cancer. The LNG-IUS delivers progestin directly to the endometrium at a steep concentration gradient and constant rate that keeps serum levels low and avoids the peaks and troughs of oral administration [25], with high success rates [24,[26][27][28]. A prospective study of intrauterine progestin reported treatment responses in 91% of 37 patients with atypical hyperplasia and 67% of 20 patients with endometrial cancer at 12 months [8].…”

Section: Discussionmentioning

confidence: 99%

Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium

Barr

Ryan

Derbyshire

et al. 2021

Cancer Prevention Research

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Intrauterine progestin is a treatment option for women with atypical hyperplasia or low-risk endometrial cancer who wish to preserve their fertility, or whose poor surgical fitness precludes safe hysterectomy. We hypothesized that in such women with obesity, weight loss during progestin treatment may improve oncological outcomes. We conducted a prospective non-randomized study of women with obesity and atypical hyperplasia or low-grade stage 1a endometrial cancer undergoing progestin treatment. Women with a BMI≥35kg/m 2 were offered bariatric surgery; those who declined and those with BMI 30-34.9kg/m 2 were encouraged to lose weight by low-calorie diet. We assessed uptake of bariatric surgery; weight lost during progestin treatment; and the impact of >10% total body weight loss on progestin treatment response at 12 months. 71 women [median age 58years (IQR 35-65); mean BMI 48kg/m 2 (SD 9.3)] completed the study. 23 women (32%) had bariatric surgery, on average 5 months (IQR 3-8) after progestin treatment commenced. Weight change during progestin treatment was -33.4kg (95%CI -42.1, -24.7) and -4.6kg (95%CI -7.8, -1.4) in women receiving bariatric surgery and low-calorie diet, respectively (p<0.001). 43 women (61%) responded to progestin, while 23 (32%) showed stabilized and 5 (7%) progressive disease. Response at 12 months was not predicted by age or baseline BMI, but women who lost >10% of their total body weight were more likely to respond to progestin than those who did not (adjusted odds ratio 3.95; 95%CI 1.3, 12.5; p=0.02). Thus weight loss may improve oncological outcomes in women with obesity-associated endometrial neoplastic abnormalities treated with progestin.

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Section: Discussionmentioning

confidence: 99%

Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium

Barr

Ryan

Derbyshire

et al. 2021

Cancer Prevention Research

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“…In clinical studies, both monotherapy with progestins and their combinations with other antitumor agents have been examined. The results of some trials indicated the effectiveness of cancer therapy with the application of progestins [ 15 , 16 , 17 , 18 ].…”

Section: Gestagens As Cytotoxic Drugs Possible Mechanisms and Targetsmentioning

confidence: 99%

Progestins as Anticancer Drugs and Chemosensitizers, New Targets and Applications

Федотчева

Shimanovsky

2021

Pharmaceutics

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Progesterone and its synthetic analogues, progestins, participate in the regulation of cell differentiation, proliferation and cell cycle progression. Progestins are usually applied for contraception, maintenance of pregnancy, and hormone replacement therapy. Recently, their effectiveness in the treatment of hormone-sensitive tumors was revealed. According to current data, the anticancer activity of progestins is mainly mediated by their cytotoxic and chemosensitizing influence on different cancer cells. In connection with the detection of previously unknown targets of the progestin action, which include the membrane-associated progesterone receptor (PR), non-specific transporters related to the multidrug resistance (MDR) and mitochondrial permeability transition pore (MPTP), and checkpoints of different signaling pathways, new aspects of their application have emerged. It is likely that the favorable influence of progestins is predominantly associated with the modulation of expression and activity of MDR-related proteins,the inhibition of survival signaling pathways, especially TGF-β and Wnt/β-catenin pathways, which activate the proliferation and promote MDR in cancer cells, and the facilitation of mitochondrial-dependent apoptosis. Biological effects of progestins are mediated by the inhibition of these signaling pathways, as well as the direct interaction with the nucleotide-binding domain of ABC-transporters and mitochondrial adenylate translocase as an MPTP component. In these ways, progestins can restore the proliferative balance, the ability for apoptosis, and chemosensitivity to drugs, which is especially important for hormone-dependent tumors associated with estrogen stress, epithelial-to-mesenchymal transition, and drug resistance.

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“…use [123], it is one of the most cost-effective reversible contraceptive methods [124]. LNG-IUD has anti-proliferative effects on the endometrium, and has been shown to be superior to nonintrauterine progestins at reversing endometrial hyperplasia [125]. Although declining plasma levonorgestrel concentrations were reported with a longer duration of use and higher BMI [126], it was still more effective than oral progestins in the treatment of endometrial hyperplasia in obese subjects [127].…”

Section: Article In Pressmentioning

confidence: 99%

An Update on Contraception in Polycystic Ovary Syndrome

Oğuz

Yildiz

2021

Endocrinol Metab

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology. Combined oral contraceptives (COCs), along with lifestyle modifications, represent the first-line medical treatment for the long-term management of PCOS. Containing low doses of estrogen and different types of progestin, COCs restore menstrual cyclicity, improve hyperandrogenism, and provide additional benefits such as reducing the risk of endometrial cancer. However, potential cardiometabolic risk associated with these agents has been a concern. COCs increase the risk of venous thromboembolism (VTE), related both to the dose of estrogen and the type of progestin involved. Arterial thrombotic events related to COC use occur much less frequently, and usually not a concern for young patients. All patients diagnosed with PCOS should be carefully evaluated for cardiometabolic risk factors at baseline, before initiating a COC. Age, smoking, obesity, glucose intolerance or diabetes, hypertension, dyslipidemia, thrombophilia, and family history of VTE should be recorded. Patients should be re-assessed at consecutive visits, more closely if any baseline cardiometabolic risk factor is present. Individual risk assessment is the key in order to avoid unfavorable outcomes related to COC use in women with PCOS.

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Levonorgestrel-releasing intrauterine system for endometrial hyperplasia

Cited by 44 publications

References 45 publications

Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium

Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium

Progestins as Anticancer Drugs and Chemosensitizers, New Targets and Applications

An Update on Contraception in Polycystic Ovary Syndrome

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