Behavioral Weight Loss + Progestin for Endometrial Hyperplasia
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Washington University School of Medicine
Must be taking: Progestin
Disqualifiers: Chemotherapy, Radiation, Pregnant, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Up to 60% of endometrial cancer cases are attributed to obesity, in part because obesity promotes development of atypical endometrial hyperplasia (AEH), and up to 40% of women with AEH go on to develop endometrial cancer. The increasing prevalence of obesity in premenopausal women has resulted in increasing rates of AEH in this age group. Hysterectomy with removal of the fallopian tubes and ovaries is 100% effective in preventing endometrial cancer, but this approach results in infertility. Fertility-sparing treatments exist, such as treatment with oral or intrauterine progestin, but these treatments do not work uniformly and do not combat the underlying cause of endometrial cancer, which is obesity and metabolic syndrome. Additionally, up to 41% of women on progestin eventually experience relapse of AEH or endometrial cancer. Third, many patients have insulin resistance that may worsen with progestin therapy. Thus, to improve treatment of AEH and grade 1 endometrial cancer, prevent and reverse endometrial cancer, and allow women to preserve their fertility, the investigators must integrate an effective weight loss strategy to be given with progestin treatment. It is the hypothesis that premenopausal women with AEH desire uterine preservation will be more likely to have atypia-free uterine preservation at one year if they receive progestin in combination with a behavioral weight loss intervention versus progestin plus enhanced usual care.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are already on progestin therapy, you can continue with it as part of the study.
What data supports the effectiveness of the treatment for endometrial hyperplasia?
Research shows that using a levonorgestrel-releasing intrauterine system (a device placed in the uterus that releases hormones) can lower the risk of developing endometrial cancer by up to 50% compared to the general population. Additionally, weight loss during progestin treatment has been found to improve outcomes in women with obesity-related endometrial conditions.
12345Is the combination of behavioral weight loss and progestin treatment safe for humans?
The levonorgestrel-releasing intrauterine system (like Mirena) has been used safely for many years, showing benefits in reducing the risk of certain cancers, although there may be a slight increase in breast cancer risk. Intrauterine progestin treatments have shown a good safety profile, with favorable effects on endometrial protection and serum lipids, and are generally well-accepted by patients.
12346How is the treatment for endometrial hyperplasia using Levonorgestrel-releasing IUD and behavioral weight loss unique?
This treatment is unique because it combines a Levonorgestrel-releasing intrauterine device (IUD), which directly delivers medication to the uterus, with a telemedicine-based behavioral weight loss program. This approach not only targets the endometrial hyperplasia but also addresses obesity, a significant risk factor, potentially improving treatment outcomes and overall health.
15789Eligibility Criteria
This trial is for premenopausal women aged 18-45 with obesity (BMI ≥ 30) and a diagnosis of complex atypical endometrial hyperplasia or grade 1 endometrial cancer, who want to preserve their uterus. They should be able to have an IUD placed, may already be on progestin therapy for less than six months, and must not have been in a weight loss trial recently or currently receiving chemotherapy/radiation.Inclusion Criteria
I have AEH or grade 1 endometrial cancer and am on progestin therapy.
I have been diagnosed with a specific type of early-stage uterine cancer or pre-cancer.
I have taken or am currently taking progestin.
+9 more
Exclusion Criteria
I cannot use an IUD due to certain health conditions or allergies.
Prior participation in a weight loss intervention trial within 3 months prior to date of registration
I am not currently receiving chemotherapy or radiation for cancer.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a levonorgestrel-releasing IUD and either a behavioral weight loss intervention or enhanced usual care
12 months
Telemedicine sessions for behavioral coaching
Crossover
Participants in the enhanced usual care arm may cross over to the behavioral weight loss intervention if they have not achieved resolution of AEH or grade 1 endometrial cancer
12 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Participant Groups
The study tests if combining a behavioral weight loss intervention via telemedicine with progestin treatment is more effective in preserving the uterus without atypia compared to just progestin treatment plus enhanced usual care. Participants will also receive either oral progestin or a levonorgestrel-releasing IUD.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss InterventionExperimental Treatment3 Interventions
* The levonorgestrel-releasing IUD is used in this study as per standard care.
* The behavioral weight loss intervention consists of a telemedicine cognitive behavioral coaching program. At each session, patients will self-report weight, number of days they kept a food journal during the past week, average daily caloric intake for the week, number of days exercised for the week, total number of minutes of moderate physical activity, and average number of steps per day for the week.
Group II: Arm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual CareActive Control2 Interventions
* The levonorgestrel-releasing IUD is used in this study as per standard care.
* Participants will be provided with 1- to 3-page handouts on topics including healthy eating, exercise, and behavioral eating strategies from materials provided on the American Cancer Society, Society of Gynecologic Oncology, and WebMD Nourish websites. These materials encourage weight loss through calorie counting, recording dietary intake, engaging in exercise programs, and using portion control strategies.
* The participants randomized to this arm will cross over to the behavioral weight loss intervention arm at 12 months if they have not achieved resolution of AEH or grade 1 endometrial cancer.
Levonorgestrel-releasing IUD is already approved in European Union, United States, Canada, Australia for the following indications:
🇪🇺 Approved in European Union as Mirena for:
- Contraception
- Heavy menstrual bleeding
- Endometrial hyperplasia
- Endometrial cancer
🇺🇸 Approved in United States as Mirena for:
- Contraception
- Heavy menstrual bleeding
- Endometrial hyperplasia
🇨🇦 Approved in Canada as Mirena for:
- Contraception
- Heavy menstrual bleeding
- Endometrial hyperplasia
🇦🇺 Approved in Australia as Mirena for:
- Contraception
- Heavy menstrual bleeding
- Endometrial hyperplasia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
University of New MexicoAlbuquerque, NM
University of OklahomaOklahoma City, OK
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium. [2023]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 nonrandomized study of women with obesity and atypical hyperplasia or low-grade stage 1a endometrial cancer undergoing progestin treatment. Women with a body mass index (BMI) ≥ 35 kg/m2 were offered bariatric surgery; those who declined and those with a BMI of 30 to 34.9 kg/m2 were encouraged to lose weight by low-calorie diet. We assessed uptake of bariatric surgery; weight lost during progestin treatment; and the impact of more than 10% total body weight loss on progestin treatment response at 12 months. 71 women [median age 58 years (interquartile range; IQR 35-65); mean BMI 48 kg/m2 (SD 9.3)] completed the study. Twenty-three women (32%) had bariatric surgery, on average 5 months (IQR 3-8) after progestin treatment commenced. Weight change during progestin treatment was -33.4 kg [95% confidence interval (CI) -42.1, -24.7] and -4.6 kg (95% CI -7.8, -1.4) in women receiving bariatric surgery and low-calorie diet, respectively (P < 0.001). Forty-three 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 more than 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. PREVENTION RELEVANCE: This study found that weight loss improves response rates in women with obesity and atypical hyperplasia or low-risk endometrial cancer undergoing conservative management with intrauterine progestin. Given the additional benefits of weight loss for fertility, cardiovascular health and quality of life, future research should focus on how best to accomplish it.
Relapse of endometrial hyperplasia after conservative treatment: a cohort study with long-term follow-up. [2013]What is the risk of relapse for women with endometrial hyperplasia treated with levonorgestrel-releasing intrauterine system (LNG-IUS) or oral progestogens?
[Levonorgestrel-releasing intrauterine system Mirena® (Bayer) for the prevention and treatment of endometrial adenocarcinoma and the incidence of other malignancies in women]. [2019]The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 pg of levonorgestrel daily. Consequently the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrel-releasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.
Treatment of nonatypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system. [2019]A "frameless" intrauterine drug delivery system that releases 14 microg/d of levonorgestrel was used to treat nonatypical and atypical endometrial hyperplasia in 12 women.
Management of endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: single arm, prospective multicenter study: Korean gynecologic oncology group study (KGOG2006). [2016]A prospective multicenter trial has been commenced in Korea to investigate the treatment efficacy of the levonorgestrel-releasing intrauterine system in patients with endometrial hyperplasia. The levonorgestrel-releasing intrauterine system is an alternative to oral progesterone without the disadvantages of oral progestogens. Therefore, we hypothesize that if the therapeutic efficacy of the levonorgestrel-releasing intrauterine system is similar to or greater than that of oral progesterone, the levonorgestrel-releasing intrauterine system could become the standard treatment for endometrial hyperplasia patients who do not want a hysterectomy. The levonorgestrel-releasing intrauterine system is inserted into uteri of patients with histologically confirmed endometrial hyperplasia. An office endometrial aspiration biopsy and transvaginal ultrasound are conducted every 3 months at an outpatients clinic. The primary endpoint is the response rate. The secondary endpoint is to estimate the consistency of the results of the office endometrial aspiration biopsy during the levonorgestrel-releasing intrauterine system being placed in uterus and a dilatation and curettage procedure.
Intrauterine application of progestins in hormone replacement therapy: a review. [2019]The intrauterine application of progestins as endometrial protection against hyperstimulation by estrogen replacement therapy has been investigated in clinical trials since the early 1990s and one product has become available for this indication. This review considers the available published and presented reports on intrauterine use of progestin to date. Reports of 19 studies were reviewed. These studies included both peri- and postmenopausal women (826 in total), treated with different types of estrogens administered via various routes. Progesterone was used in two small studies, while all other studies used different doses of levonorgestrel for periods ranging from 6 months to more than 5 years. Endometrial effects, bleeding profiles, systemic effects (symptoms and metabolic), as well as clinical experience, were considered and were comparable to other forms of continuous combined hormone replacement therapy (HRT). It is concluded that the current evidence supports complete endometrial protection and a good safety profile. The observed bleeding profiles appear favorable but have not yet been directly compared with other forms of continuous combined HRT. A favorable effect on serum lipids has been observed and also awaits direct comparative confirmation. Progestin-attributable side-effects, effects on bone and breast tissues and other systemic effects have not yet been studied. Acceptance by patients has been good, while insertion did not present undue problems for the investigating physicians. Retention of the studied intrauterine systems has been very good. Intrauterine use of progestins, especially levonorgestrel, by purpose-designed systems as part of combined HRT, is a new way of administration and carries good benefits, while some aspects require more clinical evidence.
Effect of oral versus intrauterine progestins on weight in women undergoing fertility preserving therapy for complex atypical hyperplasia or endometrial cancer. [2016]The objective of this analysis was to evaluate weight changes associated with oral progestin therapies versus the levonorgestrel-containing intrauterine device (LNG-IUD) in women undergoing fertility-preserving therapy for complex atypical hyperplasia (CAH) and endometrial cancer (EMC).
The potential role of GLP-1 receptor agonist targeting in fertility-sparing treatment in obese patients with endometrial malignant pathology: a call for research. [2023]Most patients diagnosed with endometrial hyperplasia or cancer are obese. Obesity, along with polycystic ovarian syndrome (PCOS) and type-2 diabetes mellitus (T2DM), may act synergistically to increase risk of malignant endometrial pathology. Incidence of malignant endometrial pathology is increasing, particularly in reproductive aged women. In patients who desire future fertility, the levonorgestrel intrauterine device (LNG-IUD) is often utilized. If the first-line progestin therapy fails, there is not an effective second-line adjunct option. Moreover, pregnancy rates following fertility-sparing treatment are lower-than-expected in these patients.
Development of endometrioid adenocarcinoma despite Levonorgestrel-releasing intrauterine system: a case report with discussion and review of the RCOG/BSGE Guideline on the Management of Endometrial Hyperplasia. [2017]Obesity is a significant risk factor for the development of endometrial hyperplasia and cancer. More conservative prevention and management strategies are attractive due to the increased surgical risk and complication rates associated with obesity. The Levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena) has been shown to reduce the risk of developing endometrial cancer. The recent joint Green Top Guideline on the Management of Endometrial Hyperplasia published by the Royal College of Obstetricians and Gynaecologists (RCOG) with the British Society for Gynaecological Endoscopy (BSGE) recommends the LNG-IUS for the medical management of endometrial hyperplasia without atypia. This case study reports on the development of endometrioid adenocarcinoma despite the presence of an LNG-IUS following a negative hysteroscopy in a 56-year-old woman with morbid obesity. This report highlights the need for patients and clinicians to remain vigilant to the early warning signs of developing endometrial cancer, especially in those at an increased risk secondary to obesity.