Norethindrone Acetate vs. GnRH Agonist for Endometriosis

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Must not be taking: Hormones, Progestins, GnRH agonists

Disqualifiers: Abnormal lab tests, Bone density, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for endometriosis, a condition where tissue similar to the uterine lining grows outside the uterus, causing pain and other symptoms. Researchers aim to determine if norethindrone acetate (an oral medication) is as effective as the GnRH agonist Lupron Depot (an injectable medication) in reducing these symptoms and maintaining bone health. The trial also examines how these treatments affect cholesterol levels and overall quality of life. Women diagnosed with endometriosis who continue to experience symptoms after surgery, while being in good general health, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but if you have been on hormone therapies like GnRH agonists, you must stop them and wait for a 'washout period' (time without taking certain medications) before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study tested Lupron Depot in women with endometriosis and uterine fibroids. It effectively treated these conditions but caused some side effects. Common side effects included hot flashes, pain at the injection site, and general discomfort. Some individuals experienced swelling, and men reported testicular shrinkage. More serious reactions, such as sudden allergic responses, occurred, particularly in those with asthma or sinus issues.

Research has shown that norethindrone acetate is used for endometriosis and other menstrual problems. It works by preventing the egg from fully developing each month. This medication is usually well-tolerated, but like all medications, it can have side effects, including changes in menstrual flow, headaches, and nausea. It is important to use it under a doctor's guidance, with regular check-ups.

Both treatments have been studied for safety, and each has a known list of side effects. While these side effects can occur, they are typically manageable with medical supervision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for endometriosis because they offer different approaches to managing the condition. Lupron Depot is unique as it is administered intramuscularly and works by suppressing estrogen production, potentially reducing endometriosis symptoms more effectively. On the other hand, Norethindrone Acetate is taken orally and acts as a progestin, which can help alleviate symptoms by thinning the uterine lining. These options present alternatives to standard treatments like nonsteroidal anti-inflammatory drugs (NSAIDs) and oral contraceptives, offering potentially more targeted symptom relief.

What evidence suggests that this trial's treatments could be effective for endometriosis?

This trial will compare the effectiveness of Lupron Depot and Norethindrone Acetate (NA) for treating endometriosis. Studies have shown that Lupron Depot effectively reduces pelvic pain in people with endometriosis by lowering hormone levels that cause the growth of endometrial tissue. Various studies have proven this treatment safe and effective, helping relieve symptoms while also preventing bone loss. Meanwhile, Norethindrone Acetate (NA) has been found to reduce pain and shrink endometriomas, which are cysts caused by endometriosis. Research indicates that both treatments are effective, but they work in different ways to manage endometriosis symptoms. Participants in this trial will receive either Lupron Depot followed by NA or NA alone. ^{3 6 7 8 9}

Who Is on the Research Team?

Ozgul Muneyyirci-Delale, M.D.

Principal Investigator

State University of New York - Downstate Medical Center

Are You a Good Fit for This Trial?

This trial is for pre-menopausal women over 18 with regular periods and diagnosed endometriosis, confirmed by surgery. They should be in good health, not have used certain hormone therapies recently, and agree to use double-barrier contraception. Women who are postpartum or lactating within the last 3 months, have significant abnormal lab results or Pap smears, low bone density, or a history of severe reactions to hormones are excluded.

Inclusion Criteria

I agree to use two forms of birth control or practice abstinence during the study.

I am in good health or have mild, stable conditions not related to major organ systems or mental health.

You must have a negative pregnancy test before starting the study.

Exclusion Criteria

I had an abnormal Pap smear but tested negative for high-risk HPV.

I have low bone density or a history of specific bone issues.

I've had severe side effects from hormone or GnRH treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Norethindrone Acetate (NA) or GnRH agonist (Lupron Depot) for 24 weeks, followed by NA for an additional 28 weeks

52 weeks

Visits at 12, 24, and 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3, 6, 9, and 12 months

52 weeks

Visits at 3, 6, 9, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Lupron Depot
• Norethindrone Acetate

Trial Overview

The study compares Norethindrone Acetate (NA) with GnRH Agonist (Lupron Depot) in treating endometriosis symptoms. It aims to see if NA maintains bone density better than Lupron Depot while also assessing effects on lipid profiles and quality of life through questionnaires.

How Is the Trial Designed?

Group I: LD then NA Active Control 1 Intervention

Lupron Depot(LD) given intramuscularly every 12 weeks for total of 24 weeks then switched to Norethindrone Acetate (NA) taken 1-3 tablets orally every night for remainder of treatment

Group II: NA alone Active Control 1 Intervention

Norethindrone Acetate (NA) 5mg taken 1-3 tabs orally every night for duration of treatment

Lupron Depot is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in European Union as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Canada as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Japan as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Who Is Running the Clinical Trial?

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Lead Sponsor

Trials

2,103

Recruited

2,760,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

State University of New York - Downstate Medical Center

Collaborator

Trials

67

Recruited

12,100+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/9464714/

Leuprolide acetate depot and hormonal add-back in ...

Provides effective suppression of pelvic pain symptoms associated with endometriosis while protecting against bone loss.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10537015/

Clinical Efficacy, Pharmacokinetics, and Safety of the ...

Lupron Depot (Leuprolide Acetate for Depot Suspension) in the Treatment of Endometriosis: A Randomized, Placebo-Controlled, Double-Blind Study.

3.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2025/020708s040s041lbl.pdf

LUPRON DEPOT 11.25 mg (leuprolide ... - accessdata.fda.gov

Table 8 below provides detailed efficacy data regarding relief of symptoms of endometriosis based on the two studies of co-administration of LUPRON DEPOT ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0015028216537558

Lupron depot (leuprolide acetate for depot suspension) in ...

Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis, resulting in alleviation of ...

5.

luprongyn.com

luprongyn.com/lupron-for-endometriosis

LUPRON DEPOT® - Treatment for Endometriosis

LUPRON DEPOT suppresses the hormones that cause endometrial tissue to grow.1. LUPRON DEPOT therapy suppresses the signals from the pituitary gland in the brain ...

6.

lupron.com

lupron.com/isi.html

LUPRON DEPOT (leuprolide acetate for depot suspension)

The most common side effects of LUPRON DEPOT include hot flashes/sweats; injection site reaction/pain; general pain; swelling; testicular shrinkage; difficulty ...

7.

mayoclinic.org

mayoclinic.org/drugs-supplements/leuprolide-intradermal-route-intramuscular-route-subcutaneous-route/description/drg-20067038

Leuprolide (intradermal route, intramuscular ...

Reducing the amount of estrogen in the body helps treat endometriosis. Leuprolide will also shrink tumors in the uterus, which decreases vaginal ...

8.

luprongyn.com

luprongyn.com/

LUPRON DEPOT® For Endometriosis or Anemia Related to ...

Serious sudden allergic reactions have been reported with LUPRON DEPOT use. Asthma was reported in women with a history of asthma, sinusitis, and environmental ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2025/019943s040s041,020011s047s048lbl.pdf

Warnings and Precautions, Severe Cutaneous Adverse ...

The safety of LUPRON DEPOT 3.75 mg was evaluated in controlled clinical trials in 166 women with endometriosis and 166 women with uterine fibroids. Adverse ...