What is the mechanism of action of this treatment?

Common treatments for endometriosis primarily aim to reduce estrogen levels or block its effects, as estrogen promotes the growth of endometriotic tissue. Aromatase inhibitors like Letrozole decrease estrogen production by inhibiting the enzyme aromatase, which converts androgens to estrogen. GnRH agonists suppress ovarian hormone production, leading to a hypoestrogenic state, while progestins counteract estrogen's effects on endometrial tissue. These mechanisms are vital for endometriosis patients as they help alleviate pain, reduce lesion size, and improve overall symptoms.

What side effects are associated with this type of intervention?

Common treatments for endometriosis, such as aromatase inhibitors like letrozole, are known to decrease estrogen production, which can lead to side effects including menopausal symptoms (hot flashes, night sweats), decreased bone density, and potential cardiovascular risks. Other hormonal treatments, such as GnRH analogs, can also cause menopausal symptoms and increase the risk of osteoporosis. Progestins and oral contraceptives may result in weight gain, mood changes, and breakthrough bleeding. Danazol, another treatment option, is associated with androgenic effects like weight gain, deepening of the voice, and menstrual irregularities.

What prior FDA approvals exist?

FDA-approved treatments for endometriosis that focus on decreasing estrogen production include Gonadotropin-Releasing Hormone (GnRH) agonists and antagonists, such as leuprolide and elagolix, which suppress ovarian hormone production. Danazol, an androgenic compound, has also been used but is less favored due to its side effects. Aromatase inhibitors like letrozole are being studied for their efficacy in reducing endometriosis-related symptoms by decreasing estrogen levels, although they are not yet FDA-approved specifically for endometriosis.

What other types of research exist?

Promising novel alternatives to Letrozole for endometriosis treatment include Gonadotropin-Releasing Hormone (GnRH) agonists and antagonists, which have been successfully used in various cases of endometriosis, including thoracic endometriosis. Another potential alternative is the use of combined estrogen-progestin oral contraceptives, which have been effective in managing endometriosis symptoms post-surgery. Additionally, the Levonorgestrel-releasing intrauterine device (LNG-IUD) has shown efficacy in reducing symptoms and preventing recurrence of endometriosis.

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Aromatase Inhibitor

Letrozole for Endometriosis Pain Management (APPOSE Trial)

Phase 2

Waitlist Available

Led By Marcelle I Cedars

Research Sponsored by University of California, San Francisco

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 18-42 years

Prior diagnosis of endometriosis by one of the following: (1) surgical diagnosis (2) endometrioma on pelvic ultrasound

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years.

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

Summary

This trial tests letrozole in women with endometriosis to see if it can improve their symptoms and egg quality. Letrozole works by lowering estrogen levels, potentially helping with symptom management. Letrozole has been used for a long time in various infertility treatments.

Who is the study for?

This trial is for women aged 18-42 with a prior diagnosis of endometriosis who are planning to undergo controlled ovarian hyperstimulation and intend to freeze all retrieved eggs or embryos. It's not suitable for those with significant health issues, psychiatric disorders, or hypersensitivity to letrozole.

What is being tested?

The study compares the effects of Letrozole versus a placebo on pain during ovarian stimulation in patients with endometriosis. It also examines how Letrozole affects egg/embryo quality and pregnancy rates in a randomized double-blind setup.

What are the potential side effects?

Letrozole may cause side effects such as fatigue, hot flashes, joint pain, and nausea. Since it's being compared to a placebo (a pill without active medication), some participants won't experience these drug-related side effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 42 years old.

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I have been diagnosed with endometriosis either through surgery or an ultrasound.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole

Secondary study objectives

Average Delta in Endometriosis Pain Score Pre and Post Stimulation Compared to No Endometriosis

Does Letrozole Impact Embryo and Egg Quantity in Endometriosis

Egg Maturity

+4 more

Side effects data

From 2018 Phase 4 trial • 79 Patients • NCT02137538

10%

Fracture

Acne

Scoliosis

Hair loss

Sacroiliitis

Neuro event

100%

80%

60%

40%

20%

Study treatment Arm

Anastrozole

Letrozole

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Endometriosis LetrozoleExperimental Treatment1 Intervention

Participants will be asked to take 5mg letrozole daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to letrozole. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.

Group II: No Endometriosis ControlActive Control1 Intervention

Participants will be asked to complete surveys during their ovarian stimulation and up to 12 weeks following retrieval to evaluate symptoms of pelvic pain. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.

Group III: Endometriosis PlaceboPlacebo Group1 Intervention

Participants will be asked to take one tablet placebo daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to placebo. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Letrozole

FDA approved

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for endometriosis primarily aim to reduce estrogen levels or block its effects, as estrogen promotes the growth of endometriotic tissue. Aromatase inhibitors like Letrozole decrease estrogen production by inhibiting the enzyme aromatase, which converts androgens to estrogen. GnRH agonists suppress ovarian hormone production, leading to a hypoestrogenic state, while progestins counteract estrogen's effects on endometrial tissue. These mechanisms are vital for endometriosis patients as they help alleviate pain, reduce lesion size, and improve overall symptoms.

Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis.