Aspirin for Endometriosis

Overseen By Sue Slimak, RN

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Penn State University

Must be taking: Aspirin

Must not be taking: Antihypertensives, Diuretics, Digoxin

Disqualifiers: Cardiovascular disease, Diabetes, Hypertension, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how aspirin affects blood pressure, pain responses, and platelet activity in women with endometriosis compared to those without the condition. Participants will take aspirin (acetylsalicylic acid) or a placebo and perform simple exercises like hand grips and cold tests. Women with endometriosis who experience symptoms such as frequent pain might be suitable for this trial. The research aims to determine if endometriosis influences the body's regulation of blood flow and response to pain. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how aspirin benefits more patients with endometriosis.

Will I have to stop taking my current medications?

The trial requires that you stop taking any current medications that could affect cardiovascular responses, such as blood pressure medications or diuretics.

What is the safety track record for aspirin?

A previous study showed that aspirin helps reduce pain in women with endometriosis. Research shows that aspirin is commonly used and generally well-tolerated. Most people experience only mild side effects, such as an upset stomach or heartburn, which are usually not serious. This trial is in a later phase, indicating that other studies have already provided extensive safety information. The FDA has also approved aspirin for other conditions, which adds to confidence in its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for endometriosis, such as hormonal therapies or surgery, aspirin is being explored for its anti-inflammatory properties. Most treatments aim to suppress hormones to manage symptoms, but aspirin works by reducing inflammation and pain directly. Researchers are excited about aspirin because it offers a potentially simpler and less invasive option with fewer hormonal side effects. This could lead to a more accessible and tolerable treatment for many patients.

What is the effectiveness track record for aspirin in treating endometriosis?

This trial will compare the effects of aspirin with a placebo for treating endometriosis. Research has shown that aspirin, or acetylsalicylic acid, does not significantly alleviate endometriosis symptoms compared to a placebo, which contains no active medicine. A detailed review found that aspirin was not more effective than a placebo in easing these symptoms. However, low-dose aspirin can increase blood flow to the uterus, potentially aiding issues like uterine lining thickness. While aspirin benefits some health problems, strong evidence does not support its effectiveness in treating endometriosis. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for women aged 18-45, with or without endometriosis. It's not suitable for those who are pregnant, breastfeeding, have a high BMI or certain health conditions like cardiovascular disease, diabetes, severe liver or kidney issues, hypertension/hypotension, Raynaud's syndrome; those on medications affecting blood pressure; smokers; recent hormone therapy users; and individuals with skin allergies.

Inclusion Criteria

With and without endometriosis

I was born with a uterus.

Exclusion Criteria

Currently pregnant or breastfeeding

Allergy or hypersensitivity to investigational agents

I have been diagnosed with a heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of aspirin or placebo and perform hand grip exercise and cold pressor tests, undergo iontophoresis and blood draw

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Placebo

Trial Overview The study tests how aspirin affects blood pressure and pain in response to stress in women with endometriosis compared to healthy women. Participants will take aspirin or a placebo and undergo exercises and tests to measure neurovascular regulation differences between the two groups.

How Is the Trial Designed?

Group I: Aspirin Experimental Treatment 1 Intervention

one dose of aspirin

Group II: Placebo Placebo Group 1 Intervention

Placebo pill

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Penn State University

Lead Sponsor

Trials

380

Recruited

131,000+

Published Research Related to This Trial

In a study involving 40 female rabbits with experimentally induced peritoneal endometriosis, intralesional injection of 20% aspirin led to significant destruction of endometriosis foci, showing its potential as an effective treatment.

Histopathological analysis revealed that aspirin-treated groups exhibited extensive necrosis and significantly smaller remaining endometriosis areas compared to control groups, indicating a strong therapeutic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits. Saad-Hossne, R., Barretto, AB., Siqueira, JM., et al.[2019]

Ursolic acid (UA) has been identified as a natural inhibitor of COX-2, significantly reducing cell viability and proliferation in human endometriotic stromal cells, while promoting apoptosis in a dose-dependent manner.

UA also decreases the production of COX-2 and prostaglandin E2 (PGE2), as well as vascular endothelial growth factor (VEGF), thereby inhibiting angiogenesis, which is crucial for the progression of endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive Effects of Ursolic Acid on Human Endometriotic Stromal Cells Survival. Li, J., Zeng, Z., Chang, Y., et al.[2023]

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) significantly increase the expression of the MRP4 transporter in human endometriotic epithelial cells, which is linked to the regulation of inflammation in endometriosis.

The increase in MRP4 expression due to NSAID treatment is dependent on the activation of the PPARa receptor, and this process is associated with higher levels of PGE2, suggesting a mechanism by which these drugs may influence endometriosis pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-steroidal anti-inflammatory drugs increase MRP4 expression in an endometriotic epithelial cell line in a PPARa dependent manner. Massimi, I., Pulcinelli, FM., Piscitelli, VP., et al.[2019]

A systematic review of studies indicates that low-dose aspirin (80-150 mg daily) taken in the first trimester (before 16 weeks) may effectively reduce the severity of preeclampsia in at-risk pregnancies.

In contrast, studies administering aspirin later in pregnancy showed mixed results, suggesting that the timing and dosage of aspirin are crucial for its effectiveness in preventing preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Role of Aspirin in Preeclampsia Prevention: State of the Art]. Campos, A.[2018]

Aspirin is considered safe for use during pregnancy at daily doses not exceeding 100mg and has been shown to effectively prevent pre-eclampsia and fetal growth restriction in high-risk patients.

However, aspirin has not demonstrated benefits for preventing vascular placental disease in low-risk patients or for unexplained recurrent miscarriages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aspirin: Indications and use during pregnancy]. Belhomme, N., Doudnikoff, C., Polard, E., et al.[2018]

Aspirin, celebrating its 100-year anniversary, is now recognized for its crucial role in treating cardiovascular and cerebrovascular diseases by irreversibly inhibiting thromboxane A2, which helps prevent blood clots.

While aspirin effectively reduces risks in patients with existing heart and brain conditions, its use for primary prevention is controversial due to a lack of overall mortality reduction and potential serious side effects, such as increased bleeding, especially at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases]. Landmark, K.[2013]

In a study of 189 subjects, only those who underwent surgical extraction while taking 81 mg of aspirin (ASA) showed bleeding after 24 hours, indicating a potential risk associated with surgical procedures.

However, the study concluded that patients taking daily aspirin could safely undergo simple dental extractions without significant bleeding risks, as no bleeding was observed in the other groups after 48 hours and 5 days post-operation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aspirin on bleeding after extraction of teeth. Nooh, N.[2022]

In a study of 206 patients undergoing coronary artery bypass grafting (CABG), continuing aspirin (ASA) until the day of surgery significantly increased bleeding rates and the need for blood transfusions compared to stopping ASA 4 days prior to surgery.

Despite the increased bleeding and longer hospital stays in patients who continued ASA, there was no difference in serious postoperative complications like myocardial infarction or stroke, suggesting that stopping ASA before surgery may be safer without compromising outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Sustained Use of Aspirin until the Time of Surgery on Outcomes following Coronary Artery Bypass Grafting: A Randomized Clinical Trial. Sharifi, M., Kamali, A., Ghandi, Y.[2018]

Low-dose aspirin treatment in endometriosis rat models significantly increased the expression of progesterone receptors and leukemia inhibitory factor (LIF), which are important for improving endometrial receptivity during the implantation window.

The study suggests that low-dose aspirin may help overcome progesterone resistance in endometriosis, potentially enhancing pregnancy rates in affected individuals, making it a promising treatment option for endometriosis-related infertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window. Wang, L., Zhang, J., Zhang, H., et al.[2022]

Aspirin (ASA) significantly inhibits the growth of endometrial cancer cells (Ishikawa cells) in vitro, with growth inhibition ranging from 21% to 88% at concentrations of 1-5 mM over 96 hours.

The mechanism of action includes inducing apoptosis and reducing bcl-2 expression, with higher concentrations of ASA leading to increased apoptosis and a shift in the cell cycle from the resting phase to the S phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin effects on endometrial cancer cell growth. Arango, HA., Icely, S., Roberts, WS., et al.[2019]

Celecoxib significantly inhibited the proliferation of endometrial epithelial cells (EECs) and induced apoptosis in both control and endometriosis patients, indicating its potential as a therapeutic option for endometriosis.

The drug also reduced COX-2 activity and vascular endothelial growth factor (VEGF) secretion in EECs from endometriosis patients, suggesting that celecoxib may help manage endometrial growth through its anti-inflammatory properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Olivares, C., Bilotas, M., Buquet, R., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11384985/

Endometriosis and aspirin: a systematic review - PMC Tolfenamic acid relieved endometriotic symptoms more effectively than placebo while indomethacin and acetylsalicylic acid did not differ from ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7521085/

Association of Low-Dose Aspirin and Survival of Women ... Our results suggest that low-dose aspirin use is associated with improved survival outcomes in women with endometrial cancer, especially in those who are young, ...

3. academic.oup.com academic.oup.com/ehjopen/article/8131103

Aspirin does not modify cardiovascular event risk in ... Aspirin use did not modify the effect of endometriosis on MACE (P interaction = 0.467). Among participants taking aspirin, the adjusted HR for ...

4. journals.lww.com journals.lww.com/md-journal/fulltext/2017/09150/efficacy_evaluation_of_low_dose_aspirin_in.10.aspx

Efficacy evaluation of low-dose aspirin in IVF/ICSI... The results showed that low-dose aspirin therapy helps increase blood supply to the uterus, effectively promoting the development of endometrial thickness, and ...

5. fertstert.org fertstert.org/article/S0015-0282(25)00319-X/fulltext

ASPIRIN ENHANCES ENDOMETRIAL STROMAL CELL ... This is the first known study reporting ASA enhances ESCs' decidualization and reduces ESCs' proliferation, without cytotoxicity. There was no difference based ...

6. withpower.com withpower.com/trial/phase-4-endometriosis-7-2023-e2944

Aspirin for Endometriosis Aspirin (ASA) significantly inhibits the growth of endometrial cancer cells (Ishikawa cells) in vitro, with growth inhibition ranging from 21% to 88% at ...

7. atm.amegroups.org atm.amegroups.org/article/view/39773/html

Aspirin use and endometrial cancer risk: a meta-analysis and ... Our results suggest that the use of aspirin was associated with a reduced risk of endometrial cancer, and the reduced risk was closely related to the high- ...

8. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/22840265211049669

The effect of acetylsalicylic acid on pain and recurrence of ... The results suggest that aspirin, as an antioxidant, could effectively reduce pain in women with endometriosis.