Reversing InGuinal Hernia Trial: The Evaluation of Sex Hormones to Reverse Inguinal Hernias in Males (RIGHT)

Reversing InGuinal Hernia Trial (RIGHT Trial): The Evaluation of Sex Hormones to Reverse Inguinal Hernias in Males

This is a prospective, single-center, three-arm Phase 1 safety and feasibility trial evaluating anti-estrogen therapy in men age 50 years and older with symptomatic unilateral inguinal hernias. Participants will be randomized to receive fulvestrant 250 mg intramuscularly, fulvestrant 500 mg intramuscularly, or letrozole 5 mg orally for 6 months. The study will evaluate safety, tolerability, feasibility, hormone changes, hernia size, patient-reported outcomes, bone density, and imaging-based hernia classification.

Study Overview

• Status: Recruiting
• Conditions: Inguinal Hernia Unilateral; Inguinal Hernia Without Obstruction or Gangrene; Inguinal Hernia, Without Mention of Obstruction or Gangrene; Inguinal Hernia Bilateral
• Intervention / Treatment: Drug: Fulvestrant; Drug: Anastrazole

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
      • Contact: Nancy Ly, MD; Phone Number: 3126956868; Email: nancy.ly@nm.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male sex
• Age ≥ 50 years at time of enrollment
• Symptomatic unilateral inguinal hernia confirmed on physical examination
• Hernia visible / confirmed on groin ultrasound
• Non-recurrent inguinal hernia (primary hernia only)
• Willing and able to provide written informed consent
• Able and willing to comply with all protocol-required visits, laboratory assessments, imaging, and follow-up
• Willing to use contraception and avoid fathering a child during study participation and for 12 months after last dose
• Willing to be counseled regarding vitamin D and calcium supplementation Bone safety mitigation measure per PIND response.

Exclusion Criteria:

Hernia Characteristics

• Scrotal hernia (any)
• Bilateral inguinal hernia
• Recurrent inguinal hernia (prior repair at same site)

Renal & Hepatic

• Clinically significant renal dysfunction judged by investigator to increase study risk
• Clinically significant hepatic dysfunction at baseline

Hematologic

■ Clinically significant baseline hematologic abnormality (including elevated hematocrit or polycythemia)

Urologic / Prostate

• Symptomatic benign prostatic hyperplasia (BPH) requiring active medical or procedural treatment
• Clinically significant untreated prostate disease

Skeletal / Bone

• Baseline osteoporosis (T-score ≤ -2.5 on DEXA at any site)
• Recent fragility fracture (within prior 12 months or as judged by investigator)
• Other clinically significant skeletal vulnerability judged to increase risk from estrogen suppression

Immunosuppression ■ Active immunosuppression (e.g., systemic corticosteroids, biologic agents, post-transplant regimens)

Psychiatric

■ Unstable or uncontrolled psychiatric illness that, in the investigator's judgment, would interfere with safe study participation

Reproductive / Fertility ■ Actively pursuing fertility or planning conception during study participation

Prior / Concomitant Therapy

• Current use of androgen replacement therapy, exogenous estrogen, or other endocrine-active agents that would confound study interpretation
• Prior or current use of aromatase inhibitor or selective estrogen receptor modulator / degrader within 6 months of enrollment

General

■ Any other clinically significant medical condition, laboratory abnormality, or circumstance that, in the investigator's judgment, would place the participant at unacceptable risk or compromise study integrity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fulvestrant 250 mg; Participants will receive fulvestrant 250 mg intramuscularly on Days 1, 15, and 29, then monthly for 6 months.	Drug: Fulvestrant; Participants will receive fulvestrant 250 mg intramuscularly on Days 1, 15, and 29, then monthly for 6 months.
Experimental: Anastrozole 5 mg; Participants will receive anastrozole 5 mg orally once daily for 6 months.	Drug: Anastrazole; Participants will receive anastrozole 5 mg orally once daily for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Safety Event Rate	Proportion of participants experiencing a composite safety event, defined as hernia-related complications including incarceration, strangulation, or emergent surgery; drug-related toxicity Grade 2 or higher by CTCAE v5.0; or procedure/treatment-related events Clavien-Dindo Grade III or higher.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Estradiol Level	Change in Serum Estradiol Level	Baseline to 6 months
Serum Testosterone Level	Change in Serum Testosterone Level	Baseline to 6 months
Serum LH Level	Change in Serum LH Level	Baseline to 6 months
Serum FSH Level	Change in Serum FSH Level	Baseline to 6 months
Hernia Size on Ultrasound	Change in Hernia Size on Ultrasound	Baseline to 6 months; baseline to 1 year
Bone Mineral Density on DEXA	Change in Bone Mineral Density on DEXA	Baseline to 1 year
Euro Quality of Life 5 Dimension 5 Level (EQ-5D-5L) Score	The EQ-5D-5L is a standardized quality-of-life instrument assessing mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Index scores range from 0-5, with higher scores indicating worse health-related quality of life.	Baseline to 6 months; baseline to 1 year
European Registry for Abdominal Wall Hernias Quality of Life (EuraHS-QoL) Score	The EuraHS-QoL questionnaire assesses pain, activity restriction, and cosmetic discomfort related to abdominal wall hernias. Scores range from 0 to 90, with higher scores indicating worse hernia-related quality of life and symptom burden.	Baseline to 6 months; baseline to 1 year

Collaborators and Investigators

• Sponsor: Northwestern University

Publications and helpful links

General Publications

• HerniaSurge Group. International guidelines for groin hernia management. Hernia. 2018 Feb;22(1):1-165. doi: 10.1007/s10029-017-1668-x. Epub 2018 Jan 12.
• Potluri T, You T, Yin P, Coon J 5th, Stulberg JJ, Dai Y, Escobar DJ, Lieber RL, Zhao H, Bulun SE. Estrogen receptor-alpha ablation reverses muscle fibrosis and inguinal hernias. J Clin Invest. 2025 Feb 4;135(6):e179137. doi: 10.1172/JCI179137.
• Zhao H, Zhou L, Li L, Coon V J, Chatterton RT, Brooks DC, Jiang E, Liu L, Xu X, Dong Z, DeMayo FJ, Stulberg JJ, Tourtellotte WG, Bulun SE. Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model. Proc Natl Acad Sci U S A. 2018 Oct 30;115(44):E10427-E10436. doi: 10.1073/pnas.1807765115. Epub 2018 Oct 16.
• Matthews RD, Neumayer L. Inguinal hernia in the 21st century: an evidence-based review. Curr Probl Surg. 2008 Apr;45(4):261-312. doi: 10.1067/j.cpsurg.2008.01.002. No abstract available.
• Potluri T, Taylor MJ, Stulberg JJ, Lieber RL, Zhao H, Bulun SE. An estrogen-sensitive fibroblast population drives abdominal muscle fibrosis in an inguinal hernia mouse model. JCI Insight. 2022 Apr 19;7(9):e152011. doi: 10.1172/jci.insight.152011.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: hernia; hormonal therapy; fibrosis; letrozole; aromatase inhibitor; inguinal hernia; fulvestrant; estrogen receptor; ESR1; hernia prevention; anti-estrogen therapy; male inguinal hernia; hernia regression
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Necrosis; Hernia, Abdominal; Pathological Conditions, Signs and Symptoms; Fibrosis; Hernia; Hernia, Inguinal; Gangrene; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Fulvestrant; Anastrozole
• Other Study ID Numbers: 00225501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared outside the study team. Aggregate study results may be disseminated through presentations and publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No