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

NCT07604272 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 00225501
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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 anastrozole 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.

Conditions

Inguinal Hernia Bilateral; Inguinal Hernia Unilateral; Inguinal Hernia, Without Mention of Obstruction or Gangrene; Inguinal Hernia Without Obstruction or Gangrene

Keywords

inguinal hernia; hernia; fulvestrant; letrozole; anti-estrogen therapy; aromatase inhibitor; estrogen receptor; ESR1; male inguinal hernia; hormonal therapy; fibrosis; hernia prevention; hernia regression

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Serum Estradiol Level

  Baseline to 6 months

• Serum Testosterone Level

  Baseline to 6 months

• Serum LH Level

  Baseline to 6 months

• Serum FSH Level

  Baseline to 6 months

• Hernia Size on Ultrasound

  Baseline to 6 months; baseline to 1 year

Study Arms (2)

Fulvestrant 250 mg

EXPERIMENTAL

Participants will receive fulvestrant 250 mg intramuscularly on Days 1, 15, and 29, then monthly for 6 months.

Drug: Fulvestrant

Anastrozole 5 mg

EXPERIMENTAL

Participants will receive anastrozole 5 mg orally once daily for 6 months.

Drug: Anastrazole

Interventions

Anastrazole DRUG

Participants will receive anastrozole 5 mg orally once daily for 6 months.

Anastrozole 5 mg

Fulvestrant DRUG

Participants will receive fulvestrant 250 mg intramuscularly on Days 1, 15, and 29, then monthly for 6 months.

Fulvestrant 250 mg

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: Eligibility is limited to individuals who identify as male, consistent with the biological mechanism under investigation and the study population defined in the protocol.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 39903526 BACKGROUND

• 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.

  PMID: 30327348 BACKGROUND

• 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.

  PMID: 18358264 BACKGROUND

• 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.

  PMID: 29330835 BACKGROUND

• 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.

  PMID: 35439171 BACKGROUND

MeSH Terms

Conditions

Gangrene; Hernia, Inguinal; Hernia; Fibrosis

Interventions

Fulvestrant; Anastrozole

Condition Hierarchy (Ancestors)

Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hernia, Abdominal; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Investigator

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: May 22, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)