Inguinal Hernia Bilateral, Inguinal Hernia Unilateral, Inguinal Hernia, Without Mention of Obstruction or Gangrene, Inguinal Hernia Without Obstruction or Gangrene
Conditions
Keywords
inguinal hernia, hernia, fulvestrant, letrozole, anti-estrogen therapy, aromatase inhibitor, estrogen receptor, ESR1, male inguinal hernia, hormonal therapy, fibrosis, hernia prevention, hernia regression
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 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.
Interventions
DRUGFulvestrant
Participants will receive fulvestrant 250 mg intramuscularly on Days 1, 15, and 29, then monthly for 6 months.
DRUGAnastrazole
Participants will receive anastrozole 5 mg orally once daily for 6 months.
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Safety Event Rate | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Estradiol Level | Baseline to 6 months | Change in Serum Estradiol Level |
| Serum Testosterone Level | Baseline to 6 months | Change in Serum Testosterone Level |
| Serum LH Level | Baseline to 6 months | Change in Serum LH Level |
| Serum FSH Level | Baseline to 6 months | Change in Serum FSH Level |
| Hernia Size on Ultrasound | Baseline to 6 months; baseline to 1 year | Change in Hernia Size on Ultrasound |
| Euro Quality of Life 5 Dimension 5 Level (EQ-5D-5L) Score | Baseline to 6 months; baseline to 1 year | 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. |
| European Registry for Abdominal Wall Hernias Quality of Life (EuraHS-QoL) Score | Baseline to 6 months; baseline to 1 year | 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. |
| Bone Mineral Density on DEXA | Baseline to 1 year | Change in Bone Mineral Density on DEXA |
Countries
United States
Outcome results
None listed