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

This is a prospective, single-center, two-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 or anastrozole 1 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.

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