Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications (HYPOSPADES)

Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications.

Hypospadias is a congenital abnormality of the penis that is caused by incomplete development of the anterior urethra. This pathology is one of the most common genital anomalies in paediatric urology .The incidence is reported to be 1 out of 250 live male births and is increasing regularly. The hypospadias surgeries present a high risk of post operative complications requiring re-interventions.

A great part of the post operative complications is related to imperfect healing issues. If androgen stimulation seems to be deleterious, at the opposite, oestrogen could impact positively on the skin healing process. This point leads to the hypothesis that local transcutaneous oestrogen stimulation on the ventral and dorsal penile faces decreases the number of skin healing post-operative defects.

The objective of the study is to assess the effect of oestrogen (applied once daily for 2 months prior to surgery) on the post-operative complications.

Study Overview

• Status: Completed
• Conditions: Hypospadias
• Intervention / Treatment: Drug: promestriene; Procedure: Urethroplasty; Radiation: Wrist X ray; Procedure: Blood test; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Service de Chirurgie Pédiatrique Uro-génitale, Hopital femme Mere Enfant
  • Nantes, France, 44093
    • Hôpital Mère-Enfant
  • Paris, France, 75015
    • Hopital Necker
  • Paris, France, 72015
    • Hôpital Robert Debré

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 3 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Severe hypospadias with a division of the corpus spongiosum behind the midshaft of the penis and for which repair requires a urethral substitution by onlay urethroplasty.
• Subjects operated between 9 and 36 months old.
• Subjects operated in one of the departments of paediatric urology involved in the study.
• Surgery performed by a surgeon with at least 5 years of practical experience in the hypospadias surgery.
• Written informed consent obtained from parents or legal guardians prior to the participation to the study
• All hypospadias aetiology (hormonal, karyotype or genetic)

Exclusion Criteria:

• Refusal to participate
• Subjects with glandular hypospadias
• Subjects aged <9 months or > 36months old at time of surgery.
• Subjects who had prior surgery of penis (circumcision or hypospadias surgery)
• Subjects treated with androgens (Human Chorionic Gonadotrophin or delayed testosterone) within 6 months prior to surgery.
• Intolerance to promestriene or its excipients.
• Not affiliated to a healthy or social security cover.
• Known tumoral risk
• Pure or mixed gonadal dysgenesis (45, X0/46,XY)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: promestriene; Children with severe hypospadias treated with promestriene 1%	Drug: promestriene; Promestriene cream 1%, 1g per day during 2 months, cutaneous application; Procedure: Urethroplasty; Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability); Radiation: Wrist X ray; Wrist X ray to follow the degree of bone maturation; Procedure: Blood test; Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH
Placebo Comparator: Placebo; Control group, children with severe hypospadias treated with Placebo.	Procedure: Urethroplasty; Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability); Radiation: Wrist X ray; Wrist X ray to follow the degree of bone maturation; Procedure: Blood test; Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH; Drug: Placebo; Placebo of promestriene cream, 1g per day during 2 months, cutaneous application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patient with postoperative urethral fistula and dehiscence	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Re-intervention related to wound healing	Number of re-interventions for fistula or dehiscence not related to stenosis, in the first year post surgery.	1 year
post-surgical complications	Total number and type of post-surgical complications	1 year
Re-intervention not related to wound healing	Number of re-interventions not related to wound healing	1 year
Hormone measurement	Plasmatic concentrations of Oestradiol, Testosterone, LH, FSH at inclusion and at 2 months (at the end of study treatment)	2 months
Bone age evaluation	Hand and wrist radiography at inclusion and 1 year after surgery.	14 monthes
Clinical tolerance of the treatment	Number and type of adverse events	14 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Pierre Mouriquand, Prof, HOPITAL FEMME MERE ENFANT CHU DE LYON

Publications and helpful links

General Publications

• Gorduza D, Plotton I, Remontet L, Gay CL, El Jani M, Cheikhelard A, Blanc T, El Ghoneimi A, Leclair MD, Roy P, Pirot F, Mimouni Y, Gaillard S, Chatelain P, Morel Y, Kassai B, Mouriquand P. Preoperative Topical Estrogen Treatment vs Placebo in 244 Children With Midshaft and Posterior Hypospadias. J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa231. doi: 10.1210/clinem/dgaa231.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2011
• Primary Completion (Actual): September 18, 2017
• Study Completion (Actual): September 18, 2017

Study Registration Dates

• First Submitted: June 8, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimated): June 10, 2011

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: post-operative complications; promestriene; Severe hypospadias; local oestrogen; Onlay-tube-onlay urethroplasty; fistula dehiscence
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Congenital Abnormalities; Urogenital Abnormalities; Penile Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypospadias; Substandard Drugs; Pharmaceutical Preparations; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Counterfeit Drugs; Hematologic Tests; promestriene
• Other Study ID Numbers: 2010.608; 2010-023686-22 (EudraCT Number)