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

NCT ID: NCT01370798

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 244 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-26
• Study Completion Date: 2017-09-18

Brief Summary

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.

Conditions

Hypospadias

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

promestriene

Children with severe hypospadias treated with promestriene 1%

Group Type: EXPERIMENTAL

promestriene

Intervention Type: DRUG

Promestriene cream 1%, 1g per day during 2 months, cutaneous application

Urethroplasty

Intervention Type: PROCEDURE

Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)

Wrist X ray

Intervention Type: RADIATION

Wrist X ray to follow the degree of bone maturation

Blood test

Intervention Type: PROCEDURE

Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH

Placebo

Control group, children with severe hypospadias treated with Placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo of promestriene cream, 1g per day during 2 months, cutaneous application

Urethroplasty

Intervention Type: PROCEDURE

Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)

Wrist X ray

Intervention Type: RADIATION

Wrist X ray to follow the degree of bone maturation

Blood test

Intervention Type: PROCEDURE

Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH

Interventions

promestriene

Promestriene cream 1%, 1g per day during 2 months, cutaneous application

Intervention Type: DRUG

Placebo

Placebo of promestriene cream, 1g per day during 2 months, cutaneous application

Intervention Type: DRUG

Urethroplasty

Onlay-tube-onlay urethroplasty performed by a physician expert of this technique (at least 5 years of practical ability)

Intervention Type: PROCEDURE

Wrist X ray

Wrist X ray to follow the degree of bone maturation

Intervention Type: RADIATION

Blood test

Hormonal dosage: Oestradiol, testosterone, FSH-LH and AMH

Intervention Type: PROCEDURE

Eligibility Criteria

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)

• Minimum Eligible Age: 9 Months
• Maximum Eligible Age: 36 Months
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre Mouriquand, Prof

Role: PRINCIPAL_INVESTIGATOR

HOPITAL FEMME MERE ENFANT CHU DE LYON

Locations

Service de Chirurgie Pédiatrique Uro-génitale, Hopital femme Mere Enfant

Bron, , France

Hôpital Mère-Enfant

Nantes, , France

Hôpital Robert Debré

Paris, , France

Hôpital NECKER

Paris, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 32386308 (View on PubMed)

Other Identifiers

2010-023686-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2010.608

Identifier Type: -

Identifier Source: org_study_id