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Contigen — Glutaraldehyde Cross-Linked Bovine Collagen

Contigen is a historical urethral bulking agent. FDA records give an original approval date of September 30, 1993 and a withdrawal date of October 25, 2011. The original indication was urinary incontinence due to intrinsic sphincter deficiency (ISD), after at least 12 months without improvement; it was not restricted to women. This page helps interpret older studies and assess patients with previous collagen injections.[1][2]

Material and Tissue Response​

Contigen was glutaraldehyde cross-linked bovine dermal collagen. Injection produced local bulk to improve urethral coaptation; cross-linking was intended to improve persistence. It was a biological implant capable of eliciting an immune response.[3][4]

A histological study examined specimens from 29 patients undergoing reimplantation after failed subureteral injection. Host fibroblast ingrowth and new human types I and III collagen were found, with occasional inflammatory reactions. Those selected specimens support tissue remodeling, not guaranteed complete resorption, absence of granulomas, or uncomplicated subsequent reconstruction in every patient.[5]

Historical Indications and Treatment Burden​

Contigen was studied in female and male ISD, and separately for pediatric vesicoureteral reflux. The latter literature should not be treated as an extension of its FDA urinary-incontinence indication. Current reflux treatment is discussed in Deflux.[1][5]

Older protocols used transurethral or periurethral injections, often with repeated treatments. Volumes varied substantially with population, response, and number of sessions: the collagen arm of the Coaptite trial averaged 6.6 mL over the study course, whereas a separate series of 42 women averaged 28.3 mL per patient. Neither is a universal initial dose, and the older product's technique should not be transferred to another agent.[6][7]

What the Outcome Studies Actually Showed​

StudyPopulation and follow-upFindings and limits
Smith 199796 women treated; 94 included in the reported outcome; median 14 months38.3% dry and 28.7% socially continent, giving 67% combined success. The 82.9% one-year maintenance estimate applied to 35 initially successful women with sufficient follow-up, not all treated women.[8]
Gorton 199961 women enrolled; 53 known failures or with information beyond five years14/53 (26%) reported improvement; only one was completely dry, and seven of the 14 still leaked daily. Improvement is not equivalent to continence.[9]
Westney 2005Retrospective review of 322 men after prostate-cancer or BPH treatment; mean follow-up 40.1 monthsMean 4.37 injections, pad use 5.15 to 2.98/day, and mean response duration 6.3 months. The 17% who achieved complete continence had a mean response duration of 11.1 months. These are separate outcomes from an uncontrolled series.[10]

Contigen was a comparator in pivotal trials of newer agents. For example, the Macroplastique publication reported dryness in 36.9% versus 24.8% at 12 months after the last treatment, while improvement by at least one Stamey grade was 61.5% versus 48%. Those outcomes should not be combined into one “cure” estimate.[11] Agent-specific trial populations, analysis denominators, and current formulations are maintained on Macroplastique, Coaptite, Durasphere, and Bulkamid.

Immune and Local Complications​

Historical treatment required skin testing. A negative test did not exclude a delayed reaction: a published case described delayed hypersensitivity with urinary retention lasting approximately a year. This case establishes possibility, not a reliable incidence estimate.[12]

The urethral Contigen immunology study reported anti-bovine type I collagen antibodies in approximately 28% of treated patients and characterized serum from 27 antibody responders. IgG predominated; the study did not find a correlation between immunoglobulin class and clinical adverse events. Antibody formation should not be equated with symptomatic allergy.[4]

Some frequently quoted collagen safety figures come from different exposures: the 3.8% positive skin-test figure was reported with Atelocollagen, while the dermatomyositis or polymyositis signal concerned cosmetic bovine collagen dermal implants. These are not product-specific urethral Contigen event rates.[13][14]

FDA subsequently strengthened connective-tissue disease and adverse-event information. Its uncontrolled long-term Cohort C enrolled 62 young male and female patients, with only 21% follow-up reported. FDA recommended including a possible higher incidence of autoimmune responses in women in labeling; the severe attrition and absence of a control group limit risk quantification and causal interpretation.[15][2]

In a prospective cohort of 337 women, Stothers reported complications in approximately 20%, including new urgency with incontinence in 12.6%, transient hematuria in 5%, and retention in 1.9%. Persistent symptoms were reported in some patients.[16] Late periurethral masses and obstruction are also documented: a collagenoma case required excision, followed by treatment of recurrent SUI. These reports refute a blanket guarantee that previous collagen injection cannot complicate later care.[17]

Assessment of a Patient With Previous Contigen​

Retrieve the injection history where possible, including agent, sites, dates, number of sessions, and previous reactions. Distinguish recurrent stress leakage from urgency, infection, retention, or a periurethral mass before selecting another treatment. Subsequent continence surgery may be feasible, but requires assessment of the urethra and the patient's present condition; a historical injection history alone does not determine the next operation.[16][17]

The FDA database documents withdrawal in 2011; it does not establish commercial competition, bovine spongiform encephalopathy, or a particular safety event as the reason. Avoid attributing a cause without a source.[1]

See also: Historical Bulking Agents and Urethral Bulking Agents — Procedure.

References​

1. US Food and Drug Administration. Contigen Bard Collagen Implant: original approval and withdrawal, PMA P900030. FDA record. Accessed September 12, 2026.

2. US Food and Drug Administration. Contigen: Long Term Cohort C post-approval study, P900030/PAS001. FDA study report. Accessed September 12, 2026.

3. Appell RA. Collagen Injection Therapy for Urinary Incontinence. The Urologic Clinics of North America. 1994;21(1):177-182.

4. McClelland M, Delustro F. Evaluation of Antibody Class in Response to Bovine Collagen Treatment in Patients With Urinary Incontinence. The Journal of Urology. 1996;155(6):2068-2073. doi:10.1016/S0022-5347(01)66111-1

5. Frey P, Lutz N, Berger D, Herzog B. Histological Behavior of Glutaraldehyde Cross-Linked Bovine Collagen Injected Into the Human Bladder for the Treatment of Vesicoureteral Reflux. The Journal of Urology. 1994;152(2 Pt 2):632-635. doi:10.1016/s0022-5347(17)32669-1

6. Mayer RD, Dmochowski RR, Appell RA, et al. Multicenter Prospective Randomized 52-Week Trial of Calcium Hydroxylapatite Versus Bovine Dermal Collagen for Treatment of Stress Urinary Incontinence. Urology. 2007;69(5):876-880. doi:10.1016/j.urology.2007.01.050

7. Richardson TD, Kennelly MJ, Faerber GJ. Endoscopic Injection of Glutaraldehyde Cross-Linked Collagen for the Treatment of Intrinsic Sphincter Deficiency in Women. Urology. 1995;46(3):378-381. doi:10.1016/S0090-4295(99)80223-4

8. Smith DN, Appell RA, Winters JC, Rackley RR. Collagen Injection Therapy for Female Intrinsic Sphincteric Deficiency. The Journal of Urology. 1997;157(4):1275-1278.

9. Gorton E, Stanton S, Monga A, et al. Periurethral Collagen Injection: A Long-Term Follow-Up Study. BJU International. 1999;84(9):966-971. doi:10.1046/j.1464-410x.1999.00321.x

10. Westney OL, Bevan-Thomas R, Palmer JL, Cespedes RD, McGuire EJ. Transurethral Collagen Injections for Male Intrinsic Sphincter Deficiency: The University of Texas-Houston Experience. The Journal of Urology. 2005;174(3):994-997. doi:10.1097/01.ju.0000170237.72750.64

11. Ghoniem G, Corcos J, Comiter C, et al. Cross-Linked Polydimethylsiloxane Injection for Female Stress Urinary Incontinence: Results of a Multicenter, Randomized, Controlled, Single-Blind Study. The Journal of Urology. 2009;181(1):204-210. doi:10.1016/j.juro.2008.09.032

12. Heit M. Prolonged Urinary Retention After Collagen Periurethral Injections: A Sequela of Humoral Immunity. Obstetrics and Gynecology. 1997;90(4 Pt 2):693-695. doi:10.1016/s0029-7844(97)00274-3

13. Charriere G, Bejot M, Schnitzler L, Ville G, Hartmann DJ. Reactions to a Bovine Collagen Implant. Clinical and Immunologic Study in 705 Patients. Journal of the American Academy of Dermatology. 1989;21(6):1203-1208. doi:10.1016/s0190-9622(89)70330-3

14. Cukier J, Beauchamp RA, Spindler JS, et al. Association Between Bovine Collagen Dermal Implants and a Dermatomyositis or a Polymyositis-Like Syndrome. Annals of Internal Medicine. 1993;118(12):920-928. doi:10.7326/0003-4819-118-12-199306150-00002

15. US Food and Drug Administration. Contigen labeling supplements: S005, connective tissue disease warning (1996), S010, adverse-event information (2008), and S011, Cohort C follow-up (2009). Accessed September 12, 2026.

16. Stothers L, Goldenberg SL, Leone EF. Complications of Periurethral Collagen Injection for Stress Urinary Incontinence. The Journal of Urology. 1998;159(3):806-807. PubMed.

17. Collagenoma and voiding dysfunction as complications of periurethral bulking. International Urogynecology Journal. 2015. doi:10.1007/s00192-015-2649-1. PubMed.