Pediatric Genitourinary Examination: A Clinician’s Reference Allene Pulsifer

T

he purpose of this article is to provide advanced practice clinicians with a reference to assist with the effective and efficient evaluation and diagnosis of common pediatric genitourinary (GU) problems in an outpatient setting. This article will be most useful to providers who routinely treat children but do not specialize in genitourinary disorders. Initial management strategies for these conditions will be included.

History Providing a thorough GU evaluation as a routine part of well child care is important to establish a baseline from which future comparisons can be made. In the pediatric population, GU disorders and GU complaints in otherwise well children are among the most common problems that practitioners manage. Additionally, in cases where sexual abuse is suspected, having a baseline GU examination is critical to the evaluation process. Furthermore, making the GU examination a part of each well child examination will reduce the anxiety produced by this examination as the child grows.

Allene Pulsifer, MS, RN, CRNP, is a Nurse Practitioner, Pediatric Urology, Children’s Surgical Associates, LTD, Richard D. Wood Ambulatory Care Center, Philadelphia, PA. Note: CE Objectives and Evaluation Form appear on page 169.

The importance of a genitourinary (GU) examination and how to evaluate common GU complaints are discussed. Diagnoses covered include inguinal hernia, hydrocele, varicocele, undescended testis, phimosis, hypospadias, meatal stenosis, penile adhesions, labial adhesions, and vaginal voiding. Developmental considerations and examination tips are addressed. It will also send the message to the child and the family that this area is important and requires good care in order to maintain overall well-being. The first component to any GU evaluation is a medical history. The initial GU history taken for all children should encompass the mother’s pregnancy and the child’s birth history, including any anomalies, prematurity, and birth weight. The provider should ask about a known family history of GU-specific disorders and gather a history of any urinary tract infections (UTI), including their presentation, evaluation, and treatment. It is also important to ask about any fevers of unknown origin, since this could have been an undiagnosed pyelonephritis. A voiding history is crucial for evaluating any potty-trained child. The provider should question the parent and the child about dysuria, frequency of urination, urgency, hesitancy, quality of urinary stream, straining, pre or post void leaking, day or nighttime wetting, holding maneuvers such as Vincent’s Curtsy (where the child sits on her heal to suppress the urge to void), and quality and quantity of fluid intake. A detailed bowel history is important to evaluate for concurrent

UROLOGIC NURSING / June 2005 / Volume 25 Number 3

constipation, which is linked to both incontinence and UTI. For male children, a thorough history must also include questions about the child’s circumcision status, retractability or ballooning of the prepuce with urination, any inguinal bulge or scrotal swelling, and whether or not the testicles are descended or have been in the past. History taking presents an opportunity for the provider and the caregiver to interact and for the provider to teach the caregiver important information. Once a baseline has been established, future history taking can be tailored to the specific complaint. Refer to Table 1 for additional helpful points regarding history taking and parent education.

Physical Examination The baseline genitourinary physical examination should include a full examination of the child with special attention to the abdomen, spine, lowerextremity neuromuscular status, external genitalia, and the entire perineum (Sheldon, 2001). Some of the most frequent GU complaints involve the inguinal area. For that reason, the evaluation and initial management of common inguinal problems will be highlighted. Once a baseline his163

C O N T I N U I N G E D U C A T I O N

C O N T I N U I N G E D U C A T I O N

Table 1. Developmental Considerations ■

■

In female infants, the external genitalia may be prominent due to maternal estrogen; this may result in a small amount of vaginal bleeding. The provider should reassure the family that this can be normal. The ideal time to perform a hypospadias repair is before 12 months of age, when children begin to develop significant genital awareness.

■

The potty-training years are especially risky for developing UTI. Guide parents to remind their child to void often, even if they are not having accidents.

■

Masturbation is normal in most children. Reassure parents and guide them to teach their child about appropriate time and place for this behavior.

■

For adolescent patients, always ask about sexual activity with the parents out of the room.

■

The genitourinary examination can cause parents and children much anxiety. Typically, a matter-of-fact approach combined with the provider’s personal bedside manner, and an awareness of the child’s developmental age, will result in a successful examination. Please refer to Table 2 for more information.

tory and examination are established, most common GU complaints can be easily evaluated by a nurse practitioner in an outpatient setting. Refer to Tables 1 and 2 for helpful examination techniques.

Indirect Inguinal Hernia and Hydrocele The most common presentation of an inguinal hernia is an inguinal bulge, which may be noticed by the patient, the family, or the practitioner. An indirect inguinal hernia is the protrusion of the peritoneal contents through a patent processus vaginalis (Gill, 1998). Usually, the omentum of the small intestine slips through the internal inguinal ring, causing the bulge (Sheldon, 2001). Typically this is painless, and the bulge is 164

Table 2. Tips for a Better Examination ■

Examine the genital area last in order to reduce anxiety throughout the examination.

■

Placing the child’s hands over your hands while performing the examination can reduce anxiety and prevent tickling of the child.

■

If a boy has a difficult testicular examination, have the boy assume a “catcher’s position” and repeat the examination. Sometimes this will force retractile testes to fall to the scrotum, thus differentiating them from undescended testicles. The cross-legged sitting position can also have this effect.

■

Use hand soap found in most examination rooms as a lubricant when locating undescended testicles.

■

To differentiate between a skin bridge and a filmy glanular adhesion in a circumcised male, look at the incision line from the circumcision. If the adhesion is attached at the incision line, then the adhesion is most likely a skin bridge that will need to be surgically released. If the inner prepuce is attached at the glans, then the adhesion is most likely “filmy” and will break down with time.

reducible into the peritoneal cavity. Occasionally, the small intestine can become incarcerated, altering the blood supply to either the testicle or the intestine and resulting in ischemic damage to either organ. This must be addressed emergently. Both males and females can have a hernia; however, the male to female ratio is 8 to 1 (Bogaert & Kogan, 1997; Kogan, 1997). In females, an inguinal hernia typically presents as a labial bulge. Inguinal hernias are most easily observed while the child is bearing down in a standing position. The bulge may worsen throughout the day and disappear when the child is lying down. If the history suggests that a hernia is present, but the practitioner is unable to observe the groin bulge, a positive diagnosis may be made by eliciting

a “silk glove” sign. While the child is in a supine position, the inguinal area should be palpated. When the cord structures are rolled against the pubic bone, the practitioner may feel layers of processus vaginalis slipping over one another, as if made of silk. Alternatively, the child’s caregiver could bring in a photograph of the bulge to confirm the diagnosis. There is no nonsurgical management of a true inguinal hernia. Due to the risks associated with incarceration, any child diagnosed with a hernia should be referred for surgical correction immediately. If a parent observes an inguinal bulge consistent with an inguinal hernia, he/she should be advised to apply pressure to the bulge in an attempt to reduce the hernia, and then should seek immediate attention.

UROLOGIC NURSING / June 2005 / Volume 25 Number 3

Figure 1. Right Hydrocele

If the bulge does not reduce when pressure is applied, the hernia is most likely incarcerated. The parents should be advised to seek immediate surgical attention to avoid injury to the bowel and the testicle. A hydrocele is an accumulation of fluid around the testicle, which can be transilluminated in a dark room with a flashlight. In children, hydroceles are usually caused by the persistence of a patent processus vaginalis. While hydroceles in children involve the same pathophysiology as an indirect inguinal hernia, the opening is usually smaller, thus only peritoneal fluid enters as opposed to bowel (see Figure 1). A communicating hydrocele is defined by the free passage of fluid between the peritoneal cavity and the scrotum. A history of fluctuations in size of the scrotum or scrotal swelling is usually enough to confirm a communicating hydrocele. By 6 months of age, a patent processus vaginalis usually closes spontaneously, and the fluid typically reabsorbs over time. After 6 months, if the hydrocele persists, the child may be referred for surgical correction.

Varicocele A varicocele is defined as a dilation of the pampiniform venous plexus and the internal spermatic vein (Redman & Reddy, 2001). They almost always occur on the left, possibly due to the increased venous hydrostatic pressure on that side. To diagnose a varicocele, always palpate the patient in a standing position, in a warm room to avoid activation of the cremaster reflex. A varicocele should reduce when the patient is supine (Sheldon, 2001). A grade I varicocele is only palpable when the patient is bearing down. A grade II varicocele is palpable without bearing down. A grade III varicocele is visible without palpation, and is the source of the “bag of worms” description. A varicocele is commonly painless, but can present as a dull ache, particularly after prolonged sitting or standing. A renal ultrasound is required for left varicoceles that do not reduce and all right varicoceles. This is because right varicoceles are highly uncommon, and any varicocele that does not reduce in the supine

UROLOGIC NURSING / June 2005 / Volume 25 Number 3

position suggests an abnormal interruption of the normal venous return, such as an abdominal mass. In adolescents, varicoceles are usually asymptomatic, and typically present because a health care provider, parent, or the child notices scrotal fullness; it may also be detected during a routine sports physical. By contrast, in the adult population, varicoceles are frequently diagnosed as part of an infertility workup. Referral and surgical correction in the adolescent population is only indicated if the varicocele does not reduce, if there is a significant ipsilateral testicular atrophy on physical examination or serial scrotal ultrasounds, or if the patient complains of discomfort (Sheldon, 2001). In the adolescent population, there is controversy regarding offering varicocele repair to protect the patient’s future fertility; if this is a concern, referral to a male infertility specialist should be offered.

Undescended Testis An undescended testicle is a testicle that is not in a dependent position within the scrotum at birth. Undescended testicles may descend without intervention within the first 6 months of life. If at 6 months of age the testicle remains undescended, the cryptorchidism should be corrected since undescended testicles are associated with infertility, testicular tumor, inguinal hernia, testicular torsion, and cosmetic dissatisfaction (Schneck & Bellinger, 2002). Treatment alternatives include surgical correction and the use of human chorionic gonadotropic (hCG) to stimulate testicular descent; in the United States, hCG is not routinely used because of its poor success rate. In contrast, a tethered or ascending testis is one that is thought to be initially dependent in the scrotum, but “ascends” as the child grows. This too requires

165

C O N T I N U I N G E D U C A T I O N

C O N T I N U I N G

Figure 2. Hypospadias

Figure 3. Phimosis

E D U C A T I O N referral for surgical correction. These can both be distinguished from a retractile testis, which is a dependent testis that is pulled out of the scrotum by an overactive cremasteric reflex. This reflex is normal and usually decreases as the child progresses through puberty. Retractile testes are most common in boys aged 2 to 7 years and require no intervention (Bogaert & Kogan, 1997; Kogan, 1997). Retractile testes are easily confused with undescended testes. If the primary care provider is unsure of the child’s examination, the child should be referred for serial examinations by a specialist in pediatric urology.

Hypospadias Hypospadias is the incomplete development of the anterior urethra and corpus spongiosum (see Figure 2). It is almost always diagnosed immediately at birth upon initial examination; however, in rare instances it can be diagnosed after a completed or aborted circumcision. If on initial examination the foreskin is

166

incompletely developed or asymmetrical, the child should be evaluated for hypospadias, a condition where the urethral meatus is ventrally placed. Hypospadias is often associated with chordee, or congential curvature of the penis. The goals of surgical correction are to allow the child to void while standing, to straighten the penis, and to provide a symmetrical appearance to the penis and prepuce. Megameatus is a variant of hypospadias where the urethral meatus is larger than expected and hidden beneath a full foreskin. Any patient with hypospadias and at least one nonpalpable testis should undergo karyotype analysis to rule out intersex disorders and should be referred to a pediatric urologist for surgical correction (Redman & Reddy, 2001).

Phimosis In uncircumcised infants the foreskin adheres to and completely covers the glans penis. (see Figure 3). Retraction of a full foreskin will occur over time without intervention. Usually,

nocturnal erections cause the gradual release of the glans adhesions, and therefore no intervention is required. A full prepuce that is not retractable during childhood is of no significance in the absence of symptoms (Brown, Cartwright, & Snow, 1997). A child who is uncircumcised should be taught at potty training how to gradually and gently retract the prepuce for voiding and hygiene. Phimosis can become problematic if ballooning of the prepuce occurs with voiding. This can result in local irritation, urinary tract infections, or balanitis. In the uncircumcised boy, or in children with repeated infections, phimosis can result in a cicatrix, or trapping of the glans penis behind scar tissue. This often requires surgical correction. If an uncircumcised child has symptomatic phimosis, 0.05% betamethasone cream can be applied to the phimotic ring twice daily for up to 1 month to facilitate resolution. Additionally, gentle stretching of the prepuce by placing a thumb and a forefinger on

UROLOGIC NURSING / June 2005 / Volume 25 Number 3

Figure 4. Filmy Penile Adhesions

the lateral aspects of the base of the penis and applying pressure posteriorly can augment the natural process in symptomatic boys.

Meatal Stenosis Meatal stenosis most often presents with the complaint of upward deflection of the urinary stream. Meatal stenosis is common in circumcised boys, and is thought to be from scarring of the meatus, which usually occurs prior to potty training, and as the result of the glans rubbing on the wet diaper or from poor blood supply due to ligation of the frenular artery during circumcision (Brown et al., 1997). This condition is diagnosed by direct observation of voiding and by inspection of the meatus. Surgical correction is possible in the office under local anesthesia, and requires gentle dilation of the meatus and the regular application of petrolatum to prevent recurrence of the stenosis. More complex cases will require that the case be scheduled for the operating room and general anesthesia.

Penile Adhesions Penile adhesions are usually noticed by the primary medical

provider or the caregiver and are usually asymptomatic. Circumcised boys who have a significant peri-penile fat distribution are more likely to have telescoping of the penile shaft skin towards the glans of the penis. This can result in filmy glanular adhesions or a true skin bridge. Evaluate for glanular adhesions by reducing the fat pad at the base of the penis and observing the coronal margin. Typically, the coronal margin is visible around the entire circumference of the glans. If adhesions are present, the prepuce will be covering the coronal margin in part or in full. Filmy adhesions can be differentiated from a true skin bridge by observing which portion of the prepuce is adhered to the glans. If it is the inner prepuce that is attached at the glans, then the adhesion is most likely “filmy” and will break down with time, without intervention (see Figure 4). Although debatable, it is not recommended to forcefully break down filmy adhesions, especially while the child has significant telescoping of the shaft skin since the adhesions will most likely recur. On the other hand, if the adhesion is

UROLOGIC NURSING / June 2005 / Volume 25 Number 3

C O N T I N U I N G

Figure 5. Skin Bridge

attached at the circumcision incision line, then the adhesion is most likely a skin bridge that will need to be surgically released under local anesthesia (Brown et al., 1997) (see Figure 5).

Labial Adhesions Labial adhesions are usually asymptomatic. However, occasionally a prepubescent female will present with painful urination, dampness, vaginal voiding, or a urinary tract infection. Alternatively, you may be asked to evaluate a girl for asymptomatic labial adhesions noticed by an observant caregiver. On physical examination, the labia majora should be separated and spread laterally and posteriorly. This will allow for inspection of the introitus, defined by the labia minora (Bickley, 1999). The labia majora should be smooth, and in newborns may be enlarged due to maternal estrogen. Rugated tissue on the labia majora warrants further investigation to rule out an intersex disorder. If the labia minora appear fused, the child likely has labial adhesions. The amount of morbidity associated with labial adhesions is currently unknown. Some experts feel that most labial adhesions will

167

E D U C A T I O N

C O N T I N U I N G E D U C A T I O N

resolve independently with the advent of puberty (Brown et al., 1997). Nonetheless, many pediatric urologists recommend the lysis of asymptomatic labial adhesions. In any case, if the child is symptomatic the adhesions must be addressed. The most definitive treatment for minor labial adhesions is lysis of the adhesions with local anesthetic in the office. It is critical that once the adhesions are lysed, that the caregiver applies an ointment daily to the raw edges of the labia minora so that the adhesions do not recur. Premarin® cream (conjugated estrogen), betamethasone cream, and Vaseline® (petrolatum) have all been used to treat labial adhesions with varying success; Premarin cream is usually the first choice.

Vaginal Voiding Girls with vaginal voiding usually present with post void dribbling, external vaginal irritation, and a vaginal odor. Diagnosis can be made by a consistent history and examination. While in the frog-leg position, inspect the urethral orifice and the hymenal ring, a thickened structure with a central orifice, which covers the vaginal opening. Observe the introitus for an odor and any urine collection. These may be indications of vaginal voiding, wherein urine is trapped in the vaginal vault causing proliferation of bacteria and resulting in local irritation, post void dribbling, and an odor. It is important to exclude any other more serious GU conditions prior to diagnosing a child with vaginal voiding. An ectopic ureter can be differentiated from vaginal voiding by the timing of the dribbling. Vaginal voiders are only wet immediately after urination, whereas a child with an ectopic ureter will constantly be “leaking.” Refer to the article in this issue by Berry to differentiate dysfunctional voiding from vagi-

168

nal voiding, but they are often associated with one another. Vaginal voiding can easily be addressed by having the girl remove her pants to her ankles before voiding, and instructing her to lean forward with her legs spread wide in order to void. Baking soda baths twice daily for 3 consecutive days can reduce the local irritation and decrease the odor associated with chronic vaginal voiding.

Summary The genitourinary examination is vital to the overall health maintenance of any child. A comprehensive GU history and a baseline GU examination are important to establish with each pediatric patient. Once the baseline is established, most common GU complaints can be efficiently diagnosed by an advanced practice provider in the outpatient setting. When the diagnosis or appropriate management is in doubt, referral should be made to a specialist in pediatric urology. •

References Bogaert, G., & Kogan, B. (1997). Undescended testes (Chapter 7). In L.S. Baskin, B.A. Kogan, & J.W. Ducket (Eds.), Handbook of pediatric urology. Philadelphia: Lippincott-Raven. Bickley, L.S. (1999). Bates guide to physical examination and history taking (7th ed.). Chapter 19. Philadelphia: Lippincott, Williams & Wilkins. Brown, M.R., Cartwright, P.C., & Snow, B.W. (1997). Common office problems in pediatric urology and gynecology. Pediatric Urology, 44(5), 1091-1115. Gill, F.T. (1998). Umbilical hernia, inguinal hernias, and hydroceles in children: Diagnostic clues for optimal patient management. Journal of Pediatric Health Care, 12, 231-235. Kogan, B. (1997). Hydrocele/hernia (Chapter 6). In L.S. Baskin, B.A. Kogan, & J.W. Ducket (Eds.), Handbook of pediatric urology. Philadelphia: Lippincott-Raven. Redman, J.F., & Reddy, P.P. (2001). Common urologic problems in children: Guides to evaluation and referral, part II. The Journal of the Arkansas Medical Society, 98(1) 2224. Schneck, F.Y., & Bellinger, M.F. (2002). Abnormalities of the testes and scrotum and their surgical management (Chapter 67). In P.C. Walsh, A.B. Retik, E.D. Vaughan, & A.J. Wein (Eds.), Camplbell’s urology (8th ed.). Philadelphia: Saunders. Sheldon, C.A., (2001). The pediatric genitourinary examination: Inguinal, urethral and genital diseases. Pediatric Urology, 48(6) 1339-1367.

Need additional CE credits? Visit the Urologic Nursing section of SUNA’s Web site for online CE articles. www.suna.org

UROLOGIC NURSING / June 2005 / Volume 25 Number 3

UNJ J504

Answer/Evaluation Form: Pediatric Genitourinary Examination: A Clinician’s Reference This test may be copied for use by others.

Answer Form:

Objectives This educational activity is designed for nurses and other health care professionals who care for, evaluate, and educate patients and their families regarding pediatric genitourinary (GU) examinations. For those wishing to obtain CE credit, an evaluation follows. After studying the information presented in this offering, you will be able to: 1. Describe a baseline history in a thorough GU evaluation. 2. Discuss frequent GU presentations such as indirect inguinal, hydrocele, and varicocele. 3. Define other common GU presentations such as undescended testis, hypospadias, phimosis, and meatal stenosis. 4. Describe GU presentations such as penile adhesions, labial adhesions, and vaginal voiding.

1. If you applied what you have learned from this activity into your practice, what would be different?

Posttest Instructions

COMPLETE THE FOLLOWING: Name: ______________________________________________________________ Address: ____________________________________________________________ City: ___________________________State: _______________Zip:____________ Preferred telephone: (Home)_________________ (Work)__________________ SUNA Member Expiration Date: ______________________________________ Registration fee:

SUNA Member: Nonmember:

$12.00 $20.00

______________________________________________________________________ ______________________________________________________________________ ______________________________________________________________________ ______________________________________________________________________ Evaluation

Strongly disagree

Strongly agree

2. By completing this activity, I was able to meet the following objectives: a. Describe a baseline history in a thorough GU evaluation. 1 2 3 4 5

b. Discuss frequent GU presentations such as indirect inguinal, hydrocele, and varicocele.

1

2

3

4

5

c. Define other common GU presentations such as undescended testis, hypospadias, phimosis, and meatal stenosis. 1

2

3

4

5

d. Describe GU presentations such as penile adhesions, labial adhesions, and vaginal voiding.

1

2

3

4

5

3. The content was current and relevant.

1

2

3

4

5

4. The objectives could be achieved using the content provided.

1

2

3

4

5

5. This was an effective method to learn this content.

1

2

3

4

5

6. I am more confident in my abilities since completing this material.

1

2

3

4

5

7. The material was (check one) ___new ___review for me

1. To receive continuing education credit for individual study after reading the article, complete the answer/evaluation form to the left. 2. Detach and send the answer/evaluation form along with a check or money order payable to SUNA to Urologic Nursing, CE Series, East Holly Avenue Box 56, Pitman, NJ 08071–0056. 3. Test returns must be postmarked by June 30, 2007. Upon completion of the answer/evaluation form, a certificate for 1.4 contact hour(s) will be awarded and sent to you.

This activity has been provided by the Society of Urologic Nurses and Associates, which is accredited as a provider of continuing nursing education by the American Nurses' Credentialing Center's Commission on Accreditation (ANCC-COA). SUNA is a provider approved by the California Board of Registered Nurses, provider number CEP 05556. Licenses in the state of CA must retain this certificate for four years after the CE activity is completed.

This article was reviewed and formatted for contact hour credit by Sally S. Russell, MN, CMSRN, SUNA Education Director; and Jane Hokanson Hawks, DNSc, RN, BC, Editor.

8. Time required to complete the reading assignment: _____minutes

I verify that I have completed this activity: _____________________________ Comments _________________________________________________________________________ _________________________________________________________________________

UROLOGIC NURSING / June 2005 / Volume 25 Number 3

169

C O N T I N U I N G E D U C A T I O N

FOR THE PALLIATIVE TREATMENT OF ADVANCED PROSTATE CANCER

a powerful Takedown

VANTAS is contraindicated in patients with hypersensitivity to GnRH, GnRH agonist analogs, or any components in VANTAS. VANTAS is contraindicated in women and pediatric patients and was not studied in women or children. VANTAS, like other LHRH agonists, causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new symptoms including bone pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction. Cases of ureteral obstruction and spinal cord compression, which may contribute to paralysis with or without fatal complications, have been reported with LHRH agonists. If spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted. The most common systemic side effects were hot flashes (65.5%), asthenia (9.9%), implant site reaction (5.8%), testicular atrophy (5.3%), and renal impairment (4.7%). Five of the 8 patients had a single occurrence of mild renal impairment (defined as creatinine clearance ≥30 and 2% of patients (Table 1).

WARNINGS Vantas, like other LH-RH agonists, causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new symptoms, including bone pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction (see PRECAUTIONS). Cases of ureteral obstruction and spinal cord compression, which may contribute to paralysis with or without fatal complications, have been reported with LH-RH agonists. If spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted.

Table 1: Incidence (%) of Possibly or Probably Related Systemic Adverse Events Reported by > 2% of Patients Treated with Vantas for up to 24 Months Body System

Adverse Event

Number

(%)

Vascular Disorders General Disorders

Hot flashes* Fatigue Weight increased Implant site reaction Erectile dysfunction * Gynecomastia * Testicular atrophy * Insomnia Libido decreased * Renal impairment** Constipation Headache

112 17 4 10 6 7 9 5 4 8 6 5

(65.5%) (9.9%) (2.3%) (5.8%) (3.5%) (4.1%) (5.3%) (2.9%) (2.3%) (4.7%) (3.5%) (2.9%)

Skin and Appendage Disorders Reproductive System and Breast Disorders

PRECAUTIONS General: Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy (see WARNINGS). Implant insertion is a surgical procedure. Careful adherence to the recommended Insertion and Removal Procedures (see DOSAGE & ADMINISTRATION) is advised to minimize the potential for complications and for implant expulsion. In addition, patients should be instructed to refrain from wetting the arm for 24 hours and from heavy lifting or strenuous exertion of the inserted arm for 7 days after implant insertion.

Brief Summary to come

In all clinical trials combined, an implant was not recovered in 8 patients. For two of these (see CLINICAL PHARMACOLOGY; Clinical Studies), serum testosterone rose above castrate level and the implant was neither palpable nor visualized with ultrasound. These two implants were believed to have been extruded without appreciation by the patients. In the other six, serum testosterone remained below the castrate level, but the implant was not palpable. No further diagnostic tests were conducted. One of these patients underwent in-clinic surgical exploration that did not locate the implant. Based upon these findings, it is important to know that Vantas is not radio-opaque and therefore will not be visible through X-ray. However, in the instance where the implant is difficult to locate by palpation, ultrasound and CT scan may be used. Information for Patients: An information leaflet for patients is included with the product and should be given to the patient.

Laboratory tests: Response to Vantas should be monitored by measuring serum concentrations of testosterone and prostate-specific antigen periodically, especially if the anticipated clinical or biochemical response to treatment has not been achieved. Results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions. Drug Interactions: See PHARMACOKINETICS.

Psychiatric Disorders

Drug/Laboratory Test Interactions: Therapy with histrelin results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after histrelin therapy may be affected.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity studies were conducted in rats for 2 years at doses of 5, 25 or 150 mcg/kg/day (up to 15 times the human dose) and in mice for 18 months at doses of 20, 200, or 2000 mcg/kg/day (up to 200 times the human dose). As seen with other LH-RH agonists, histrelin acetate injection administration was associated with an increase in tumors of hormonally responsive tissues. There was a significant increase in pituitary adenomas in rats. There was an increase in pancreatic islet-cell adenomas in treated female rats and a non-dose-related increase in testicular Leydig-cell tumors (highest incidence in the low-dose group). In mice, there was significant increase in mammary-gland adenocarcinomas in all treated females. In addition, there were increases in stomach papillomas in male rats given high doses, and an increase in histiocytic sarcomas in female mice at the highest dose. Mutagenicity studies have not been performed with histrelin acetate. Saline extracts of implants with and without histrelin were negative in a battery of genotoxicity studies. Fertility studies have been conducted in rats and monkeys given subcutaneous daily doses of histrelin acetate up to 180 mcg/kg for 6 months and full reversibility of fertility suppression was demonstrated. The development and reproductive performance of offspring from parents treated with histrelin acetate has not been investigated.

Renal and Urinary Disorders Gastrointestinal Disorders Nervous System Disorders

* Expected pharmacological consequences of testosterone suppression. ** 5 of the 8 patients had a single occurrence of mild renal impairment (defined as creatinine clearance > 30 < 60 mL/min), which returned to a normal range by the next visit. Hot flashes were the most common adverse event reported (65.5 % of patients). In terms of severity, 2.3% of patients reported severe hot flashes, 25.4 % of patients reported moderate hot flashes and 37.7% reported mild hot flashes. In addition, the following possibly or probably related systemic adverse events were reported by 15 mm seemed to be diagnosed with an UPJ obstruction, compared with none of the fetuses with an APRPD