Chapter 37. Pediatric & Adolescent Gynecology

Pediatric and adolescent gynecology is a unique subspecialty of gynecology that encompasses reproductive health care of girls and young women under the age of 20 years, although some experts extend the age limit to 22 years.

This field has expanded greatly over the last decades, as increased attention has been directed to disorders of developmental physiology. The spectrum of gynecologic problems that a physician might encounter in young girls is age specific and involves different skills than those applied for adults. Currently, pediatric and adolescent gynecology includes a vast array of diagnoses and treatment modalities for these particular patients.

Pediatric and adolescent gynecology starts with an observation of abnormal external genitalia in a newborn. Later on in childhood, it involves early detection of infections, labial adhesions, congenital anomalies, and even genital tumors. With adolescents, normal pubertal development, evaluation of menstrual disorders, and treatment of genetic and hormonal ailments need to be addressed. Educational approach should be implemented for issues of budding sexuality in teenagers. Concomitantly counseling of proper use of contraceptives is imperative to lower the rates of teen pregnancies and sexually transmitted infections.

The American College of Obstetricians and Gynecologists recommends that adolescents should have their first visit to a gynecologist for health guidance, general physical screening, and the provision of preventive health care services at age 13–15 years. A pelvic examination of adolescents who are sexually active may be deferred until the age of 18 years, unless medically indicated. This first visit should provide an opportunity for the gynecologist to start the physician–patient relationship, recommend proper health behaviors, and dispel myths and fears.

The first gynecologic visit is of paramount importance in establishing a trustful relationship between the young woman and her health care provider for many years to come.

Newborn Infants

During the first few weeks after birth, follicle-stimulating hormone (FSH) rises in the newborn due to the abrupt withdrawal of placental and maternal sex steroid hormones, resulting in hyperestrogenic physiologic effect. Breast budding occurs in nearly all female infants born at term. In some cases, breast enlargement is marked, and there may be fluid discharge from the nipples. No treatment is indicated. The labia majora are bulbous, and the labia minora are thick and protruding (Fig. 37–1). The clitoris is relatively large, with a normal index of 0.6 cm2 or less.* The hymen initially is turgid, covering the external urethral orifice. Vaginal discharge is common in some cases and can even be bloody for the first 2 weeks, and is composed mainly of cervical mucus and exfoliated vaginal cells. Endometrial cell shedding might occur.

The vagina is approximately 4 cm long at birth. The uterus is enlarged (4 cm in length) and without axial flexion; the ratio between the cervix and the corpus is 3:1. Columnar epithelium protrudes through the external cervical os, creating a reddened zone of physiologic eversion. The ovaries remain abdominal organs in early childhood before descending into the pelvis.

*Clitoral index (cm2) = Length (cm) × width (cm). For example, a clitoris 1 cm long and 0.5 cm wide = 0.5 cm2.

Young Children

In early childhood, the female genital organs receive little estrogen stimulation. The labia majora flatten. The labia minora are thin structures running beside the upper part of vestibule and ending at the 3 and 9 o'clock positions. The hymen become thin (Fig. 37–2) and atrophic. The clitoris remains relatively small, although the clitoral index is unchanged. The vagina, lined with atrophic mucosa with relatively few rugae, offers very little resistance to trauma and infection. The vaginal barrel contains neutral or slightly alkaline secretions and mixed bacterial flora. Because vaginal fornices do not develop until puberty, the cervix in childhood is flush with the vaginal vault, and its opening appears as a small slit. The uterus regresses in size and does not regain the size present at birth until approximately age 6 years. At laparotomy, the uterus may appear as merely a strip of dense tissue in the anteromedial area of the broad ligaments. The ovaries at this age have the volume of 1–2.7 mL with small resting follicles (Table 37–1).

Older Children

During late childhood (age 7–10 years), the external genitalia again show signs of estrogen stimulation: the mons pubis thickens, the labia majora fill out, and the labia minora become rounded. The hymen thickens, losing its thin, transparent character. The vagina elongates to 8 cm, the mucosa becomes thicker, the corpus uteri enlarge, and the ratio of cervix to corpus becomes 1:1. The cervix remains flush with the vault (Fig. 37–3).

By the time a girl reaches age 9–10 years, uterine growth begins, with alteration in uterine shape resulting primarily from myometrial proliferation. Rapid endometrial proliferation occurs as menarche is imminent. Prior to this time, the endometrium gradually thickens, with modest increases in the depth and complexity of the endometrial glands. As the ovaries enlarge and descend into the pelvis, the number of ovarian follicles increases. Although these follicles are in various stages of development, ovulation generally does not occur.

Young Adolescents

During early puberty (age 10–13 years), the external genitalia take on adult appearance. The major vestibular glands (Bartholin's glands) begin to produce mucus just prior to menarche. The vagina reaches adult length (10–12 cm) and becomes more distensible, the mucosa thickens, vaginal secretions grow more acidic, and lactobacilli reappear. With the development of vaginal fornices, the cervix becomes separated from the vaginal vault, and the differential growth of the corpus and cervix becomes more pronounced. The corpus grows twice as large as the cervix. The ovaries descend into the true pelvis.

Secondary sexual characteristics develop, often rapidly, during the late premenarchal period. Body habitus becomes more rounded, especially the shoulders and hips. Accelerated somatic growth velocity (the adolescent growth spurt) occurs. At the same time, estrogen increases adipose tissue deposition and initiates stromal and ductal growth in the breasts. Physiologic leukorrhea often is noted.

Pubic hair growth, or pubarche (adrenarche), appears to be under the control of adrenal androgens and is a process that is independent of although associated with gonadarche. Sparse, long, slightly curly, pigmented hair over the pubic area gives way to coarse, pigmented curly hair. The pubic hair pattern assumes the characteristic triangle with the base above the mons pubis. Hair growth in the axilla appears later, also as a result of adrenocorticosteroid stimulation. The development of secondary sexual features described by Marshall and Tanner is summarized in Table 37–2 (see Fig. 4–3).

Examination of the Newborn Infant

Newborns should be examined immediately upon delivery or in the nursery. When an infant is born with ambiguous genitalia, immediate actions should be to counsel the parents and to prevent dehydration, as congenital adrenal hyperplasia accounts for >90% of cases of ambiguous genitalia, and salt-wasting forms may lead to rapid dehydration and fluid imbalances. In most cases, an internal examination is unnecessary, as most gynecologic abnormalities that should be recognized at this stage are limited to the external genitalia.

General Examination

As in adults, the first step in a genital evaluation of the newborn is a careful general examination, which may reveal abnormalities suggesting genital anomaly (eg, webbed neck, abdominal mass, edema of the hands and legs, coarctation of the aorta).

Clitoris

Clitoral enlargement in the newborn almost always is associated with congenital adrenal hyperplasia. Other causes, such as hermaphroditism and neoplasms, also must be considered.

Vulva & Vagina

The vaginal orifice should be evident when the labia are separated or retracted. If the vaginal orifice cannot be located, the infant most likely has an imperforate hymen or vaginal agenesis. Inguinal hernias are uncommon in females, and the presence of bilateral inguinal masses suggests the possibility that the child is a genetic male and may require karyotype testing.

Rectoabdominal Examination

Usually, the uterus and adnexa in the newborn cannot be palpated on rectal examination; therefore, is occasionally needed. An ovary that is palpable on abdominal examination denotes enlargement, and the possibility of an ovarian tumor should be investigated, even though pelvic masses in newborns likely represent a Wilms' tumor.

Examination of the Premenarchal Child

The examination of the premenarchal and peripubertal child should focus on the main symptoms identified in this population: pruritus, dysuria, skin color changes, and discharge.

Parents can be helpful during the examination of a young child because they provide a sense of security and they can distract the patient. Placing a child up to age 5 years on her parent's lap affords a better opportunity to perform an adequate examination. Older children can be placed on the examination table so the examiner may have adequate exposure of the genitalia when the patient is asked to flex her knees and abduct her legs. Asking the young patient to assist in the examination may distract the child as well as provide her with a sense of control. In rare cases, the knee–chest position may be useful in visualizing the upper vagina and cervix.

In older girls, explaining procedures and providing health information during the examination may decrease apprehension and help establish a good patient–physician relationship.

Physical Examination

General Inspection

The examination begins with an evaluation of the patient's general appearance, nutritional status, body habitus, and any gross congenital anomalies.

Breasts

Breast budding does not normally begin before the age of 7.5–8 years. Prominence of the nipple and breast development at an earlier age may be early signs of sexual precocity. Appropriate monitoring may include assessment of bone age, as well following height and breast development at 3-month intervals.

Abdomen

Inspection and palpation of the abdomen should precede examination of the genitalia. If the child is ticklish, having her place one hand on or under the examiner's hand usually will overcome the problem.

The ovary of a premenarchal child is situated high in the pelvis. This location and the small size of the pelvic cavity tend to force ovarian tumors above the true pelvic brim. Thus, large neoplasms of the ovary are likely to be mistaken for other abdominal masses (eg, polycystic kidney). Although inguinal hernias are less common in females than in males (approximately 1:10), they may occur, usually without discomfort. An excellent method of demonstrating an inguinal hernia is to have the child stand up and increase the intra-abdominal pressure by blowing up a balloon.

Genitalia

The vulva and vestibule can be exposed by light lateral and downward pressure on each side of the perineum, a technique referred to as labial separation. When exposure of the vaginal walls is necessary, the labia can be grasped between the examiner's thumb and forefinger and pulled forward, downward, and sideways, a technique called labial traction (Fig. 37–4). Particular attention should be paid to the adequacy of perineal hygiene, because poor hygiene may predispose a child to local inflammation. The examiner should look for skin lesions, perineal excoriations, ulcers, and tumors. Signs of hormonal stimulation in early childhood and absence of such signs later in adolescence are important signs of endocrine disorders associated with precocious or delayed puberty. Enlargement of the clitoris is of diagnostic significance, especially during early pubertal development, because it alerts the clinician to the presence of an endocrinopathy.

The normal hymen has multiple configurations including annular, crescentic, and fimbriated/redundant. Special attention to hymen appearance is given during forensic examination of sexual abuse victims, and the examiner should be familiar with vast variations of normal anatomy.

In some patients, the vestibule or the vaginal orifice may not be visible because of labial adhesions or congenital anomalies. The former condition is frequently mistaken for vaginal agenesis or imperforate hymen.

It is unnecessary to perform a digital vaginal examination in a child whose vagina is very narrow and in whom the hymeneal orifice is small and extremely sensitive. Gentle rectal digital examination can be accomplished, but accurate intrapelvic evaluation is better achieved by other diagnostic procedures such as sonography, computed tomography, vaginoscopy, or laparoscopy.

Vaginoscopy

Instrumentation is required when it is necessary to carefully visualize the upper third of the vagina for a source of abnormal vaginal bleeding, to detect and remove foreign bodies, or to exclude penetrating injuries. The water endoscope (hysteroscope, cystoscope) distends the vagina and permits visualization of the vaginal mucosa, while washing away secretions, blood, and debris (Fig. 37–5).

In infancy and childhood, the hymenal orifice normally is smaller than 1 cm. An instrument 0.3–0.4 cm in diameter can be used to examine those girls. Topical lidocaine gel can be used to anesthetize the vulva and provide lubrication in older premenarchal girls. In younger girls and in cases where the aperture is too small to allow instrument passage without patient discomfort, vaginoscopy should not be further attempted without general anesthesia.

Vaginoscopy is a safe and short procedure with few, if any, adverse effects; therefore, it should be used frequently as a diagnostic tool. A “see and treat” approach may be applied to both diagnose and take care of the problem with the same equipment.

Examination of the Adolescent

The adolescent's first trip to the gynecologist is often laden with fear and apprehension. Time spent putting the patient at ease and winning her confidence will save time and frustration in the examining room. The communicative skills that permit establishment of a good physician–patient relationship with teenagers can be acquired by training. The physician should make it clear that the adolescent is the patient, rather than the accompanying adult, if present. Questions about high-risk behaviors, including sexual behavior and sexually transmitted diseases (STDs), should be asked privately without the presence of the accompanying adult.

The American College of Obstetricians and Gynecologists recommends that adolescents should have their first visit to a gynecologist for health guidance, general physical screening, and the provision of preventive health care services at age 13–15 years. It is reasonable to observe even those who are not sexually active in each stage of adolescence: early adolescence, ages 13–15; middle adolescence, ages 15–17; and late adolescence, ages 17–19.

Unfortunately, many adolescents do not seek health care until after first intercourse. In the United States, the median age of first sexual intercourse is 16.5 years, but as many as 7% of adolescents report their first vaginal intercourse before 13 years of age.

After the history is taken, the patient should be given a brief description of what the examination entails. Girls under the age of 18 years should be informed that pelvic examination is not necessary unless medically indicated, yet an external genital examination can provide an opportunity to familiarize adolescents with normal anatomy and allow the practitioner an opportunity to visualize the perineum for any anomalies. The girl should be assured that any examination will not be painful. While performing the physical examination, the health care provider should reassure the adolescent about her normal anatomy and proper development. Following the examination, the patient is given an opportunity to speak alone with the examiner. Confidentiality is essential to the physician–patient relationship, and problems can be discussed with the patient's guardians only with the patient's consent.

The examination should start with general inspection. A breast examination is an integral part of the physical examination of every female patient, followed by abdominal palpation.

The examination is also used to provide the patient with health maintenance instructions and explanations about her body and its various functions. Many adolescents are not familiar with the appearance of their own genitalia. Some physicians use mirrors during the examination to show normal anatomic details, to demonstrate abnormalities, and to provide explanations regarding health maintenance. Others use a colposcope attached to a video monitor; this provides an enlarged image seen simultaneously by the examiner and the patient and permits direct communication.

The introitus of most virginal adolescents is approximately 1 cm in diameter and will admit a narrow speculum when clinically indicated. The Huffman-Graves and Pedersen specula both are designed to allow for easy inspection of the cervix in adolescents, in whom the vagina is 10–12 cm long (Fig. 37–6). In a patient with a large hymenal opening, bimanual examination is performed by inserting a finger into the vagina. If the hymenal orifice is too small for digital examination, rectal examination can be performed.

All sexually active girls should be screened annually for chlamydia and gonorrhea. Urine-based sexually transmitted infection (STI) testing is an efficient means for accomplishing such screening without speculum examination.

The gynecologic visit serves as an excellent opportunity to review basic health care maintenance. For example, current recommendations advise universal vaccination for hepatitis B for all adolescents at ages 11–12 years, with immunization for older adolescents based on risk status and discussion regarding human papillomavirus vaccine. In addition, screening for eating disorders, depression, and behavioral risks including sexual activity and tobacco, alcohol, and substance abuse should be done routinely. To assist providers of adolescent health care, the American Medical Association has issued recommendations based on annual health guidance, screening, and immunization schedules. For more information regarding specific legal rights for adolescents, the Guttmacher Institute has established a Web site for practitioner assistance (www.guttmacher.org).

Examination of the Young Victim of Sexual Abuse

Studies show that approximately 38% of girls are sexually victimized before age 18 years. Among adolescent girls in grades 9–12, 26% report experiencing physical or sexual abuse. Therefore, all adolescents should be asked about history of abuse. Many children who are possible victims of sexual abuse are brought to a hospital emergency room or to their physician's office for a comprehensive medical evaluation. Statutes vary from state to state as to the need for legal consent from a parent or guardian to perform a genital examination and collect evidence in cases of suspected abuse.

History

In some facilities, a designated individual conducts an investigative interview to minimize repetitive questioning of the child. When asking young children about abuse, line drawings, dolls, or other aids are generally used only by professionals trained in interviewing young children. However, this does not preclude the physician from asking relevant questions to obtain a detailed history, a review of systems, and basic information about the assault. An account of the incident is extremely valuable, as it can later be used in court as evidence, or it may reveal an unusual area of injury and thus uncommon sites for collection of evidence. It is important to know how and from whom the patient sustained the injury and whether the child is in a safe environment.

It is imperative that the clinician use questions that are not leading, avoid showing strong emotions such as shock or disbelief, and maintain a “tell me more” or “and then what happened” approach. The courts have allowed physicians to testify regarding specific details of the child's statements obtained in the course of taking a medical history to provide a diagnosis and treatment. The American Academy of Child and Adolescent Psychiatry and the American Professional Society on the Abuse of Children have published guidelines for interviewing sexually abused children.

The examiner should note the patient's composure, behavior, and mental state, as well as how she interacts with her parents and other persons. Victims of physical or sexual abuse must be removed immediately from an unsafe environment.

The information should be recorded carefully, using the patient's own words. Written notes in the medical record or audiotape or videotape should be used to document the questions asked and the child's responses. Although a detailed history is desirable, the victim should not be made to repeatedly recount the incident. When obtaining a history from a very young child is not possible, the physician should obtain accounts of the incident from other sources.

Physical Examination

The physical examination has 2 purposes: to detect and treat injuries and to collect samples that later can be used as evidence.

Detection of Injuries

Nonspecific findings are relatively common in young children. Vulvar irritation is often seen in small children as a result of poor local hygiene, maceration of the skin because of wetness from diapers, or excoriations caused by local infection. Such nonspecific findings should not be regarded as diagnostic of sexual abuse. It is important to remember that the examination is often normal in most children who were sexually abused. In one study of 2384 children who were seen in a tertiary referral center, <5% had genital findings suggesting abuse. The examination was deemed normal in 96.3% of children referred for the evaluation. Even so, interviews of the children indicated that 68% of the girls reported penetration of vagina or anus.

The physician should be familiar with normal genital anatomy, particularly that of the hymen, and should be able to distinguish hymenal trauma. A “clock system” approach is applied to describe hymen lacerations, which usually appear in the form of notches and clefts in the posterior rim between 3 and 9 o' clock. Studies showing that partial tears of the hymen, as well as abrasions and contusions, may heal to leave very little or no sign of previous injury emphasize the importance of urgent evaluations. Additional methods to demonstrate hymenal continuity involve saline irrigation on the posterior rim of the hymen or gentle pulling of Foley catheter balloon against the hymenal margins. In postpubertal girls, penetration and stretch trauma can result in hymeneal remnants.

Collection of Evidence

During the general inspection, all foreign material (eg, sand and grass) should be removed and placed in clearly labeled envelopes. Scrapings from underneath the fingernails and loose hairs on the skin are collected. Semen can be detected on the skin many hours after the assault. A Wood's lamp can be used to detect the presence of seminal fluid on the patient's body, because the ultraviolet light causes semen to fluoresce. The stain can be lifted off the skin with moistened cotton swabs for further analysis.

If vaginal penetration is suspected, vaginal fluid is collected and sent for sexual disease evaluation, wet-mount preparation, cytology, acid phosphatase determination, and enzyme p30. To avoid additional psychological trauma in a prepubescent child, these specimens can be collected without the insertion of a pediatric speculum, via vaginal aspiration using a feeding tube or Angiocath. An immediate wet-mount preparation done by the examining physician may detect motile sperm.

Culture swabs are obtained from the rectum, vagina, urethra, and pharynx. Current data indicate that a prepubertal child with gonorrhea or trichomonas most likely had genital–genital contact. The mode of transmission of other STIs is controversial. Testing for STIs, including human immunodeficiency virus (HIV), should be offered. In pubertal girls, postcoital contraception should be recommended.

All specimens must be clearly labeled and the containers and envelopes sealed and signed by the examiner. All persons handling the materials must sign for them. Such a system is necessary to maintain the chain of evidence; otherwise, these specimens may not be admissible in court. Some hospitals provide preassembled “rape kits” that guide the examiner in documenting and collecting specimens in a manner suitable for legal uses.

If an STI or other signs of abuse are found, all states require that the findings be reported to child protective service agencies for investigation of sexual abuse. Furthermore, it is important to keep in mind that a normal physical examination does not exclude the possibility of sexual abuse.

The reproductive organs in the female consist of external genitalia, internal duct system (the müllerian ducts), and the gonads. These 3 components originate embryologically from different primordia. External genitalia, including the lower part of vagina, are formed predominantly from the urogenital sinus. The müllerian (paramesonephric) duct system, after complex developmental changes, ends with a final configuration of fallopian tubes, the uterine corpus and cervix, and the upper portion of the vagina. The gonads are derived from the endoderm beneath the coelomic epithelium (detailed embryologic development is described in Chapter 2).

The etiology of these defects is not fully understood. Most forms are of isolated occurrence. Müllerian duct and urogenital sinus malformations are inherited in a polygenic/multifactorial fashion. Considering the influence of embryologic development on adjacent structures (gastrointestinal and urinary systems), one may encounter associated malformations in those systems as well.

Anomalies of the Vulva & Labia

Minor differences in the contour or size of vulvar structures are not unusual. Often there is considerable variation in the distance between the posterior fourchette and the anus or between the urethra and the clitoris. Rare anomalies of the vulva include bifid clitoris, a caudal appendage resembling a tail; congenital prolapse of the vagina; and variations in the insertion of the bulbocavernosus muscle, which may alter the appearance of the labia majora and at times obliterate the fossa navicularis. Duplication of the vulva is an extremely rare anomaly, which may be associated with duplication of the urinary or intestinal tracts.

There is considerable variation in the size and shape of the labia minora. One of the labia may be considerably larger than the other, or both labia may be unusually large. These variations usually require no treatment (Fig. 37–7). If asymmetry is significant or if large labia are pulled into the vagina during intercourse, the hypertrophied labia can be trimmed surgically to provide a more symmetric appearance or to relieve dyspareunia.

Anomalies of the Clitoris

Clitoral enlargement almost invariably suggests exposure to elevated levels of androgens. Such enlargement is often associated with fusion of the labioscrotal folds and could be part of the sexual ambiguity and disorders of sex development. Recklinghausen's neurofibromatosis, lymphangiomas, and fibromas may also involve the clitoris and cause enlargement. When an isolated neoplasm causes enlargement of the clitoris, therapy consists of excision of the neoplasm with reduction of the clitoris to normal size.

In children with disorders of sex development, clitoral reduction is often performed as part of therapy once the diagnosis is made and a female gender is assigned. Many techniques have been described. Although the surgery is often performed in early childhood, the long-term effects on sexual function are unknown. A recent study of 39 adults who had intersex conditions with ambiguous genitalia and who were living as females showed that those who had undergone clitoral surgery had higher rates of nonsensuality and of inability to achieve orgasm. The authors concluded that sexual function of adult females could be compromised by clitoral surgery.

Anomalies of the Hymen

Hymenal anomalies result from incomplete degeneration of the central portion of the membrane. Variations include imperforate, microperforate, septate, and cribriform hymens. Hymenal anomalies require surgical correction if they block vaginal secretions or menstrual fluid, interfere with intercourse, or preclude the use of tampons.

Providers should be aware that there have been reports of familial occurrence of hymenal abnormalities and thus alert young women that their daughters may have a similar abnormality.

Imperforate Hymen

Imperforate hymen has an incidence of 1 in 1000 and represents a persistent portion of the urogenital membrane. It occurs when the mesoderm of the primitive streak abnormally invades the urogenital portion of the cloacal membrane. The normal perforation occurs late in fetal life. When mucocolpos develops from accumulation of vaginal secretions behind the hymen, the membrane is seen as a shiny, thin bulge (Fig. 37–8). The distended vagina forms a large mass that may interfere with urination and at times may be mistaken for an abdominal tumor. The diagnosis is quite easy, and resection of the hymen is recommended in the symptomatic infant only. Topical anesthetic is used to prevent discomfort to the newborn, and the central portion of the obstructing membrane is excised. Aspiration should be avoided due to the risks of recurrence and ascending infection. Asymptomatic girls can be monitored throughout childhood, with the optimal time for surgery being just after the onset of puberty.

Imperforate hymen often is not diagnosed until an adolescent presents with complaints of primary amenorrhea and cyclic pelvic pain. It may present as back pain or difficulty with defecation or urination secondary to mass effect from vaginal distention. Inspection of the vulva may reveal a purplish-red hymenal membrane bulging outward as a result of accumulation of blood above it (hematocolpos) (Fig. 37–9). Blood may fill the uterus (hematometra) and spill through the fallopian tubes into the peritoneal cavity. Endometriosis and vaginal adenosis are known but not inevitable complications.

The procedure is usually done under general anesthesia with the patient in lithotomy position. A Foley catheter is used to drain the bladder and properly delineate the urethra. A primary small crescentic incision is done in the central part of hymenal bulging membrane; after evacuation of the old blood, the hymenal orifice should be enlarged to allow the egress of menstrual flow, tampon use, and eventually comfortable sexual intercourse. A small incision may coalesce, allowing the obstructing membrane to reform.

The actual incidence of müllerian anomalies is not definitively known. An incidence of 3.2% was identified in several studies on fertile women. Urinary tract abnormalities are the most common anomalies associated with müllerian defects, including ipsilateral renal agenesis, duplex collecting systems, renal duplication, and horseshoe kidneys. In female patients with renal anomalies, the incidence of genital defects is estimated to be between 25% and 89%.

Anomalies of the Vagina

Transverse Vaginal Septum

Transverse vaginal septa result from faulty fusion or canalization of the urogenital sinus and müllerian ducts. The incidence is approximately 1 in 30,000 to 1 in 80,000 women. Approximately 46% occur in the upper vagina, 40% in the midportion, and 14% in the lower vagina. When the septum is located in the upper vagina, it is likely to be patent, whereas those located in the lower part of the vagina are more often complete. The septum is usually less than 1 cm thick and is rarely associated with uterine anomalies.

A complete septum results in signs and symptoms similar to those of an imperforate hymen. Diagnosis is often delayed until after menarche, when menstrual blood is trapped behind an obstructing membrane. An incomplete septum usually is asymptomatic at menarche, as the central aperture allows for vaginal secretions and menstrual flow to egress from the vagina. The first symptoms may appear at the beginning of sexual intercourse, resulting in dyspareunia.

Treatment

If the diagnosis of a complete septum is established prior to menarche, ultrasound or magnetic resonance imaging (MRI) may help define the septum and its thickness preoperatively. It is extremely important to identify a cervix, most reliably seen on MRI, to differentiate between a high septum and congenital absence of the cervix. The corrective surgery consists of septum incision, creating an aperture to allow drainage. Incision of a complete septum is most easily accomplished when the upper vagina is distended and the membrane is bulging, reducing the risk of injury to adjacent structures. Because of the technical difficulties in performing intravaginal surgery on immature structures, it is best to limit the procedure only to allow the establishment of vaginal drainage.

Surgical correction of vaginal narrowing should be performed only when the patient is contemplating initiation of sexual activity. Thin septum can be excised with its surrounding ring of subepithelial connective tissue at the level of partition followed by primary end-to-end anastomosis of the upper and lower vaginal mucosa; thicker septum may require undermining and mobilization of the upper and lower vaginal mucosa before anastomosis. To avoid scar contracture and vaginal stenosis, a circumferential Z-plasty can be helpful. Postoperatively, use of vaginal mold or dilators may further decrease the risk of vaginal stenosis.

Longitudinal Vaginal Septum

Longitudinal vaginal septum forms when the distal ends of the müllerian ducts fail to fuse properly. The uterus may be septate or bicornuate, with 1 or 2 cervices (Fig. 37–10). As many as 20% of patients with longitudinal vaginal septum may present with associated renal abnormalities and occasionally with anorectal malformations, including imperforated anus with rectovestibular fistula and cloaca.

Asymptomatic longitudinal septum requires no treatment. Division of the septum is indicated when dyspareunia is present, vaginal delivery dystocia is anticipated, or worsening of dysmenorrhea occurs. The menstrual pain derives from accumulation of blood in obstructed hemivagina, while normal blood exits from the nonobstructed portion. Care should be taken to avoid damage to the cervix while resecting the upper part of the septum.

Vaginal Agenesis (MüLlerian Aplasia)

Vaginal agenesis includes the congenital absence of the vagina accompanied by variable müllerian duct development (Mayer-Rokitansky-Kuster-Hauser [MRKH] syndrome). The incidence of vaginal agenesis is approximately 1 in 5000. The external genitalia of patients with vaginal agenesis are normal or may reveal only a small dimple at the vaginal introitus (Fig. 37–11). Vaginal agenesis is usually accompanied by cervical and uterine agenesis; however, 7–10% of affected individuals may have a normal uterus or rudimentary uterus with functional endometrium.

Other developmental defects are often present, affecting the urinary tract (45–50%), the spine (10%), and, less frequently, the middle ear and other mesodermal structures. Evaluation of those systems should be performed soon after diagnosis.

Persons with vaginal agenesis typically have normal female karyotypes with normal ovaries and ovarian function; thus, they develop normal secondary sexual attributes. Patients often present with primary amenorrhea or, in women with functioning uteri, with cyclic pelvic pain. Serum testosterone level and karyotyping may identify the rare instances in which müllerian agenesis represents the effects of testicular activity, indicating male pseudohermaphroditism.

Treatment

The consultation of the adolescent with vaginal agenesis and her family involves a multidisciplinary approach. It should consist of confirmation of the ability to create a functional vagina and emphasize that she has normal ovarian function and thus preserved fertility with assisted reproductive technology and surrogacy.

Creation of a satisfactory vagina is the objective of treatment of vaginal agenesis. Treatment should be deferred until the patient is contemplating sexual activity. Nonoperative creation of a vagina using serial vaginal dilators, in a method described by Frank and later modified by Ingram, is relatively risk-free but requires patient motivation and cooperation. The procedure takes a few months to complete. Repetitive coitus can also be used to create a functioning vagina. Recent studies have shown that use of dilators resulted in 85–90% success for creation of functional vagina.

Surgical creation of neovagina is another option, and discussion should fully describe that many surgical techniques will require postoperative dilatation to maintain vaginal adequacy. Currently, there are multiple operative methods but no consensus on the best approach.

The modified Abbé–McIndoe vaginoplasty is most commonly performed. The procedure involves the creation of a cavity by surgical dissection between the urethra and bladder anteriorly and the perineal body and rectum posteriorly. The cavity is lined by a split-thickness skin graft overlying a plastic or soft silicone mold. The labia minora are secured around the mold for 7 days prior to removal. Postoperatively, the patient must continue to use dilators for several months to maintain vaginal patency. Patient satisfaction rates greater than 80% have been reported. Complications include graft failure, hematoma, fistula formation, and rectal perforation.

The laparoscopic Davydov technique uses the patient's own pelvic peritoneum to line the neovagina. It involves dissection of the perineum to create a neovaginal space while laparoscopically mobilizing the peritoneum. The peritoneum is then sutured to the introitus, and a purse-string suture closes the cranial end of the neovagina. A vaginal mold is left in situ for 6 weeks, and the patient then begins daily dilation until regularly sexually active. Complications related to laparoscopic injury and fistula formation have occurred; however, patients report similar sexual function to women with a native vagina.

The modified laparoscopic Vecchietti procedure creates a dilation-like neovagina in 7–9 days. It involves placement of an acrylic 2-cm olive-shaped bead onto the vaginal dimple that is gradually pulled superiorly by threads laparoscopically placed that are then connected to the traction device placed on the patient's abdomen. The threads are then gradually tightened approximately 1.0–1.5 cm per day for a week. Postoperatively, the patients must comply with daily vaginal dilation until regularly sexually active.

Bowel vaginoplasty is the preferred method of most pediatric general surgeons, given the immediate and long-term correction of the anomaly. Each bowel segment has advantages and disadvantages. Bowel vaginoplasty is performed by selecting an approximately 10-cm segment of bowel that can be mobilized but retain an adequate vascular pedicle to reach the perineum. Sigmoid vaginoplasty has been the most commonly used bowel segment, given its proximity to the perineum and therefore little difficulty performing a tension-free anastomosis to the introitus.

Postoperative sexual satisfaction has been assessed in a validated fashion in only a relatively small number of patients who underwent bowel vaginoplasty. Seventy-five percent of patients reported satisfaction.

Partial Vaginal Agenesis (Atresia)

Vaginal atresia occurs when the urogenital sinus fails to contribute to the lower portion of the vagina. The affected segment of the vagina is replaced by a soft mass of tissue. The cause of this uncommon anomaly is unknown. Absence of the distal vagina may be identified by sonographic visualization of the accumulated blood in the upper vagina, cervix, and uterus.

The symptoms are similar to those associated with imperforate hymen after the menarche. Vulvar inspection reveals findings identical with those of vaginal agenesis, but rectoabdominal palpation reveals a large, boggy pelvic mass. Diagnostic imaging using sonography, computed tomography (CT), or MRI will confirm the diagnosis.

Treatment

Surgery is indicated because obstruction to menstrual flow may occur. In some patients, drainage of the uterus can be achieved through a reconstructed vagina. In others, particularly when the uterus is rudimentary, consideration may be given to performing a hysterectomy.

Anomalies of the Uterus

Uterine anomalies result from agenesis of the müllerian duct or a defect in fusion or canalization. The classification by the American Society for Reproductive Medicine (ASRM) is most accepted. These anomalies include bicornuate uterus (37%), arcuate uterus (15%), incomplete septum (13%), uterine didelphys (11%), complete septum (9%), and unicornuate uterus (4%).

Most uterine anomalies are asymptomatic and therefore are not detected during childhood or early adolescence. Symptoms during adolescence are primarily caused by retention of menstrual flow. MRI can be helpful in determining the anatomy in cases complicated by obstructive anomalies and is often considered as the “gold standard” for imaging of anomalies in reproductive tract (Fig. 37–12).

Asymptomatic abnormalities often escape detection until they interfere with reproduction; thus, they are described in more detail in other chapters of this text.

Unicornuate Uterus & Rudimentary Uterine Horn

A unicornuate uterus is a single-horned uterus with its corresponding fallopian tube and round ligament. It results from agenesis of 1 müllerian duct, with absence of structures on that side. When the other hemiuterus is present, it often creates a small rudimentary uterine horn. If this rudimentary horn does not communicate with the other uterine cavity or the vagina, menstrual blood cannot escape, resulting in severe dysmenorrhea, hematometra, or pyometra. A pregnancy that occurs in a rudimentary horn may result in rupture, a complication that is potentially fatal for both mother and fetus (Fig. 37–13).

Ideally, a rudimentary horn should be resected before conception. The tube and ovary on the affected side can be preserved, provided that the blood supply is not impaired. If the endometrial cavity of the remaining horn is entered during the operation, caesarean section is a reasonable mode of delivery for any subsequent pregnancies.

As suspected with unilateral impairment in müllerian development, associated renal anomalies are common. Patients with müllerian anomalies with a unicornuate uterus are at increased risk of premature labor and breech presentation. As in other obstructive anomalies, endometriosis and subsequent fertility issues may be significant in patients with an associated obstructed uterine horn or hemiuterus (Fig. 37–14).

Bicornuate Uterus & Septate Uterus

The bicornuate uterus results from partial fusion of the müllerian ducts, leading to varying degrees of separation of the uterine horns. The fundus is deeply indented, often heart-shaped. Presently, no surgical intervention is recommended, and patients are followed closely for obstetric concerns, although reproductive function is good overall. In most cases, the vagina is normal.

The septate uterus has a smooth, normal external surface at the fundus, but the endometrial cavity is split into 2 by a midline septum. There are higher risks for miscarriage and other obstetrical complications. Hysteroscopic resection of septum is currently the technique of choice and almost totally replaces abdominal metroplasty. The surgical correction may improve reproductive performance. However, in young women, the decision to surgically intervene before attempts at pregnancy still remains unclear. The presence of a concomitant vaginal septum may influence the timing of intervention.

Anomalies of the Ovaries

During development, the ovaries, which are abdominally located in the neonate, descend to the pelvis at puberty. The ovaries may be drawn by the round ligament into the inguinal canal or the labium major. A firm inguinal mass should alert the examiner to the possible presence of an aberrant gonad, possibly containing testicular elements, even in the presence of female external genitalia. A karyotype should be obtained. At the time of hernia repair, the gonad should be biopsied. If it proves to be an ovary, it should be returned to the peritoneal cavity and the hernia repaired. If a testis is identified, the gonad should be removed. During childhood, the ovary is never at rest, and follicles grow and degenerate continuously.

Gonadal Dysgenesis (Turner's Syndrome)

Turner's syndrome is a disorder in females characterized by the absence of all or part of a normal second sex chromosome. Approximately half of patients have monosomy X (45,X). Most of the rest have mosaicism for 45,X, with 1 or more additional cell lineages, and others (5–10%) have a duplication (isochromosome) of the long arm of 1 X chromosome [46,X,i(Xq)]. Turner's syndrome occurs in 1 in 2500 to 1 in 3000 live-born girls.

The genetic disorder leads to a constellation of physical findings that often includes congenital lymphedema, short stature, and gonadal dysgenesis. In addition, broad chest and small nipples, webbed neck, coarctation of the aorta, renal abnormalities, prominent epicanthal folds, nevi, and other somatic anomalies (eg, short fourth metacarpal) frequently occur. In most adults with gonadal dysgenesis, the normal gonad is replaced by a white fibrous streak, 2–3 cm long and approximately 0.5 cm wide, located in the gonadal ridge. Histologically, the streak gonad is characterized by interlacing waves of dense fibrous stroma, indistinguishable from normal ovarian stroma.

Increased atresia and failure of germ cell formation deplete oocyte supply, but when atresia is incomplete, pubertal changes, spontaneous menstruation, and even pregnancies have been reported.

One-fifth to one-third of affected girls receive a diagnosis as newborns because of puffy hands and feet or redundant nuchal skin. However, in many, the condition is not diagnosed until adolescence when they fail to enter puberty. Turner's syndrome is the most common cause of short stature in otherwise healthy girls; therefore, karyotype testing should be considered in children and adolescents with height stature below the third percentile.

Girls with Turner's syndrome need gonadal hormone therapy for sexual development, enhancement of growth, maintenance of reproductive tissue, and psychosocial health. In addition, prevention of chronic disease, specifically bone loss and possible early heart diseases, needs to be addressed in these girls.

The administration of very-low-dose estradiol (ethinyl estradiol 100 ng/kg/d) in combination with growth hormone at an early age has been shown to assist in enhancing and promoting optimal pubertal height and age-appropriate feminization.

Anomalies of the Urethra & Anus

Failure of a newborn infant to pass meconium or urine demands investigation. Passage of feces or urine through the vagina suggests a fistulous communication, and usually either the urethra or the anus is imperforate.

In general, anomalies are divided into 2 major groups: those that form complete obstruction of the intestinal tract and those that are associated with some type of abnormal opening or fistula.

Because findings are so diverse, only broad generalizations on the management of urogenital anomalies of this type can be offered. Most intestinal and urinary tract obstructions must be corrected soon after birth; however, some associated genital tract anomalies (eg, müllerian anomalies), although diagnosed at the same time, might benefit from postponing final correction until after the onset of puberty.

Vulvovaginitis

Pruritus vulvae and vulvovaginitis are common gynecologic disorders in children. Pruritus vulvae refers to itching of the external female genitalia. Vulvovaginitis, although inconsistently delineated in the literature, generally involves irritation of the skin or mucosal tissue and vaginal discharge. The child is susceptible to both these conditions for several reasons: The prepubertal vulva is thin without labial fat pads and pubic hair, as well as anatomically in close proximity to the anus and its contaminants; the unestrogenized vagina is atrophic with pH ranges excellent for bacterial growth; and perineal hygiene often is suboptimal as supervision declines with age. Table 37–3 lists classification of vulvovaginitis according to cause.

Clinical Findings

Acute vulvovaginitis may denude the thin vulvar or vaginal mucosa; however, bleeding usually is minimal. Vaginal discharge may vary from minimal to copious mucopurulent, and at times, it is blood-stained. Symptoms vary from minor discomfort to relatively intense perineal pruritus. The child often complains of a burning sensation, particularly when urine flows, accompanied by a foul-smelling discharge. Vulvovaginitis should be excluded in children prior to treatment for urinary tract infection. The irritating discharge inflames the vulva and often causes the child to scratch the area to the point of bleeding. Inspection of the vagina reveals an area of redness and soreness that may be minimal or may extend laterally to the thighs and backward to the anus.

Diagnosis is suspected by the typical appearance of the inflamed tissue. A wet-mount preparation reveals numerous leukocytes and occasional red blood cells. Culture of vaginal secretions sometimes identifies the offending organism.

Evaluation of the vaginal secretions may include smears for Gram stain, bacterial cultures, cultures for mycotic organisms, wet prep, Trichomonas, and parasitic ova.

Improvement of perineal hygiene is important to relieve the symptoms and to prevent recurrences. Most cases of nonspecific pruritus vulvae resolve with improvements in hygiene and avoidance of irritants, including soaps.

Any evidence of pathogens that are usually involved in STIs must be followed by evaluation of sexual abuse.

Amoxicillin (20–40 mg/kg/d in 3 divided doses) is effective against a variety of potentially pathogenic organisms in nonspecific vulvovaginitis. A concomitant tonsillitis should raise the suspicion of genital inoculation by Streptococcus group A pathogens and should be treated the same way as the throat infection. In cases with intense perianal pruritus that is especially bothersome during the night, antiparasitic treatment could alleviate the symptoms. Infection with Candida species is quite rare in healthy children after diaper weaning until the onset of puberty. When the infection is severe and extensive mucosal damage is seen, a short course of topical estrogen cream is given to promote healing of vulvar and vaginal tissues. When irritation is intense, hydrocortisone cream may be necessary to alleviate the itch. In recurrent infections refractory to treatment or associated with a foul-smelling, bloody discharge, vaginoscopy is necessary to exclude a foreign body or tumor.

Foreign Bodies

Vaginal foreign bodies induce an intense inflammatory reaction and result in blood-stained, foul-smelling discharge. Usually, the child does not recall inserting the foreign object or will not admit to it. Radiographs are not reliable for revealing a foreign body because many objects are not radiopaque, the most common being a small piece of reincarnated toilet paper. Foreign bodies in the lower third of the vagina can be flushed out with warm saline irrigation. If the vagina cannot be adequately inspected in the office even after removal of the foreign body, vaginoscopy is indicated to confirm that no other foreign bodies are present in the upper vagina. General anesthesia is applied in some cases, based on the age and psychosocial development of the patient.

Urethral Prolapse

Occasionally, vulvar bleeding is the result of urethral prolapse. The urethral mucosa protrudes through the meatus and forms a hemorrhagic, sensitive vulvar mass that is separated from the vagina. Treatment consists of warm soaks and a short course of therapy using estrogen cream, when the lesion is small and urination is unimpaired. Resection of the prolapsed tissue should be reserved for a symptomatic child with indwelling catheter inserted for 24 hours after surgery.

Lichen Sclerosus

Lichen sclerosus of the vulva is a hypotrophic dystrophy with prevalence of 1 in 900 girls. It has bimodal age distribution in postmenopausal period and in prepubertal age. Histologically, the findings in both age groups are similar, with flattening of the rete pegs, hyalinization of the subdermal tissues, and keratinization.

The clinical presentation includes a whitish ivory colored lesion that does not extend beyond the middle of the labia majora laterally or into the vagina medially (Fig. 37–15). The clitoris, posterior fourchette, and anorectal areas are frequently involved, forming a figure of 8. Although most lesions are predominantly white, some have pronounced vascular markings. They tend to bruise easily, forming bloody blisters, and they are susceptible to secondary infections. Symptoms consist of intense pruritus, vulvar irritation, and dysuria. Scratching is common and occasionally provokes bleeding or leads to secondary infection and introital distortion.

Histologic confirmation is not necessary in children as opposed to postmenopausal women because of no known malignant potential in this age group. Treatment usually consists of improved local hygiene and reduction of trauma. Currently, the use of ultrapotent topical corticosteroids (clobetasol propionate 0.05%) once or twice daily for 4–8 weeks is accepted as first-line therapy. Occasionally, symptom relief does not occur before 12 weeks of treatment. New treatments with topical calcineurin inhibitors seem to be effective; however, their long-term safety has not been determined. Over half of children improve significantly or recover during puberty.

Labial Adhesion

Labial adhesion is common in prepubertal children with an estimated occurrence of 0.6–3.0% and a peak incidence at 13–23 months. The cause is not known but probably is related to low estrogen levels. The skin covering the labia is extremely thin, and local irritation may induce scratching, which may denude the labia. The labia then adhere in the midline, and re-epithelialization occurs on both sides (Fig. 37–16). It is important to differentiate this condition from congenital absence of the vagina.

Most children with small areas of labial adhesions are asymptomatic. Dysuria and recurrent urinary infections are cardinal symptoms in those with complete or anterior adhesion, although infrequent.

Asymptomatic minimal to moderate labial fusion does not require treatment. Symptomatic fusion may be treated with a course of estrogen cream applied twice daily for 3–12 weeks resulting in successful separation in 50–88% of the cases. When approaching puberty in girls with medical treatment failure or if severe urinary symptoms exist, surgical separation of the labia is indicated. This can be performed in the operating room under anesthesia or as an in-office procedure using 1–2% topical lidocaine (Xylocaine) gel. Because of low estrogen levels, recurrences of labial adhesion are common until puberty. After puberty, the condition resolves spontaneously. Improved perineal hygiene and removal of vulvar irritants may help prevent recurrences.

Genital Injuries

Most injuries to the genitalia during childhood are accidental. Many are of minor significance, but a few are life-threatening and require surgical intervention. The physician must determine how the child sustained the injury, bearing in mind that the child requires protection if she is the victim of physical or sexual abuse.

Vulvar Injuries

Contusion of the vulva mainly from straddle injury usually does not require treatment. A hematoma manifests as a round, tense, ecchymotic, tender mass (Fig. 37–17). A small vulvar hematoma usually can be controlled by pressure with an ice pack. The vulva should be kept clean and dry. A hematoma that is large or continues to increase in size may require incision, with removal of clotted blood and ligation of bleeding points. If the source of bleeding cannot be found, the cavity should be packed with gauze and a firm pressure dressing applied. The pack is removed in 24 hours. Prophylactic broad-spectrum antibiotics may be advisable.

When a large hematoma obstructs the urethra, insertion of a catheter is necessary, usually by a suprapubic approach. Radiography of the pelvis may be necessary to rule out pelvic fracture.

Vaginal Injuries

Vaginal injuries occur when a girl falls on a sharp object and impales herself; additionally, there is an increasing rate of accidents involving insufflation injuries caused by a fall off jet skis or direct contact with pool or spa jets, allowing pressurized water to enter the vagina. Such injuries might produce no sign of external genital trauma, but careful examination (often under anesthesia) will reveal the extent of injury.

When the hymen is lacerated or other evidence indicates an object has entered the vagina or penetrated the perineum, a detailed examination of the whole vaginal canal is necessary to exclude injuries to the upper vagina or intrapelvic viscera (Fig. 37–18).

Most vaginal injuries involve the lateral walls. Generally, there is relatively little blood loss, and the child does not have much pain if only the mucosa is damaged. If the laceration extends beyond the vaginal vault, exploration of the pelvic cavity is necessary to rule out extension into the broad ligament or peritoneal cavity. Bladder and bowel integrity must be confirmed by catheterization and rectal palpation. Because of the small caliber of the organs involved, special instruments, as well as proper exposure and assistance, may be required for repair of vaginal injuries in young girls. Alternatively, the bleeding may be controlled by angiographic embolization of the bleeding vessel. Many vaginal lacerations are limited to the mucosal and submucosal tissues and are repaired with fine suture material after complete hemostasis is secured.

Anogenital Injuries Caused by Abuse

Sexual abuse is defined as coerced or forced vaginal, anal, intercrural, and oral–genital fondling or penetration. Many children who are victims of sexual abuse do not sustain physical injuries. The hymen is examined in a “clock”-defined method, being at the 12 o'clock position under the clitoris and 6 o'clock position above the anus, independent of child position during the evaluation. The diagnosis of sex abuse, which was once focused on genital measurements, mainly hymenal configuration, is currently based on descriptive statements made by a child.

The hymen is an elastic structure, and therefore, it does not always demonstrate signs of abuse on examination. In a published study of 2310 children referred for possible sexual abuse, 96.3% of all children had a normal examination. In another study, pregnant adolescents were found to have an intact hymen as well. Unfortunately, even when injured, many of these children may not be seen for weeks, months, or even years after the incident. The delay allows for semen and debris to wash away and for most, if not all, injuries to heal.

Injuries to the vulva may be caused by manipulation of the vulva or introitus, without vaginal penetration, or by friction of the penis against the child's vulva (“dry intercourse”). Erythema, swelling, skin bruising, and excoriations are found on the labia and vestibule. These injuries are superficial and often limited to the vulvar skin; they should resolve within a few days and require no special treatment.

Meticulous perineal hygiene is important in the prevention of secondary infections. Sitz baths should be used to remove secretions and contaminants. In some patients with extensive skin abrasions, broad-spectrum antibiotics should be given as prophylaxis. Large vulvar tears require suturing, which is best performed under general anesthesia. For infected wounds or bites, antitetanus immunization should be given if the child is not already immunized. Broad-spectrum antibiotics should be used for therapy rather than prophylaxis.

Most vaginal injuries occur when an object penetrates the vagina through the hymenal opening. A detailed examination including vaginoscopy is necessary to exclude injuries to the upper vagina.

Examination of the anus and rectum is easier than is examination of the vagina, and most children tolerate it well. Because the anal sphincter and anal canal allow for some dilatation, a tear of the anal mucosa or sphincter rarely occurs following a digital assault. However, penetration by a larger object almost always results in some degree of injury, which varies from swelling of the anal verge to gross tearing of the sphincter. In the period immediately following penetration, the main findings are sphincter laxity resulting in anal dilatation, swelling, and small tears of the anal verge. If the sphincter is not severed, it may be in spasm and will not permit a digital examination. Within days, the swelling subsides and the mucosal tears heal, occasionally forming skin tags. If not severed, the anal sphincter regains function. Repeated anal penetration over a prolonged period may cause the anal sphincter to become loose, forming an enlarged opening. The anal mucosa thickens and loses its normal folds. Although some investigators suggest that many children who experience anal assault exhibit perianal scars and tags, longitudinal studies show that anal injuries heal completely in most children.

Occasionally, child victims of abuse contract an STI. The risk of a prepubertal child contracting an STI after sexual assault is relatively low, estimated to range from 2–5%. Treatment of gonorrhea, chlamydia, and syphilis may be deferred until the results of tests become available. A repeat VDRL (Venereal Disease Research Laboratory) test to detect seroconversion is required 6 weeks later. Prophylaxis for hepatitis B with hepatitis B vaccination is recommended following sexual assault. For nonimmune victims with a high-risk exposure, practitioners may also consider adding hepatitis B immune globulin to the regimen. The Sexually Transmitted Diseases Treatment Guidelines do not recommend the routine screening for HIV for all child victims of sexual abuse. Clinicians should try to identify children who are at high risk for HIV exposure and consider offering them counseling and prophylactic therapy. In pubertal girls, the need for postcoital contraception must be addressed. Guidelines for the care of the child and adolescent who has experienced sexual abuse are best found in the literature dedicated to the topic.

Female genital mutilation (female circumcision), which can be viewed as a form of child abuse, is still practiced in some parts of the world. It is estimated that 100–140 million girls and women have undergone some form of female genital mutilation. Victims may suffer from infections, bleeding injury to adjacent tissue, and scarring of the damaged tissue, resulting in urinary and menstrual retention, dyspareunia, and difficulties with childbirth. The World Health Organization and other health organization have openly condemned this practice.

Protective Services & Counseling

It is imperative to ensure that the child will be discharged to a safe environment. When the child is suspected of being a victim of sexual abuse, it is advisable to admit her to the hospital, followed by referral to child protective services for further evaluation.

In the period immediately following sexual assault or disclosure of sexual abuse, the child and her family often require intensive day-to-day emotional support, counseling, and guidance. Child victims often show signs of depression and have feelings of guilt, fear, and low self-esteem. Appropriate referral for counseling is imperative. The major emphasis of emotional support involves strengthening the child's ego, improving her self-image, and helping her to learn to trust others and feel secure again. To begin the strengthening process, the child needs to realize that she was a victim. Often, the child has both positive and negative feelings toward the perpetrator and may need help in sorting out these feelings. The child's relationships with her parents and other family members are critical and may need restructuring. Following this crisis intervention phase, a treatment program using individual and peer-group therapy is initiated.

Genital Neoplasms

Genital tumors are uncommon but must be considered when a girl is found to have a chronic genital ulcer, nontraumatic swelling of the external genitalia, tissue protruding from the vagina, a fetid or bloody discharge, abdominal pain or enlargement, or premature sexual maturation. Virtually every type of genital neoplasm reported in adults has also been found in girls younger than 14 years. Approximately 50% of the genital tumors in children are premalignant or malignant and account for 1% of all childhood malignancies.

Benign Tumors of the Vulva & Vagina

Teratomas, hemangiomas, simple cysts of the hymen, retention cysts of the paraurethral ducts, benign granulomas of the perineum, and condylomata acuminata are some of the benign vulvar neoplasms observed in children and adolescents.

Obstruction of a paraurethral duct may form a relatively large cyst that distorts the urethral orifice. The recommended treatment is surgical intervention.

Teratomas usually present as cystic masses arising from the midline of the perineum. Although a teratoma in this area may be benign, local recurrence is likely. To prevent recurrences, a generous margin of healthy tissue is excised about the periphery of the mass.

Capillary hemangiomas usually require no therapy except reassurance. However, because of their tendency to bleed, cavernous hemangiomas are best treated surgically.

Most benign tumors of the vagina in children are unilocular cystic remnants of the mesonephric duct (Fig. 37–19) and do not require surgery. Symptomatic cysts (eg, those that block the vagina) can be treated surgically. Removal of a large portion of the cyst wall and marsupialization of the edges, which prevents reaccumulation of fluid, usually are sufficient.

Malignant Tumors of the Vagina & Cervix

Botryoid Sarcoma (Embryonal Rhabdomyosarcoma)

Embryonal rhabdomyosarcomas are most commonly seen in very young girls (<3 years old). The tumor usually involves the vagina, but the cervix may be affected as well, particularly in the teenager group, and these tumors have a better prognosis. The clinical presentation is characterized by vaginal bleeding in a child and irregular bleeding in the pubertal girl. Tumors arise in the submucosal tissues and spread rapidly beneath an intact vaginal epithelium. In the early stages, the tumor can be seen by vaginoscopy as 1 or more polypoid projections into the vaginal cavity; later on, it bulges into a series of grapelike growths out of the vestibule (thus the term botryoid sarcoma; Fig. 37–20). The diagnosis is made on the basis of histologic evaluation. Occasionally, electron microscopy may be required to confirm the final diagnosis.

Over the years, there has been a shift in the treatment of this condition from radical surgery to a multimodal approach involving conservative surgery with chemotherapy and radiotherapy. This approach has been associated with improved survival and preservation of normal anatomy and function.

The operative intervention frequently consists just of cervical conization or simple hysterectomy with preservation of the ovaries. It is then followed by combination chemotherapy (vincristine, dactinomycin, and cyclophosphamide).

Early detection and the combination of surgery, chemotherapy, and occasionally radiation for residual tumor have improved the prognosis of patients, with 2- and 5-year survival rates for early disease reaching >96% and 83%, respectively.

Other Malignant Tumors of the Vagina

Three types of vaginal carcinoma may appear during childhood and the early teens. Endodermal carcinoma occurs most often in young children. Carcinoma arising in a remnant of a mesonephric duct (mesonephric carcinoma) occurs more often in girls 3 years of age or older. Clear cell adenocarcinoma of müllerian origin, often associated with a history of antenatal exposure to diethylstilbestrol (DES), is encountered most frequently in postmenarchal teenage girls. The clinical features and treatment of malignant lesions of the vagina and cervix are similar to those in adult women.

Ovarian Tumors

With the increasing use of imaging modalities, greater numbers of ovarian cysts are being diagnosed. The majority of these cysts are asymptomatic and regress spontaneously with time; therefore, many clinicians prefer to observe only. The decision to intervene is based on cyst size, ultrasound characteristics, and clinical symptoms.

Ovarian Torsion

Based on the abdominal location of the ovary and the long utero-ovarian ligament, the adnexa of prepubertal girls are at increased risk of torsion, with a reported prevalence of 3%. The diagnosis is complicated by its vague clinical presentation. The only consistent symptoms are abdominal pain and ovarian enlargement on the same side as demonstrated by sonography. Doppler flow studies may further contribute to the diagnosis; however, even presence of flow in the ovarian vessels should not preclude the clinical impression. When ovarian torsion is suspected, a prompt surgical procedure should be carried out for diagnosis and appropriate management, usually accomplished by operative laparoscopy. During surgery, a conservative approach is advocated because of the enormous revitalization ability of ovarian tissue in these patients and the low rate of true neoplasms; 25% of patients have normal ovaries, and another almost 50% of patients have functional cysts involved. Oophoropexy should be considered in cases of recurrent torsion or single ovary involvement.

Although ovarian tumors are the most common genital neoplasm encountered in children and adolescents, they represent only 1% of all neoplasms in premenarchal children. Ovarian tumors of all varieties (except Brenner's tumors) have been reported in premenarchal children, but in this population, they are rarely malignant.

Benign Tumors

Benign cystic teratomas (dermoid cysts) account for at least 30% of all neoplasms in this age group, with an 18% incidence and bilaterality in 10% of cases. They are usually asymptomatic and diagnosed by abdominal sonography performed for other indications. Expectant management for cysts smaller than 6 cm might be reasonable, considering the low risk for torsion and malignant transformation (<0.17%) and the increased risk of jeopardizing reproductive function with surgical treatment.

Other tumors, such as functional teratoma and gonadoblastoma, are rare and managed by surgical removal.

Malignant Tumors

Seventy percent of ovarian cancers in youth are of germ cell origin, with dysgerminoma accounting for half of them. Although the most common symptoms of ovarian tumors are abdominal pain and an abdominal mass, acute severe pain, peritoneal irritation, or intra-abdominal hemorrhage can be the presenting sign. Despite the advancement in imaging technology applied for exploration of ovarian masses, at least 25% of all childhood ovarian tumors elude diagnosis until exploratory laparotomy is performed. The use of serum markers, such as inhibin or α-fetoprotein, may be helpful in children with ovarian enlargement.

The management of ovarian neoplasms in premenarchal children varies from that in older patients, because continued ovarian function is necessary to complete sexual and somatic maturation in children. In postpubertal patients, surgical intervention should aim, whenever possible, to preserve reproductive potential. Unilateral salpingo-oophorectomy is usually undertaken in young women with stage IA tumors (<10 cm, removed unruptured without evidence of metastatic spread). Approximately 8–15% of dysgerminomas are bilateral, and thus, the contralateral ovary is inspected and any suspicious areas are biopsied. If there is bilateral involvement, then the uterus can be left in situ for future reproduction options with ovum donation. The survival rate for patients treated for dysgerminoma in earlier stage was found to be 96.9%. If a tumor has extended beyond the ovary, more radical surgery (bilateral salpingo-oophorectomy with hysterectomy) is indicated, regardless of age. Germ cell tumors are highly responsive to chemotherapy, with the exception of dysgerminomas, which respond well to radiation; however, multiagent chemotherapy is used in those tumors as well in order to preserve reproductive potential.

Puberty

Puberty is the process by which sexually immature persons become capable of reproduction. These changes occur largely as the result of maturation of the hypothalamic–pituitary–gonadal axis. Puberty is characterized by progressive incline in gonadotropin-releasing hormone (GnRH) production, leading to increasing levels of FSH and luteinizing hormone (LH). These changes are obtained by 2 mechanisms occurring in the hypothalamus: increasing resistance to circulating estrogen levels and a decrease in inhibitory activity of neurotransmitters upon GnRH-secreting neurons. Changes are determined by genetic and environmental factors, such as geographic location and body fat composition, and mediated by the leptin and kisspeptin proteins. As a rule, breast development, which initially may be unilateral, growth of genital hair, and a marked increase in growth rate (adolescent growth spurt) precede uterine bleeding by approximately 2 years. The normal sequence of events in sexual development is outlined in Figure 37–21. Pubic and axillary hair may appear before, at about the same time, or well after the appearance of breast tissue. The vaginal mucosa, which in prepubertal girls is a deep red color, takes on a moist pastel pink appearance as estrogen exposure increases. Menarche—the first menstrual shedding of thickened endometrial lining—indicates the process of development of secondary sexual features. Regular ovulatory cycles, which usually occur 20 months later, mark the end of pubertal maturation.

The first menstrual period occurs at an average age of 12.43 years in girls in the United States. Although the age of menarche in African-American girls is quite similar, secondary sexual features often occur earlier.

Normal range of menarche is from age 10 to 14 years. In the presence of secondary sexual characteristics, medical intervention can be deferred until 16 years of age.

Disorders of Sexual Maturation

Precocious Puberty

Sexual precocity is the onset of sexual maturation at any age that is 2.5 standard deviations earlier than the normal age for that population, being usually before the age of 8 years. It may be classified as central, or GnRH-dependent, precocious puberty (true precocious puberty), or peripheral, or GnRH-independent, precocious puberty (pseudoprecocious puberty).

Central Precocious Puberty

Central precocious puberty (CPP), or GnRH-dependent precocious puberty, is normal pubertal development that occurs at an early age. Premature activation of the hypothalamic–pituitary axis is followed by gonadotropin secretion, which in turn stimulates the gonads to produce steroid hormones and, subsequently, pubertal changes. GnRH-dependent precocious puberty is seen more frequently in girls than in boys. The cause of such early development often remains unclear. Most girls suspected of having CPP are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curve. In general, the older the child is, the less the chance of finding an organic etiology for CPP. Central nervous system (CNS) imaging studies of these otherwise healthy 6- to 8-year-old girls usually reveal no structural abnormalities.

Occasionally, precocious puberty is associated with CNS abnormalities, including hypothalamic hamartomas, optic gliomas, and neurofibromas, as well as other CNS neoplasms. Cranial irradiation and CNS injuries may also be associated with precocious puberty. Prolonged excessive therapy with exogenous sex steroids or endocrine disorders such as hypothyroidism may accelerate hypothalamic–pituitary axis maturation, resulting in precocious puberty.

The diagnosis is made with the help of a careful history and physical examination in conjunction with radiologic and laboratory evaluations.

Peripheral GnRH-Independent Precocious Puberty

Peripheral precocious puberty, or GnRH-independent precocious puberty, is the appearance of pubertal development, but the presence of sex steroids is independent of pituitary gonadotropin release. Causes of precocious puberty include congenital adrenal hyperplasia, tumors that secrete human chorionic gonadotropin, tumors of the adrenal gland or gonads, McCune-Albright syndrome (MAS), and exposure to exogenous sex steroid hormones.

Endogenous Estrogens

The ovary in the newborn female contains 1–2 million primordial follicles, most of which undergo atresia during childhood without producing significant quantities of estrogen. However, large follicular cysts capable of estrogen production occur occasionally and may cause early feminization. Benign tumors of the ovary (eg, teratoma, cystadenoma) may produce estrogen or may induce surrounding ovarian tissue to produce steroids. Circulating sex steroids (estrogen or testosterone) come from either the adrenal gland or the gonad, independent of the hypothalamic–pituitary portion of the pubertal axis. Granulosa cell tumors capable of estrogen production are a rare cause of prepubertal feminization. Other rare tumors of extragonadal origin, including adrenal adenomas and hepatomas, may produce estrogens as well.

Exogenous Estrogens

Ingestion of estrogens or prolonged use of creams containing estrogens is a possible, but uncommon, cause of early feminization. A phytoestrogen-enriched diet (mostly soybean extracts) could exert a similar effect. Prompt discontinuation is indicated. Xenoestrogens (endocrine disruptors) found in rivers and soil of industrial regions might stimulate the estrogen receptors as well.

Mccune-Albright Syndrome

MAS in its classic form consists of at least 2 features of the triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation (Fig. 37–22), and autonomous endocrine hyperfunction, the most common form of which is GnRH secretion and subsequent precocious puberty. Other endocrine and nonendocrine tissues also may be affected, including the adrenal, thyroid, pituitary, liver, and heart.

MAS is caused by a postzygotic somatic mutation in the gene coding for the subunit of the stimulatory G protein, which is involved in transmitting hormone signals. In patients with MAS, the signaling cascades are activated in the absence of hormone stimulation.

Affected children usually present at a younger age than those with idiopathic precocious puberty. Vaginal bleeding occurs early and, in most, is the first sign of puberty. The diagnosis is made on the basis of skin pigmentation and demonstration of bone lesions or pathologic fractures.

The prognosis for children with MAS is unfavorable. Adult height is significantly reduced. Multiple endocrinopathies often exist as well. As in adults, most patients have menstrual abnormalities, and many are infertile.

Incomplete Forms of Pubertal Development

Occasionally, for reasons that remain unclear, only 1 sign of pubertal development is present. Premature thelarche and premature pubarche, which are more common conditions than true precocious puberty, are 2 benign normal variant conditions that can look like precocious puberty but are nonprogressive or very slowly progressive. It possibly results from transient elevations of the levels of circulating steroid hormones or from extreme sensitivity of the end organ (eg, breast tissue) to the low, prepubertal levels of sex hormones. Such isolated development, however, may represent the initial sign of precocious puberty, and these patients should be re-evaluated at regular intervals.

Premature Thelarche

Premature thelarche is the isolated development of breast tissue prior to age 8 years, most commonly occurring between 1 and 3 years of age. It may affect 1 or both breasts (Fig. 37–23). A thorough history, physical examination, and growth curve review can help distinguish this normal variant from true sexual precocity. On examination, the somatic growth pattern is not accelerated and bone age is not advanced. The diagnosis is made by exclusion of other disorders. Occasionally, premature thelarche occurs when the child is exposed to exogenous estrogens.

Premature Pubarche

Premature pubarche previously was defined as the appearance of pubic or axillary hair prior to age 8 years, without other signs of precocious puberty (Fig. 37–24). However, new guidelines suggest that this presentation should not be considered precocious unless noted before age 7 years in white girls and before age 6 years in black girls. Such hair growth may be idiopathic and of no clinical significance.

Premature pubarche probably results from an earlier-than-usual increase in the secretion of androgens by the adrenal glands. Regulation of adrenal androgen secretion is distinct from that of gonadal steroids. Early appearance of pubic hair may be a very early sign of developing polycystic ovary disorder and, therefore, should be followed up closely. The diagnosis of idiopathic premature pubarche is made only after thorough evaluation of adrenal and gonadal function that fails to detect an abnormality.

Signs of severe androgen excess (eg, clitoral enlargement, growth acceleration, acne) should prompt further investigation for a rare virilizing tumor (Leydig cell tumor) or a variant form of congenital adrenal hyperplasia.

Premature Menarche

Premature menarche denotes the appearance of cyclic vaginal bleeding in children in the absence of other signs of secondary sexual development. The cause is unknown but may be related to increased end-organ sensitivity of the endometrium to low prepubertal levels of estrogens. Alternatively, bleeding may be related to transient elevation of estrogens due to premature follicular development. These patients have estradiol levels in the prepubertal range, and when given GnRH, the response of the pituitary gland is similar to that seen in prepubertal children.

Thorough evaluation of the genital tract should be done to exclude other pathologies like tumors, which are seen in up to 20% of patients.

The diagnosis of premature menarche is formulated by exclusion and is confirmed when the cyclic nature of the bleeding becomes apparent. The prognosis is excellent. Adult height is uncompromised, the menstrual pattern is normal, and fertility potential remains unimpaired.

Evaluation of the Patient with Precocious Puberty

When evaluating the patient with sexual precocity, the age at onset, duration, and progression of signs and symptoms constitute important historical information. Family history and review of systems may add important facts.

General Changes

Enhancement of general growth and advanced skeletal maturation are coincident with the onset of estrogen-stimulated change acting directly on the growth plate of the bone.

Skin

Additional androgen-dependent findings include acne and adult-type body odor.

Breast Development

Breast development is at least at Tanner stage II, with the areolae having a broadened, darkened appearance.

Genitalia

Genital changes reflect estrogen-induced thickening of the genital tissues. Increased vaginal secretions may result in leukorrhea. Dark, coarse pubic hair may be present.

Diagnosis

The diagnosis of GnRH-dependent precocity requires demonstration of pubertal gonadotropin secretion. The diagnostic evaluation required to document early pubertal development and differentiate central from peripheral causes includes the determination of serum LH, FSH, and estradiol levels, and a GnRH stimulation test. In patients with GnRH-dependent precocious puberty, the results of these tests will be in the normal pubertal range.

With improvements in imaging technology, clinicians often order such studies to help establish the diagnosis. Sonography may aid in the evaluation of the ovaries and adrenal glands. Uterine size and endometrial thickness are estrogen dependent and serve as a good bioassay to determine the length of time and magnitude of estrogen exposure. Ovarian cysts and tumors are also visible. Sonography of the adrenal glands is less sensitive than abdominal CT and MRI. Skeletal imaging to document skeletal age and a bone scan may identify areas of fibrous dysplasia in patients with MAS. Brain MRI is indicated in patients with sexual precocity or with neurologic signs.

Treatment of GnRH-Dependent Precocious Puberty

The treatment of choice for GnRH-dependent precocious puberty is GnRH analogues. Analogues of GnRH are modifications of the native hormone, which have greater resistance to degradation and increased affinity for the pituitary GnRH receptors.

Treatment with GnRH analogues decreases gonadotropins and sex steroids to prepubertal levels, which is followed by regression of secondary sexual features. Treatment also causes a deceleration in the skeletal maturation rate, preserving or even improving predicted height, unless bone age is so advanced that further growth is precluded. The efficacy of GnRH analogs in increasing adult height is undisputed only in girls with early-onset (<6 years old) central precocious puberty. The decision of whether to treat with GnRH analogues is made based on the girl's predicted final height and her emotional maturity. Treatment is continued until puberty is appropriate based on age. Resumption of puberty occurs promptly after discontinuation of GnRH analogue therapy.

Delayed Sexual Maturation

Delayed sexual development has been defined as the absence of normal pubertal events at an age 2.5 standard deviations later than the mean. The absence of thelarche by age 14 years or the absence of menarche by age 16 years is an indication for investigation. Classification can be based on the gonadotropic level: eugonadotropic, hypogonadotropic, or hypergonadotropic primary amenorrhea.

Delayed Menarche with Eugonadotropic Function Including Hyperprolactinemia

Patients with functioning gonads and delayed sexual maturation usually consult a physician while they are in their mid-teens because of amenorrhea. Most have well-formed female configuration with adequately developed breasts. Many of these patients suffer from an inappropriate hypothalamic–pituitary–ovarian feedback mechanism, leading to anovulation and in some cases androgen excess as well. Primary amenorrhea may persist until a progestin challenge is given. Patients should be monitored for continued menstrual shedding. Persistent amenorrhea is treated with progestins administered every other month to prevent endometrial hyperplasia. A sexually active girl should be given oral contraceptives rather than cyclic progestins. Further evaluation is required for diagnosis of adult-onset congenital adrenal hyperplasia and those with polycystic ovarian disease.

The possibility of pregnancy in an adolescent who has not begun to menstruate is highly unlikely but must be borne in mind when considering causes of delayed menarche in patients with normal pubertal development.

Congenital Anomalies

Patients with congenital anomalies of the paramesonephric (müllerian) structures may complain of primary amenorrhea. The most common defect is congenital absence of the uterus and vagina. Other causes are obstructive abnormalities, such as imperforate hymen, transverse vaginal septa, and agenesis of the cervix. Gynecologic examination supplemented by pelvic sonogram or MRI establishes the diagnosis of these congenital anomalies.

Androgen Insensitivity

The complete forms of androgen insensitivity are also associated with amenorrhea and normal breast development. Affected persons have normal testicular function but are not responsive to testosterone, and the development of breasts is secondary to the small amounts of unopposed estrogens produced by the testis. Pubic and axillary hair is scant or often absent. A short blind vaginal pouch is present. Once pubertal development has been completed, surgical extirpation of the gonads and reconstruction of the vagina are necessary. Recent data suggest that regardless of the technique used, sexual function may be impaired in some of these young women. A study of 66 women with complete forms of androgen insensitivity showed that 90% had sexual difficulties, most commonly sexual infrequency and vaginal penetration difficulty.

Delayed Puberty with Hypogonadotropic (Hypothalamic) Dysfunction

Hypothalamic–pituitary dysfunction is characterized by low to normal levels of gonadotropins (FSH, LH), similar to prepubertal state.

Constitutional Growth Delay

The onset of puberty depends on an ill-defined stage of maturity that is reflected in skeletal age. Maturation is partly genetically determined but also depends on multiple environmental factors; thus the chronologic age of puberty varies considerably. Statistical limits of normal variation in a defined population group indicate that, by definition, 2.5% of all normal adolescents will develop later than the age defined as “normal.” This group has been labeled “late bloomers” or as having a constitutional growth delay (CGD). These girls often have retarded linear growth within the first 3 years of life, and then their growth resumes at a normal rate. As a result, these girls grow either along the lower growth percentiles or beneath the curve but parallel to it for the remainder of the prepubertal years.

At the expected time of puberty, the height of children with CGD begins to drift further from the growth curve because of delayed onset of the pubertal growth spurt. Catch-up growth, onset of puberty, and pubertal growth spurt occur later than average, resulting in normal adult stature and sexual development. Although CGD is a variant of normal growth rather than a disorder, absence of signs of puberty (including the growth spurt) often concerns the patient when her adolescent friends have developed secondary sexual features and gained the characteristic increase in height.

The diagnosis of hypothalamic–pituitary dysfunction is made by exclusion of other causes of delayed sexual maturation. Growth charts, bone age, and the GnRH challenge test differentiate constitutional delay from similar conditions associated with GnRH deficiency. Reassurance is the only treatment necessary, but the patient must be kept under observation until regular menstrual cycles are established. Occasionally, an adolescent requires hormonal replacement therapy because of emotional distress over her condition.

Kallmann's Syndrome

Kallmann's syndrome is a genetic condition characterized by hypogonadotropic hypogonadism and anosmia. It affects approximately 1 in 40,000 females, with most presentations of the “sporadic” type. Various forms of Kallmann's syndrome are inherited, and the gene responsible for the X-linked form has been identified.

The clinical features include deficiency of GnRH associated with anosmia. Because GnRH neurons originate extracranially within the olfactory system, both can be simultaneously affected, and the defects are believed to be secondary to abnormalities of neuronal migration during development. Patients with Kallmann's syndrome fail to develop secondary sexual features, and blood levels of gonadotropins are very low.

Patients with Kallmann's syndrome have a diminished gonadotropin response to the GnRH stimulation test. Pulsatile administration of GnRH for 1 week usually restores subsequent pituitary responsiveness to GnRH. All postpubertal-age patients with Kallmann's syndrome are candidates for gonadal steroid replacement therapy in the absence of specific contraindications. Estrogen replacement therapy is used to initiate and sustain sexual development. Induction of ovulation with human menopausal gonadotropins or GnRH is necessary when pregnancy is desired.

Brain Tumors

A pituitary or parasellar tumor, particularly craniopharyngioma or pituitary adenoma, must be considered in the evaluation of a patient with delayed sexual maturation. Craniopharyngiomas are rapidly growing tumors that often develop in late childhood. Pituitary adenomas are slow growing, may become symptomatic during puberty, and may interfere with sexual maturation.

Hyperprolactinemia

An occult pituitary prolactinoma in adolescents with unexplained delayed sexual maturation must be ruled out. Serum prolactin levels should be measured yearly in patients with unexplained delayed sexual maturation.

Eating Disorders

Weight loss due to extreme dieting causes marked decrease of fat tissue concentration, resulting in suppression of GnRH activity, even in cases of almost normal weight without notable loss of muscle (often seen in athletes). It should be emphasized that the very first sign of anorexia nervosa could be primary or secondary amenorrhea.

Heroin addiction may cause amenorrhea, but its effects on sexual maturation have not been documented.

Delayed Puberty with Hypergonadotropic Dysfunction

Gonadal Failure

Gonadal failure is characterized by high levels of gonadotropins (FSH, LH), similar to the menopausal state. The common pathway of all ovarian failure disorders is the prominent deficiency of estrogen and the essential need for estrogen-containing replacement therapy in order to achieve normal development and prevent late consequences of estrogen deprivation.

Most patients with gonadal dysgenesis present during adolescence with delayed puberty and primary amenorrhea. For young women with gonadal failure, the most common cause is Turner's syndrome, which occurs with an incidence of 1 in 2500 to 1 in 10,000 live births. The syndrome is sex chromosomal aberration of 45,X monosomy. If untreated, estrogen and androgen levels are decreased, and FSH and LH levels are increased. Estrogen-dependent organs show the predictable effects of hormonal deficiency. Breasts contain little parenchymal tissue, and the areolar tissue is only slightly darker than the surrounding skin. The well-differentiated external genitalia, vagina, and müllerian derivatives remain small. Pubic and axillary hairs fail to develop in normal quantity. These patients should be closely monitored for development of illness caused by affected systems, such as the cardiovascular, urinary, and endocrine systems.

However, normal pubertal development, menstruation, and even pregnancies have been reported in adults with gonadal dysgenesis. It is possible that a few of these persons maintain some germ cells into adulthood. Spontaneous development is more commonly observed in patients with mosaicism with a 46,XX line. The rare offspring of these women probably do not have an increased risk for chromosomal abnormalities. In order to achieve pregnancy in a majority of women with gonadal dysgenesis, ovum donation treatment by using assisted reproductive technology may be offered.

Some patients may have ovarian failure even though they have a normal chromosome complement and 2 intact sex chromosomes (46,XX). An autosomal recessive form of ovarian failure has been demonstrated in some families. A small percentage of ovarian failures may be reversible and may be predicted by detection of anti-müllerian hormone levels, although the assay has not yet demonstrated clinical yield. Other causes of follicular depletion include chemotherapy, irradiation, infections (eg, mumps), infiltrative disease processes of the ovary (eg, tuberculosis), autoimmune diseases, and unknown environmental agents.

A karyotype is necessary to rule out the presence of Y chromosome material. DNA probes and assays for the minor histocompatibility antigen H-Y have also been used to identify Y chromosome material. A high incidence of neoplastic changes in the gonadal ridge has been reported in the presence of a Y chromosome (Fig. 37–25), so prophylactic gonadectomy is recommended. Replacement hormonal therapy is then given in a cyclic manner.

Some patients have similar features, yet follicles are present but unresponsive, a condition called the resistant ovary syndrome. It is characterized by delayed menarche or primary amenorrhea, a 46,XX chromosome complement, high FSH levels, and ovaries with apparently normal follicular apparatus that do not respond to endogenous gonadotropins. Absence of follicular receptors for gonadotropins is assumed to be responsible for ovarian dysfunction in these patients. These individuals may have normally developed secondary sexual characteristics. Estrogen replacement therapy is required to prevent long-term complications of estrogen deficiency (eg, vaginal dryness, osteoporosis). Pregnancies have been reported in some patients treated with menotropins or following discontinuation of estrogen therapy.

Evaluation of the Patient with Delayed Sexual Development

Determination of gonadal function can be accomplished by obtaining a medical history and performing a detailed physical examination, supplemented by selected laboratory studies. Historical information should center around previous growth and pubertal development. Linear and velocity growth charts as well as a pubertal development chart clarify previous growth patterns and are useful in subsequent follow-up. Knowledge of previous medical disorders may immediately identify the cause of aberrant puberty.

Physical examination must include height and weight assessments and a careful search for somatic anomalies. Staging of pubertal development by Tanner criteria is most important in the determination of gonadal function. Presence of breast development signifies prior gonadal function. Imaging studies such as pelvic sonogram and CT and MRI are required for confirmation of congenital absence of the vagina and uterus.

Absence of pubic hair is suggestive of the androgen insensitivity syndrome. Karyotype will identify the 46,XY cell line in patients with testicular feminization syndrome. Patients with complete pubertal development and well-formed female configuration (“pear shape”) display evidence of continued estrogen production, and normal müllerian systems probably have inappropriate positive feedback and thus chronic anovulation. Progesterone challenge in such patients is helpful. A withdrawal bleed signifies a normal müllerian system and acceptable estrogen production.

Serum gonadotropin assays are performed for further elucidation. Elevated FSH levels suggest gonadal failure. Karyotype determination is crucial in diagnosing the various etiologies of gonadal failure. The presence of a Y chromosome in either group dictates gonadal removal.

Low FSH levels suggest interference with hypothalamic–pituitary maturation and gonadotropin release. Skull films and prolactin assays must be obtained for all patients to rule out the presence of pituitary or hypothalamic tumors. Appropriate endocrine evaluation identifies the occasional patient with hypothyroidism or congenital adrenal hyperplasia and the rare patient with Cushing's syndrome. Diagnosis of Kallmann's syndrome is suspected in hypogonadotropic patients who have an associated anosmia, and the diagnosis is confirmed by GnRH challenge tests. The presumed diagnosis of constitutional delay is made by exclusion of all other causes and by the typical GnRH release patterns after GnRH challenge.

Bleeding Disorders

Vaginal Bleeding in the Premenarchal Child

When vaginal bleeding occurs in children, 2 sources generally should be suspected: (1) the endometrium (bleeding usually is a manifestation of precocious puberty) and (2) a local vulvar or vaginal lesion (eg, vulvovaginitis, foreign bodies, urethral prolapse, trauma, botryoid sarcoma, adenocarcinoma of the cervix or vagina, and vulvar skin disorders).

Vaginal bleeding during childhood should always alert the physician to the possibility of a genital tumor, which could be present in up to 20% of girls with no signs of pubertal maturation. Vaginoscopy and examination under anesthesia are the mainstays of evaluation to exclude the presence of tumors, foreign bodies, and other local lesions. Suspicious lesions require biopsy for diagnosis. Sexual abuse should be always be kept in mind by the physician attending a prepubertal girl with vaginal bleeding.

Disorders of Menstrual Cycle in Adolescents

One of the most common gynecologic complaints of adolescents is a problem with the menstrual period. In most cases, there is no true medical disorder, especially in the first 2 years after menarche, when 50–80% of periods are anovulatory. Dysfunctional uterine bleeding accounts for 95% of abnormal vaginal bleeding in teenagers. Screening for inherited coagulation disorders, such as von Willebrand's disease, may be indicated, as 18% of adolescents hospitalized for menorrhagia have an underlying bleeding disorder.

Pubertal Menorrhagia

In the adolescent, the normal cycle length is 21–45 days, the length of the period is 7 days or less, and product use is no more than 3–6 pads or tampons per day. Menorrhagia is defined as heavy menstrual bleeding that lasts for more than 7 days or results in the loss of more than 80 mL of blood per menstrual cycle.

Heavy bleeding starting from the first menstrual period after menarche might be the first sign of a bleeding disorder, such as von Willebrand's disease (5–20%) or platelet dysfunction.

Pubertal menorrhagia is a result of dysfunctional uterine bleeding more often secondary to anovulation. This is reflection of the immaturity of the hypothalamic–pituitary–ovarian axis; in fact, in 55–82% of adolescents, it takes 24 months for onset of regular ovulatory cycles after menarche. This abnormality is even more common in girls with polycystic ovary syndrome (PCOS), and bleeding disorders such as abnormal platelet function or von Willebrand's disease are the most common inherited bleeding disorders. A positive bleeding history alone had a sensitivity for detecting any bleeding disorder of 82%. It should be followed by initial laboratory evaluation including a complete cell count, prothrombin time, activated partial thromboplastin time (aPTT), and fibrinogen or thrombin clot time, although all of these tests might be normal in patients with VWD. Further evaluation is better done in collaboration with hematologists with expertise in bleeding disorders.

Management of anovulatory bleeding is directed toward controlling symptoms and preventing blood loss based on degree of anemia. Hormonal contraception is the first-line treatment for menorrhagia, and the dosage is adjusted based on severity of the bleeding. Daily administration could reach several pills a day until control of bleeding is achieved, followed by tapering during the following days. Other preparations include medroxyprogesterone acetate and levonorgestrel-secreting intrauterine devices, which have been used by several experts. Consideration of the negative effect on final height caused by the estrogen component must be done based on clinical condition of the patient.

In severe cases, hospitalization and intravenous conjugated equine estrogen in doses of 25 mg every 4–6 hours until bleeding stops for 24 hours have been used successfully. If oral contraceptives are given for secondary amenorrhea, they should be continued for at least 9–12 months before attempting to stop. If menses do not resume within 8 weeks, oral contraceptive pills should be resumed for another 9–12 months.

Adolescents who fail hormonal management should be referred for consideration of hemostatic therapies including desmopressin (DDAVP), antifibrinolytic medications (aminocaproic acid, tranexamic acid), and clotting factor concentrates. In the management of acute severe menorrhagia, every effort is made to preserve future fertility. Invasive intervention should be reserved as a last resort treatment.

Polycystic Ovarian Syndrome in Adolescents

The prevalence of PCOS in the general population has been estimated to be 5–10%. The classic presentation is characterized by features of anovulation, amenorrhea, oligomenorrhea, or irregular cycles in combination with signs of androgen excess, acne, hirsutism, or alopecia. It is associated frequently with insulin resistance.

PCOS usually presents at the late pubertal age but may also present before menarche in the form of androgen excess as premature pubarche/adrenarche.

Recent literature has identified a specific biochemical marker (adiponectin) that is significantly lower in concentration in the daughters of women who have PCOS before the onset of hyperandrogenism and may be an early marker of metabolic derangement in adolescent girls.

Primary amenorrhea as the initial feature occurs in 1.4–14% of adolescents with PCOS. As with adults, Rotterdam Criteria should be used to make the diagnosis of PCOS in adolescents; however, some researchers have challenged the consensus of Rotterdam Criteria in adolescents because they may lead to overestimation of the syndrome, because the physiologic process of early puberty is characterized by relative androgenemia, insulin resistance, cystic ovaries, and anovulatory cycles. They have proposed alternative diagnostic criteria in adolescents, which include 4 of the following 5 criteria: (1) oligo- or amenorrhea 2 years after menarche; (2) clinical hyperandrogenism; (3) hyperandrogenemia; (4) insulin resistance or hyperinsulinemia; and (5) polycystic ovaries. The finding of polycystic ovaries in adolescents as the only sign should be considered with caution because 25% of healthy adolescents may present with similar finding.

Adolescents who are obese and have a diagnosis of PCOS should undergo a 2-hour 75-g oral glucose tolerance test (OGTT). This is a more sensitive test than the fasting glucose test to detect diabetes and impaired glucose tolerance, which is a significant risk factor for diagnosis. A fasting glucose/insulin ratio has been proposed as a rapid and easy screening alternative; in adolescents, a ratio of <7 is suggestive as compared with a ratio of <4.5 in adults.

An early diagnosis should be made in order to avoid late health consequences such as diabetes, cardiovascular disease, endometrial hyperplasia, and infertility. Any adolescent with androgen excess should be monitored for evidence of hypertension and hypertriglyceridemia regardless of body weight because of the higher risk for metabolic syndrome.

Treatment

Treatment options for adolescents with PCOS include weight loss for obese girls and lifestyle modifications, including calorie restriction and an increase in formal exercise; symptom-directed therapy to address the main symptoms noted by the adolescent; and metabolic correction of the underlying insulin resistance using insulin-sensitizing medications.

Although weight loss of as little as 5–10% has been shown to result in reduction in testosterone increase in sex hormone-binding globulin and resumption of menses and ovulation, unfortunately, diet and behavioral therapies have been shown to fail in adolescents, with follow-up showing weight regain of 75–121% at 5 years. Obesity can exacerbate the PCOS phenotype in previously asymptomatic individuals. Weight reduction has been shown to improve free androgen levels, insulin sensitivity, and ovulatory function. When menstrual irregularity is accompanied by symptoms such as acne, hirsutism, and obesity, PCOS should be suspected, and treatment may need to address some of these symptoms as well.

Pregnancy should always be considered in a young woman with abnormal bleeding or amenorrhea until proven otherwise. Nonmenstrual causes of bleeding, such as hypothyroidism, cervicitis, condylomas, polyps, cervical cancer, estrogen-producing ovarian tumors, and vaginitis, also should be considered.

Adolescent Pregnancy and Contraception

Juvenile pregnancy is rare. The youngest known patient was a Peruvian girl aged 5 years 8 months, who in 1939 delivered at term by caesarean section a healthy male infant weighing 2950 g (6 lb 8 oz). Both mother and infant survived. In every reported instance, the underage mothers were sexually precocious, and most had menstruated for several years before becoming pregnant. Juvenile pregnancy per se does not increase the chance of congenital anomalies in the offspring. However, in many cases, the mother is a victim of sexual abuse, and if the pregnancy is the result of incest, there is a greater likelihood of genetic malformations carried by recessive genes.

Most precocious mothers and their babies have not done well, with increased incidences of spontaneous abortion, pregnancy-induced hypertension, and premature labor and delivery. In patients younger than 9 years, <50% have normal labor, with a 35% likelihood of neonatal loss.

The underage mother and her family may need psychiatric counseling, both during pregnancy and after delivery. Lessening the emotional, social, and medical trauma associated with such a gestation is an important task for all who assist in the care of the pregnant child.

For years it has been accepted that adolescent pregnancy is a high-risk pregnancy. Many pregnant adolescents come from low socioeconomic backgrounds and have poor education and perhaps poor general health due to inadequate nutrition, iron deficiency anemia, cigarette smoking, drug abuse, or STDs. Proper education and dietary counseling may improve nutritional status and prevent anemia.

Complications of labor and delivery are highly dependent on the quality of prenatal care. Preeclampsia–eclampsia, which is more common in a first pregnancy, occurs more frequently among adolescents than among adult women. Prematurity and small for gestational age infants are a major problem in adolescent pregnancies. Predisposing factors are high-risk factors such as low prepregnancy weight, poor weight gain, adverse socioeconomic conditions, cigarette smoking, anemia, first pregnancy, and deficient prenatal care, all of which occur more commonly in adolescents. To minimize prenatal complications and to improve maternal and fetal outcome, the young patient should be enrolled in an aggressive prenatal care program. That care should not only improve the pregnancy outcome of adolescents, but also enhance their social, educational, and emotional adjustment.

Pregnancy Termination

The rate of teenage abortion remains higher in the United States than in other Western countries for which data are available. In many countries, the legal authorities ruled in favor of a minor's right to have an abortion. In others systems, the evacuation of uterine contents can be performed by medical (RU-486) or surgical (dilatation and currettage) technique, both of which are accepted in adolescents; the preferable method is still undetermined. For minors who do not want parental involvement social support is required to perform it on them.

Contraception in Adolescents

More than 95% of adolescent pregnancies are unintended. By age 18 years, 1 in 4 adolescents experiences a pregnancy. Half of adolescent pregnancies occur in the first 6 months after initiation of sexual activity. Despite a decline in teenage pregnancy rates during the 1990s, teenage pregnancy rates remain higher in the United States than in other Western countries. In addition, teenagers in the United States use contraceptives less frequently and use less effective methods of contraception than do their European counterparts. Although great inroads in adolescent access to health care have been made over the last decade, problems of cost and fears of lack of confidentiality still appear to inhibit young women from obtaining contraceptives, ultimately resulting in high teenage pregnancy rates.

These findings reinforce the importance of addressing contraception during an adolescent's initial health care evaluation.

Postponing sexual activity is an appropriate option to suggest. If this is not realistic, counseling regarding various methods of contraception requires consideration not only of the side effects and efficacy of the various methods but also of the personal requirements of each teenager. Extended regimens such as available 84/7 day and no “placebo” regimens have shown similar efficacy; these may be new options for patient who desire lower frequency of menses such as athletes and military personnel, although studies in adolescents are lacking. Using “Quik Start” (same day of the visit) seems to improve compliance from 56 to 72%.

The common hormonal contraceptive methods are applicable in adolescents with the same success as in adult women; however, teenagers are more likely to forget taking a daily pill, thus resulting in a high failure rate of 9–18% and low long-term compliance of 44%. Long-lasting methods such as the patch, vaginal ring, and hormonal Depo system may be more efficient in preventing pregnancy in young girls. Inserting an IUD in girls before first pregnancy is reasonable under some conditions but still remains controversial. Screening patients for STIs before insertion should be encouraged.

Health benefits of adolescents taking hormonal contraceptive methods include decreased menstrual pain; increased menstrual regularity; decreased risk of pelvic inflammatory disease, anemia, and fibrocystic breast disease; improved long-term fertility; and treatment of acne and hirsutism. The importance of both contraception and STI prevention should be reviewed, and the use of barrier methods together with hormonal method should be encouraged.

Emergency contraception with progestin-only regimens is a highly effective means of preventing pregnancy if taken up to 72 hours after intercourse; despite decreasing efficacy, it should be provided up to 120 hours after unprotected coitus. Improving access through education or prescribing pills in advance or over the telephone may give a young woman a second chance at preventing unintended pregnancy.

Sexually Transmitted Infections

STIs are the most common infectious diseases in adolescents today. Approximately 25% of all sexually active adolescents aged 13–19 years become infected each year. By age 15 years, 1 in 4 girls in the United States has had sexual relations. The younger the age of first intercourse, the higher is the risk for STIs. Chlamydia is the most prevalent of the bacterial STIs, with almost 30% of inner-city female adolescents aged 12–19 showing positive cultures in a longitudinal 2-year study of family planning, school-based, and STI clinics. Sequelae of chlamydial infections include pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. This age group accounts for 8% of cases of HIV in females, with the majority of these women asymptomatic at the time of positive testing. In the United States, 15- to 24-year-olds accounted for approximately 60% of gonorrhea cases, 25% of syphilis cases, and 17% of hepatitis B cases in 1996. By the time they reach college age, 43% of women are infected with human papillomavirus.

Nearly 70% of patients with PID are younger than 25 years. The estimated incidence of PID in sexually active females is approximately 1 in 8 for 15-year-olds and 1 in 10 for 16-year-olds. PID in adolescents should be treated with hospitalization and intravenous antibiotics. Tubo-ovarian abscess has been found in 2–4% of adolescents with adnexal masses. Treatment includes broad-spectrum antibiotics and possible surgical drainage. Patients who have had PID or tubo-ovarian abscess are at high risk for pelvic pain, pelvic adhesive disease, infertility, and ectopic pregnancy.

Cervical Cancer Screening & Human Papillomavirus Vaccine in Adolescents

Human papillomavirus (HPV) is the most common sexually acquired infection in the world, with a prevalence of 50% among young sexually active adolescents. Most of these infections are self-limiting and harmless, but persistent infection with oncogenic HPV types can cause cervical cancer in women. HPV also causes other anogenital cancers (eg, of the vagina, vulva, and penis), head and neck cancers, and genital warts in both men and women.

The availability of the new vaccine (2006) against carcinogenic types of HPV (mainly types 16 and 18) has led to major changes in the prevention and management of cervical disease. Two vaccines are currently approved for use in humans, and both have shown more than 95% efficacy in preventing cervical dysplasia associated with vaccine type and a high safety profile.

Several organizations, including the American College of Obstetricians and Gynecologists (ACOG), have recommended vaccination for young women aged 9–26 years. Because current HPV vaccines are prophylactic, the greatest impact will be seen by vaccinating girls before they are exposed to HPV and thus before sexual debut.

Some countries introduced the vaccine as a part of scholar vaccination program, which severed the administration of the vaccine from the sexual permissiveness context. The duration of protection seems to be longer than 6 years, but the exact duration of protection and other details on the future of the vaccine are still not clear and need more clinical trials.

Health care providers should encourage vaccinated adolescents to continue with the use of protective methods against other STDs and emphasize the importance of cervical cancer screening with a Papanicolaou (Pap) test. Screening in low-risk adolescent should be initiated 3 years after the onset of sexual activity and not later than age 21 years.

Considering the rarity of cervical cancer among adolescents, the management of abnormal cervical cytology differs from that of the adult population. The American Society for Colposcopy and Cervical Pathology (ASCCP) advises against HPV testing and against treatment of low-grade squamous intraepithelial lesions or cervical intraepithelial neoplasia I. In adherent adolescents, treatment of cervical intraepithelial neoplasia II should also be deferred. In patients with high-grade lesions or incompliant adolescents with lower grade lesions, ablative or excisional procedures are indicated. Cryotherapy offers a 92–95% cure rate for cervical intraepithelial neoplasia 2–3 in young women. Loop electrosurgical excisional procedure offers similar cure rates and does not appear to impact cervical competence in future pregnancies with depths of excision of 1.5 cm or less.