CHAPTER 14: Pediatric Gynecology

Pediatric gynecology is a unique subspecialty that encompasses knowledge from various specialties including general pediatrics, gynecology, reproductive endocrinology, as well as pediatric endocrinology and pediatric urology. Treatment of a particular patient may thus require the collaboration of clinicians from one or more of these fields.

Gynecologic disorders in children can differ greatly from those encountered in the adult female. Even the simple physical examination of the genitalia differs significantly. A thorough understanding of these differences can aid in diagnosing the various gynecologic abnormalities seen in this age group.

Hypothalamic-Pituitary-Ovarian Axis

A carefully orchestrated cascade of events unfolds in the neuroendocrine system and regulates development of the female reproductive system. In utero, gonadotropin-releasing hormone (GnRH) neurons develop in the olfactory placode. These neurons migrate through the forebrain to the arcuate nucleus of the hypothalamus by 11 weeks’ gestation (Fig. 16-5). They form axons that extend to the median eminence and to the capillary plexus of the pituitary portal system (Fig. 15-11). Gonadotropin-releasing hormone, a decapeptide, is influenced by higher cortical centers and is released from these neurons in a pulsatile fashion into the pituitary portal plexus. As a result, by midgestation, the GnRH “pulse generator” stimulates secretion of gonadotropins, that is, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the anterior pituitary. In turn, the pulsatile release of gonadotropins stimulates ovarian synthesis and release of gonadal steroid hormones. Concurrently, accelerated germ cell division and follicular development begins, resulting in the creation of 6 to 7 million oocytes by 5 months’ gestation. By late gestation, gonadal steroids exert a negative feedback on secretion of both hypothalamic GnRH and pituitary gonadotropins. During this time, oocyte number decreases through a process of gene-related apoptosis to reach a level of 1 to 2 million by birth (Vaskivuo, 2001).

At birth, FSH and LH concentrations rise abruptly in response to the fall in placental estrogen levels and are highest in the first 3 months of life (Fig. 14-1). This transient rise in gonadotropin levels is followed by an increase in gonadal steroid concentrations, which is thought to explain instances of neonatal breast budding, minor bleeding from endometrial shedding, short-lived ovarian cysts, and transient white vaginal mucous discharge. Following these initial months, gonadotropin levels gradually decline to reach prepubertal levels by age 1 to 2 years.

The childhood years are thus characterized by low plasma levels of FSH, LH, and estradiol. Estradiol levels typically measure <10 pg/mL, and LH values are <0.3 mIU/mL. Both may be assessed if precocious development is suspected (Neely, 1995; Resende, 2007). During childhood, ovaries undergo active follicular growth and oocyte atresia. As a result of this attrition, by puberty, only 300,000 to 500,000 oocytes remain (Fritz, 2011).

Anatomy

Pelvic anatomy also changes during early childhood. In the neonate, sonographically, the uterus measures approximately 3.5 cm in length and 1.5 cm in width. Because the cervix is larger than the fundus, the neonatal uterus is typically spade-shaped (Fig. 14-2) (Nussbaum, 1986). An echogenic central endometrial stripe is common and reflects the transiently elevated gonadal steroid levels described earlier. Fluid is seen within the endometrial cavity in 25 percent of female newborns. Ovarian volume measures ≤1 cm³, and small cysts are frequently found (Cohen, 1993; Garel, 2001).

During childhood, the uterus measures 2.5 to 4 cm and is tubular as a result of the cervix and fundus becoming equal size. The ovaries increase in size as childhood progresses, and volumes range from 2 to 4 cm³ (Ziereisen, 2005).

Pubertal Changes

Puberty marks the normal physiologic transition from childhood to sexual and reproductive maturity. With puberty, primary sexual characteristics of the hypothalamus, pituitary, and ovaries initially undergo an intricate maturation process. This maturation leads to the complex development of secondary sexual characteristics involving the breast, sexual hair, and genitalia, in addition to a limited acceleration in body growth. Each landmark of hormonal and anatomic change during this time represents a spectrum of what is considered “normal.”

Marshall and Tanner (1969) recorded breast and pubic hair development in 192 English schoolgirls and created the Tanner stages to describe pubertal development (Fig. 14-3). Initial pubertal changes begin between ages 8 and 13 years in most North American females (Tanner, 1985). Changes before or after are categorized as either precocious puberty or delayed puberty and warrant evaluation. In most girls, breast budding, termed thelarche, is the first physical sign of puberty and begins at approximately age 10 years (Aksglaede, 2009; Biro, 2006). In a minority, pubic hair growth, known as pubarche, develops first. Following breast and pubic hair growth, adolescents undergo an accelerated increase in height, termed a growth spurt, during a 3-year span from ages 10.5 to 13.5 years.

Since these original population studies, U.S. girls have trended to start thelarche and menarche earlier. Differences in onset timing are also related to race and higher body mass index (BMI) (Biro, 2013; Rosenfield, 2009). For example, higher BMI correlates with earlier pubertal development. The mean age of menarche in white girls is 12.7 years and 6 months earlier, or 12.1, in black girls (Tanner, 1973).

An adolescent who has reached the age of 18 may consent to medical examination and treatment. Prior to this age, individual state laws govern whether minors can give their own consent for certain kinds of health care. Some examples include: emergency contraception, substance abuse, or sexually transmitted disease treatment. Every state has laws allowing minors to consent to care if they are emancipated, living apart from their parents, or pregnant. The Guttmacher Institute publishes an overview of Minors’ Consent Law regularly at www.agi-usa.org.

A routine yearly examination of a child by her pediatrician generally includes a brief examination of the breasts and external genitalia. Congenital anomalies that are visible externally, such as imperforate hymen, may be identified. Alternatively, if parent or child has a specific complaint regarding vulvovaginal pain, rash, bleeding, discharge, or lesions, a gynecologic examination is directed toward the area of concern.

A parent or guardian should be present at the examination. This allows the child to understand that the examination is sanctioned. Moreover, clinicians can use this opportunity to inform a parent regarding findings and potential treatment. They can also emphasize the concept of inappropriate genital touching by others and parental notification if this occurs. In mid-to-late adolescence, however, a patient may prefer, for privacy reasons, not to be examined with a parent present.

“Child-friendly” objects or pictures and distracting conversation can ease fears and aid examination. Similarly, using an anatomically appropriate doll to explain the steps may decrease anxiety. The examination begins with a less-threatening approach of checking the ears, throat, heart, and lungs. Breasts are inspected. The external genital examination is best performed with the child in a frog-leg or knee-chest position to improve visualization. Occasionally, the patient may feel more comfortable sitting in a parent’s lap. Sitting on a chair or examination table, the parent allows the child’s legs to straddle the parent’s thighs (Fig. 14-4).

Once the child is optimally positioned, each labium may be gently held with a thumb and forefinger and pulled toward the examiner and laterally. In this manner, the introitus, hymen, and lower portion of the vagina are inspected (Fig. 14-5). An internal examination is rarely necessary unless a foreign body, tumor, or vaginal bleeding is suspected. This evaluation is best accomplished under general anesthesia. Vaginoscopy may be performed using a hysteroscope or cystoscope to provide illumination as well as irrigation. During vaginoscopy, normal saline is used as the distention medium (Fig. 14-6). The labia majora are manually approximated to occlude the vagina and achieve vaginal distention.

Adhesion between the labia minora begins as a small posterior midline fusion, which is usually asymptomatic. This fusion may remain an isolated minor finding or may progress toward the clitoris to completely close the vaginal orifice. Also termed labial agglutination, this adhesion develops in 1 to 5 percent of prepubertal girls and in approximately 10 percent of female infants within the first year of life (Berenson, 1992; Christensen, 1971).

The cause of labial adhesion is unknown, although hypoestrogenism is implicated. This fusion typically develops in a low-estrogen environment. Namely, it is seen in infants and young girls and tends to undergo spontaneous resolution at puberty (Jenkinson, 1984). Additionally, erosion of the vulvar epithelium is implicated in some cases of labial adhesion. For example, adhesion can be associated with lichen sclerosus, with herpes simplex viral infection, and with vulvar trauma following sexual abuse (Berkowitz, 1987).

The diagnosis is made visually. The labia majora appear normal, whereas the labia minora are fused with a distinct thin line of demarcation or raphe between them (Fig. 14-7). Extensive agglutination may leave only a ventral pinhole meatus between the labia. Located immediately beneath the clitoris, this small opening may lead to urinary dribbling as urine pools behind the adhesion. In these cases, urinary tract infection or urethritis can develop.

Treatment varies according to the degree of scarring and symptoms. In many instances, if the patient is asymptomatic, no intervention is necessary as the adhesion will typically resolve spontaneously with the rise of estrogen levels at puberty. Extensive adhesion with urinary symptoms, however, will require estrogen cream therapy. Estradiol (Estrace) cream or conjugated equine estrogen (Premarin) cream is applied to the fine, thin raphe twice daily for 2 weeks, followed by daily applications for an additional 2 weeks. A generous pea-sized amount of cream is placed with a finger or cotton-tipped applicator onto the raphe. With each application, gentle outward traction is exerted on the labia majora to help separate the adhesion. Similarly, light pressure may also be applied with the cotton applicator itself, as tolerated. After adhesion separation, a petroleum jelly (Vaseline) or vitamins A and D ointment (A&D ointment) may be applied nightly for 6 months to decrease the risk of recurrence. If the adhesion reforms during the subsequent months or years, the process may be similarly repeated. Occasionally, with overuse of estrogen cream, local irritation, vulvar pigmentation, and minor breast budding may develop, at which time topical treatment is discontinued. These side effects are reversible once treatment is halted. Alternatively, the use of 0.05-percent betamethasone cream applied twice daily for 4 to 6 weeks is another topical option (Mayoglou, 2009; Meyers, 2006).

Manual separation of labial adhesion in an outpatient setting without analgesia is painful and thus generally not advised. In addition, recurrence is much more common. However, if the adhesion persists despite consistent use of estrogen cream, then labia minora separation may be attempted several minutes after applying 5-percent lidocaine ointment to the adhesion raphe.

If separation is not easily accomplished or tolerated, surgical separation is recommended in an operating room under general anesthesia as an outpatient procedure. Midline division of the fused labia, also termed introitoplasty, uses an electrosurgical fine tip and does not require suturing. To prevent repeated agglutination after surgery, an estrogen cream is applied nightly for 2 weeks. This is followed by an emollient cream nightly for at least 6 months.

Several anatomic and müllerian abnormalities present in early adolescence as obstructions to menstrual outflow. Described in Chapter 18, those most commonly presenting with outlet obstruction include imperforate hymen, transverse vaginal septum, cervical and vaginal agenesis with an intact uterus, obstructed (non-communicating) uterine horn, and the OHVIRA syndrome (obstructed hemivagina with ipsilateral renal agenesis) (Smith, 2007). These are often diagnosed in an adolescent with primary amenorrhea and cyclic pain. Notably, an adolescent with OHVIRA or with an obstructed uterine horn will have menses, but these often become increasingly painful over 6 to 9 months.

Allergic and Contact Dermatitis

Vulvar inflammation may develop in isolation or in association with vaginitis. Allergic and contact dermatitis are common, whereas atopic dermatitis (eczema) and psoriasis are less frequent sources of itching and rash. With allergic and contact dermatitis the underlying pathophysiology varies, but the clinical appearance is usually similar. Vesicles or papules form on bright-red, edematous skin. However, in chronic cases, scaling, skin fissuring, and lichenification may be seen. In response, information regarding the degree of hygiene and continence and exposure to potential skin irritants is sought.

Typical offending agents include bubble baths and soaps, laundry detergents, fabric softeners and dryer sheets, bleach, and perfumed or colored toilet paper (Table 4-1). Topical creams, lotions, and ointments used to soothe an area may also be an irritant to some children. For most, removing the offending agent and encouraging once- or twice-daily sitz baths is sufficient. These baths consist of placing two tablespoons of baking soda in warm water and soaking for 20 minutes. If itching is severe, an oral medication may be prescribed, such as hydroxyzine hydrochloride (Atarax) 2 mg/kg/d divided in four doses. Alternatively, a 2.5-percent topical hydrocortisone ointment can be applied twice daily for 1 week. Aside from chemical irritants, children can also develop diaper dermatitis from urine and stool exposure. Corrective measures keep the skin dry by more frequent diaper changes, or they create a moisture barrier by application of emollient creams, such as Vaseline or A&D ointment.

Lichen Sclerosus

Vulvitis may also be caused by lichen sclerosus. With this, the vulva displays hypopigmentation; atrophic, parchment-like skin; and occasional fissuring. Lesions are usually symmetrical and may form an “hourglass” appearance around the vulva and perianal areas (Fig. 14-8). Occasionally, the vulva develops dark purple vulvar ecchymoses, which may bleed. Over time, if left untreated, the periclitoral area may scar, the labia minora may become attenuated, and the posterior fourchette may fissure and bleed.

Similar to labial adhesion, lichen sclerosus can develop concurrently with hypoestrogenism or with inflammation. Lichen sclerosus more commonly affects postmenopausal women and carries risks for vulvar malignancy. This association is not found in affected pediatric patients. The exact pathophysiology of lichen sclerosus is unknown, although an autoimmune process is suspected given its association with Graves thyroiditis, vitiligo, and pernicious anemia. Twin and cohort studies suggest a genetic role (Meyrick Thomas, 1986; Sherman, 2010).

Patients may complain of intense itching, discomfort, bleeding, excoriations, and dysuria. Diagnosis typically relies on visual inspection. However, rarely, a vulvar biopsy may be indicated in children if the classic skin changes are absent.

Treatment consists of topical corticosteroid cream such as 2.5-percent hydrocortisone, applied nightly to the vulva for 6 weeks. If improvement is noted, the dose may be lowered to 1-percent hydrocortisone and continued for 4 to 6 weeks. Thereafter, petroleum-based ointment use and strict attention to hygiene are recommended. Severe cases require a more potent corticosteroid such as 0.05-percent clobetasol propionate (Temovate), applied twice daily for 2 weeks. This initial dosing is followed by an individualized regimen, which slowly tapers the dose to a once-weekly bedtime application. The long-term prognosis for childhood lichen sclerosus is unclear. Although some cases resolve at puberty, small case series suggest that as many as 75 percent of affected children have disease that persists or recurs following puberty (Berth-Jones, 1991; Powell, 2002; Smith, 2009).

Infection

Some common infectious organisms that may cause prepubertal vulvitis include group A beta-hemolytic streptococcus, Candida species, and pinworms. With group A beta-hemolytic streptococcus, the vulva and introitus may be bright “beefy” red, and symptoms include dysuria, vulvar pain, pruritus, or bleeding. In most cases, vulvovaginal culture and clinical setting typically lead to diagnosis. Group A beta-hemolytic streptococcus is treated with an oral first-generation penicillin or cephalosporin or other appropriate antibiotic for 2 to 4 weeks.

Candidiasis is rare in prepubertal girls. It more often develops during the first year of life, after a course of antibiotics, or in females with juvenile diabetes or immunocompromise. A reddened, raised rash with well-demarcated borders and occasional satellite lesions is typical. Microscopic examination of a vaginal sample prepared with 10-percent potassium hydroxide (KOH) will help identify hyphae (Fig. 3-6). For treatment, antifungal creams such as clotrimazole, miconazole, or butoconazole are applied to the vulva twice daily for 10 to 14 days or until the rash clears.

Enterobius vermicularis, also known as pinworm, can create intense vulvar itching. Nocturnal pruritus results from an intestinal infection with these 1-cm-long threadlike white worms that often exit the anus at night. Inspecting this area with a flashlight at night, parents may identify worms perianally. The “Scotch-tape test” entails pressing a piece of cellophane tape to the perianal area in the morning, affixing the tape to a slide, and visualizing parasite eggs by microscopy. Treatment is albendazole (Albenza) 200 to 400 mg in a single-dose chewable tablet.

Several months after birth, as estrogen levels wane, the vulvovaginal epithelium becomes thin and atrophic. As a result, the vulva and vagina are more susceptible to irritants and infections until puberty, and vulvovaginitis is a common prepubertal problem. Three fourths of vulvovaginitis cases in this age group are nonspecific, with culture results yielding “normal flora.” Alternatively, several infectious agents, discussed subsequently, may be identified.

With nonspecific vulvovaginitis, the pathogenesis is not well defined, but known instigating factors are included in Table 14-1. Symptoms include itching, vulvar redness, discharge, dysuria, and odor. Most children and those adolescents who are not sexually active tolerate speculum examination poorly. But a vaginal swab for bacterial culture can be comfortably obtained. In cases of nonspecific vulvovaginitis, cultures typically only isolate normal vaginal flora. Culture results that reveal bowel flora suggest contamination with fecal aerobes. Treatment attempts to correct the underlying cause. Itching and inflammation may be relieved with a low-dose topical corticosteroid such as hydrocortisone, 1 or 2.5 percent. Occasionally, severe itching can lead to a secondary bacterial infection that requires oral antibiotics. Oral agents often selected are amoxicillin, an amoxicillin plus clavulanic acid combination, or a similar cephalosporin given during a 7- to 10-day course.

Infectious vulvovaginitis often presents with a malodorous, yellow or green purulent discharge, and vaginal cultures are routinely obtained in these cases. The respiratory pathogen group A beta-hemolytic streptococcus is the most common specific infectious agent found in prepubertal females and is isolated from 7 to 20 percent of girls with vulvovaginitis (Pierce, 1992; Piippo, 2000). Treatment of group A beta-hemolytic streptococcus consists of amoxicillin, 40 mg/kg, taken orally three times daily for 10 days. Less frequently, other respiratory pathogens found include: Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. Enteric pathogens such as Shigella and Yersinia species may also be found by culture of vaginal discharge. Classically, Shigella species incite a mucopurulent bloody discharge, which typically follows diarrhea caused by the same organism. Treatment is with oral trimethoprim-sulfamethoxazole (TMP-SMZ), 6 to 10 mg/kg/d, divided and given every 12 hours (Bogaerts, 1992).

As discussed in Chapter 13, sexual abuse may lead to infections, including those caused by Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus (HSV), Trichomonas vaginalis, and human papillomavirus (HPV). The clinical presentation of each mirrors the infectious findings in adults. Perinatal vertical transmission and latency may permit some of these to persist into infancy and childhood (Chap. 13). Long latency and several possible modes of transmission rendered HPV especially difficult to assign origin (Fig. 14-9) (Unger, 2011). That said, child protective services are notified of any child suspected to be the victim of sexual abuse.

The prepubertal vulva is less protected from blunt injury due to the lack of labial fat pads. In addition, children are more physically active, thereby increasing the trauma risk. Fortunately, most injuries to the vulva are blunt, minor, and accidental. Sharp-object penetration, however, may cause more serious injury to the vulvovaginal area. Sexual or physical abuse is also considered. Management of vulvovaginal trauma is discussed in more detail in Chapter 4.

Ovarian masses, typically cysts, are common in childhood. They may be found prenatally during maternal sonographic evaluation or during prepubertal years and adolescence. Although most are benign, approximately 1 percent of all malignant tumors in this age group are ovarian (Breen, 1977, 1981).

Fetal and neonatal ovarian cysts are typically cystic and identified incidentally during maternal sonographic examination. Although the true incidence of fetal ovarian cysts is not known, some cystic development has been reported in 30 to 70 percent of female fetuses (Brandt, 1991; Lindeque, 1988). Most fetal cysts result from maternal hormonal stimulation in utero. Those during the neonatal period and infancy usually develop from the postnatal gonadotropin surge seen with the withdrawal of maternal hormones after birth. They are usually simple, unilateral, asymptomatic, and regress spontaneously by 4 months after birth, whether they are simple or complex. The risk of malignancy is low, although rupture, intracystic hemorrhage, visceral compression, and torsion followed by autoamputation of the ovary or adnexa may be uncommon complications.

For uncomplicated fetal or neonatal cysts measuring less than 5 cm in diameter, appropriate management is observation and sonographic examination every 4 to 6 weeks (Bagolan, 2002; Nussbaum, 1988; Papic, 2014). For simple cysts measuring greater than 5 cm, percutaneous cyst aspiration has been described to prevent torsion (Bryant, 2004; Noia, 2012). Large complex ovarian cysts that do not regress postnatally require surgical excision.

In children, most ovarian masses are cystic and symptoms vary. Asymptomatic cysts may be discovered incidentally during abdominal examination or during sonographic examination for some other indication. Enlarging cysts can increase abdominal girth or cause chronic pain. Hormone-secreting cysts may lead to isosexual or heterosexual precocious puberty, and thus evaluation for signs of early pubertal development is indicated. Moreover, rupture, hemorrhage, or torsion may precipitate acute abdominal pain, similar to that seen in adults.

For imaging, a prepubertal child will not tolerate sonographic examination with a transvaginal probe. Thus, in this age group, transabdominal pelvic sonography is most frequently used. Computed tomography (CT) is helpful if a mature cystic teratoma (dermoid cyst) is suspected, as fat is better appreciated with this modality. Although magnetic resonance (MR) imaging is preferred for congenital müllerian anomaly evaluation, it is less helpful than pelvic sonography for ovarian mass determination. The most common complex cysts found in childhood and adolescence are germ cell tumors, specifically benign mature cystic teratoma (Panteli, 2009). Rarely, tumors may be malignant germ cell tumors or epithelial ovarian tumors (Schultz, 2006; Tapper, 1983).

As with those of the fetal and neonatal periods, small simple ovarian cysts without septation or internal echoes may be monitored with serial sonographic examination. Most less than 5 cm will resolve within 1 to 4 months (Thind, 1989). Persistent or enlarging cysts warrant surgical intervention, and laparoscopy is preferred. Optimal management includes fertility-sparing ovarian cystectomy with preservation of normal ovarian tissue.

Following puberty, ovarian cysts in adolescents, as in adults, are frequent. Management mirrors that of adnexal masses found in adults as described in Chapter 9.

Some newborns may have minor breast budding due to transplacental passage of maternal hormones in utero. Similarly, newborn breasts may produce witches’ milk, which is a bilateral white nipple discharge, also a result of maternal hormone stimulation. Both effects are transient and diminish over several weeks to months.

At puberty, under the influence of ovarian hormones, the breast bud grows rapidly. The epithelial sprouts of the mammary gland branch further and become separated by increasing deposition of fat. Such breast development, termed thelarche, begins in most girls between the ages of 8 and 13 years. Thelarche prior to age 8 or lack of breast development by age 13 is considered abnormal and investigated.

Breast examination begins in the newborn period and extends through the prepubertal and adolescent years, as abnormalities can develop in any age group. Assessment includes inspection for accessory nipples, infection, lipoma, fibroadenoma, and premature thelarche.

Polythelia

Accessory nipples, also termed polythelia, are common and noted in 1 percent of patients. Most frequently, a small areola and nipple are found along the embryonic milk line, which extends from the axilla to the groin bilaterally. Accessory nipples are usually asymptomatic, and excision is not required. Rarely, however, they may contain glandular tissue that can lead to pain, nipple discharge, or development of fibroadenomas.

Premature Thelarche

Thelarche may begin before age 8 in some girls and if early, is most commonly seen in girls younger than 2 years. This early breast maturation is termed premature thelarche. It differs from precocious puberty in that it is self-limited and develops in isolation, without other signs of pubertal development. Premature thelarche is suspected when minimal breast tissue growth or nipple maturation is noted during surveillance, but the patient’s height, which is measured to exclude a growth spurt, falls within established percentile curves. Monitoring body growth and breast changes alone may suffice, but in those with increased height or weight or with other pubertal changes, additional testing for precocious puberty is warranted. Thus, analysis of the patient’s growth curve and Tanner stage; a radiographic bone age study; and gonadotropin measurement may be indicated.

To explain bone age, as children develop, their bones change in size and shape. These changes can be seen radiographically and can be correlated with chronologic age. Thus, the radiographic “bone age” is the average age at which children in general reach a particular stage of bone maturation. Girls with early estrogen excess from precocious puberty show growth-rate acceleration, rapid bone age advancement, early cessation of growth, and eventual short stature because of this early cessation. Bone age can be determined at many skeletal sites, and the hand and wrist are the most commonly selected.

Premature thelarche is suggested if the bone age is synchronous and thus falls within 2 standard deviations of chronologic age. However, if the bone age is advanced by 2 or more years, puberty has begun and evaluation of precocious puberty is indicated. In those with isolated premature thelarche, serum estradiol levels may be slightly elevated, and this is seen more commonly in those who were very low-birthweight infants (Klein, 1999; Nelson, 1983). In addition, serum gonadotropin levels are in the prepubertal range. In most cases, premature breast development regresses or stabilizes, and treatment consists of reassurance with careful surveillance for other signs of precocious puberty.

Breast Shape

Growth during early breast development in girls aged 13 to 14 years may be asymmetric. The etiology is not known. However, in some cases, sports injury or surgical trauma during early breast development may lead to asymmetry (Goyal, 2003; Jansen, 2002). Examination seeks to exclude a breast mass such as a fibroadenoma or cyst. If no mass is identified, then yearly breast examinations determine the extent and persistence of asymmetry. In most cases, asymmetry will resolve by the completion of breast maturity (Templeman, 2000). Therefore, a decision toward surgical intervention is not made until full breast growth is attained. Until that time, adolescents may be fitted with padded bras or even prosthetic inserts to ensure symmetry when fully clothed.

Extremely large breasts without concurrent large breast masses can rarely develop in adolescence. Such breast hypertrophy can incite back pain, shoulder discomfort from bra-strap pressure, kyphosis, and psychologic distress. These young women will often seek reduction mammoplasty, but surgery is delayed until breast growth is completed. This is determined by serial breast measurements and is typically between the ages of 15 and 18 years.

Tuberous breasts are another growth variant (Fig. 14-10). With normal development, growth on the breast’s ventral surface projects the areola forward, and circumferential peripheral growth enlarges the breast base. In some adolescents, the fascia is densely adhered to the underlying muscle and prohibits peripheral breast growth. Only forward breast growth is permitted, and tuberous breasts form. This appearance can also follow exogenous hormone replacement that may be prescribed to girls with a lack of breast development from genetic, metabolic, or endocrine conditions. In these conditions, to avoid tuberous development, hormone replacement is initiated at small dosages and gradually increased over time. For example, transdermal estrogen (estradiol patch), 0.025 mg, may be applied twice a week for 6 months, followed by incremental dose increases every 6 months, through doses 0.05 mg and 0.075 mg, to finally reach 0.1 mg twice a week. Medroxyprogesterone acetate (Provera), 10 mg, is given orally each day for 12 days of the month to prompt withdrawal periods. Once estrogen patch dosing has reached 0.1 mg daily, the patient may alternatively be placed on a low-dose oral contraceptive pill instead.

Absent Breast Development

Congenital absence of breast glandular tissue, termed amastia, is rare. More commonly, a lack of breast development results from low estrogen levels caused by constitutionally delayed puberty, chronic disease, Poland syndrome, radiation or chemotherapy, genetic disorders such as gonadal dysgenesis, or extremes of physical activity. Treatment is based on the etiology. For example, once a competitive athlete completes her career, breast development may begin spontaneously without hormonal treatment. In contrast, to prompt breast development and prevent osteoporosis, patients with gonadal dysgenesis will require some form of hormonal replacement, such as that described in the preceding section.

Breast Mass or Infection

Breast lump complaints in an adolescent often reflect fibrocystic changes. These are characterized by patchy or diffuse, bandlike thickenings. For discrete breast masses, sonography is selected to distinguish cystic from solid mass and to define cyst qualities (Garcia, 2000). In contrast, mammography has a limited role. Its limited sensitivity and specificity in young developing dense breast tissue yields high rates of false-negative results (Williams, 1986).

Actual breast cysts are found on occasion and will usually resolve spontaneously over a few weeks to months. If a cyst is large, persistent, or symptomatic, a fine-needle aspiration may be performed using local analgesia in an office setting.

Similarly, most breast masses in children and adolescents are benign and may include normal but asymmetric breast bud development, fibroadenoma, fibrocyst, lymph node, or abscess. The most common breast mass identified in adolescence is a fibroadenoma, which accounts for 68 to 94 percent of all masses (Daniel, 1968; Goldstein, 1982). Fortunately, breast cancer in pediatric populations is rare, and cancer complicated less than 1 percent of breast masses identified in this group (Gutierrez, 2008; Neinstein, 1994). Primary breast cancer may develop more frequently in pediatric patients with a history of prior radiation, especially treatment directed to the chest wall. Additionally, metastatic disease is a consideration in those with cancer.

Treatment of breast masses includes observation, needle biopsy, and surgical excision. Observation may be appropriate for small asymptomatic lesions considered to be fibroadenomas. Masses that are symptomatic, large, or enlarging are preferably excised, and techniques mirror those in the adult (Chap. 12). For any mass not surgically excised, clinical surveillance is recommended to ensure mass stability.

Mastitis is rare in the pediatric population. Its incidence displays a bimodal distribution that peaks in the neonatal period and in children older than 10 years. The etiology in these cases is unclear, but the association with breast enlargement during these two periods has been implicated. Staphylococcus aureus is the most common isolate, and abscess develops more commonly than in the adult (Faden, 2005; Montague, 2013; Stricker, 2006). In adolescents, infections may be associated with lactation and pregnancy, trauma from sexual foreplay, shaving periareolar hair, and nipple piercing (Templeman, 2000; Tweeten, 1998). Infections are treated with antibiotics and occasional drainage if an abscess has formed.

Neonates may present with vaginal bleeding during the first week of life due to the withdrawal of maternal hormones at birth. Bleeding typically resolves after a few days. Prepubertal bleeding in a child, however, merits careful evaluation (Table 14-2). Most instances of vaginal bleeding in these girls are due to local causes and can be elucidated with a simple history and physical examination. Occasionally, an examination under anesthesia with saline vaginoscopy is required for diagnosis, particularly if a foreign body is present in the upper vagina (Fig. 14-11).

Early pubertal development may be seen in both sexes, but females are much more commonly affected, with a sex ratio of 23:1 (Bridges, 1994). For girls, precocious puberty has historically been defined as breast or pubic hair development in those younger than 8 years. However, Herman-Giddens and colleagues (1997) noted that girls in the United States overall are undergoing normal pubertal development at younger ages than previously reported. In addition, racial differences exist. Puberty begins earliest in black girls, followed by Hispanic and white girls. Accordingly, to limit the proportion of girls requiring unneeded assessment for precocious puberty, some have suggested lowering the threshold age for evaluation (Herman-Giddens, 1997; Kaplowitz, 1999).

Premature pubertal development may result from various causes. These have been categorized based on pathogenesis and include central precocious puberty, peripheral precocious puberty, heterosexual precocious puberty, and temporal variation of normal puberty. Most girls evaluated are found to have normal pubertal development that has merely begun prior to standard temporal milestones and does not stem from identifiable pathology. However, because many of the underlying etiologies of precocious puberty carry significant sequelae, girls with early pubertal development are fully evaluated when identified.

Central Precocious Puberty (Gonadotropin Dependent)

Early activation of the hypothalamic-pituitary-ovarian axis leads to pulsatile GnRH secretion, increased gonadotropin formation, and in turn, increased gonadal steroid levels. Often termed true precocious puberty, central precocious puberty is rare and affects 1 in 5000 to 10,000 individuals in the general population (Partsch, 2002). The most common cause of central precocious puberty is idiopathic, however, central nervous system lesions must be excluded (Table 14-3).

Symptoms of central precocious puberty are similar to those of normal puberty but at an earlier age. As outlined in Table 14-4, testing includes radiographic measurement of hand and wrist bone age. In affected girls, advanced skeletal maturation is seen. In addition, serum FSH, LH, and estradiol levels are elevated for chronologic age and typically lie in the pubertal range. Early in the process, however, FSH and LH levels may be elevated only in the evenings, and a leuprolide stimulation test can be helpful. During leuprolide stimulation, baseline FSH, LH, and estradiol levels are obtained. Leuprolide (Lupron) (20 μg/kg intravenous and not to exceed 500 μg) is given, and FSH plus LH levels are measured at 1, 2, and 3 hours. An estradiol level is measured at 24 hours. Central precocious puberty is confirmed by a rise in serum LH levels following infusion. In those with elevated gonadotropin levels, MR imaging of the central nervous system may identify a cerebral abnormality associated with central precocious puberty. Pelvic sonography is performed when the estradiol level is high and gonadotropin levels are suppressed to check for ovarian cysts.

Treatment goals focus on preventing short adult height and limiting the psychologic effects of early pubertal development. Epiphyseal fusion is an estrogen-dependent process. Accordingly, girls with precocious puberty are at risk for early growth-plate closure and short stature in adulthood. Treatment consists of a GnRH agonist, which serves to downregulate pituitary gonadotropes and inhibit FSH and LH release. Estrogen levels drop, and often there is a marked regression of breast and uterine size. If therapy is instituted after menses have begun, menstrual periods will cease. Timing for the discontinuation of GnRH therapy and reinitiation of pubertal development is determined by the primary therapy goals: maximizing height, synchronizing puberty with peers, and allaying psychological distress. From a review of several studies, the mean age at treatment discontinuation was approximately 11 years (Carel, 2009).

Peripheral Precocious Puberty (Gonadotropin Independent)

Less commonly, elevated estrogen levels may originate from a peripheral source, such as an ovarian cyst. Termed peripheral precocious puberty, this category is characterized by lack of GnRH pulsatile release, low levels of pituitary gonadotropins, yet increased serum estrogen concentrations.

Although the originating source is variable, the most common cause is a granulosa cell tumor, accounting for more than 60 percent of cases (Emans, 2005). Other types of ovarian cysts, adrenal disorders, iatrogenic disorders, and primary hypothyroidism are additional causes (see Table 14-3). McCune-Albright syndrome is characterized by a “triad” of polyostotic fibrous dysplasia, irregular café-au-lait spots, and endocrinopathies. Precocious puberty is a frequent finding and results from estrogen production in the ovarian cysts that are common in these girls.

Testing of girls with peripheral precocious puberty finds estrogen levels that are characteristically elevated, whereas serum levels of LH and FSH are low. Bone age determination shows advanced aging, and GnRH stimulation shows no elevation in serum LH levels.

Treatment aims to eliminate estrogen. For those with exogenous exposure, halting the estrogen source, such as hormonal pills or creams, is sufficient. An estrogen-secreting ovarian or adrenal tumor will require surgical excision, and hypothyroidism is treated with thyroid hormone replacement.

Heterosexual Precocious Puberty

Androgen excess with signs of virilization is rare in childhood (Chap. 17). Termed heterosexual precocious puberty, this condition is most commonly caused by increased androgen secretion in young females from the adrenal gland or ovary. Causes include androgen-secreting ovarian or adrenal tumors, congenital adrenal hyperplasia, Cushing syndrome, and exposure to exogenous androgens. Treatment is directed at correction of the underlying etiology.

Variations of Normal Puberty

Although standardized age guidelines accurately reflect the timing of pubertal development in most girls, others begin development early. Premature thelarche, premature adrenarche, and premature menarche describe the premature pubertal development of breast tissue, pubic hair, and menses, respectively. Each develops in isolation and without other evidence of pubertal development.

As described earlier, premature thelarche is a diagnosis of exclusion, and evaluation for precocious puberty in these girls reveals bone ages consistent with chronologic age. Normal FSH and LH levels, normal or slightly elevated estradiol levels, normal pelvic sonographic examination, and normal growth are noted. Treatment consists of careful surveillance and reassurance that the remainder of pubertal development will progress at a normal age.

Adrenarche is the onset of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) production from the adrenal zona reticularis, which can be detected around age 6 years. The phenotypic result of adrenarche is axillary and pubic hair development, termed pubarche, which begins in girls at approximately age 8 years (Auchus, 2004). Premature adrenarche is defined therefore as the growth of pubic hair prior to age 8, but other signs of estrogenization or virilization are absent. Most girls will have an increased level of DHEAS, which suggests that the adrenal gland is maturating prematurely (Korth-Schultz, 1976). Some girls with premature adrenarche are found to develop polycystic ovarian syndrome in adolescence (Ibanez, 1993; Miller, 1996). Others have a partial deficiency of 21-hydroxylase. Therefore, girls with premature adrenarche are screened for precocious puberty. When isolated, premature adrenarche treatment includes reassurance and monitoring at 3- to 6-month intervals for other signs of puberty.

Uterine bleeding that occurs once for several days or monthly, without other signs of puberty, is termed premature menarche. The condition is rare, and other sources of bleeding are considered and excluded first.

Puberty is considered delayed if no secondary sexual characteristics are noted by age 13, which is more than 2 standard deviations from the mean age, or if menses have not commenced by age 16. Delayed puberty affects 3 percent of adolescents. Causes include those in Table 14-5. With the exception of constitutional delay, these other abnormalities are discussed in greater detail in Chapters 16 and 18.

Constitutional delay is the most common cause, and adolescents lack both secondary sexual characteristics and pubertal growth spurt by age 13 years (Albanese, 1995; Malasanoa, 1997). The probable cause is a delay in reactivation of the GnRH pulse generator (Layman, 1994). Patients may be started on low-dose estrogen until puberty progresses, at which point estrogen may be discontinued. During low-dose estrogen treatment, it is not necessary to introduce progesterone withdrawal because in early puberty there is a similar long period of unopposed estrogen prior to ovulatory cycles.

Gender Identity

In most cases, phenotypic gender directs rearing practices, and girls are “raised as girls” and boys are “raised as boys.” Gender-appropriate clothes and behaviors are adopted by the child and reinforced by parental approval. Behaviors in conflict with gender are generally discouraged. However, young children will often explore various behaviors, both masculine and feminine, which make up normal experiences in the process of sex-role socialization (Mischel, 1970; Serbin, 1980).

In cases of ambiguous genitalia in the newborn, sexual assignment is more challenging. Initially, life-threatening disease such as congenital adrenal hyperplasia is excluded. As outlined in Chapter 18, gender assignment may be best delayed until test results identify genetic gender and the underlying problem.

The final gender assignment in such cases is termed the sex of rearing and reflects the pattern of gender behavior to be emphasized. The final determination for the sex of rearing is based not only on the individual’s karyotype but also on the functional capacity of the external genitalia. For example, boys born with congenital absence of the penis, a rare disorder, are usually raised as females after bilateral orchiectomy and reconstruction of the scrotum to have the appearance of labia. If parental attitudes towards the assigned gender are consistent, most children assume the sex of rearing regardless of their genotype.

Gender dysphoria describes individuals who perceive themselves to be different from their assigned gender. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), this is a recognized psychiatric diagnosis but is not considered a psychiatric disorder (American Psychiatric Association, 2013). That said, the discordance may cause depression and anxiety. One New Zealand survey of 8166 adolescents showed a prevalence of 1.2 percent for this condition (Clark, 2014). This perception can present as early as age 2 to 3 years. At our institution, the Gender Education and Care Interdisciplinary Support (GENCIS) Clinic provides a multidisciplinary approach to treating the psychological, social, and medical needs of this population of children.

Adolescent Sexuality

Adolescent sexuality develops during a period of rapid change that provides opportunities for adolescents to experience both risk-taking and health-promoting behaviors. Data from a large surveys of U.S. adolescents reveal that the percentage of those who become sexually active increases steadily after age 14 (Liu, 2015).

Adolescents view providers as an important resource for information and education regarding healthy sexual development. However, many parents and educators oppose sexuality education because of concerns that providing such information will encourage the onset of intercourse, termed coitarche, and will increase intercourse frequency. On the contrary, studies find that such education actually delays the onset and frequency of sexual activity, increases contraceptive use, and reduces the rate of unprotected intercourse (Kirby, 1999, 2001). One survey noted that 75 percent of adolescents attending grades 7 through 12 reported that they received classes in sexuality education (Hoff, 2000). A large percentage wanted more information on specific topics such as contraception, sexually transmitted diseases (STDs), condom use, and emotional issues.

Oral sex is now more commonplace among adolescents. The National Survey of Family Growth in 2005 reported that one in four adolescents aged 15 to 19 years who had not had vaginal intercourse reported practicing oral sex with an opposite partner. Of those adolescents who practiced sexual intercourse, 83 percent of females and 88 percent of males stated they had engaged in oral sex (Mosher, 2005). Adolescents may see oral sex as an alternative way to maintain their “virginity,” prevent pregnancy, or avoid STDs, or they may perceive it as a step on the way to engaging in sexual intercourse with a dating partner.

Sexual activity and partner violence appear to have a frequent association in adolescent populations (Chap. 13). For example, Kaestle and Halpern (2005) noted that violent victimization was more likely to occur in romantic relationships that included sexual intercourse (37 percent) compared with those that did not (19 percent). Abma and colleagues (2010) reported that among females with coitarche before age 20, 7 percent described their first intercourse as nonvoluntary.

Contraception

Despite wide availability of contraceptive options, nearly one half of pregnancies in the United States are unintended (Finer, 2014). Of adolescents, more than 20 percent do not use contraception at first intercourse, and there is a median delay of 22 months before seeking prescription methods after the sexual debut (Finer, 1998).

The most commonly used contraceptive by adolescents is the combination oral contraceptive (COC) pill. The intrauterine device and the etonogestrel implant are long-acting reversible contraceptives (LARC), and the American College of Obstetricians and Gynecologists (2014) now recommends the etonogestrel implant and the intrauterine device as first-line contraceptive options for adolescents. One study of 179 adolescents found an 85-percent continuation rate after 1 year with the levonorgestrel-releasing IUD (Paterson, 2009). Ideally, counseling begins prior to onset of sexual activity and includes discussion of emergency contraception. Many adolescents have misperceptions about contraception, including beliefs that it may cause infertility or birth defects. Such concerns may be important topics during contraceptive counseling.

Pelvic examination is not necessary when a contraceptive is prescribed if no other complaints are present. Moreover, guidelines from the American College of Obstetricians and Gynecologists (2012) note that cervical cancer screening does not usually begin until age 21 regardless of sexual activity. HIV-positive status is an exception, and full screening recommendations are described in Chapter 29. Sexually active adolescents are counseled and screened for gonorrhea and chlamydial infection (U.S. Preventive Services Task Force, 2014). For adolescents, the preferred method is collection of a urine sample for nucleic acid amplification testing (NAAT). Other STDs are screened as clinically indicated.

Information on HPV vaccination can also be offered. HPV vaccines, Cervarix, Gardasil 4, and Gardasil 9 are approved by the Food and Drug Administration for females aged 9 through 26 years and males ages 9 through 15. A series of three doses for girls, beginning with a first injection at age 11 or 12 years, is recommended (Kim, 2015). A second dose is administered 1 to 2 months later, and a third dose is given 6 months after the initial one. These vaccines are discussed further in Chapter 29.

For these types of services, the Supreme Court has ruled that minors have the right to contraceptives (Carry v. Population Services International). Moreover, current law dictates that all states provide consent to adolescents for treatment of “medically emancipated” conditions such as contraception, STDs, pregnancy, substance abuse, and mental health. These are legally designated medical situations for which an adolescent may receive care without the permission or knowledge of a parent or legal guardian (Akinbami, 2003).

To smooth the transition to adult care, the American College of Obstetricians and Gynecologists (2015) has published guidelines, which include ages 18 to 26 years. In addition to contraception, providers ideally discuss and screen for sexual and mental health, sleep disorders, nutrition, safety, and substance abuse.