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.
Table 37–3. Classification of Vulvovaginitis According to Cause. ||Download (.pdf)
Table 37–3. Classification of Vulvovaginitis According to Cause.
|Polymicrobial infection associated with disturbed homeostasis: secondary to poor perineal hygiene or a foreign body|
|Vulvovaginitis due to secondary inoculation|
|Infection resulting from inoculation of the vagina with pathogens affecting other areas of the body by contact or bloodborne transmission: secondary to upper respiratory tract infection or urinary tract infection|
|Specific primary infection, most commonly sexually transmitted: Neisseria gonorrhoeae, Gardnerella vaginalis, herpesvirus, Treponema pallidum, others|
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.
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.
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 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.
Lichen sclerosus of the vulva in a 6-year-old child.
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 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.
Labial adhesion in a young girl. Note the translucent vertical line in the center where the labia are fused together.
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.
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.
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.
Large vulvar hematoma secondary to bicycle injury.
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 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).
Transvaginal perforation of cul-de-sac and penetration of peritoneal cavity by a fall on a mop handle. Scanty bleeding from a hymenal tear was the only symptom on admission.
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.
Adams JA. Guidelines for medical care of children evaluated for suspected sexual abuse: an update for 2008. Curr Opin Obstet Gynecol
Kelly P, Koh J, Thompson JM. Diagnostic findings in alleged sexual abuse: symptoms have no predictive value. J Paediatr Child Health
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.
Simple vulvar or hymeneal cyst arising posterior to the urethra of a newborn infant.
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.
Botryoid sarcoma presenting as a hemorrhagic growth extruding from the vagina.
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.
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.
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 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.
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.
Anders JF, Powell EC
. Urgency of evaluation and outcome of acute ovarian torsion in pediatric patients. Arch Pediatr Adolesc Med
Libby L, Shadinger MD, Rochelle F, et al. Preoperative sonographic and clinical characteristics as predictors of ovarian torsion. J Ultrasound Med
Panteli C, Curry J, Kiely E, et al. Ovarian germ cell tumours: A 17-year study in a single unit. Eur J Pediatr Surg
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.
Pubertal development chart for a normally developing female adolescent. Growth data are converted to growth velocity and plotted. The growth velocity curve shows initial acceleration in growth, followed by the growth spurt and subsequent deceleration. Superimposed on this curve are the following pubertal events: A, thelarche; B, pubarche; C, menarche; D, onset of ovulation. (Reproduced, with permission, from Reindollar RH, McDonugh PG. Delayed Sexual Development: Common causes and basic clinical approach. Pediatr Annals. 1981;May;10(5):30-39.)
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.
Roy JR, Chakraborty S, Chakraborty TR. Estrogen-like endocrine disrupting chemicals affecting puberty in humans—a review. Med Sci Monit
Shafii T. The adolescent sexual health visit. ObstetGynecol Clin North Am
Sisk CL, Foster DL. The neural basis of puberty and adolescense. Nat Neurosci
Disorders of Sexual Maturation
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.
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.
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.
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.
Four-year-old child with idiopathic precocious puberty.
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 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 thelarche in a child 5 years of age.
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 in a child 4 years of age.
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 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.
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.
Additional androgen-dependent findings include acne and adult-type body odor.
Breast development is at least at Tanner stage II, with the areolae having a broadened, darkened appearance.
Genital changes reflect estrogen-induced thickening of the genital tissues. Increased vaginal secretions may result in leukorrhea. Dark, coarse pubic hair may be present.
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.
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.
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 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.
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.
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.
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 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.
Gonadoblastoma developing in a gonadal ridge in a patient with gonadal dysgenesis and 45,XO/46,XY karyotype.
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.
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.
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 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.
American Academy of Pediatrics Committee on Adolescence. Contraception and adolescence. Pediatrics
Das S, Dhulkota JS, Brook J, et al. The impact of a dedicated antenatal clinic on the obstetric and neonatal outcomes in adolescent pregnant women. J Obstet Gynecol
Lara-Torre E, Schroeder B. Adolescent compliance and side effects with quick start initiation of oral contraceptive pills. Contraception
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.
Adams Hillard PJ. Menstruation in adolescents: what's normal, what's not. Ann N Y Acad Sci
American College of Obstetricians and Gynecologists. Guidelines for Women's Health Care: A Resource Manual. 3rd ed. Washington, DC: American College of Obstetricians and Gynecologists; 2007.
American College of Obstetricians and Gynecologists. Menstruation in Girls and Adolescents: Using a Menstrual Cycle as a Vital Sign. Washington, DC: American College of Obstetricians and Gynecologists; 2006.
American Society for Reproductive Medicine Practice Committee. Current evaluation of amenorrhea. Fertil Steril
Bayas J, Costas L, Munoz A. Cervical cancer vaccination, indications, efficacy and side effects. Gynecol Oncol
2008;110 (3 Suppl 2):S11–S14.
Beyith Y, Hardoff D, Rom E, et al. A simulated patient-based program for training gynecologists in communication with adolescents girls presenting with gynecological problems. J Pediatr Adolesc Gynecol
Bidet M, Bachelot A, Touraine P. Premature ovarian failure: predictability of intermittent ovarian function and response to ovulation induction agents. Curr Opin Obstet Gynecol
Blank SK, Helm KD, McCartney CR, et al. Polycystic ovary syndrome in adolescence. Ann N Y Acad Sci
Breech LL, Laufer MR. Mullerian anomalies. Obstet Gynecol Clin North Am
Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics
Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol
Committee on Adolescent Health Care. ACOG Committee Opinion No. 436: evaluation and management of abnormal cervical cytology and histology in adolescents. Obstet Gynecol
Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis
Genazzani AD, Ricchieri F, Lanzoni C, et al. Diagnostic and therapeutic approach to hypothalamic amenorrhea. Ann N Y Acad Sci
Giannesi A, Marchiole P, Benchaib M, et al. Sexuality after laparoscopic Davydov in patients affected by congenital complete vaginal agenesis associated with uterine agenesis or hypoplasia. Hum Reprod
Hertwick SP. Pediatric and adolescent gynecology. Obstet Gynecol Clin North Am
Ibñez L, Díaz R, López-Bermejo A, et al. Clinical spectrum of premature pubarche: links to metabolic syndrome and ovarian hyperandrogenism. Rev Endocr Metab Disord
Ismail IS, Cutner AS, Creighton SM. Laparoscopic vaginoplasty: alternative techniques in vaginal reconstruction. BJOG
James AH. Bleeding disorders in adolescents. Obstet Gynecol Clin North Am
Karateke A, Gurbuz A, Haliloglu B, et al. Intestinal vaginoplasty: is it optimal treatment of vaginal agenesis? A pilot study. Surgical method of sigmoid colon vaginoplasty in vaginal agenesis. Int Urogynecol J Pelvic Floor Dysfunct
Legro RS. Detection of insulin
resistance and its treatment in adolescents with polycystic ovary syndrome. J Pediatr Endocrinol Metab
Leung AKC, Robson WLM, Kao CP, et al. Treatment of labial fusion with topical estrogen therapy. Clin Pediatr
McCann J, Miyamoto S, Boyle C, et al. Healing of hymenal injuries in prepubertal and adolescent girls: a descriptive study. Pediatrics
Pena A, Levitt MA, Bischhoff A, et al. Rectovestibular fistula: rarely recognized associated gynecologic anomalies. J Pediatr Surg
Petermann T, Maliqueo M, Codner E, et al. Early metabolic derangements in daughters of women with PCOS. J Clin Endocrinol Metab
Phillipp CS, Faiz A, Dowling N, et al. Age and the prevalence of bleeding disorders in women with menorrhagia. Obstet Gynecol
Poindexter G, Morrell D. Anogenital pruritus: lichen sclerosus in children. Pediatr Ann
Rosenfield RL, Devine N, Hunold JJ. Salutary effects of combining early very low-dose systemic estradiol
with growth hormone therapy in girls with Turner syndrome. J Clin Endocrinol Metab
Rotterdam ESHRE/tASRM-Sponsored PCOS consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome. Hum Reprod
Sanfilippo JS, Larra-Torre E. Adolescent gynecology. Obstet Gynecol
Satyaprakash A, Creed R, Ravanfar P, et al. Human papilloma virus vaccines. Dermatol Ther
Solomon LA, Zurawin RK. Vaginoscopic resection for rhabdomyosarcoma of the vagina: a case report and review of the literature. J Pediatr Adolesc Gynecol
Stranzinger E, Strouse PJ. Ultrasound of the pediatric female pelvis. Semin Ultrasound CT MR
Sybert VP, McCauley E. Turner's syndrome. N Engl J Med
Tena-Sempere M. GPR54 and kisspeptin in reproduction. Hum Reprod Update
Troiano RN, McCarthy SM. Müllerian duct anomalies: imaging and clinical issues. Radiology