Part 4: Reproductive Health Problems

INTRODUCTION

The normal anatomy of the breast is shown in Figure 77-1. A variety of benign breast lesions occur in the female adolescent. The most typical presentation is a self-detected, asymptomatic mass. Complaints such as bloody discharge, nipple retraction, or skin dimpling are rare.

ANATOMIC CHANGES AND CONGENITAL ABNORMALITIES

Breast asymmetry, a common condition in which one breast develops earlier or grows more rapidly than the other, usually occurs between sexual maturity rating (SMR) 2 and 4 and persists into adulthood in 25% of women. It is important to consider the age of the patient when assessing the etiology of a breast mass or enlargement. Normal thelarche usually occurs between 8 and 13 years of age. Rare congenital abnormalities of the breast include amastia (absent breast, associated with chest wall deformities such as pectus excavatum or Poland syndrome) and athelia (absent nipple). Polymastia (accessory breast tissue) and polythelia (accessory nipples) occur along the mammalian nipple line in 1% to 2% of girls and may be inheritable conditions. Breast atrophy developing after thelarche can be one sign of an eating disorder or other chronic illness such as scleroderma. The associated loss of both fat and glandular tissue in the breast results from significant weight loss. Virginal (juvenile) hypertrophy, the massive enlargement of one or both breasts caused by either increased tissue sensitivity to pubertal hormones or endogenous production of hormones from within breast cells, can be associated with a variety of problems, including headache, neck and back pain, dermatitis, embarrassment, and psychological difficulties. Reduction mammoplasty after completion of breast maturation may be indicated in female adolescents with severe virginal hypertrophy.

CYSTS, FIBROCYSTIC CHANGE, AND FIBROADENOMAS

The most common breast masses in adolescents are solitary cysts, fibrocystic change, and fibroadenomas. Masses resulting from inflammation or trauma occur less frequently. Cancer is rare among female adolescents. A solitary cyst contains sterile fluid. Over half resolve spontaneously within 2 to 3 months, so fine-needle aspiration or biopsy is often unnecessary. Recurrent or multiple cysts in the adolescent may represent early fibrocystic change.

Fibrocystic change (benign proliferative breast change) is a physiological response of breast tissue to cyclic hormonal activity. The result is a dilation and proliferation of duct epithelium to form gross cysts. A benign condition more common during the third and fourth decades, fibrocystic change may occur during adolescence. Bilateral breast pain in the upper outer quadrants beginning in the premenstrual phase of the menstrual cycle and subsiding thereafter is the typical presentation. Adolescents tend to have dense breast tissue. Physical examination reveals areas of diffuse, cordlike thickening as well as discrete mobile lesions, which often increase in size during the premenstrual period. Supportive care, including nonsteroidal anti-inflammatory agents for pain and a well-fitting supportive bra, is the most common approach to treatment. Oral contraceptives reduce symptoms in 70% to 90% of cases.

The majority (70–90%) of adolescent breast masses that undergo biopsy are identified as fibroadenomas, which can be classified as simple fibroadenomas, juvenile fibroadenomas, and phyllodes tumor. A fibroadenoma is a benign proliferation of stromal elements, ducts, and acini. Physical examination reveals a rubbery, painless, well-demarcated mass, 1 to 3 cm in size, usually located in the upper outer quadrant of the breast. Fibroadenomas may regress spontaneously but usually persist and may require excisional biopsy. Peak incidence occurs during late adolescence, but fibroadenomas may present up to 2 years before menarche. Multiple and recurrent fibroadenomas may occur, but malignant potential has not been established.

Juvenile fibroadenoma, a histologically similar lesion but with less well-defined edges, presents as a rapidly enlarging breast mass that can reach immense proportions. Giant fibroadenomas are defined as being > 5 cm, and are found most commonly in young African American women. Complete excision is curative.

Phyllodes tumors are rare. These tumors are rapidly growing lesions that are usually large, are well demarcated, and have a small potential for malignancy. The large phyllodes tumor may cause overlying skin to become stretched and shiny with distended veins, erythema, and even ulceration. Intraductal papilloma, a slow-growing benign tumor located under the areola, often presents with a serous or bloody nipple discharge.

BREAST CANCER

Primary breast cancer is rare in teenagers. Only 0.2% to 2% of all breast cancers occur before 25 years of age. The data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (2009–2013) had 0% new cases for women < 20 years, and 1.8% of new cases in women 20 to 34 years of age. More than 60% of breast cancers in adolescents are not primary breast tumors but arise metastatically from distant sites (eg, lymphoma) or locally from nonbreast tissue (eg, angiosarcomas). Cancer, in contrast to benign breast disease, is characterized by a hard, fixed mass beneath the nipple. Approximately one-third to one-half of breast cancer cases have a positive family history. Only a small fraction of breast cancers (5–9%) are associated with breast cancer–associated genes (BRCA1 or BRCA2). Risk factors for the development of adult breast cancer established during adolescence include menarche before age 12 years and cancer treatment–related radiation in the breast area (eg, for lymphoma). There is no clear association between use of oral contraceptives and later development of breast adenocarcinoma.

OTHER BREAST MASSES

A contusion may present as a poorly defined tender mass, with or without overlying hematoma. Less than half of patients will give a history of antecedent trauma. Contusions usually resolve over several weeks but may persist for several months. Occasionally, scar tissue or fat necrosis develops, resulting in small areas of calcification. Treatment consists of local excision. Trauma may also draw attention to a preexisting lesion unrelated to the injury.

Mastitis, or breast infection, presents with the rapid onset of unilateral pain and localized inflammation. Infection is more common in newborns and lactating women but can occur in adolescents secondary to trauma, nipple piercing, ductal abnormalities, or reduced immune defenses. Staphylococcus aureus is the most common etiologic organism. The initial management of mastitis includes systemic antibiotics, warm compresses, and analgesia. Acute mastitis may lead to fluctuance and abscess formation. Circumareolar incision and drainage is then indicated. Abscess formation must be considered with persistent, unresponsive mastitis.

ASSESSMENT

When assessing a breast mass, the history should identify previous trauma, fever, weight loss, nipple discharge, and medications. A family history of breast disease and the nature of any previous lesions should be obtained. A menstrual history of cyclic pain can be helpful in diagnosing fibrocystic changes. The history often elicits the use of oral contraceptive pills or other hormonal agents that can alter the breast. The physical examination includes assessment of SMR to avoid confusing the normal breast bud (especially if unilateral) with an abnormal mass. The size, location, and characteristics of the lesion should be described. Tenderness, warmth, and lymphadenopathy are consistent with infection. A hard, fixed lesion with overlying skin changes must be evaluated for cancer. Prolactin, thyroid, and gonadotropin levels are obtained to evaluate the symptom of galactorrhea.

Management of a suspected benign breast mass in an adolescent begins with reassurance and an observation period of 1 to 3 months. During this time, any change that occurs with the menstrual cycle should be noted. Masses that persist beyond this time should be referred for further evaluation. Fine-needle aspiration will distinguish a cystic from a solid lesion. Any aspirate obtained should undergo cytologic evaluation. A cyst will collapse after aspiration, yielding a clear yellow or brownish fluid, and the breast should be reexamined in 3 months. Breast core biopsy is a newer method to obtain tissue diagnosis. Excisional biopsy is indicated for a large solid or growing mass or one that yields an abnormal aspirate. The purpose of excision is to obtain a definitive diagnosis, avoid cosmetic deformity, and alleviate patient anxiety. Normal breast tissue can be spared because there is no need to remove a wide margin.

Mammography is rarely indicated in the evaluation of a palpable mass in an adolescent. The normally dense parenchymal tissue in the adolescent breast makes interpretation difficult. Mammography is not indicated for screening in this age group because of the low prevalence of malignancy. Ultrasonography is useful to differentiate between solid and cystic masses and to guide the fine-needle aspiration.

The value of teaching breast self-examination (BSE) to adolescents remains controversial. There is a lack of evidence of the benefits of a breast exam. The American Cancer Society’s current recommendation is that “regular clinical breast exam and breast self-exam are not recommended.” Some professionals argue that routine BSE in adolescents creates unnecessary anxiety and serves to identify a greater number of benign lesions. Teaching modified BSE may be a valuable educational component in the routine physical examination of the adolescent by leading to a discussion of normal development.

ADOLESCENT GYNECOMASTIA

Pubertal gynecomastia, the glandular enlargement of breast tissue in males, is a common complaint (see Fig. 77-1). Gynecomastia, which occurs transiently in 40% to 60% of 10- to 16-year-old boys and peaks in incidence at SMR 2 to SMR 4 (age 14 years), results from a decreased ratio of androgen to estrogen and a change in end-organ receptor sensitivity. The breast tissue is frequently firm, tender, and often asymmetric. Spontaneous resolution occurs in 90% of boys within 2 years. Rare causes of gynecomastia include endogenous states of estrogen excess, such as testicular, adrenal, or pituitary tumors; hyperthyroidism and hypothyroidism; hepatic disorders; refeeding poststarvation; endogenous androgen deficiency states such as hypogonadism, Klinefelter syndrome, renal hemodialysis, and congenital adrenal hyperplasia; and specific drugs, including estrogen, testosterone, anabolic steroids, human chorionic gonadotropins, tricyclic antidepressants, insulin, alcohol, marijuana, amphetamines, methadone, cimetidine, digitalis, and cytotoxic agents, among others. Pseudogynecomastia (fatty tissue or muscle development), frequently confused with true gynecomastia (glandular enlargement), can be distinguished by comparing the consistency of the breast tissue with that of adipose tissue in the anterior axillary fold.

Diagnosis of gynecomastia is based on the typical history and examination and the exclusion of other causes of gynecomastia. The history includes a review of current medications and illicit drug use (eg, marijuana use has been associated with gynecomastia). Physical assessment should describe the SMR and findings of the testicular examination as well as the amount and quality of breast tissue present. If glandular tissue is less than 4 cm (eg, SMR 2–3 female breast), reassurance is the most appropriate treatment. In contrast, pubertal macrogynecomastia resembles female SMR 3 to SMR 5 breasts, extends more than 5 cm, and usually does not regress spontaneously. A surgical referral is indicated when pubertal gynecomastia has a prolonged course (> 2 years), when it causes psychological impairment, or if macrogynecomastia is present. Medications such as danazol, tamoxifen, and testolactone are not generally recommended for adolescents because of their side-effect profiles, lack of documented efficacy, and frequent return of breast tissue after the drug is discontinued.

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TESTICULAR TORSION

Testicular torsion is a surgical emergency, and clinicians caring for adolescent males must have a high index of suspicion given the short window for salvage of the testicle.

ETIOLOGY

The exact etiology of torsion is unknown. However, the most common testicular anatomical abnormality, called the “bell clapper” deformity, can predispose to testicular torsion (Fig. 78-1). In this deformity, the tunica vaginalis completely surrounds the testicle, including the posterior aspect, and the absence of the normal posterior anchoring at the gubernaculum testis allows the testicle to twist freely.

CLINICAL MANIFESTATIONS AND DIAGNOSIS

Common presentation includes abrupt onset of severe scrotal pain with associated nausea, vomiting, fever, and abdominal pain. Symptomatic males may describe prior transient episodes of scrotal pain consistent with intermittent torsion/detorsion. Typically, the adolescent presents later in the course with a scrotum that is swollen, tender, erythematous, and often difficult to examine. The cremasteric reflex is nearly always absent. Prehn’s sign (ie, lessening of pain with scrotal elevation) had been used in the past to differentiate torsion from epididymitis, but it has since been found to be inferior to ultrasound. Diagnosis can be made on physical examination or with the assistance of color Doppler ultrasound, which has a sensitivity of 100% and a specificity of 75% (Fig. 78-2).

TREATMENT

Treatment involves prompt surgical exploration and detorsion. Time is of the essence because testicular viability declines to 0 after 24 hours. Given the high incidence of retorsion, as well as torsion of the contralateral testis, the affected testis and the contralateral testis are fixed to the scrotum in a procedure called scrotal orchiopexy.

TORSION OF TESTICULAR OR EPIDIDYMAL APPENDAGE

ETIOLOGY

Both the testis and the epididymis have appendages (Fig. 78-3) that are remnants of the wolffian and müllerian ducts, respectively. The pedunculated shape of the appendages predisposes them to torsion.

CLINICAL PRESENTATION

The typical presentation of appendiceal torsion occurs in boys ages 7 to 12 years and includes pain that may be accompanied by nausea and vomiting. Palpation of the testis reveals tenderness over the superior or inferior pole of the testes with or without a palpable mass. The cremasteric reflex is usually present. The classic “blue dot” sign, if present, represents the infarcted appendage viewed through the scrotal skin.

DIAGNOSIS

The diagnosis is usually made by clinical examination. If torsion of the testis cannot be ruled out, a color flow Doppler examination is indicated. Blood flow will be normal in appendiceal torsion.

TREATMENT

Treatment is usually supportive, including analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and scrotal elevation. If pain persists for longer than 5 days, consultation by a pediatric urologist is recommended.

TRAUMA

Trauma may be a cause of pain and swelling of the scrotum. When the presentation includes an overlying hematocele, surgical exploration and repair may be required for testicular salvage.

HYDROCELE

ETIOLOGY

Hydroceles are related to congenital abnormalities in the inguinal canal. Communicating hydroceles develop when fluid tracks down the inguinal canal into the tunica vaginalis. Hydroceles may also form from trauma, infection (eg, epididymitis and orchitis), testicular torsion, or tumors.

CLINICAL PRESENTATION AND DIAGNOSIS

Hydroceles are usually painless on exam. Communicating hydroceles may shift in size when the patient is upright or performs a Valsalva maneuver, whereas noncommunicating hydroceles will not. In most patients, a hydrocele will transilluminate, showing the presence of fluid. When palpated, it may feel like a supple, fluid-filled cyst.

TREATMENT

Hydroceles are corrected electively, if at all. They are corrected if the patient is symptomatic with pain and/or pressure. Correcting the underlying cause of the hydrocele usually causes resolution.

SPERMATOCELE

Spermatocele refers to the accumulation of sperm within the head of the epididymis (Fig. 78-4). Spermatoceles, which are benign cysts, are commonly found on routine physical examination or by the adolescent himself and usually do not require intervention unless symptomatic. On palpation, they are predominantly smooth, soft, well circumscribed, and found on the superior aspect of the testicle. They generally range in size from 2 to 5 cm. In addition, these cystic lesions may transilluminate. A spermatocele is corrected if the patient is symptomatic with pain and/or pressure.

ORCHITIS

ETIOLOGY

Orchitis rarely occurs in prepubertal males. The mumps virus is the most common cause of orchitis, but other viruses have been implicated (eg, coxsackievirus, echovirus, adenovirus, varicella). Bacterial orchitis is usually a consequence of contiguous spread from an epididymal infection. Mumps orchitis usually follows parotitis by about 4 to 8 days, but presentation up to 6 weeks later has been reported. In contrast, symptoms with other viruses occur commensurate with the other viral symptoms. There is also some evidence that these viruses cause post-viral inflammatory changes in the testicle.

CLINICAL PRESENTATION AND DIAGNOSIS

The typical presentation includes edema, erythema, and tenderness of the testicle and may be associated with constitutional symptoms (eg, fever, nausea, lower abdominal pain). It is most often unilateral. The diagnosis is usually made by clinical examination.

TREATMENT

Viral orchitis is treated supportively with rest and NSAIDs. Bacterial orchitis is treated with antibiotics and supportive care. Infertility is a rare complication of orchitis and most often results after bilateral cases.

VARICOCELES

ETIOLOGY

A varicocele is a dilatation of the pampiniform venous plexus within the scrotum. There are several theories as to the etiology of varicoceles. One theory involves the presence of incompetent valves within the veins along the spermatic cord, resulting in the backup of blood. Another theory is the “nutcracker effect,” wherein the left renal vein is compressed between the aorta and superior mesenteric artery, resulting in an increase in pressure, which is then transmitted to the left testicular vein due to its right angle insertion. Support for this theory includes the fact that 85% to 95% of varicoceles are left-sided. Right-sided varicoceles can be associated with tumors and should always be investigated further using Doppler ultrasound to evaluate for inferior vena cava (IVC) obstruction. Varicoceles most often appear beginning at puberty. This is due to rapid growth of the testicles, with subsequent increased blood flow.

CLINICAL PRESENTATION AND DIAGNOSIS

Varicoceles are usually asymptomatic in adolescents but occasionally may cause a dull ache after long periods of standing.

The diagnosis is usually made by clinical examination. Varicoceles may be graded on physical examination. A grade I (small) varicocele is detectable only when the patient performs a Valsalva maneuver, a grade II (moderate) varicocele may be palpated while standing but is not visible on examination, and a grade III (large) varicocele is visible through the skin (ie, a “bag of worms”).

TREATMENT

The clinical relevance of asymptomatic varicoceles in adolescents is that they have been associated with both time-dependent testicular growth arrest and abnormal semen analyses in adolescents. Urologic referral to discuss surgical repair should be offered to adolescents with testicular growth arrest, bilateral varicoceles, and/or symptomatic (eg, painful) varicoceles, regardless of the grade of the varicocele. Semen analysis should be performed for all patients with high-grade varicoceles. However, there is no evidence that semen analysis is a direct correlate with future fertility when performed in adolescents.

EPIDIDYMITIS

ETIOLOGY

Epididymitis is an inflammatory disease of the epididymis. In prepubertal children, epididymitis may be caused by underlying genitourinary abnormalities, such as posterior urethral valves, ectopic ureters, and genitorectal fistulas. The causative organisms are often coliform bacteria, such as Escherichia coli. Among sexually active adolescents, most cases of epididymitis are attributed to the retrograde extension of Chlamydia trachomatis from the vas deferens; Neisseria gonorrhoeae is the second-most common organism.

CLINICAL PRESENTATION

Patients may present with the gradual onset of scrotal pain and edema along with nausea, fever, abdominal or flank pain, and urethral discharge. On examination, the scrotum is often edematous and erythematous. Additionally, the epididymis is often tender to palpation. Fluctuance or fixation of the scrotal tissue around the epididymis is concerning for the presence of a scrotal abscess.

DIAGNOSIS

The diagnosis is usually made by clinical examination. In contrast to testicular torsion, the cremasteric reflex should be intact and there should be a positive Prehn’s sign. However, Prehn’s sign has been found to be inferior to ultrasound to differentiate epididymitis from torsion.

TREATMENT

Treatment includes appropriate antibiotic therapy for both the patient and his sexual partners. Patients who fail to improve during the initial 72 hours of outpatient management must be evaluated for the possibility of an abscess.

TESTICULAR NEOPLASMS

ETIOLOGY

According to the National Cancer Institute, testicular neoplasms represent the most common solid tumor in males age 15 to 34 years. Histologic types that occur most frequently in adolescence are germ cell tumors (95%) and include seminoma, embryonal carcinoma, teratoma, and choriocarcinoma. Leydig and Sertoli cell tumors are of stromal origin and may occur at any age, including adolescence.

CLINICAL PRESENTATION

Patients often present with painless scrotal swelling of gradual onset. Adolescents with testicular cancer are more likely than other adolescents to have had cryptorchidism or testicular atrophy. Pain may be present if the tumor has hemorrhaged or become necrotic. When pain accompanies a tumor, it can lead to an erroneous diagnosis of an infectious or inflammatory process.

Physical examination usually reveals a firm, irregular mass that is opaque to transillumination, but cystic or necrotic areas of the tumor can be soft on palpation. Scrotal ultrasound may reveal intratesticular lesions. A hydrocele or varicocele may also be detected. The contralateral testis must be examined not only for comparison but also to rule out the presence of bilateral disease. The detection of cervical or supraclavicular lymph nodes may indicate an advanced stage of disease. Other possible findings include gynecomastia and breast tenderness. Because stromal tumors tend to produce androgens and/or estrogens, the prepubertal boy may present with early virilization, whereas the pubertal boy may present with feminization.

DIAGNOSIS

Testicular tumor markers, most commonly beta human chorionic gonadotropin (hCG) and alpha-fetoprotein, are useful tests for certain histologic types and should be obtained before orchiectomy. The hCG level is elevated in choriocarcinoma, nonseminomatous mixed germ cell tumors, and seminoma with syncytiotrophoblasts. The alpha-fetoprotein level is elevated in nonseminomatous germ cell tumors, especially yolk sac tumors and embryonal carcinoma. However, these tumor markers should not be used for screening. Imaging of a scrotal mass is done using ultrasound or magnetic resonance imaging. Staging of a proven tumor requires chest and abdominal computed tomography.

TREATMENT

Therapy is determined by staging and definitive histology and includes orchiectomy, retroperitoneal lymph node dissection, radiation, and chemotherapy. This results in an overall 5-year survival rate of more than 95%.

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INTRODUCTION

Normal menstrual cycles during adolescence occur every 21 to 45 days, with duration of bleeding up to 7 days and blood loss of 20 to 60 mL (see Chapter 533). For those whose cycles are abnormal, the most common menstrual disorders in adolescents include amenorrhea, abnormal uterine bleeding, and dysmenorrhea, which are discussed in this chapter.

AMENORRHEA

Amenorrhea, the absence of menses, can be either temporary or permanent. Traditionally, there are two categories: primary amenorrhea and secondary amenorrhea. Primary amenorrhea is defined as failure to menstruate either (1) by age 15 in the presence of breast development and normal growth, (2) within 3 years of thelarche, or (3) by age 13 with the absence of secondary sexual characteristics. Also, when delay in secondary sexual development and amenorrhea exists or cyclic pelvic pain accompanies primary amenorrhea, prompt evaluation should occur.

Secondary amenorrhea is cessation of menses for greater than 3 months or 90 days. While the etiologies of primary amenorrhea are typically genetic or anatomic, all causes of secondary amenorrhea may also present as primary amenorrhea. The evaluation of infrequent menses with cycle length longer than 6 weeks is the same as amenorrhea in this discussion. See Chapter 534 for further discussion on amenorrhea in the setting of delayed puberty.

DIFFERENTIAL DIAGNOSIS

Do not overlook pregnancy, the most common cause of secondary amenorrhea, as a cause of primary amenorrhea. (See Chapter 80 for more information on the diagnosis of pregnancy.) Beyond pregnancy, the etiologies of primary and secondary amenorrhea include anatomic abnormalities or fall into three categories depending on the function of the pituitary gland in relation to the ovary: hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, and eugonadotropic eugonadism. Another common classification system divides causes based on location of dysfunction within the hypothalamic–pituitary–adrenal (HPA) axis: hypothalamic, pituitary, ovarian, or other.

Hypogonadotropic Hypogonadism

Hypogonadotropic hypogonadism indicates inadequate hypothalamic–pituitary stimulation of the ovary, and low levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen characterize this state. Hypothalamic amenorrhea results from partial or complete inhibition of gonadotropin-releasing hormone (GnRH) release from the hypothalamus. See Table 79-1 for causes of amenorrhea characterized by hypogonadotropic hypogonadism. Excessive exercise and weight loss leading to amenorrhea may represent an eating disorder (see Chapter 76). Local lesions in the hypothalamus (eg, infiltrative processes, calcifications, gliomas, and germinomas), traumatic brain injury (TBI), and central nervous system radiation are all rare causes of GnRH deficiency. Isolated GnRH deficiency is associated with the absence (anosmia) or impairment (hyposmia) of the ability to smell (Kallman syndrome). Medications and illicit drugs may also result in amenorrhea.

Pituitary dysfunction and deficiencies or the inability to synthesize adequate amounts of gonadotropins may result from pituitary lesions, but panhypopituitarism and prolactinomas are more common. In panhypopituitarism, gonadotropin deficiency occurs before the development of changes in thyroid or adrenal function; isolated gonadotropin deficiency is rare.

The most common pituitary tumor causing amenorrhea is the prolactinoma. This type of tumor causes inhibition of the hypothalamic–pituitary–gonadal axis by secreting abnormally high levels of prolactin. Only 50% to 60% of females with adenomas have galactorrhea. The absence of galactorrhea does not eliminate suspicion for the tumor. Rarely, adenomas increase in size, causing symptoms such as vision change and headache associated with space-occupying lesions. Other causes of hyperprolactinemia include psychoactive drugs (eg, haloperidol, phenothiazines, amitriptyline, benzodiazepine, and cocaine), breastfeeding, and renal failure. Both hypercortisolism and hypothyroidism are associated with hyperprolactinemia and amenorrhea.

Hypergonadotropic Hypogonadism

High levels of LH and FSH characterize hypergonadotropic hypogonadism. This ovarian dysfunction manifests clinically with menstrual irregularities. Such disorders include gonadal dysgenesis (abnormal ovarian development) and primary ovarian insufficiency (POI). There are multiple etiologies for POI (Table 79-1). Gonadal dysgenesis is seen in Turner syndrome (45,XO) (see Chapter 534) and fragile X, and in women with normal karyotype (46,XX) gonadal dysgenesis. Secondary amenorrhea is also associated with mosaic Turner syndrome.

Rarer causes of hypergonadotropic hypogonadal amenorrhea include pseudo-ovarian failure secondary to gonadotropin-resistant ovary syndrome (an abnormality of ovarian follicle-stimulating hormone receptors) and defects in estrogen biosynthesis, including 17-hydroxylase deficiency and 17-ketosteroid reductase deficiency. Late-onset congenital adrenal hyperplasia (CAH, 21-hydroxylase deficiency) may first present with secondary amenorrhea and signs of virilization (eg, clitoromegaly and hirsutism). Androgen insensitivity (46,XY) is the insensitivity of peripheral tissues to circulating androgens, external female phenotype, and amenorrhea.

Eugonadotropic Eugonadism

Normal FSH, LH, and estrogen levels characterize the eugonadotropic state. If primary amenorrhea occurs in this context, it is anatomic in origin. Defects in the development of the müllerian duct system are associated with primary amenorrhea resulting in imperforate hymen, vaginal atresia or absence, or other malformations of the cervix and the uterus. Except in cases of absence of the uterine cavity or endometrium, developmental genital tract obstructions present with painful swelling of the reproductive tract above the area of the blockage. These include hematocolpos (vaginal), hematometra (uterus), and hematoperitoneum (leakage of menstrual blood into the peritoneal cavity). The pain is cyclic in nature, coinciding with the timing of a menstrual cycle. Mayer-Rokitansky-Küster-Hauser syndrome is müllerian agenesis with primary amenorrhea resulting from absence or hypoplasia of the vagina, cervix, and/or uterus.

Secondary amenorrhea associated with normal FSH, LH, and estrogen levels has a wide differential diagnosis (Table 79-1), including uterine scarring and hyperandrogenic states. Uterine synechiae (Asherman syndrome) occurring after endometrial manipulation (eg, pregnancy, dilation and curettage) or infection (eg, pelvic inflammatory disease, tuberculous endometritis) can lead to secondary amenorrhea. Causes of amenorrhea and hyperandrogenism (eg, hirsutism and/or virilization) include polycystic ovarian syndrome (PCOS), virilizing ovarian or adrenal tumors, and drugs, including phenytoin, oral contraceptives, cocaine, and anabolic steroids.

Polycystic Ovarian Syndrome

PCOS is the most common endocrine disorder in reproductive-aged women and a common cause of eugonadotropic secondary amenorrhea in adolescents. PCOS can also cause primary amenorrhea. Differing definitions and diagnostic criteria describe this clinically heterogeneous syndrome. The hallmarks of PCOS include ovulatory dysfunction and hyperandrogenism. Ovulatory dysfunction is clinical evidence of menstrual cycle irregularity or polycystic ovaries on ultrasound or other imaging. Hyperandrogenism is either (1) the clinical presence of hirsutism, inflammatory acne, or androgenic alopecia, or (2) biochemical elevations in serum testosterone and/or dehydroepiandrosterone sulfate (DHEAS). The hyperandrogenism is secondary to ovarian thecal cell proliferation and the resultant excess androgen production. The current hypothesis is that peripheral insulin resistance, which may or may not manifest as increased serum insulin levels, and an increase in serum LH relative to FSH contribute to thecal cell proliferation and further stimulation of androgen production. Although LH elevations and insulin resistance are common in women with PCOS, they are not required for diagnosis. Other clinical comorbidities include obesity, insulin resistance, glucose intolerance, and type II diabetes; mixed dyslipidemia (eg, low high-density lipoprotein, elevated triglycerides); metabolic syndrome; infertility; and endometrial cancer.

There are four accepted sets of diagnostic criteria. The National Institutes of Health criteria (1990) define PCOS by evidence of hyperandrogenism and chronic anovulation with exclusion of other causes of androgen excess. The Rotterdam criteria (2003) state that 2 of the following 3 findings are required for diagnosis: menstrual irregularity due to anovulation or oligo-ovulation, clinical and /or biochemical signs of hyperandrogenism, or polycystic ovaries (by ultrasound). The Androgen Excess and PCOS Society criteria (2006) specify that both androgen excess and ovulatory dysfunction must be present. Recent Pediatric Endocrine Society criteria for adolescent PCOS include the otherwise unexplained combination of abnormal uterine bleeding that persists for 1 to 2 years post-menarche and evidence of hyperandrogenism.

Since increased androgen levels may occur during normal pubertal development, confirmatory testing of hyperandrogenism is advisable. While PCOS accounts for up to 85% of adolescent hyperandrogenism, it is important to exclude other potential causes including CAH and other disorders of adrenal steroid metabolism, virilizing tumors, acromegaly, drugs such as valproic acid, and others. Routine ultrasound examination of the ovaries for diagnosing PCOS during adolescence is controversial since polycystic appearing ovaries may be a normal finding.

Evaluation of Amenorrhea

See Table 79-2 for a guide to history, physical examination, and evaluation.

History

The evaluation of amenorrhea requires a careful history and physical assessment. Taking a developmentally appropriate sexual history is essential. Exclude pregnancy via urine or serum pregnancy test before performing further workup. Constitutional delay is more common in boys and should be a diagnosis of exclusion. Inquire about family history of pubertal delay, stature in relation to family members, and presence of neonatal health problems including prematurity. Elucidate information suggesting additional causes of secondary amenorrhea, including symptoms of estrogen deficiency (eg, hot flashes, vaginal dryness) or risk factors for uterine scarring.

Physical Examination

Neurologic examination is required to assess for increased intracranial pressure (papilledema) or expanding mass (bitemporal hemianopsia is one hallmark of pituitary tumors). If a complete pelvic examination is not possible for anatomic, cultural, or psychosocial reasons, an alternative is recto-abdominal examination. Patency and depth of the vagina can be determined by passing a lubricated cotton swab through the vaginal opening. If a pelvic examination cannot be completed or anatomic abnormalities are noted, a pelvic ultrasound or MRI should be performed.

Screening Laboratory Tests

After ruling out pregnancy, initial tests should include serum FSH levels, prolactin, and thyroid function tests (TSH) (Fig. 79-1). If physical examination reveals hyperandrogenism, obtain serum testosterone (free and total) and DHEAS levels. Very high DHEAS levels are concerning for adrenal dysfunction. Prolactin levels of 20 to 60 µg/L may be difficult to interpret and need repeating while levels > 200 µg/L suggest macroadenoma. Some clinicians will also order a serum estradiol level. High FSH levels warrant a chromosomal evaluation.

Management of Amenorrhea

Management

Confirm any abnormal laboratory results. A progesterone challenge indirectly evaluates the presence of endogenous estrogen and the competence of the reproductive outflow tract from uterus to vaginal opening. Prescribe medroxyprogesterone acetate 10 mg by mouth daily for 7 days; within 2 to 7 days of completion, uterine withdrawal bleeding should occur. Bleeding confirms competence of the hypothalamic–pituitary–gonadal axis and patency of the outflow tract. If no bleeding occurs after progesterone challenge, the reproductive outflow tract is abnormal or endogenous estrogen is inadequate. In such situations, the second step of the hormonal challenge test is to prime the endometrium: 2.5 mg of oral conjugated estrogen for 25 days with 10 mg of oral medroxyprogesterone acetate added from day 16 to day 25. It may be necessary to repeat this a second time if no bleeding is elicited. If no bleeding occurs after the second round, obtain pelvic sonography and further hormonal assays, including a serum estradiol level.

TREATMENT

Suspected outflow obstruction of the reproductive tract necessitates appropriate imaging studies, further defining existing anatomy. Treatment of anatomic abnormalities is reconstructive surgery. Surgical correction of vaginal agenesis is appropriate prior to adulthood and before sexual debut.

Chapters 516 and 534 review the complete evaluation and treatment of hypothalamic-pituitary failure. Elevated prolactin levels in an asymptomatic patient suggest pituitary microadenoma; consider bromocriptine (a dopamine agonist) therapy. Treat ovarian failure with hormone replacement therapy, 0.3 to 0.625 mg of conjugated estrogen (the lowest amount to achieve the desired estrogen effect) on days 1 through 25 along with medroxyprogesterone acetate 10 mg on days 16 through 25 to avoid the effect of unopposed estrogen on the endometrium, which is linked to endometrial cancer. Counseling regarding bone health and calcium requirements is imperative. Provide appropriate counseling resources for those diagnosed with irreversible infertility of any cause.

PCOS treatment begins with lifestyle modification, emphasizing dietary adjustment and exercise. A 5% reduction in weight may regulate ovulation and improve cycle regularity. Combined oral contraceptives (or the combination patch or vaginal ring) is the first-line pharmacologic intervention since each provides cycle regulation and endometrial protection along with anti-androgenic effects mediated by increases in sex hormone-binding globulin. For women in whom estrogen is contraindicated, progesterone-only therapies (eg, the pill, monthly injection, subdermal implant, or IUD) will also provide endometrial protection but are limited in anti-androgenic effects. Anti-androgens such as spironolactone are effective against acne and hirsutism. Treatments for facial hirsutism include topical eflornithine and electrolysis. Metformin therapy improves insulin sensitivity and may decrease circulating androgen levels in women with PCOS, both decreasing hirsutism and improving ovulation and cycle regularity. Simultaneous use of metformin and combination oral contraceptives is beneficial. All patients with PCOS should be screened for dyslipidemia (fasting lipid profile) and glucose intolerance/type 2 diabetes (2-hour oral glucose tolerance test or hemoglobin A1C) regardless of body mass index or weight.

ABNORMAL UTERINE BLEEDING

Abnormal uterine bleeding (AUB) is vaginal bleeding that occurs in cycles shorter than 21 days or longer than 45 days, lasts longer than 8 days, results in blood loss greater than 80 mL, and/or is associated with anemia. There are two general types: anovulatory and ovulatory dysfunctional uterine bleeding, with further classification by etiology: hormonal, local pathology (ie, vagina, cervix, and uterus), coagulopathy, and pregnancy related.

DIFFERENTIAL DIAGNOSIS

The International Federation of Gynecology and Obstetrics (FIGO) recommends using the PALM-COEIN classification system to identify the etiology of AUB and heavy menstrual bleeding (HMB). PALM- COEIN stands for polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified. Under this system, etiologies are written as AUB followed by the corresponding letter, eg, AUB- P (AUB caused by polyps). Multiple etiologies may exist in one patient; some conditions are uncommon in the adolescent population. The most common adolescent causes are AUB-C, AUB-O, and AUB-I.

Polyp, Adenomyosis, Leiomyoma, Malignancy, and Endometrial

In general, polyps (AUB-P), adenomyosis (AUB-A), leiomyoma (AUB-L), and malignancies of the vagina and uterus (AUB-M) do not occur frequently in adolescents but should be included in the differential diagnosis when evaluating an adolescent with AUB and HMB. Cervical factors associated with bleeding include cervicitis, dysplasia, malignancy, hemangiomas, cervical polyps, and large fragile condylomas. Cervical and vaginal abnormalities are usually associated with light spotting or postcoital bleeding rather than frank vaginal bleeding. Endometritis (AUB-E) most commonly results from subclinical infections with sexually transmitted organisms such as Chlamydia trachomatis. Submucosal myomas, endometriosis, arteriovenous malformations, and uterine cancers are associated with irregular bleeding.

Ovulatory Dysfunction

Ovulatory dysfunction (AUB-O) is the most common cause of AUB in adolescents, resulting from the immaturity or dysfunction of the hypothalamic–pituitary–gonadal axis. Anovulatory cycles are common during the first 1 to 2 years after menarche (75% are normal by year 1, 95% by year 5) and are characterized by oscillations in estrogen levels and lack of, or inadequate, progesterone production (see Chapters 66 and 533). This results in an abnormally thick and fragile endometrial lining that may slough in a disorderly and irregular fashion, leading to irregular menstrual bleeding and HMB. Bleeding secondary to anovulation is a diagnosis of exclusion and made only after a careful evaluation to eliminate other more serious causes. Potential hormonal causes of AUB include those previously described for secondary amenorrhea (Table 79-1).

Iatrogenic

Iatrogenic (AUB-I) causes include common medications such as hormonal contraceptives (injectable, implants, oral contraceptive pills, IUD), antiepileptics, anticoagulants, chemotherapy, etc. Drug interactions with hormonal contraceptives and noncompliance can cause AUB.

Coagulopathy

Coagulopathies (AUB-C) are the most common cause of HMB requiring hospitalization. AUB at the time of menarche may be the initial manifestation. Soiling clothes, soaking through double protection, or leaking onto the sheets at night indicates the need for further evaluation. The most common cause is von Willebrand disease, which has a prevalence of 1%; one should consider other primary and acquired coagulopathies and thrombocytopenias as well. The depletion of vitamin K–dependent clotting factors, fibrinogen, and plasminogen secondary to liver or mucosal bowel disease may also contribute to excessive bleeding. Patients with renal disease or hemodialysis might have AUB leading to HMB.

AUB Not Yet Classified

Vaginal causes of AUB (AUB-N) include foreign bodies (eg, forgotten tampons or condoms), lacerations from either sexual abuse or intravaginal insertion of objects, and hymen tears. Ovarian cysts and malignant and benign tumors may also cause abnormal bleeding.

Pregnancy-Related Causes

Complications of pregnancy may present as AUB (Chapter 80). Medical emergencies include ectopic pregnancy and threatened abortions.

EVALUATION AND MANAGEMENT

The primary goals of clinical assessment are to determine the acuity, duration, and volume of blood loss as well as assess the need for medication, hospitalization, surgical intervention, or transfusion. First, exclude causes requiring immediate intervention. Table 79-2 outlines the pertinent history, physical examination, and laboratory evaluation. Women with vaginal bleeding, an acute abdominal complaint, and/or positive pregnancy test need immediate gynecologic consultation as this may indicate an ectopic pregnancy. Patients with significant blood loss resulting in anemia should be evaluated for both coagulopathies and thyroid disorders.

Stabilize patients with hemodynamic changes or an acute abdomen using appropriate fluid, electrolyte, and hemostatic stabilization. Stop acute HMB by administering conjugated estrogen, 25 mg intravenously every 6 hours for a total of 6 doses, with simultaneous use of combination oral contraceptives to stabilize the endometrium. If the patient is hemodynamically stable and only mildly anemic, prescribe a fixed-dose estrogen-progesterone combination oral contraceptive, one pill every 6 hours until bleeding stops. Taper the dose over the following 3 to 4 weeks, at which time a withdrawal bleed of 3 to 5 days is permitted, followed by cyclic combination oral contraceptive therapy. An antiemetic may be necessary with high-dose estrogen therapy. After 4 to 6 months, attempt to discontinue medication under close medical supervision. Other regimens include cyclic progesterone therapy; this regimen appears to be less efficacious in patients with primary AUB. Iron and folate replacement may be necessary for anemic patients (Hgb < 12 g/dL). For patients with mild breakthrough bleeding secondary to hormone use (eg, progesterone-only contraception), a trial of nonsteroidal anti-inflammatory drugs (NSAIDs) is recommended to decrease blood flow to the endometrium. Treatment of adolescents with AUB rarely requires dilation and curettage; it is contraindicated in patients with bleeding disorders.

Management strategies for AUB-O include decreasing the frequency of menstrual flow and/or inducing an atrophic endometrium. Options include continuous daily combined oral contraceptive use with a controlled withdrawal bleed every 3 to 4 months or induction of endometrial atrophy with either daily oral progesterone, intramuscular Depo-Provera every 3 months, or GnRH analogs such as leuprolide acetate. In addition to hormonal therapy, intranasal 1-deamino-8-D-arginine vasopressin (DDAVP) is an alternative therapy for individuals with von Willebrand disease or platelet dysfunction. Other therapies include antifibrinolytics (eg, tranexamic acid). An inherited bleeding disorder is a contraindication for the use of NSAIDs.

DYSMENORRHEA

Dysmenorrhea, the experience of painful menstrual cramping and other menstruation-associated symptoms, remains one of the most common reproductive system complaints of menstruating female adolescents and is a leading cause of school and work absenteeism and decreased quality of life. The prevalence of dysmenorrhea approaches 50% to 93% during adolescence, peaking 1 to 2 years after menarche. This coincides with the establishment of ovulatory cycles. Most experience mild-to-moderate pain, but incapacitation occurs in 10% to 20% for 1 to 3 days each month; even more miss school and social activities.

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION

Alterations in four chemicals cause primary dysmenorrhea: prostaglandins, leukotrienes, prostacyclin, and vasopressin. Increased levels of prostaglandin (PGF_2α) and leukotriene C4 and D4 stimulate uterine vasoconstriction, pain sensitization, and myometrium contractions. Prostacyclin is a vasodilator and muscle relaxant, but decreased levels occur in women with dysmenorrhea. Lastly, overproduction of vasopressin further increases uterine contractions. These four alterations lead to intense uterine contractions, vasoconstriction, and ischemic pain. During the first 36 to 48 hours of menses, prostaglandins increase within the endometrium, corresponding with the time of greatest discomfort. Beyond pain, systemic effects of the altered chemical milieu include nausea, vomiting, diarrhea, fatigue, headache, low back pain, thigh pain, dizziness, and syncope.

Secondary dysmenorrhea is associated with specific physiological and pathologic conditions, including pelvic infections (eg, endometritis, pelvic inflammatory disease), ectopic pregnancy, miscarriage, endometriosis, adhesions, IUD placement, uterine leiomyomas (rare in adolescence), ovarian cyst, cervical stenosis, and other anatomic abnormalities causing obstruction of the outflow tract. Nongynecologic causes include inflammatory bowel disease, irritable bowel syndrome, urinary tract problems, musculoskeletal conditions, and psychogenic (abuse).

EVALUATION

A thorough history should detail age at menarche, date of onset of pain, relationship of onset and duration of pain to menses, date of last menstrual period, and impact of previous pain medications by type. A confidential interview should include the assessment of sexual activity and practices, history of abuse, use of contraceptives including condoms, sexually transmitted disease history, and previous pregnancies and outcomes. A review of systems will identify associated systemic symptoms. Evaluation includes a complete physical examination and pelvic examination with screening for secondary causes as described earlier in this chapter. If there is a secondary cause or there is minimal improvement after 6 months of treatment, proceed with additional laboratory studies, diagnostic imaging, and surgical procedures as necessary.

MANAGEMENT

Therapy for primary dysmenorrhea focuses on inhibiting the synthesis or action of prostaglandins. Standard therapy includes appropriately dosed NSAIDs such as ibuprofen, naproxen sodium, or mefenamic acid begun 1 to 2 days before the expected onset of menses and continued through day 2 to 3 of bleeding. The 30% to 40% of females who do not respond to cyclooxygenase inhibitors (NSAIDs) potentially have dysmenorrhea mediated primarily through the lipoxygenase-dependent leukotriene pathway. Combination oral contraceptive pills (OCPs) improve symptoms in 90% of young women with primary dysmenorrhea, but it may take 3 cycles to achieve maximum therapeutic benefit. NSAIDs and OCPs used together can improve symptom relief. In addition, patients should be counseled to avoid smoking and caffeine. Alternative treatments noted to be effective include omega-3 polyunsaturated fatty acids, vitamin E, vitamin B₁, and minerals such as magnesium. Patients diagnosed with primary dysmenorrhea who do not improve with 6 months of adequate therapy should be evaluated for causes of secondary dysmenorrhea.

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INTRAUTERINE PREGNANCY

INTRODUCTION

Adolescent pregnancy is an important pediatric health concern. Pediatricians and general practitioners can play a vital role in the early diagnosis of pregnancy and promoting prenatal care. The World Health Organization reports a global average teenage birth rate among 15- to 19-year-olds of 49 births per 1000 females. Globally, the second leading cause of death in females aged 15 to 19 is complications occurring during pregnancy or delivery. The teenage birth rate in the United States has dramatically declined over the last 2 decades. The current preliminary rate of 22.3 per 1000 females aged 15 to 19 years is the lowest recorded rate.

HISTORY

During any assessment of an adolescent female, it is advisable to record the date and normality of the last menstrual period. Once menarche is achieved, pregnancy should be ruled out any time a sexually active patient reports missing 1 or more menses. A history of unprotected intercourse since the last menses with or without amenorrhea or unusual vaginal bleeding should alert the physician to the possibility of pregnancy. The absence of historical information does not preclude pregnancy because the adolescent may be unwilling or unable to communicate a sexual history to the clinician for a variety of reasons. The typical symptoms associated with pregnancy (nausea, vomiting, intermenstrual spotting, breast tenderness, unexplained weight gain, urinary frequency, and fatigue, among others) may be present in any combination or may be absent early in pregnancy (Table 80-1).

PHYSICAL EXAMINATION

A physical assessment, often including a pelvic examination, is critical to the evaluation of a possible pregnancy. Uterine size can be estimated based on a bimanual exam; in general, at 6 weeks, the uterus may be slightly softened but enlargement is difficult to appreciate, an 8-week uterus is about the size of an orange, and a 12-week uterus is the size of a grapefruit. As pregnancy progresses, the uterine fundus can be appreciated via an abdominal exam after 12 weeks, a 16-week uterus can be felt at the midpoint between the pubic symphysis and the umbilicus, and a 20-week uterus at the umbilicus.

EVALUATION FOR PREGNANCY

The first day of the last menstrual period forms the basis of dating of pregnancy. The urine or serum pregnancy test confirms the presence of an early pregnancy, using detection of beta-human chorionic gonadotropin (β-hCG). Within 24 hours of implantation (which occurs 6 to 12 days after ovulation), the placenta produces hCG (≤ 5 IU/L) and concentrations double every 48 to 72 hours in a normal pregnancy. By 2 weeks, the level rises to more than 200 IU/L in a normal pregnancy, and concentration peaks at approximately 100,000 IU/L at 8 to 10 weeks gestation. Thereafter, the level drops to about 10,000 IU/L at 20 weeks and remains stable until term. Standard urine pregnancy tests are an accurate, sensitive, easy, and inexpensive diagnostic tool to detect early pregnancy with β-hCG sensitivities at levels of 20 to 50 IU/L. In contrast, the minimum serum β-hCG levels required for positive pregnancy tests are 5 to 10 IU/L for qualitative tests and 1 to 2 IU/L for ultrasensitive quantitative tests (Table 80-2).

MANAGEMENT OF PREGNANCY

Options Counseling

Once an intrauterine pregnancy is confirmed, the provider is tasked with providing confidential counseling to the adolescent about her options. Outcome options include continuation of the pregnancy with subsequent parenting, adoption, or fostering of the child, or termination of the pregnancy. Based on her locale, an adolescent who desires to terminate a pregnancy should be made aware of whether or not she may provide consent independently or if parental notification and/or consent (or the legal alternative option of judicial bypass) is required. In addition, she should be advised of the legal restrictions related to the estimated gestational age and/or limited sources of care in some localities.

Prenatal Care

Ideally the adolescent should have an initial prenatal care visit within 1 to 2 weeks of diagnosis. Early prenatal care is associated with fewer adverse maternal, obstetrical, and neonatal outcomes in this high-risk population. The gold standard of adolescent prenatal care is utilization of a multidisciplinary, comprehensive, and adolescent-centered model. Prenatal care should include promotion and instruction regarding a healthy diet and appropriate weight gain. A daily prenatal vitamin and nutrition education pertaining to the developing fetus is important. Daily folic acid (folate) supplement (400 mg) included in prenatal vitamins is important in preventing neural tube defects, especially in the first 3 to 4 weeks of pregnancy.

All pregnant adolescents should be screened for chlamydia, gonorrhea, hepatitis B, HIV, and syphilis early during pregnancy, and repeat testing should occur in the third trimester (Table 80-3). Pregnancy is also a compelling motivator for adolescents to cease or at least reduce use of tobacco, alcohol, and other substances. Education about the risks of the aforementioned substances is an essential element of prenatal care. Positive screening should prompt a referral for treatment. Particular attention should be devoted to screening for depression. There is an association between untreated maternal depression and postpartum depression, both of which can lead to adverse maternal, neonatal, and childhood sequelae. Further evaluation and treatment should be initiated for those with positive depression screening. Intimate partner violence (IPV), either past or present, is associated with poor perinatal outcomes. A history of abuse within the last year is a prognostic indicator of violence during pregnancy. Brief screening tools and safety card–based guides to assessment and intervention are available. If child abuse or exploitation is suspected, the pediatrician should assure that the appropriate agencies/authorities are involved.

ECTOPIC PREGNANCY

EPIDEMIOLOGY

Ectopic pregnancy is a significant problem for young sexually active women, as reflected by a fourfold increase in incidence of the problem between 1970 and 1992, with 20 ectopic pregnancies reported per 1000 pregnancies in 1992, the last time national data was reported by the CDC. Its incidence is difficult to estimate today. However, it remains the leading cause of maternal death in the first trimester of pregnancy and accounts for 4% to 10% of all pregnancy-related deaths annually. Overall, recent advances in determining early pregnancy coupled with the successful conservative management of early ectopic pregnancies have decreased mortality and morbidity while preserving fertility.

PATHOPHYSIOLOGY

Approximately 97% of ectopic pregnancies conceived naturally occur in the fallopian tube itself. The most common factor that predisposes the young woman to tubal damage and therefore ectopic pregnancy is acute salpingitis, especially chlamydial infection. Other predisposing factors include congenital anomalies, previous pelvic or abdominal surgery, prior ectopic pregnancy, and endometriosis within the tube. When an adolescent with an IUD in place becomes pregnant, due to method failure, her risk for having an ectopic pregnancy is higher than the risk for ectopic in a non-contracepting adolescent. Cofactors linked to ectopic pregnancy include multiple sexual partners, cigarette smoking, vaginal douching, and early sexual debut. The outcome of an ectopic pregnancy depends on the location of implantation. A spontaneous “tubal abortion” is most likely to occur when the site of implantation is in the ampulla of the tube, whereas the more dangerous tubal rupture is most likely with implantation within the tube’s isthmus.

CLINICAL FEATURES

The common clinical presentation of an ectopic pregnancy includes lower abdominal pain (100%), amenorrhea (75%), intermenstrual spotting (75%), abdominal tenderness (90%), adnexal tenderness (85%), adnexal/pelvic mass (50%), and uterine enlargement mimicking early changes of pregnancy (most). Women with ectopic pregnancies have normal vital signs unless rupture occurs. When acute rupture into the peritoneum occurs, it is usually accompanied by acute hemorrhage, hypovolemia, and shock, resulting in a life-threatening situation.

DIAGNOSIS

Key to the diagnosis of ectopic pregnancy are the assessment of presenting symptoms and physical findings, diagnostic features found on ultrasound examination, and laboratory test results. Laboratory tests helpful in differentiating between ectopic, intrauterine, and failing intrauterine pregnancies include serial quantitative hCG and serum progesterone levels (Table 80-2).

Ectopic pregnancy often produces hCG at a slower rate, although there is considerable overlap of concentrations in normal intrauterine and ectopic pregnancies early in gestation. If ectopic pregnancy is suspected, quantitative serum β-hCG should be obtained and repeated at 48 hours.

The differential diagnosis of the young woman presenting with abdominal pain, amenorrhea, and/or spotting includes a normal intrauterine pregnancy (IUP), a failing IUP (spontaneous abortion), an ectopic pregnancy, pelvic inflammatory disease, chronic salpingitis, ovarian torsion or ruptured ovarian cyst, appendicitis, bladder/kidney disease, acute gastroenteritis, intra-abdominal inflammation, and vascular ischemic (bowel) or hemorrhagic (aorta or abdominal vessels) disease.

TREATMENT

Management of ectopic pregnancy in adolescents frequently requires emergent surgical intervention such as laparotomy and salpingectomy on the affected side because of delayed diagnosis and rupture, with subsequent poor fertility prospects. With earlier recognition of the ectopic pregnancy before rupture, however, more conservative management can be employed, including expectant management, medical management with methotrexate, and salpingostomy by laparoscopy with comparable resolution of ectopic pregnancies and preservation of subsequent fertility. Expectant management is restricted to those adolescents who are asymptomatic with falling hCG levels who can understand and accept the potential risk of rupture and hemorrhage and adhere to follow-up recommendations. A good indication of potential for spontaneous reabsorption and resolution of an ectopic pregnancy is an initial hCG level under 200 IU/L. Candidates for medical management with single or two-dose methotrexate regimens include hemodynamically stable adolescents who are willing and able to comply with post-treatment monitoring, have a serum β-hCG level of < 5000 IU/L, and have no evidence of fetal cardiac activity on ultrasound and no contraindications to methotrexate use. For adolescents with hCG levels > 5000, fixed multidose methotrexate regimens may be appropriate if they meet all other criteria. Careful weekly follow-up is essential with β-hCG until the titer is less than 5 IU/L. Studies comparing treatment with methotrexate to tube-sparing laparoscopic surgery show no difference in overall tubal preservation, tubal patency, repeat ectopic pregnancy, or ability to conceive in the future. Management of ectopic pregnancy generally requires specialty consultation and co-management or referral.

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INTRODUCTION

Contraception is a health behavior that often begins during adolescence and evolves throughout reproductive life. Approximately 80% of pregnancies in adolescents between 15 and 19 years of age in the United States are unintended. The Youth Risk Behavior Survey (2015) found that 30% of high school students had had sex within the last 3 months, and of those, 13.8% did not use a condom or any other form of contraception. This is significant in that more sexually active teens are utilizing contraceptive methods. Meanwhile, there was a decline in teen births in the United States to women between 15 and 19 years of age: 229,888 births in 2015 compared to 553,000 in 2011. This may be due in part to more teens remaining abstinent longer; more effective means of contraception, particularly long-acting reversible contraception (LARC); and the use of emergency contraception.

Discussions of sexual decision-making, abstinence, sexual activity, reproduction, and contraception occur frequently as a normal part of the well-adolescent visit for female adolescents. Females are more likely to seek out a contraceptive method if they perceive getting pregnant to be negative; they have long-term educational goals; and/or they have friends, family, and clinicians who promote the use of contraception. In contrast, male adolescents, who are not at risk for pregnancy and do not require prescriptive contraceptives, may have clinician contact only during a sports physical or treatment of an injury or acute illness. Although sexuality and contraceptives are not traditionally discussed during “the sports check,” which often substitutes for the annual examination for male adolescents, clinicians should emphasize the need for such discussions because this visit may be the only contact between the male adolescent and a clinician.

TYPE OF CONTRACEPTIVE

Common methods of contraception for male and female adolescents are reviewed in Table 81-1. Providers are encouraged to use an efficacy-based approach to discussing contraceptive options, starting with LARC methods, which have the highest efficacy for pregnancy prevention. Efficacy-based charts, such as those available from the CDC (https://www.cdc.gov/reproductivehealth/unintendedpregnancy/pdf/contraceptive_methods_508.pdf) or Bedsider (htpp://www.bedsider.org) can help providers explain and adolescents understand the effectiveness of different methods. Adolescents should be encouraged to choose a contraceptive method that they feel comfortable with, that they believe they can use successfully, and that meets their needs related to both pregnancy and sexually transmitted infection (STI) risk reduction. For some, the choice is condoms, which are relatively inexpensive, easily obtained, and highly effective for protection from pregnancy and STIs, but only when used consistently and correctly. For adolescents who choose to use a contraceptive method (LARC, Depo-Provera, or a combined hormonal method), it should be emphasized that when used correctly the methods are effective against pregnancy but do not protect against STIs. Counseling regarding emergency contraception and its effectiveness is imperative for individuals not using a LARC method in anticipation of method failure or lapse in contraceptive use. Heterosexual adolescents, like adults, tend to decrease their use of condoms over time in a relationship, and higher relationship quality and more frequent intercourse are associated with less condom use.

LONG-ACTING REVERSIBLE CONTRACEPTIVES

LARC methods are considered the most effective contraceptive methods because once they have been inserted they function independent of the adolescent. Both the American Academy of Pediatrics (AAP) and the American College of Obstetrics and Gynecology (ACOG) support LARC methods as first-line options. LARC includes the contraceptive implant (Nexplanon) and intrauterine devices (IUDs), which include progestin-only IUDs (Skyla and Mirena) that last between 3 and 5 years and a nonhormonal IUD (Paragard) that lasts for 10 years.

The single etonogestrel implant, Nexplanon, is an alternative delivery system for progestin-only contraception. Inserted under the skin in the upper arm, the implant is barely visible, long acting (3 years), and highly effective. As with depot medroxyprogesterone acetate (DMPA), menstrual side effects may limit the appeal of this method for some adolescents, but unlike DMPA, concerns about weight gain and bone mineral density are not an issue. Both DMPA and the etonogestrel implant may be excellent contraceptive methods for those adolescents who want long-term contraception not linked to coitus, are unable to use oral contraceptives, or cannot use estrogen-containing preparations.

Modern intrauterine contraceptive devices containing copper, such as Paragard (which impairs sperm function and prevents fertilization), or progestin, such as Mirena or Skyla (which thickens cervical mucus, induces reversible endometrial atrophy, and may suppress ovulation), can be an excellent choice for the adolescent seeking reliable long-term contraception, particularly if she has had a child. A few absolute contraindications for IUD insertion include current STI (eg, cervicitis or pelvic inflammatory disease), unexplained vaginal bleeding, and a uterine anomaly that could affect placement of the device. The use of intrauterine contraceptives requires careful consideration of the patient’s history and current sexual risk. Although the risk of expulsion is slightly higher in women who have never had a child, nulliparity is not a contraindication to intrauterine contraceptive devices.

ESTROGEN-PROGESTIN COMBINATION CONTRACEPTION

Combination hormonal methods, including oral contraceptive pills, the contraceptive patch, and the contraceptive ring, are the contraceptive methods of choice for many adolescents soon after their sexual debut because using these methods is independent of sexual intercourse. The mechanism of action for combined hormonal contraception, regardless of the mode of delivery of the estrogen and progestin, includes the inhibition of ovulation through the hypothalamic and pituitary effects of the exogenous hormones. A reduction of gonadotropin-releasing hormone (GnRH) pulses as well as decreased pituitary responsiveness to GnRH results in the suppression of luteinizing hormone and follicle-stimulating hormone production, inhibiting ovulation. The thickening of cervical mucus, which inhibits sperm transport and decreases sperm capacitation (the ability of the sperm to enter the egg), are additional mechanisms of action primarily attributable to progestins. Such hormonal methods are generally safe and highly effective, but because they afford essentially no protection against STIs including human immunodeficiency virus, the additional use of condoms is recommended. Dual-method (hormonal contraception plus condom) use, however, is reported by less than 10% of sexually active adolescents.

Combined hormonal contraceptives are associated with a number of minor side effects, including nausea, breast tenderness, occasional weight gain, and breakthrough bleeding, especially within the first 3 months of use. The United States Medical Eligibility Criteria for Contraceptive Use provides guidelines to counsel women on the safety of various methods in relation to numerous medical conditions. Please refer to the following for the complete listing: http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm. Conditions designated as 4 are considered unacceptable health risks in relation to the contraceptive method, and conditions designated as 3 represent risks that outweigh the benefits of using the contraceptive method. A few of the medical conditions within these categories include abnormal vaginal bleeding, liver disease, deep venous thrombosis, migraine with aura, and hypertension. Weight is also a factor to be considered when prescribing the contraceptive patch. For example, a patient who weighs over 198 pounds may have reduced contraceptive patch efficacy.

Constant advances are being made in combination hormonal contraception. New formulations, dosing regimens, and delivery methods have expanded the options for young women choosing these methods.

PROGESTIN-ONLY CONTRACEPTION

The options for use of progestin-only contraception have also expanded. The mechanisms of action for progestin-only contraceptives include the inhibition of luteinizing hormone production and thus the inhibition of ovulation, thickening of cervical mucus to impact sperm capacitation, and an alteration in the endometrium including reversible endometrial atrophy. DMPA is given in a 150-mg intramuscular dose or a 104-mg subcutaneous dose every 13 weeks, providing reliable, highly effective injectable contraception. The subcutaneous formulation is newer, and an advantage is that it may allow for self-administration. DMPA use has been widely initiated by adolescents and is prescribed for over 1 million adolescent girls in the United States annually. DMPA appeals to adolescents because it is comparably long lasting, easy to use, and invisible to parents and partners. However, there are some significant concerns for adolescents and physicians. Primary among these concerns are weight gain, irregular bleeding/amenorrhea, and a reduction in bone mineral density associated with DMPA use. Weight gain is a common side effect, with an average weight gain of 5.4 pounds in the first year and 16.5 pounds after 5 years in adult women. For obese young women already struggling with their weight, this may be a significant deterrent to DMPA use. Irregular bleeding is a common reason for any method’s discontinuance among adolescents, and amenorrhea, while a potentially beneficial side effect for adults, is often poorly tolerated by adolescents, who equate lack of menses with pregnancy. Of greatest concern to physicians is the black box warning related to decreased bone mineral density in DMPA users. In response to this concern, the Society for Adolescent Health and Medicine has issued a position paper on DMPA and bone density, recommending that providers continue to prescribe DMPA for patients who desire it, with an adequate explanation of benefits and potential risks. Bone density is most often regained after discontinuance of the method.

EMERGENCY CONTRACEPTION

Clinicians play an important role in promoting the use of and providing prescriptions in advance for emergency contraception (EC). Adolescents have high failure rates of using contraceptive methods correctly, with the exception of LARC methods. Available EC methods in order of effectiveness are the copper IUD (pregnancy failure rate 0.09% and efficacy up to 5 days that is unaffected by the amount of time since unprotected sex or the patient’s BMI), ulipristal acetate and mifepristone (pregnancy failure rate 0.9–2.1%, with decreasing efficacy over 5 days and appropriate for women with a BMI < 35), and levonorgestrel (pregnancy failure rate 0.6–3.1% with decreasing efficacy over 5 days and appropriate for women with a BMI < 26). The FDA approves ulipristal up to 5 days postcoitus, and levonorgestrel up to 3 days postcoitus. The Yuzpe regimen, which utilizes combined oral contraceptive pills, is least effective, but is an option if the previously mentioned methods are unavailable. All methods should be used within 5 days of unprotected sex. Indicated for use after unprotected or underprotected intercourse, EC reduces the risk of pregnancy by 88% to 99% with a primary mechanism of action of delaying or inhibiting ovulation for the oral methods, and the prevention of fertilization by inhibiting sperm motility and survival for the copper IUD. Despite the safety and efficacy of postcoital contraceptive methods, physicians may create barriers to adolescents’ ability to use EC by limiting access based on timing in the menstrual cycle, requiring an office visit and a pregnancy test, and refusing to prescribe EC in advance due to concerns about overuse or that access to EC will discourage regular reproductive health care. EC efficacy is extremely time sensitive, with an increased risk of pregnancy as the time from unprotected intercourse to EC use increases. There are no contraindications to using EC except pregnancy. To facilitate quick and easy access to EC, physicians should educate all adolescents, male and female, sexually active and not, about EC and its use and consider providing a prescription for EC to female adolescents in advance so that it can be used as soon as possible when indicated.

MEDICAL ASSESSMENT AT THE CONTRACEPTIVE VISIT

A complete medical and sexual history and limited physical assessment are recommended as a part of the first contraceptive visit to evaluate specific needs and eliminate serious contraindications to contraceptive use. Most methods of contraception can be initiated without a pelvic exam. Current recommendations to initiate Pap screening at age 21 years, combined with the ability to perform urine or vaginal self-swab screening for chlamydia and gonorrhea, have made it unnecessary to perform a pelvic examination in the asymptomatic adolescent requesting contraception. Follow-up may be individualized based on the adolescent’s needs. A discussion of any side effects and difficulties in using the method and the need for continued contraception should be reviewed briefly with the patient at each visit. For the male adolescent, a brief review of need and type of contraceptive should be done at each well visit.

METHOD INITIATION

Effective use of a contraceptive method is enhanced if the adolescent can initiate the method right away rather than waiting for her next menses. In the interest of enhancing the adolescent patient’s ability to effectively prevent an unplanned pregnancy, the physician may opt for a “quick start” approach to initiating most contraceptive methods. The principles of the quick start approach include (1) immediate initiation of the method if it is 5 days or fewer since the onset of the last menstrual period; (2) a negative urine pregnancy test if it is greater than 5 days since the last menstrual period; (3) administration of emergency contraception if there has been unprotected sex in the prior 5 days, followed by initiation of the hormonal method the same day; (4) use of a backup method (condoms) for the next week; and (5) a follow-up pregnancy test in 2 weeks if the method was initiated after day 5 of the current menstrual cycle. Detailed instructions for the use of a quick start for method initiation (including LARC methods) can be found at http://www.rhedi.org/contraception/quick_start_algorithm.php.

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