Clinical Expert Series Continuing medical education is available online at www.greenjournal.org Adolescent Gynecology Joseph S Sanfilippo, MD, MBA, and Eduardo Lara-Torre, MD Given new developments in the field of adolescent reproductive health, this review focuses on highlighting new guidelines and practice patterns in evaluation and management of adolescent gynecologic problems First, understanding the proper techniques for the initial examination is key to establishing a long-term relationship with this age group Reservations about the first gynecologic examination are common, and the practitioner’s goal is foremost to make the patient as comfortable as possible Preventive health in this patient population is key, and practitioners should become comfortable with providing education about topics as diverse as sexuality, eating disorders, and dating violence Furthermore, the frequency with which teenagers report sexual activity and the high unintended pregnancy rate in this age group makes counseling regarding effective contraception essential Additionally, practitioners are encouraged to take the opportunity to discuss the availability of the human papillomavirus (HPV) vaccine with adolescents In 2007, adolescents were designated as a special population, given the frequency with which they acquire and clear mild HPV-related cervical dysplasia More conservative treatment in this population is generally favored During their transition through puberty, disorders of menstruation become the most common complaint requiring the attention of the gynecologist Most commonly, anovulation serves as the cause behind such abnormal bleeding Polycystic ovarian syndrome can develop in early puberty and carry its consequences into adulthood Infertility, diabetes, and hirsutism mark the most important components of the syndrome and require age-appropriate management Finally, the consequences of endometriosis on the future fertility of adolescents have brought early intervention to light Recognition and prompt treatment are advocated to prevent the future implications of this disease (Obstet Gynecol 2009;113:935–47) From the Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Fertility and Reproductive Endocrinology, University of Pittsburgh Physicians, Magee-Womens Hospital, Pittsburgh, Pennsylvania; and Ambulatory Gynecology and Pediatric and Adolescent Gynecology, Carilion Medical Center, Roanoke, Virginia The authors thank Dr Serena Dovey for her constructive comments Continuing medical education for this article is available at http://links.lww com/A816 Corresponding author: Joseph S Sanfilippo, MD, MBA, Professor, Department of Ob-Gyn & Reproductive Sciences, Vice Chairman, Reproductive Sciences, Director, Center for Fertility & Reproductive Endocrinology, University of Pittsburgh Physicians, Magee-Womens Hospital, 300 Halket Street, Room 2309, Pittsburgh, PA 15213; e-mail: jsanfilippo@mail.magee.edu Financial Disclosure Dr Sanfilippo did not report any potential conflicts of interest Dr Lara-Torre has been a speaker for Merck (Whitehouse Station, NJ) and Werner-Chilcott (Rockaway, NJ), and he has been an Implanon trainer for Organon (Roseland, NJ) © 2009 by The American College of Obstetricians and Gynecologists Published by Lippincott Williams & Wilkins ISSN: 0029-7844/09 VOL 113, NO 4, APRIL 2009 G iven new developments in the field of adolescent reproductive health, this article focuses on highlighting new guidelines and practice patterns in evaluation and management of adolescent gynecologic problems Unique clinical problems in adolescents require particular expertise, caring, and consideration THE ADOLESCENT GYNECOLOGIC EVALUATION The adolescent patient may present a challenge for the practitioner Understanding the proper techniques for the initial examination is key to establishing a long-term relationship with this age group In these patients, self-consciousness about their own body may make the examination more difficult to perform The extreme variation in psychosocial and sexual development among teenagers contrib- OBSTETRICS & GYNECOLOGY 935 utes to the challenge Teenagers develop at varying rates; whereas some are menarcheal at the age of 10 years, others may just be starting their pubertal development at age 13 years Therefore, careful interviewing and counseling should precede an examination Although some teenagers may like to know and see everything that will happen, some prefer otherwise Using educational videos that explain the examination process and the common reasons why they are done may benefit the interaction with the patient Delaying the genital examination, even in some sexually active teenagers, may prevent the patient from having reservations about her examiner and allow rapport to be established in a facilitated manner These preferences should be taken into account to make the gynecologic experience as comfortable as possible Preventive health care is one of the most important parts of the clinical visit in this age group As recommended by the American College of Obstetricians and Gynecologists (ACOG), the initial visit to the obstetrician– gynecologist should occur between the ages of 13 and 15 years.1 During this visit, important components of general health, such as immunizations, risk prevention, intimate partner and dating violence, sexual orientation and history of involuntary sexual experiences, and eating disorders, including issues with obesity, should be evaluated Additionally, screening for tobacco and substance abuse and depression should be completed As the human papillomavirus (HPV) vaccine has been approved by the U.S Food and Drug Administration (FDA), new challenging horizons await the obstetrician– gynecologist health care provider as a “vaccinator.” Opportunities to interact with the adolescent will present during these immunization visits, which allow for practitioners to improve their relationships with the parents and teenager as other reproductive needs arise After the initial gynecologic visit, which may or may not include a pelvic examination, based on the clinical circumstance, annual/semiannual visits should be scheduled thereafter In those not sexually active, a visit in each stage of adolescence may be preferred (early adolescence, ages 13–15 years; middle adolescence, ages 15–17 years; late adolescence, ages 17–19 years) With adolescents, if possible, it is important to meet initially together with the teenager and her parents/guardian to explain the concept of confidentiality and privacy Remember when screening, begin with less sensitive issues like safety (eg, seat belt use) before addressing emotional and sexual issues A 936 Sanfilippo and Lara-Torre Adolescent Gynecology sexual history is an integral component of the initial gynecologic visit Tools for this purpose are available through a number of professional societies, including the North American Society for Pediatric Adolescent Medicine and the Society for Adolescent Medicine as well as ACOG.2 As discussed, this examination does not necessarily include a pelvic examination Box 1, “Common Indications for Pelvic Examination in the Adolescent,” lists indications for a pelvic examination in the adolescent Besides the components of a complete physical examination, key points should be included in the adolescent examination such as body mass index (BMI) Assessment of breast development should precede the pelvic examination; the external genitalia should be inspected, if allowed, in all patients who present for preventive care, even if not sexually active This will allow determining any genital anomalies in this age group as well as facilitating the first step toward a complete pelvic examination Asymptomatic patients who are not sexually active may delay their initial pelvic examination up to the age of 21.3 After the initiation of intercourse, teenagers may choose to delay their cervical cytology screening up to years Annual Pap testing should be considered beginning with the initial visit in those patients with multiple partners or immunocompromised conditions and in whom follow-up is unlikely Care should be taken to obtain sexually transmitted diseases (STD) screening with each new sexual partner With the development of urine and vaginal swab testing for gonorrhea and Chlamydia, STD screening has become easier without the need for a pelvic examination BOX COMMON INDICATIONS FOR PELVIC EXAMINATION IN THE ADOLESCENT Delayed puberty Precocious puberty Abnormal vaginal bleeding Abdominal or pelvic pain History of vaginal intercourse Pathologic vaginal discharge Suspicion of intraabdominal pathology Presented with permission from Lara-Torre E The physical examination in the pediatric and adolescent patient In Sanfilippo JS, Lara-Torre E, Templeman C, Edmonds K, eds Clinical pediatric and adolescent gynecology London (UK): Informa Healthcare; 2009 p 120 OBSTETRICS & GYNECOLOGY Proper examination equipment for this age group should be available and provided as clinically indicated The use of tampons before their examination in the presence of menses may facilitate the use of a speculum, because they may be more comfortable with vaginal manipulation The use of a pediatric or a Huffman speculum (1/2 inch wide ϫ 1/4 inches long) may be of help in those patients not sexually active, along with the use of a water-based lubricant A Huffman or Pederson speculum (7/8 inch wide ϫ 1/2 inches long) may be used in those sexually active The use of a finger applying pressure to the perineal area, away from the introitus, allows for lessening or diffusing of the sensation from the examination (“extinction of stimuli”) and may be of benefit in those undergoing their first pelvic examination Once a finger has been placed in this area, the insertion of a speculum may be easier When clinically indicated, attempting to palpate the internal reproductive organs may require the use of a rectovaginal or single-digit bimanual examination The approach used will depend on the patient’s preference, tolerance, and sexual history as well as the pathology suspected All adolescents should be reassured that the examination, although uncomfortable, is not painful and will not alter their anatomy This may reassure parents and teenagers who may believe that the examination will alter their “virginity.” After the examination, it is helpful to meet again with the family and the teenager together to explain the examination findings and to further plan management In the sexually active teenager, if confidentiality is a concern, first discuss findings with the patient alone while in the examination room Encourage the patient to allow you to be the liaison between her and the family, stressing the benefits of education regarding contraceptive use and her particular situation; if the patient disagrees, confidentiality should be maintained according to local law Because each state varies in its specific legal rights for adolescents, the Guttmacher Institute has established a Web site where the practitioner may access state-specific information and handouts, which is updated frequently Practitioners may access this site at www.guttmacher.org CERVICAL CYTOLOGY, HISTOLOGY, AND HUMAN PAPILLOMAVIRUS In 2006, ACOG published a Committee Opinion regarding cervical cytology screening and histology in adolescents.4 In late 2007, the American Society for Colposcopy and Cervical Pathology published their revised management of abnormal cytology and histology, and in their review, they considered adoles- VOL 113, NO 4, APRIL 2009 cents as a special population with significant differences in their management (Table 1).5,6 One main difference was to better define how to perform cervical cytology in adolescents (defined as those 20 years of age or younger) and the management of those with low-grade squamous intraepithelial lesions and atypical squamous cells of undetermined significance (ASC-US) Previous guidelines indicated that patients with ASC-US should have a human papillomavirus (HPV) test If the test was positive, then a colposcopy was recommended Since then, new guidelines have determined that, given the high prevalence of HPV in these patients as well as the high rate of spontaneous resolution, it is recommended that this population not have an HPV test in the presence of ASC-US If the HPV test is performed, then the result should not be used for deciding upon colposcopy, and patients should be observed with annual cytology for up to a period of years These guidelines hold true as long as the results are not consistent with a high-grade squamous intraepithelial lesion, in which case a colposcopy is recommended In those patients with high-grade squamous intraepithelial lesion, the management did not change.5,6 The Committee also reemphasized the importance of observation and repeat testing as the first line of management for patients with mild and moderate dysplasia, rather than using ablative or excisional procedures The management of severe dysplasia did not change and still requires treatment The availability of the quadrivalent HPV vaccine and soon-to-be-released bivalent vaccine provides Table Recommendations for Adolescents’ Cervical Cytology and Histology Management Diagnosis ASC-US (no HPV testing) ASC-H LSIL (no HPV testing) HSIL AGC Cancer Mild dysplasia Moderate dysplasia Severe dysplasia or CIS Recommendation Repeat cytology in 12 mo Colposcopy Repeat cytology in 12 mo Colposcopy Colposcopy (may need to refer to a specialist) Refer to specialist Repeat cytology in y Repeat colposcopy and cytology in 4–6 mo Treat per ASCCP guidelines ASC-US, atypical squamous cells of undetermined significance; HPV, human papillomavirus; ASC-H, atypical squamous cells cannot exclude high grade; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; AGC, atypical glandular cells; CIS, carcinoma in-situ; ASCCP, American Society for Colposcopy and Cervical Pathology Sanfilippo and Lara-Torre Adolescent Gynecology 937 new challenges to the gynecologist Manufacturers’ information on the effectiveness of these vaccines shows a prevention rate of more than 90% with HPV types 6, 11, 16, and 18 (quadrivalent) and 16 and 18 (bivalent) in patients not previously exposed to HPV.7,8 The duration of protection seems to be longer than years, but the exact duration of protection is still not known Some details on the future of the vaccine, such as ideal age of initial dosing, use in boys, and boosters, are still not clear, but current trials are under way to answer these questions Gynecologists involved with the care of teenagers should be well-versed on the new recommendations for cervical and histologic management of cervical disease as well as the indications, risks, and benefits of the HPV vaccine Many adolescents seen for the provision of other reproductive health care would benefit from our knowledge in these topics The need to properly counsel these patients on the implications, natural history, and prevention of HPV disease is part of the daily practice of an adolescent provider ABNORMAL UTERINE BLEEDING In the adolescent, abnormal uterine bleeding is, more often than not, secondary to anovulation This is a reflection of the immaturity of the hypothalamic– pituitary– ovarian axis In fact, in 55– 82% of adolescents, it takes up to 24 months for onset of regular ovulatory cycles after menarche; after 24 months, 22% of girls remain either anovulatory or oligoovulatory Furthermore, in some teenagers, it may take up to years postmenarche to establish regular ovulatory cycles.9 As an aside, persistence of irregular menses after menarche may be indicative of problems such as polycystic ovarian syndrome and should be further investigated Recently, ACOG and the American Academy of Pediatrics published recommendations regarding the menstrual cycle as a “vital sign.” Important information and guidelines are included in the document and guide the practitioner in identifying those patients with possible pathology.10 A number of causes of abnormal uterine bleeding have been proposed, as outlined in Box 2, “Causes of Abnormal Vaginal Bleeding.” A menstrual calendar is often useful to document the exact bleeding pattern and can help in narrowing the differential diagnosis In addition to anovulation, bleeding diatheses, stress, and pregnancy are all common causes of abnormal bleeding in adolescents A thorough history and physical examination, in addition to basic laboratory tests such as human chorionic gonadotropin, thyroid-stimulating hormone, complete blood count, and platelet level can help guide the physician in determining the 938 Sanfilippo and Lara-Torre Adolescent Gynecology cause of bleeding If a bleeding diathesis is suspected based on the patient’s history, clinicians can proceed with the laboratory assessment as described in Box 3, “Laboratory Assessment of the Adolescent With Dysfunctional Uterine Bleeding.” Treatment will clearly be based on the patient’s presumptive diagnosis However, for those patients whose bleeding is deemed secondary to oligoovulation, specific management can be provided based upon the degree of anemia: • Mild anemia: hematocrit greater than 33% or hemoglobin greater than 11 g/dL can be treated with iron supplementation If there is a need for contraception, combined oral, transdermal, or intravaginal methods can also be prescribed to aid with anemia • Moderate anemia: hematocrit 27–33% or hemoglobin –11 g/dL can be treated with oral contraceptives to control the abnormal menstrual bleeding • Severe anemia: hematocrit less than 27% or hemoglobin less than g/dL should be addressed with oral contraceptives prescribed as one every hours until bleeding decreases and then a tapered dose to complete a 21-day pill pack This dosage of estrogen will require an antiemetic.11 The patient should then be placed on oral contraceptives in the manner prescribed for contraception over the following months to allow improvement in her anemia The patient can then be reevaluated to determine whether there is a continued need to remain on oral contraceptives Other therapies to treat anovulation include use of progestins either cyclically or in depot form, eg, depomedroxyprogesterone acetate POLYCYSTIC OVARIAN SYNDROME AND OTHER ANDROGEN DISORDERS First described by Stein and Leventhal in 1935, this common endocrine disorder affects – 6% of the female population and is characterized by increased androgens emanating from the ovary and possibly the adrenal gland.12,13 The earliest clinical manifestations can occur in the adolescent and carry its consequences into adulthood In 2003 in Rotterdam, an international reproductive medicine group met and reached the current consensus to establish the diagnostic criteria14 as outlined in Box 4, “Rotterdam Diagnostic Criteria for Polycystic Ovary Syndrome.” Because oligoovulation and acne can be common in adolescence, the diagnosis may be less straightforward in this patient population, and evidence of hy- OBSTETRICS & GYNECOLOGY BOX CAUSES OF ABNORMAL VAGINAL BLEEDING Vaginal or uterine abnormalities Trauma (coitus; rape; abuse) Foreignbody(intrauterinedevice,tampon,andsoforth) Infection • • • • • Vaginitis (Trichomonas; gonorrhea) Cervicitis Endometritis (tuberculosis) Pelvic inflammatory disease Sexually transmitted condylomata (human papillomavirus • HPV of cervix or vagina Tumors • Botryoid sarcoma • Polyps (uterine; cervical) • Ovarian cyst or tumor (mature teratoma; endometrioma) • Leiomyomatosis • Clear cell carcinoma of cervix or vagina (diethylstilbestrol) • Other ovarian malignancy and metastatic malignancy Endometriosis Congenital malformations of uterus Complications of pregnancy • • • • Threatened or spontaneous abortion Ectopic pregnancy Molar pregnancy Self- or medically induced abortion Coagulopathies • Generalized coagulopathy • Thrombocytopenia (idiopathic thrombocytopenic purpura, leukemia, lymphoma, aplastic anemia, hypersplenism) • Platelet dysfunction (von Willebrand’s disease, Glanzmann’s disease) • Clotting disorders (hemophilia; other coagulation factor deficiencies) • Uterine production of menstrual anticoagulants Dysfunctional uterine bleeding Normal variation • Midcycle ovulatory bleeding • Early postmenarcheal anovulation • Early postmenarcheal estrogen irregularities (continued) VOL 113, NO 4, APRIL 2009 Chronic anovulation Exogenous steroids Oral contraception • Midcycle breakthrough bleeding • Relative luteal progesterone deficiency • Progestogens (oral agents, Norplant, DepoProvera) • Continuous estrogens Other drugs • • • • • • Danazol Spironolactone Anticoagulants Platelet inhibitors Chemotherapy drugs Natural hormones from plant extracts (Dehydroepiandrosterone [DHEA]; dong quai; yam extract) Systemic diseases • • • • • • • • • • Hyperthyroidism or hypothyroidism Adrenal insufficiency Cushing’s syndrome Diabetes mellitus Chronic liver disease Crohn’s disease; ulcerative colitis Chronic renal disease Systemic lupus erythematosus Ovarian failure Hyperprolactinemia Androgen excess • Exogenous androgens, polycystic ovary syndrome • Congenital adrenal hyperplasias • Androgen-producing ovarian or adrenal tumor Estrogen excess • Granulosa-theca cell tumor of the ovary • Other tumors Hypothalamic disorders Emotional stress Physical stress, especially exercise Ovulation disorders • Short luteal phase • Prolonged luteal phase (Halban’s disease) • Luteal progesterone insufficiency Matytsina LA, Zoloto EV, Sinenko LV, Greydanus DE Dysfunctional uterine bleeding in adolescents: concepts of pathophysiology and management Prim Care 2006;33:503–15 Sanfilippo and Lara-Torre Adolescent Gynecology 939 BOX LABORATORY ASSESSMENT OF THE ADOLESCENT WITH DYSFUNCTIONAL UTERINE BLEEDING Initial Evaluation • • • • • • Complete blood count and differential Platelet count Fibrinogen Prothrombin time Partial thromboplastin time Bleeding time If bleeding is severe or prolonged or associated with menarche or if the initial screen is abnormal then other tests should be performed: • • • • • von Willebrand’s factor antigen Factor VIII activity Factor XI antigen Ristocetin C cofactor Platelet aggregation studies Reprinted from Strickland JL, Wall JW Abnormal uterine bleeding in adolescents Obstet Gynecol Clin North Am 2003;30:321–35 Copyright 2003, with permission from Elsevier http://www.sciencedirect.com/science/journal/ 08898545 BOX ROTTERDAM DIAGNOSTIC CRITERIA FOR POLYCYSTIC OVARY SYNDROME Two of the following three criteria must be met after ruling out other causes of hyperandrogenic disorders: • Oligoovulation • Clinical and/or biochemical evidence for hyperandrogenism • Ultrasonographic evidence of polycystic ovaries perandrogenism should be sought In fact, unlike the Rotterdam criteria, in which patients can be classified as having polycystic ovary syndrome (PCOS) based solely on polycystic ovaries on ultrasound examination and ovulatory dysfunction, the Androgen Excess Society emphasizes the need to demonstrate hyperandrogenism to truly secure the diagnosis.15 Tests to order to help clarify the diagnosis include total testosterone, dehydroepiandrosterone sulfate, and 17-OH progesterone Androstenedione may be added to monitor response to treatment, because this is the main androgen secreted by the ovary in PCOS The teenager with PCOS presents with hirsutism, acne, irregular menstrual cycles, and obesity as inte- 940 Sanfilippo and Lara-Torre Adolescent Gynecology gral components of the diagnosis Other manifestations may include alopecia and acanthosis nigricans, a clinical expression of hyperinsulinemia The stringent criteria of a 2:1 or 3:1 ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) are no longer required, because PCOS is now considered a clinical diagnosis.15 The pathophysiology behind PCOS remains an area of controversy Current research suggests that PCOS may be related to intrauterine growth restriction and premature pubarche, although the true cause is not well understood.16,17 Recent advancements in the understanding of PCOS have demonstrated that patients with PCOS are much more prone to developing the metabolic syndrome than those without PCOS The metabolic syndrome is defined as having at least three of the following18: • Increased abdominal fat mass (waist circumference more than 35 inches [more than 88 cm]) • Increased triglycerides (150 mg/dL or more) • Decreased high density lipoproteins (50 mg/dL or less) • Increase blood pressure (130/85 mm Hg or more) • Increased plasma glucose (100 mg/dL or more) Given the serious health implications associated with the metabolic syndrome, patients with PCOS should be educated at an early stage, beginning in adolescence, about the importance of healthy lifestyle habits, and they should be counseled regarding the long-term sequelae of the disorder, which include type diabetes and cardiovascular disease Although the cause of PCOS remains an intriguing question, currently it is thought that an increase in Gonadotropin-releasing hormone (GnRH) pulsatility results in an excess release of LH in relation to FSH from the pituitary.19 This elevated level of LH then drives the ovary to produce increased androgens, especially androstenedione, which is converted peripherally to estrone Without sufficient levels of FSH to promote follicle recruitment and dominant follicle development, ovulation is inhibited The lack of progesterone from anovulation promotes increased GnRH pulsatility, all of which result in a persistent feedback loop between the ovary and the central nervous system Additionally, elevated insulin levels act at the level of the ovary to promote androgen production Other metabolic factors thought to be involved in PCOS include dysregulation of ovarian thecal enzymatic machinery, ie, cytochrome P450c, promoting more efficient synthesis of androgens.20 Research has also demonstrated a genetic predisposition to the syndrome.21,22 OBSTETRICS & GYNECOLOGY Clinically, quantification of the degree of hirsutism is helpful The Ferriman Gallwey classification assists in this goal (the classification system may be reviewed in its original publication).23 Although clinicians approach the evaluation differently, the basic assessment should include early morning serum testosterone (total and free), 17-OH progesterone, dehydroepiandrosterone sulfate, prolactin, thyroid stimulating hormone, and fasting glucose and insulin levels Clinicians should emphasize counseling adolescents with PCOS as an important part of their management Weight loss should be encouraged, because it seems that a 10% reduction in weight is sufficient to reestablish regular ovulatory menstrual cycles in many women Because adolescents’ understanding and commitment to treatment may vary throughout their teenage years, education and counseling should cater to the changing environments and maturity of the patients Pharmacologic treatment includes use of the oral contraceptive pill and the insulin sensitizer metformin as the mainstay and more common components of management Combined oral contraception promotes regular withdrawal bleeding and protects the uterine lining against the effects of unopposed estrogen seen in PCOS, in addition to helping to improve the hormonal milieu and lower circulating androgen levels Metformin helps to address the component of insulin resistance seen in PCOS Other medications, depending on the clinical circumstance, include glucocorticoids and anti-androgens such as spironolactone Treatment with glucocorticoids is reserved for the less common presentation of PCOS in nonobese teenagers with a significant degree of functional adrenal hyperandrogenism If pregnancy is of interest and oligoovulation persists, clomiphene citrate is usually the initial treatment.24 ADOLESCENT CONTRACEPTION Adolescent pregnancy rates in Europe and Canada are approximately 50% lower than those in the US.25 For this reason, the use of appropriate contraception is especially important in this age group As adolescents mature and become capable of reproduction, visits to their practitioner should include counseling on adequate methods of birth control to target their needs and abilities to improve their compliance (Fig 1) Providing this information does not result in increased rates of sexual activity, earlier age of first intercourse, or a greater number of sexual partners On the contrary, if the adolescent perceives that there is an obstacle to obtaining contraception, they are more likely to experience negative outcomes related VOL 113, NO 4, APRIL 2009 Fig Contraceptive methods Clockwise from top right: intrauterine system, vaginal ring, single-rod implant, hormonal patch Modified from Blumenthal PD, Edelman A Hormonal contraception Obstet Gynecol 2008;112:670 – 84 Illustration: John Yanson Sanfilippo Adolescent Gynecology Obstet Gynecol 2009 to sexual activity.26 The 2007 Youth Risk Behavior Surveillance System that tracks different health risk behaviors among high school students, including sexual behaviors that contribute to unintended pregnancies, surveyed more than 14,000 high school students from every state and the District of Columbia.27 Important findings of this survey included • A total of 47.8% of students reported ever having had sexual intercourse (46.8% in 2005) • Only 7.1% of students reported having had sex before age 13 (6.2% in 2005) • A total of 14.9% of students reported having had sex with four or more sexual partners (14.3% in 2005) • A total of 35.0% of students reported being currently sexually active, defined as having had sexual intercourse in the months before the survey (33.9% in 2005) • Only 61.5% of sexually active students reported that either they or their partner had used a condom during last intercourse (62.8% in 2005) These finding reinforce the importance of addressing contraception during the adolescents’ health care evaluation Abstinence During the first part of the decade, the U.S administration placed emphasis on abstinence-only education Sanfilippo and Lara-Torre Adolescent Gynecology 941 for pregnancy prevention Unfortunately, recent data suggests that abstinence-only programs are not as effective as those in which other contraceptive options are offered at the same time.28 Although abstinence is the most effective means of birth control, the lack of other contraception education during their efforts has caused controversy and disagreement with the specialty societies Although many teenagers who present for contraception are already sexually active, a review of abstinence as a choice should be an integral part of the discussion of the options available to the adolescent Progestin-Only Methods The oral contraceptive pill (OCP) is the most commonly used method of contraception in the adolescent group, with rates of use approaching 50%.29 The contraceptive and noncontraceptive benefits of the pill, such as with acne, pelvic pain, and premenstrual dysphoric disorder, may contribute to the preference of adolescents’ for this contraceptive Extended regimens such as the available 84/7 day and “no placebo” regimens have shown similar efficacy and compliance with only mild increase in breakthrough bleeding in the adult population; this may be a new option for patients that desire lower frequency of menses, such as athletes and military personnel, although studies in adolescents are lacking.30 Using a “quick start” (same day as the visit) method compared with the traditional Sunday start initiation seems to improve compliance and still maintain an acceptable adverse effect profile without any teratogenic effects even if pregnant.31 These methods are used by adolescents with contraindications to the use of estrogen, such as breastfeeding teenagers The oral formulation’s increase in failure rate may be due to patient compliance and short half life, which requires taking the pill around the same time of the day (within hours).33 Depot medroxyprogesterone acetate is a contraceptive frequently used by the adolescent population because of the minimal intervention required to achieve compliance Although its efficacy has been shown to be better than OCPs, most of its effect seems to be related to compliance and ease of use Weight gain and irregular bleeding are common and unpleasant adverse effects for adolescents A recent concern has been the effect of the hypoestrogenic state created by long-term use of depot medroxyprogesterone acetate on bone density in adolescents New trials have shown the recovery of bone density after discontinuation of the method Those patients who are smokers and sedentary should be counseled on the detrimental implication on bone health and encouraged to quit smoking, and ideally focus on athletic endeavors Appropriate calcium intake (1,200 –1,500 mg per day) should be encouraged in those adolescents The introduction in 2007 of a single etonogestrel implant, with a three-year contraceptive duration, and easy insertion and removal, will reopen new alternatives for adolescents looking for long-term contraception, although long-term studies in adolescents are not available at this time.34 Other Combination Hormonal Methods Emergency Contraception In the adult population, failure rates and adverse effect profiles of other methods such as the patch and the ring are similar to OCPs Recent safety data released by the manufacturer of the patch warns of an increased exposure to estrogen compared with the average dose OCP, which may increase the risk for cardiovascular events.32 Adolescents should be cautioned about these risks and counseled about the potential adverse effects before prescribing the method The vaginal contraceptive ring requires motivation from the patient to insert and remove the contraceptive device once a month from the vagina, and has not been well studied in adolescents Both of these methods may increase compliance and efficacy in adolescents by reducing the number of doses per month Adequate trials on adolescents are still underway and should provide additional information regarding other applications such as extended regimens Emergency contraception, the use of nonabortifacient, hormonal medications within 72–120 hours after unprotected/underprotected coitus for the prevention of unintended pregnancy, is an important part of the contraception counseling in adolescents The use of levonorgestrel 1.5 mg divided into two doses taken 12 hours apart is the only FDA approved method available; recent studies show that taking a single dose of levonorgestrel 1.5 mg may be as efficacious as when taken in divided doses, possibly increasing compliance.35 Advanced prescription of emergency contraception has been shown to increase the likelihood of young women’s and teenagers’ use of emergency contraception when needed and yet not increase sexual or contraceptive risk-taking behavior when compared with those receiving only education about emergency contraception.36 Combined Oral Contraceptive Pills 942 Sanfilippo and Lara-Torre Adolescent Gynecology OBSTETRICS & GYNECOLOGY Barrier Methods Barrier methods include devices such as male condoms, female condoms, cervical caps, diaphragms, spermicidals, and contraceptive film and ovules Although effective, the use of these devices by adolescents is not consistent, even when chosen as their method to protect against STDs.37 The need for application before each sexual encounter decreases the use of the method by “decreasing the spontaneity” of the act, as some teenagers explain Practitioners should encourage the use of barrier methods, such as the male and female condom, to prevent against STDs, even when the teenager is on another form of contraception Intrauterine Devices and Systems The available literature with intrauterine devices (IUDs) in adolescents was very limited until recently Traditionally, use of IUDs has been avoided in adolescents, because this population has the highest rates for STDs However, no increase in infertility or STD incidence is seen with the use of these devices.38 Most of the ascending infections are probably related to contracting the infection from lack of condom use, rather than the presence of the IUD facilitating it, and occur at the time of insertion With proper counseling and condom use, an intrauterine system may be a viable option for some teenagers, regardless of their gravidity and parity status, and should be considered as part of the available armamentarium for contraception The Adolescent Health care Committee of ACOG in 2007 advocated for the increase in use of this method in this population.39 ENDOMETRIOSIS From a historical perspective, von Rokitansky first described evidence of endometriosis in 1860.40 In 1921, Sampson41 elaborated on the variable appearance of endometriotic implants, and in 1946, Fallon42 suggested that the development of endometriosis requires a minimum of years of ovulatory menstrual cycles Although the exact pathophysiology behind endometriosis is not well understood, several theories have been put forth The theory of retrograde menstruation, or Sampson’s Theory, suggests that endometrial implants arrive in the pelvis by retrograde transportation through the fallopian tubes The theory of coelomic metaplasia, or Myer’s theory, suggests that the peritoneal cavity contains undifferentiated VOL 113, NO 4, APRIL 2009 cells capable of differentiating into endometrial tissue Other authors have suggested that endometrial tissue can also travel hematogenously or through lymphatic channels More recently, it has been demonstrated that patients with endometriosis have both cell-mediated immunologic defects as well as humoral-related abnormalities These immunologic deficiencies provide evidence for the theory of a defective immune surveillance, leading to an inability of the immune system to recognize autologous endometrial tissue in abnormal locations Research indicates that peritoneal macrophages and cytokines are found in increased concentration in patients with endometriosis Additionally, neovascularization, with associated release of interleukins and chemokines, is felt to be an integral part of the pathophysiology Tumor necrosis factor (TNF) alpha, matrix metalloproteins, and other growth factors are associated with adhesion-promoting factors and thus set the ground work for development of endometrial implants.43 Reese and coworkers44 described two premenarcheal girls, aged 12 and 13 years, with evidence for endometriosis Subsequent to this, Marsh and Laufer reported on five premenarcheal patients with chronic pelvic pain (more than months duration) with laparoscopically biopsied lesions indicative of endometriosis that, on histologic examination, noted mesothelial hyperplasia, vascular proliferation, and fibrous granulation.45 There was no associated outflow tract obstruction in this study This is the earliest age-related evidence for endometriosis Others have reported documented endometriosis within month after menarche.46 Table describes the presence and appearance of lesions consistent with endometriosis in a series of adolescents presenting with chronic pelvic pain (Fig and 3).47 The American Society for Reproductive Medicine Classification of Endometriosis describes the extent of disease based upon location, extent (super- Table The Presence and Appearance of Lesions Consistent With Endometriosis in a Series of Adolescents Presenting With Chronic Pelvic Pain Lesion Type Percent Clear Red White Black Peritoneal pockets Sanfilippo and Lara-Torre 76 84 44 22 18 Adolescent Gynecology 943 Fig Endometriosis appearance in adolescents A Clear vesicles B Small red punctuations C Red polyps Reproduced with permission from Martin DC, editor Laparoscopic appearance of endometriosis Web revision, color atlas 2nd ed Memphis (TN): Resurge Press; 1990 p 16, 20, 23 Sanfilippo Adolescent Gynecology Obstet Gynecol 2009 ficial compared with deep lesions), size of lesions, and presence of adhesions.48 A major distinction between adolescents and adults in the development of endometriosis is its association with mullerian anomalies in ă the former age group A number of mullerian anomă alies, especially those associated with outflow tract obstruction, have been reported to be associated with endometriosis In a study by Schifrin and coworkers,49 15 patients (40%) younger than 20 years of age with Fig Common location of endometriosis implants Modified from American College of Obstetricians and Gynecologists Endometriosis ACOG Patient Education Pamphlet AP013 Washington, DC: ACOG; 2008 Illustration: John Yanson Sanfilippo Adolescent Gynecology Obstet Gynecol 2009 944 Sanfilippo and Lara-Torre Adolescent Gynecology endometriosis had a genital tract anomaly This is as opposed to findings by Goldstein et al50 who noted congenital anomalies in 11% of 74 teenagers with endometriosis The clinical course of endometriosis associated with reproductive tract anomalies is quite different from that in the adult Sanfilippo et al51 reported a series of patients with extensive endometriosis in association with outflow tract obstructions Once correction of the outflow tract occurred there was virtually 100% reversal of intraabdominal endometriosis on follow-up laparoscopy It is thought that the pathophysiology of the disease process is different in the adult in comparison with the adolescent with an outflow tract obstruction.51 Others have reported no association between endometriosis, pelvic pain not responding to medical therapy, and mullerian anomalies.52 One group of ă patients underwent laparoscopy; mullerian anomaly ă was noted in 6.5% of patients.53 Nonobstructive mulă lerian anomalies not seem to be associated with an increased incidence of endometriosis Important points regarding adolescent endometriosis are presented in Table In adolescents who present with chronic pelvic pain, the following systems should be considered with regard to the underlying cause of the problem: • Gastrointestinal • Genitourinary • Musculoskeletal • Gynecologic • Psychological/psychiatric OBSTETRICS & GYNECOLOGY Table Summary Points in Adolescents With Endometriosis Characteristic Incidence Prevalence Incidence with chronic pelvic pain identified in premenarcheal girls who have started puberty and have breast development Age of onset of symptoms in adults began before 20 y of age Average time from onset of symptoms to diagnosis (y) Varied presentation in adolescents Most common—dysmenorrhea Other acyclic pain Measure 19–73 47 25–38 66 9.28 64–94 36–91 Data are % except where otherwise specified A detailed history and physical examination oftentimes rules in or out the majority of these systems Endometriosis should be suspected in adolescents aged younger than 18 years with recurrent dysmenorrhea refractory to oral contraceptive and nonsteroidal therapy The use of a pain diary is helpful to document the patient’s symptomatology The American College of Obstetricians and Gynecologists recommends proceeding with laparoscopy in adolescents with persistent dysmenorrhea who not respond to OCP and nonsteroidal antiinflammatory drug therapy and who are less than 18 years of age The American College of Obstetricians and Gynecologists advocates that it is acceptable in patients aged 18 years or older to be offered an empiric course of GnRH agonist.54 With long-term use, more than months therapy, there is an associated bone loss It has been recommended that add-back therapy (ie, a progestin) be prescribed in an effort to minimize this effect If there is persistence of symptoms, proceeding with operative laparoscopy is appropriate management Prescription of GnRH agonist in adolescents aged younger than 18 years is not commonly used in light of potential effects on bone Close follow-up of these patients is necessary if this therapy is selected Expectant management remains an alternative The theoretical problem is that endometriosis is a slowly progressive disease Depending on the clinical circumstance, once endometriosis is diagnosed, expectant management is not a frequently acceptable mode of management Other medical therapy options may include some of the following, by themselves or in combination: • Analgesics (nonsteroidal antiinflammatory agents) • Oral contraceptives (continuous compared with cyclic) VOL 113, NO 4, APRIL 2009 • Danazol • Progestin-only protocols Danazol is androgen derived and, although an effective treatment in the adult population, minimal data supports its efficacy in adolescents Progestinonly protocols are still an option and include oral as well as depot preparations Long-term use of depomedroxyprogesterone acetate has been equated with bone demineralization, which seems to recover after discontinuation The best mode of treatment remains a topic of debate In one prospective study, 57 patients were randomly assigned to oral contraceptive therapy, ethinyl estradiol (E2) 20 micrograms with desogestrel 0.15 mg compared with the GnRH agonist goserelin At months, both arms of the study demonstrated improvement in pelvic pain; however, the GnRH agonist group had greater improvement in regard to dyspareunia.55 When comparing continuous with cyclic oral contraceptive therapy, a 2-year prospective study noted continuous to be more efficacious.56 Symptomatic improvement was noted with use of 20 –30 micrograms of ethinyl E2 over a –9 month period in 75–100% of patients, and it is felt to be the best initial therapy for endometriosis after laparoscopic diagnosis and management.57 The goal of surgical treatment is to remove visible areas of endometriosis and restore normal anatomy by lysis of adhesions if present SUMMARY Adolescent gynecology is an area of care that requires particular expertise and understanding of the dynamics of the adolescent from a social, psychological, and medical perspective The first gynecologic examination can leave a lasting impression on a patient Guidelines developed for the first gynecologic encounter are important to understand The updated recommendations regarding abnormal Pap test management provide a more conservative approach for clinical care Sexually transmitted diseases evaluation no longer requires a pelvic examination with the advent of polymerase chain reaction and other advanced technology Now merely a vaginal swab suffices for detection of an STD, making screening less invasive and more feasible in this vulnerable population Human papillomavirus vaccination belongs in the obstetrician– gynecologist’s armamentarium and should routinely be offered Dysfunctional uterine bleeding is more often than not secondary to anovulation Clinicians must understand that endometriosis is now diagnosed in the prepubertal female Pelvic Sanfilippo and Lara-Torre Adolescent Gynecology 945 pain in the adolescent deserves careful consideration for a mullerian anomaly Understanding these basic ¨ concepts sets the stage for complete care in a very important and a unique age group REFERENCES American College of Obstetricians and Gynecologists A guideline for women’s health care 2nd ed Washington, D.C.: ACOG; 2002 American College of Obstetricians and Gynecologists Toolkit for teen care Washington, D.C.: ACOG; 2003 American College of Obstetricians and Gynecologists Primary and Preventive Care: periodic assessments ACOG Committee Opinion Obstet Gynecol 2003;102:1117–24 Evaluation and management of abnormal cervical cytology and histology in the adolescent ACOG Committee Opinion No 330 American College of Obstetricians and Gynecologists Obstet Gynecol 2006;107:963–8 Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, et al 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests Am J Obstet Gynecol 2007;197:346–55 Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, et al 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ Am J Obstet Gynecol 2007;197: 340–5 Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, et al Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial Lancet 2004;364:1757–65 Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, et al Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial Lancet Oncol 2005;6:271–8 Rimsza M Dysfunctional uterine bleeding Pediatr Rev 2002; 23:227–33 10 Menstruation in girls and adolescents: using the menstrual cycle as a vital sign ACOG Committee Opinion No 349 American College of Obstetricians and Gynecologists Obstet Gynecol 2006;108:1323–8 17 Ibanez L, Potau N, Francois I, de Zegher F Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth J Clin Endocrinol Metab 1998;83:3558–62 18 Fleischman A, Mansfield J Diagnosis and treatment of polycystic ovarian syndrome and insulin resistance Pediatr Ann 2005;34:733–42 19 Pastor CL, Griffin-Korf ML, Aloi JA, Evans WS, Marshall JC Polycystic ovary syndrome: evidence for reduced sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone J Clin Endocrinol Metab 1998;83:582–90 20 Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, et al The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome J Clin Endocrinol Metab 2001;86: 5925–33 21 Amato P, Simpson JL The genetics of polycystic ovary syndrome Best Pract Res Clin Obstet Gynaecol 2004;18:707–18 22 Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson R, et al Genetics of polycystic ovary syndrome Mol Cell Endocrinol 1998;145:123–8 23 Ferriman D, Gallwey JD Clinical assessment of body hair growth in women J Clin Endocrinol Metab 1961;24:1440–7 24 Buggs C, Rosenfield RL Polycystic ovary syndrome in adolescence Endocrinol Metab Clin North Am 2005;34:677–705 25 Darroch JE, Singh S, Frost JJ Differences in teenage pregnancy rates among five developed countries: the roles of sexual activity and contraceptive use [published erratum appears in Fam Plann Perspect 2002;34:56] Fam Plann Perspect 2001;33: 244–50 26 Smith CA Factors associated with early sexual activity among urban adolescents Soc Work 1997;42:334–46 27 Eaton DK, Kann L, Kinchen S, Shanklin S, Ross J, Hawkins J, et al Youth risk behavior surveillance- United States 2007 MMWR Surveill Summ 2008;57 (SS-4):1–131 28 Thomas MH Abstinence-based programs for prevention of adolescent pregnancies A review J Adolesc Health 2000;26: 5–17 29 Hewitt G, Cromer B Update on adolescent contraception Obstet Gynecol Clin North Am 2000;27:143–62 30 Anderson FD, Hait H A multicenter, randomized study of an extended cycle oral contraceptive [published erratum appears in Contraception 2004;69:175] Contraception 2003;68:89–96 11 Matytsina LA, Zoloto EV, Sinenko LV, Greydanus D Dysfunctional uterine bleeding in adolescents: concepts of pathophysiology and management Prim Care 2006;33:503–15 31 Lara-Torre E, Schroeder B Adolescent compliance and side effects with Quick Start initiation of oral contraceptive pills Contraception 2002;66:81–5 12 Stein IF, Leventhal ML Amenorrhea associated with bilateral polycystic ovaries Am J Obstet Gynecol 1935;29:181–91 32 U.S Food and Drug Administration FDA updates labeling for Ortho Evra contraceptive patch 2005 Available at: http:// www.fda.gov/bbs/topics/news/2005/NEW01262.html Retrieved January 16, 2009 13 Kent SC, Legro RS Polycystic ovary syndrome in adolescents Adolesc Med 2002;13:73–88 14 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovarian syndrome Fertil Steril 2004;81:19–25 33 Graham S, Fraser IS The progestogen-only mini-pill Contraception 1982;26:373–88 15 Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline J Clin Endocrinol Metab 2006;91:4237–45 35 Cheng L, Gulmezoglu AM, Oel CJ, Piaggio G, Ezcurra E, Look PF Interventions for emergency contraception The Cochrane Database of Systematic Reviews 2004, Issue Art No.: CD001324 DOI: 10.1002/14651858.CD001324 16 Ibanez L, Dimartino-Nardi J, Potau N, Saenger P Premature adrenarche—normal variant or forerunner of adult disease? Endocr Rev 2000;21:671–96 946 Sanfilippo and Lara-Torre Adolescent Gynecology 34 Le J, Tsourounis C Implanon: a critical review Ann Pharmacother 2001;35:329–36 36 Belzer M, Yoshida E, Tejirian T, Tucker D, Chung K, Sanchez K Advanced supply of emergency contraception for adolescent mothers increased utilization without reducing condom or primary contraception use J Adolesc Health 2003;32:122–23 OBSTETRICS & GYNECOLOGY 37 Stuart GS, Castano PM Sexually transmitted infections and contraceptives: selective issues Obstet Gynecol Clin North Am 2003;30:795–808 38 Grimes DA, Schulz KF Prophylactic antibiotics for intrauterine device insertion: a metaanalysis of the randomized controlled trials Contraception 1999;60:57–63 39 Intrauterine device and adolescents ACOG Committee Opinion No 392 American College of Obstetricians and Gynecologists Obstet Gynecol 2007;110:1493–5 40 von Rokitansky C Uberusdausen-neubuildung in uterus and ovarian sarcoma Ztschrdkk Gesellsch Aertweinezu 1860;37: 577 41 Sampson J Perforating hemorrhagic (Chocolate) cysts of the ovary Arch Surg 1921;3: 245–323 42 Fallon J Endometriosis in youth JAMA 1946;131:1405–6 43 Bontis JN, Vavilis DT Etiopathology of endometriosis Ann NY Acad Sci 1997;817:305–9 44 Reese KA, Reddy S, Rock JA Endometriosis in an adolescent population: the Emory experience J Pediatr Adolesc Gynecol 1996;9:125–8 45 Marsh EE, Laufer MR Endometriosis in premenarcheal girls who not have an associated obstructive anomaly Fertil Steril 2005;83:758–60 46 Yamamoto K, Mitsuhashi Y, Takaike T, Takase K, Hoshiai H, Noda K Tubal endometriosis diagnosed within one month after menarche: a case report Tohoko J Exp Med 1997;181: 385–7 47 Laufer M, Sanfilippo J, Rose G Adolescent Endometriosis: diagnosis and treatment approaches J Pediatr Adolesc Gynecol 2003;16:S3–11 VOL 113, NO 4, APRIL 2009 48 Revised American Fertility Society classification of endometriosis: 1985 Fertil Steril 1985;43:351–2 49 Schifrin BS, Erez S, Moore JG Teen-age endometriosis Am J Obstet Gynecol 1973;116:973–80 50 Goldstein DP, deCholnoky C, Leventhal JM, Emans SJ New insights into the old problem of chronic pelvic pain J Pediatr Surg 1979;14:675–80 51 Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA Endometriosis in association with uterine anomaly Am J Obstet Gynecol 1986;154:39–43 52 Gao X, Yeh YC, Outley J, Simon J, Botteman M, Spalding J Health-related quality of life burden of women with endometriosis: a literature review Curr Med Res Opin 2006;22: 1787–97 53 Laufer MR, Goitein L, Bush M, Cramer DW, Emans SJ Prevalence of endometriosis in adolescent girls with chronic pelvic pain not responding to conventional therapy J Pediatr Adolesc Gynecol 1997;10:199–202 54 Endometriosis in adolescents ACOG Committee Opinion No 310 American College of Obstetricians and Gynecologists Obstet Gynecol 2005;105:921–7 55 Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG A gonadotropin-releasing hormone agonist vs a low-dose oral contraceptive for pelvic pain associated with endometriosis Fertil Steril 1993;60:75–9 56 Vercellini P, De Georgio O, Aimi G, Panazza S, Uglietti A, Crosignani PG Menstrual characteristics in women with and without endometriosis Obstet Gynecol 1997;90:264–8 57 Moghissi K Medical treatment of endometriosis, Clin Obstet Gynecol 1999;42:620–32 Sanfilippo and Lara-Torre Adolescent Gynecology 947 ... pediatric and adolescent patient In Sanfilippo JS, Lara-Torre E, Templeman C, Edmonds K, eds Clinical pediatric and adolescent gynecology London (UK): Informa Healthcare; 2009 p 120 OBSTETRICS & GYNECOLOGY. .. bleeding in adolescents: concepts of pathophysiology and management Prim Care 2006;33:503–15 Sanfilippo and Lara-Torre Adolescent Gynecology 939 BOX LABORATORY ASSESSMENT OF THE ADOLESCENT WITH... Washington, DC: ACOG; 2008 Illustration: John Yanson Sanfilippo Adolescent Gynecology Obstet Gynecol 2009 944 Sanfilippo and Lara-Torre Adolescent Gynecology endometriosis had a genital tract anomaly This