Introduction
Dysmenorrhea, which is pain associated with menstrual cycles, has a significant impact on the day-to-day functioning of adolescents. This chapter aims to review dysmenorrhea and endometriosis (the most common cause of secondary dysmenorrhea in adolescent females).
Definitions
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Dysmenorrhea is pain associated with menstrual bleeding, often described as abdominal cramps.
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Primary dysmenorrhea is the presence of pain before or during cycles without an underlying pathology.
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Secondary dysmenorrhea is the presence of pain before or during cycles with an underlying pathology, commonly found to be endometriosis.
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Endometrial cells (found normally within the uterus) are located outside of the uterus. Common locations are the ovaries, fallopian tubes, and peritoneum.
Prevalence and epidemiology
The prevalence rates of dysmenorrhea vary across the globe but range from 16% to 93% of patients who menstruate. The prevalence of endometriosis is 10% to 15% in reproductive-age women and 35% to 50% in women with pelvic pain. The true prevalence of endometriosis in adolescents is unknown. A majority of adolescent females with chronic pelvic pain or dysmenorrhea unresponsive to hormonal therapies and nonsteroidal antiinflammatory drugs (NSAIDs) will be diagnosed with endometriosis at the time of diagnostic laparoscopy.
Etiology and pathophysiology
Dysmenorrhea is subdivided into primary and secondary. We briefly describe primary dysmenorrhea, including pathophysiology, diagnosis, and treatment. Secondary dysmenorrhea, with a primary focus on endometriosis as the most common etiology, is covered in depth in this chapter.
The etiology of dysmenorrhea is poorly understood. Primary dysmenorrhea is primarily linked to two prostaglandins, prostaglandin F2α and prostaglandin E2. The changes in estrogen, progesterone, and prostaglandins levels are thought to trigger an inflammatory cascade that leads to myometrial hypercontractility. , The resultant hypoxia and ischemia of the uterine muscle thus lead to pain. The increased contractility of the musculature is also thought to be the cause of associated symptoms of nausea and diarrhea.
In order to diagnose primary dysmenorrhea, careful attention to history regarding time of onset, characteristics, locations, and menstrual regularity is necessary. A common history for primary dysmenorrhea is a patient who started menses 1 to 2 years prior with minimal pain, and as the menstrual cycle becomes more predictable, the pain worsens. The pain of primary dysmenorrhea is closely associated with pain 1 to 2 days before menses onset and for the first 2 days, with improvement by the end of menses. Primary dysmenorrhea responds well to NSAIDs or hormonal suppression, or both, and does not have an underlying pathology. To differentiate primary dysmenorrhea from secondary dysmenorrhea, it is key to note how the pain responds to antiinflammatory medications. If there is minimal response or a response followed by worsening pain or debilitating pain, it is recommended to then proceed with additional testing and evaluation for secondary dysmenorrhea. The underlying pathology of secondary dysmenorrhea is discussed later. Various potential etiologies of endometriosis are listed in Table 10.1 .
| Sampson’s Theory | Meyer’s Theory | Halban’s Theory | ||
|---|---|---|---|---|
| Retrograde menstruation | Embryologic totipotent cells | Vascular/lymphatic spread | Deficient cell-mediated immunity | Genetic predisposition |
| Transport of viable fragments of endometrium through fallopian tubes during menstruation | Cells undergo metaplastic transformation into functional endometrium | Endometrial cells spread via the vascular or lymphatic system, explains remote locations | Deficiency in cellular immunity allows proliferation | Polygenic/multifactorial predisposition, 7× higher greater risk of endometriosis if first-degree relative with endometriosis |
Clinical presentation and evaluation for endometriosis
A thorough history, including gynecologic, medical, surgical, and family history, is of paramount importance. Special attention is paid to the menstrual history—onset of menses (menarche), cyclicity, length of menses, and rate of flow (light, moderate, heavy). The onset of pelvic pain should be elicited, with astute attention paid to the fact whether pain has been the same in severity or has been getting worse. The latter may lead to workup for an obstructive müllerian anomaly, characterized by a slow building of the pain progressively with each cycle. 
The most common clinical presentation of endometriosis in adolescents is pain associated with the menstrual cycle and outside menses, cyclical and noncyclical pain, respectively. The levels and concentrations of active macrophages, interleukin (IL)-1β, IL-6, and IL-8; nerve growth factor (NGF); and other inflammatory factors are increased in peritoneal fluid (PF) and endometriotic lesions in patients with endometriosis. These molecular changes contribute to dysmenorrhea, dyspareunia and pelvic pain. Innervation is also altered, namely, there is increased number of total intact nerve fibers, increased sensory and decreased sympathetic nerve fiber density.
In addition to dysmenorrhea, endometriosis is associated with dyspareunia in sexually active adolescents (pain during sexual intercourse), dyschezia (pain on bowel movement), and dysuria (pain on urination). Notably, adolescent females with endometriosis commonly have both acyclic and cyclic pain in 62.5%, acyclic only in 28.1%, and cyclic only in 9.4%. In the same cohort, the authors described multiple associated symptoms such as gastrointestinal (34.3%), urinary (12.5%), and irregular menses (9.4%). Fibromyalgia and chronic fatigue syndrome were found in 7% and 4%, respectively, in adolescent patients in one study. Other associated symptoms may include migraines, nausea, frequent urination, and changes in bowel movement pattern ( Table 10.2 ).
| Organ System | Condition/Symptom | |
|---|---|---|
| Gynecologic |
| |
| Nongynecologic | Gastrointestinal |
|
| Urologic |
| |
| Neurologic |
| |
| Psychological/psychiatric |
| |
| Rheumatologic |
| |
| Social |
|
Providers taking care of the adolescent patient presenting with vague complaints of pelvic or abdominal pain must entertain a diagnosis of endometriosis, as there is a notorious delay—up to 12.1 years—in the diagnosis, particularly in adolescent patients. Pain characteristics vary, so careful history documentation via a pain dairy is helpful. Either a paper format or web-based application can be useful. Various characteristics of pain are described in Table 10.3 . Of note, Wüest and colleagues report that young patients (ages ≤24 years) with clinically diagnosed endometriosis have significantly higher pain scores for dysmenorrhea, dyspareunia, and noncyclic pelvic pain compared with older patients.
| Pelvic and Abdominal Pain in Adolescent Females | |
|---|---|
| Location |
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| Severity |
|
| Length/frequency |
|
| Relation to menses |
|
| Type |
|
| Associated symptoms |
|
| Provoking factors |
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| Alleviating factors |
|
As mentioned earlier, various associated symptoms are common. Dun and colleagues describe a case series of 25 females (mean age 17.2 years) with laparoscopically diagnosed endometriosis of which 53% reported at least one genitourinary symptom and 56% reported at least one gastrointestinal symptom. A cross-sectional study reported that adolescents with endometriosis were more likely to experience migraines (69.3%) than those without endometriosis (30.7%). Bowel health plays an important role in the pathophysiology of abdominal pain, especially functional abdominal pain. Functional constipation is highly prevalent in adolescents. A 2021 systematic review of functional gastrointestinal disorders (FGIDs) using the Rome IV criteria has demonstrated that functional constipation is the most common functional abdominal pain disorder (FAPD) in children older than age 4 years, with a prevalence of 3% to 28.7%. Because of this high prevalence of FGIDs, routine screening for these conditions is part of the workup in any adolescent patient with pelvic pain.
Physical examination
The physical examination is comprehensive and includes vital signs, body mass index (BMI) with assessment of growth chart, and overall health. A general examination, including abdominal examination, is performed, with attention paid to abdominal tenderness at rest, with palpation, presence of mass(es), and points of tenderness along the abdominal muscles (trigger points).
In most adolescents, the pelvic examination will be limited to inspection of the external genitalia to assess Tanner stage, anatomy, and level of estrogenation of the vulva and the configuration and patency of the hymen. Speculum and/or digital vaginal examination is deferred in sexually nave adolescents. If there is suspicion for reproductive tract obstruction (i.e., müllerian anomaly), a rectal abdominal examination may be better tolerated after informed consent is obtained. Additionally, a lubricated cotton swab can be inserted into the vagina to assess the vaginal length and patency. A bimanual pelvic examination assessing for palpable nodularity, thickened uterosacral ligaments, point tenderness in the rectovaginal space, pouch of Douglas, adnexa, and rectosigmoid space is reserved for sexually active females in the late stage of adolescence (ages 18–21 years). Abnormal bimanual examination findings are rare in early-stage endometriosis, which most adolescents will be diagnosed with (stage I and II).
Musculoskeletal etiologies of pelvic pain, including myofascial pain, can be evaluated by palpating for abdominal wall tenderness (e.g., Carnett sign) while asking patient to raise a straight leg. Left lower quadrant tenderness elicited during palpation should raise concern for constipation. In many cases abdominal examination and external inspection of the genitalia will not reveal any abnormalities.
Laboratory assessment
Currently there are no approved specific blood tests or noninvasive biomarkers in the United States to identify endometriosis. Active ongoing research is directed toward the identification of noninvasive biomarkers such as CA-125, microRNAs, menstrual effluent, and proteomics.
In specific cases if there is a suspicion for an inflammatory process, a complete blood count (CBC) or erythrocyte sedimentation rate (ESR) may be obtained. In adolescents with bowel symptoms such as diarrhea, bloating, constipation, abdominal pain, or weight loss, laboratory evaluation may include workup for celiac disease with tissue transglutaminase and endomysial and deamidated gliadin peptide antibodies. If there are any symptoms associated with bladder function, urinalysis or urine culture should be obtained. In sexually active teens, a urine pregnancy test and/or sexually transmitted infection testing is indicated, specifically, nucleic acid amplification test (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae. It should be noted that at this time there are no approved specific blood tests or markers to identify endometriosis in clinical practice in the United States.
Imaging techniques and findings
Transabdominal ultrasound (US) is the preferred modality for the evaluation of pelvic organs in adolescent females. The yield of detecting endometriosis is not high. According to a retrospective observational study, two-dimensional (2D), three-dimensional (3D), and power Doppler US pelvic examination (transvaginal or transrectal in pre–sexually active adolescents) identified at least one ultrasound feature of endometriosis in 36 (13.3%) of 270 cases. Ovarian endometriomas were found in 22 (11%) patients, adenomyosis in 16 (5.2%), and deep infiltrating endometriosis (DIE) in 10 (3.7%).
Comparison of the diagnostic accuracy of 2D and 3D transvaginal US in comparison with magnetic resonance imaging (MRI) for identification of DIE in one prospective observational study (albeit in women older than 18 years of age) showed that there was a statistically significant difference between 2D US and MRI for the intestinal location of DIE, whereas no differences were found among the techniques for the other locations (retrocervical septum, rectovaginal septum, uterosacral ligaments, and vaginal fornix). There are no studies analyzing MRI utility in the diagnosis of endometriosis in adolescent females. Thus endometriosis remains predominantly a clinical diagnosis, with imaging studies reserved for cases in which structural anomalies are suspected and the standard treatment course is unsuccessful.
Classic signs
The 3 Ds: Dysmenorrhea/dyschezia/dyspareunia
Differential diagnosis of pelvic pain in adolescents
The differential diagnosis of endometriosis is extensive and is usually grouped into gynecologic and nongynecologic causes, with the latter including gastrointestinal, genitourinary, musculoskeletal, and psychological origins ( Table 10.4 ). There may be a cross-section of a few diagnoses, and a multidisciplinary approach to diagnosis should be pursued.
| Gastrointestinal | Genitourinary | Musculoskeletal | Psychological | Gynecologic |
|---|---|---|---|---|
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