CHAPTER 61
Menstrual Disorders
Monica Sifuentes, MD
CASE STUDY
A 16-year-old girl presents with a 9-day history of vaginal bleeding. She has no history of abdominal pain, nausea, vomiting, fever, dysuria, or anorexia, and she reports no dizziness or syncope. Her menses usually lasts 4 to 5 days and, in general, occurs monthly. Her last menstrual period was 3 weeks ago and was normal in duration and flow. Menarche occurred at 14 years of age. She is sexually active, has had 2 partners, and reportedly uses a condom “most of the time.” Neither she nor her current partner has ever been diagnosed with or treated for a sexually transmitted infection. She has no family history of blood dyscrasia or cancer, has no history of chronic illness, and takes no medications.
On physical examination, she is in no acute distress. Her temperature is 36.9°C (98.4°F). Her heart rate is 100 beats/min, and her blood pressure is 110/60 mm Hg. Her body mass index is at the 50th percentile. The physical examination, including a pelvic examination, is unremarkable except for minimal blood noted at the vaginal introitus.
Questions
1. What menstrual disorders commonly affect adolescent girls?
2. What factors contribute to the manifestation of menstrual disorders, particularly during adolescence?
3. What relevant menstrual history should be obtained from the adolescent?
4. What options are available for managing primary dysmenorrhea?
5. How is abnormal uterine bleeding managed in the adolescent patient?
Gynecologic concerns and symptoms are common reasons for adolescent girls to visit their primary care physician. The challenge for the pediatrician is to differentiate between an organic etiology, a functional condition, and psychogenic symptoms. When this cannot be readily done or if the physical examination is equivocal, multiple diagnostic procedures may be performed, often with variable results. Additionally, many pediatricians are uncomfortable evaluating gynecologic problems in adolescents and performing pelvic examinations, which contributes to this diagnostic dilemma. The purpose of this chapter is to review some of the more common gynecologic conditions affecting adolescent girls and to highlight the significant historical and physical findings associated with each problem. For a discussion of the infectious conditions that cause pelvic pain, see Chapter 60.
Epidemiology
The overall prevalence of menstrual disorders during adolescence is estimated to be 50% in the United States, with the most common gynecologic symptom being dysmenorrhea, or painful menstruation. At least 70% to 90% of women have some pain associated with menses; the extent of discomfort varies. Although most menstruating women report mild to moderate discomfort, severe dysmenorrhea occurs in 10% to 15% of women and has been reported to be responsible for significantly limiting activities of daily living, including school attendance, participation in athletics, and socialization with peers. Uterine anomalies or pelvic abnormalities (eg, endometriosis) occur in approximately 10% of female adolescents and young women with severe dysmenorrhea.
Prevalence estimates concerning premenstrual syndrome (PMS) are difficult to assess because most studies in adolescents are retrospective, and self-reports can be unreliable and misleading. In these studies, between 20% and 30% of older adolescents report significant PMS-type symptoms. An estimated 20% to 40% of adult women experience PMS symptoms sufficiently bothersome to impair daily functions, and 5% to 10% have debilitating symptoms that warrant the diagnosis of premenstrual dysphoric disorder (PMDD). Other menstrual problems in adolescents include abnormal uterine bleeding, primary and secondary amenorrhea, and vaginal discharge.
Several factors contribute to the occurrence of menstrual disorders in adolescence. The average age of menarche in the United States remains at 12.5 years (range: 9–16 years), although the age of onset of puberty has decreased in some racial groups and in children with obesity. Bleeding may be irregular or prolonged initially in young adolescents because most early menstrual cycles are anovulatory and irregular, especially during the first few years after menarche. Bleeding problems may resolve after ovulatory cycles are established; however, menstrual symptoms, such as lower abdominal pain, breast tenderness, headache, bloating, and vomiting, may predominate. Early sexual activity among adolescents and associated sexually transmitted infections (STIs) also may contribute to the presence of certain gynecologic conditions in this age group, particularly vaginitis, abnormal uterine bleeding, and pelvic pain.
Clinical Presentation
The adolescent with a menstrual disorder may present in a variety of ways. Specific symptoms include heavy menstrual bleeding, irregular periods, and painful menses, and more general symptoms include fatigue, dizziness, and syncope (Box 61.1). The adolescent with PMS may experience mood swings, stress, and nervousness accompanied by abdominal bloating and pain before menses. Additionally, the adolescent or her parent or guardian may have questions or concerns about delayed pubertal development and primary or secondary amenorrhea.
Pathophysiology
Puberty and the Normal Menstrual Cycle
Figure 61.1 depicts the menstrual cycle, which typically lasts for 21 to 35 days, with a mean length of approximately 28 days. Normal duration of menses is 4 to 7 days. Blood loss is usually 30 to 40 mL per cycle; most women do not lose more than 60 mL per cycle. Regular ovulatory cycles usually do not occur until 2 to 3 years after menarche, although 10% to 20% of cycles remain anovulatory as long as 5 years after menarche. It has been reported that girls with earlier menarche establish regular ovulatory menstrual cycles more rapidly than girls with later menarche.
One-quarter of females begin menstruating when they reach sexual maturity rating (SMR [ie, Tanner stage]) 3 of sexual maturation, but approximately two-thirds do not menstruate until they reach SMR 4 breast and genital development. Several other processes occur before the onset of menstruation. Thelarche, or the beginning of breast development, takes place approximately 2 to 3 years before menarche, and growth acceleration usually begins approximately 1 year before thelarche.
Dysmenorrhea
Dysmenorrhea often is accompanied by other symptoms, such as nausea, vomiting, diarrhea, fatigue, bloating, low back pain, and headaches. It can be classified as primary or secondary. Primary dysmenorrhea occurs in the absence of any pelvic pathology, comprising 90% of adolescent menstrual pain, and most commonly occurs in older adolescents after ovulatory cycles are established. Secondary dysmenorrhea refers to painful menses associated with some underlying pelvic pathology, such as pelvic inflammatory disease (PID), endometriosis, ovarian cysts or tumors, Müllerian anomalies, or cervical stenosis. A complete list of causes of secondary amenorrhea can be found in Box 61.2. Endometriosis is the most common cause of secondary dysmenorrhea in the adolescent.
Figure 61.1. The normal ovulatory menstrual cycle.
Abbreviations: FSH, follicle-stimulating hormone; LH, luteinizing hormone.
Box 61.1. Diagnosis of Menstrual Disorder in the Adolescent Patient
Primary Dysmenorrhea
•Painful menstruation
•Lower abdominal pain associated with menstruation, usually worse on the first few days of bleeding
•Associated back pain
•Pain sometimes accompanied by nausea, vomiting, fatigue, headache, bloating, and diarrhea
•Symptoms begin 6–12 months after menarche
Abnormal Uterine Bleeding
•Prolonged bleeding (>8 days) or
•Excessive bleeding (>6 tampons/pads per day) or
•Frequent uterine bleeding (≤21 days)
•No demonstrable organic etiology
•Normal laboratory studies, with the possible exception of anemia
Primary Amenorrhea
•No spontaneous menstruation in a girl of reproductive age
•Absence of menarche by age 15 years in a girl with normal pubertal development or
•Absence of menarche by age 13 years in a girl with no secondary sexual development or
•Absence of menarche within 1–2 years of reaching full sexual maturation (sexual maturity rating 5)
Numerous studies have shown that cell membrane phospholipids, endometrial prostaglandins, and leukotrienes play a role in the pathogenesis of primary dysmenorrhea. After ovulation, fatty acids build up in the phospholipids of the cell membrane in response to the production of progesterone. Arachidonic acid as well as other omega-6 fatty acids are released after the onset of progesterone withdrawal before menstruation. A cascade of prostaglandins and leukotrienes is initiated in the uterus during menses, which results in an inflammatory response. Prostaglandin F2α, which is produced locally by the endometrium from arachidonic acid, is a potent vasoconstrictor and myometrial stimulant that causes uterine contractions, resulting in tissue ischemia and pain. Prostaglandin E2α causes hypersensitivity of the pain nerve terminals in the uterine myometrium. The cumulative effect of these prostaglandins may cause the pain of primary dysmenorrhea. Hormonal and endocrine factors also may play a role in the etiology of primary dysmenorrhea, because ovulatory cycles with estrogen and progesterone are necessary for development of the condition.
Box 61.2. Differential Diagnosis of Common Menstrual Disorders
Secondary Dysmenorrhea
•Endometriosis
•PID
•Uterine myomas, polyps, or adhesions
•Adenomyosis
•Ovarian cysts or tumors
•Presence of an intrauterine device
•Cervical stenosis or strictures
•Congenital malformations (ie, septate uterus, imperforate hymen)
Excessive Uterine Bleeding
•Ovulatory dysfunction: physiologic anovulation
•Complications of pregnancy: spontaneous/threatened/incomplete abortion, ectopic pregnancy, hydatidiform mole
•Infections of the lower and upper genital tract: endometritis, PID, cervicitis/vaginitis
•Blood dyscrasia and thrombocytopenia: von Willebrand disease, ITP, leukemia, platelet defects, aplastic anemia
•Endocrine disorders: hypothyroidism and hyperthyroidism, hyperprolactinemia, late-onset 21-hydroxylase deficiency, Cushing or Addison disease, PCOS
•Vaginal anomaly: carcinoma
•Cervical/uterine abnormalities: endometriosis, polyp, hemangioma, rhabdomyosarcoma
•Ovarian abnormalities: primary ovarian failure, tumors, cysts
•Systemic/chronic illness: IBD, malignancy, SLE, diabetes mellitus
•Foreign body: retained condom or tampon, IUD
•Medications: aspirin, anticoagulants, hormonal contraception, androgens, chemotherapy
•Trauma or sexual assault (ie, high vaginal laceration)
Amenorrhea (Primary and Secondary)
•Pregnancy
•Systemic abnormalities: endocrinopathies (hypothyroidism, Cushing syndrome), chronic diseases (IBD, sickle cell disease), poor nutrition (anorexia nervosa), obesity, intense exercise, stress, drugs (opiates, valproate)
•Hypothalamic lesions: tumors, infiltrative lesions (TB, CNS leukemia)
•Pituitary lesions: prolactinoma, drugs causing elevated prolactin (eg, marijuana, cocaine), cranial irradiation
•Ovarian failure: gonadal dysgenesis (ie, Turner syndrome); autoimmune failure associated with diabetes mellitus, adrenal insufficiency, thyroid disease, and celiac disease; radiation- or chemotherapy-induced oophoritis; galactosemia
•Congenital abnormalities of the reproductive tract: imperforate hymen, transverse vaginal septum, absence or abnormality of the uterus, complete androgen insensitivity syndrome (complete or partial receptor defects), Mayer-Rokitansky-Küster-Hauser syndrome
•Androgen excess: PCOS, benign ovarian androgen excess
Abbreviations: CNS, central nervous system; IBD, inflammatory bowel disease; ITP, idiopathic thrombocytopenic purpura; IUD, intrauterine device; PCOS, polycystic ovary syndrome; PID, pelvic inflammatory disease; SLE, systemic lupus erythematosus; TB, tuberculosis.
Most cases of primary dysmenorrhea begin 1 to 2 years after menarche, and symptoms gradually increase until patients reach their early 20s. Parity and advancing age are associated with a decrease in symptomatology.
Abnormal Uterine Bleeding
Abnormal uterine bleeding (formerly called dysfunctional uterine bleeding) is abnormal or excessive endometrial bleeding in the absence of any pelvic pathology. Menstruation is considered excessive if the cycles are short (≤21 days) and the bleeding is prolonged (>8 days). Although ovulatory dysfunction is the most common cause of abnormal or excessive uterine bleeding in adolescents, it is a diagnosis of exclusion. Other causes of abnormal bleeding should first be investigated by obtaining a thorough history, performing a complete physical examination, and obtaining laboratory studies as indicated.
Excessive uterine bleeding typically is the result of anovulatory, immature menstrual cycles. In adolescents, 50% of menstrual cycles are anovulatory within the first 2 years after menarche. If menarche occurs later in adolescence (ie, at SMR 5), the interval from anovulatory to ovulatory cycles reportedly lasts even longer. Most cases of abnormal uterine bleeding in adolescents are thought to result from the delayed maturation of the hypothalamic-pituitary-ovarian axis. Normally, a positive feedback mechanism manifests with rising estrogen levels, resulting in a surge in luteinizing hormone and follicle-stimulating hormone, which triggers ovulation. The progesterone-producing corpus luteum then stimulates development of the secretory endometrium, with subsequent shedding after approximately 14 days if no fertilization occurs (ie, menses). With anovulation, progesterone-producing corpus luteum is absent; thus, no development of a secretory endometrium occurs. Estrogen thus remains unopposed, and proliferative endometrium continues to accumulate. When the tissue can no longer maintain its integrity, it sloughs. Additionally, without progesterone the normal vasospasm that helps limit endometrial bleeding does not occur. As a result, bleeding is prolonged, frequent, and heavy.
Premenstrual Syndrome
Premenstrual syndrome refers to a group of physical, cognitive, affective, and behavioral symptoms that occur 1 to 2 weeks before menses, that is, during the luteal phase of the menstrual cycle, and resolve within 4 days after the onset of menstruation. Various mechanisms have been proposed, including an increased sensitivity to the normal cyclic fluctuations in steroid hormones and releasing factors and alterations in central neurotransmitters, such as endorphins, γ-aminobutyric acid, and serotonin. The exact etiology remains unknown, however, despite multiple studies with a focus on pin-pointing the cause of this complex condition.
Amenorrhea
Amenorrhea is the lack of spontaneous menstruation in women of reproductive age. Similar to dysmenorrhea, it can be classified as primary or secondary. Traditionally, primary amenorrhea was defined by the following criteria: an absence of menarche by age 16 years in the girl with otherwise normal pubertal development, an absence of menarche by age 14 years in the girl with no secondary sexual development, and an absence of menarche within 1 to 2 years of reaching SMR 5 pubic hair. Causes of primary amenorrhea range from congenital anatomic anomalies to genetic and endocrine conditions. Because many of these disorders can be diagnosed and treated earlier than 16 years of age, however, guidelines have been modified to address when menstrual conditions should be evaluated. Current guidelines encourage a more proactive medical evaluation for girls who lack menses by age 15 years or more than 3 years after the onset of secondary sexual development. Additionally, absence of secondary sexual characteristics by age 13 years is considered abnormal (Box 61.3). A detailed discussion of each etiology that causes primary amenorrhea is beyond the scope of this chapter; see Selected References for more information.
Secondary amenorrhea is a state of 3 or more consecutive months of amenorrhea in the girl who has already established menstruation. The most common cause of secondary amenorrhea is pregnancy, which must be ruled out in all adolescents presenting with this symptom, regardless of their acknowledgment of sexual activity. Other causes include systemic illness, significant change in weight, stress, intense physical exertion, eating disorders (eg, anorexia nervosa), and certain medications, such as phenothiazines, glucocorticoids, and heroin. Polycystic ovary syndrome is another common cause of secondary amenorrhea in young adult women, but often it is characterized by a wide range of menstrual irregularities, including abnormal uterine bleeding, oligomenorrhea, and amenorrhea of perimenarcheal onset.
Box 61.3. Menstrual Conditions That May Require Evaluation
Menses That:
•Have not started within 3 years of thelarche
•Have not started by 13 years of age with no signs of pubertal development
•Have not started by 14 years of age with
— Signs of hirsutism or
— A history or physical examination suggestive of excessive exercise or eating disorder or
— Concerns about an outflow tract obstruction or anomaly
•Have not started by 15 years of age
•Are regular, occurring monthly, then become markedly irregular
•Occur more frequently than every 21 days or less frequently than every 45 days
•Occur 90 days apart even for 1 cycle
•Last longer than 7 days
•Require frequent pad/tampon changes (soaking more than 1 every 1–2 hours)