Consultation with the Specialist: Dysmenorrhea

After completing this article, readers should be able to: A 15½-year-old girl came to the office with complaints of the recent onset of painful menstrual periods. She experienced her first menstrual period at the age of 13 years and except for an occasional mildly uncomfortable menstrual period, had not experienced significant pain until recently. She reported regular monthly menses, although she did not write down the dates. She described additional symptoms that also had not been present previously, including headache, loose stools, and breast tenderness. She has tried several over-the-counter medications, including acetaminophen, without significant relief. She has missed 3 days of school in the last 6 weeks because of these complaints. She is otherwise healthy, having no major illnesses, no history of surgeries, and no other genitourinary complaints. There is no family history of endometriosis; severe dysmenorrhea; menorrhagia; irregular periods; infertility; uterine fibroids; or breast, ovarian, colon, or uterine cancer. Her mother recalled that she had been prescribed oral contraceptives at the age of 16 years to alleviate her severe menstrual cramps. When spoken with privately, having been assured confidentiality, the girl denied sexual activity or abuse. She was doing well in school, making As and Bs, and felt that the relationship with her parents and one sister were good. She reported that she experienced crampy midline lower abdominal pain that began with the onset of vaginal bleeding and lasted 1 to 2 days. She rated the pain as being 8 on a scale of 10 and reported that she had to go to bed and sleep to cope with the pain.This patient has a classic history of dysmenorrhea with moliminal symptoms–other painful or uncomfortable symptoms associated with ovulatory menses, including breast tenderness, bloating, nausea, and headaches. She has no history of significant gynecologic or family medical problems. Given her previous inadequate trial of nonsteroidal anti-inflammatory drugs (NSAIDs), she was encouraged to chart her menstrual periods to allow her to predict their onset and to take an adequate dose and scheduled frequency (not prn) of NSAIDS beginning prior to the onset of bleeding and continuing through the first 2 days of menstrual flow. It was the clinician’s judgment that a pelvic examination was not indicated, given the classic symptoms of primary dysmenorrhea. A follow-up visit in 3 months was scheduled.On return, the patient reported that she had experienced some relief of her pain and now rated her cramps as being 5 on a scale of 10, but she had missed 2 additional days of school over the 3 months. She and her mother both were interested in additional therapy; she reported that one of her girlfriends took oral contraceptives to help her periods. The family history was reviewed to confirm that there was no history of early cardiovascular events, including venous thromboembolism. No relatives had had gynecologic malignancies, including breast cancer. The clinician indicated that a pelvic ultrasonographic examination would provide information to help rule out structural causes of pelvic pain (Table 1), but a pelvic examination still was not believed to be required. Findings from pelvic ultrasonography were normal. The patient was prescribed combination oral contraceptives; told the potential risks, benefits, and adverse effects; and given specific guidelines to maximize compliance.After 3 months, the patient returned, stating that she still had not experienced complete relief of her dysmenorrhea. She continued to rate her pain as being 5 on a 10-point scale when on oral contraceptives and NSAIDS. A bimanual examination was performed to assess for uterine tenderness that might suggest pelvic infection or endometriosis. No localized areas of tenderness were palpated posterior to the uterus or in the adnexal regions, as might be present with pelvic endometriosis. However, given the persistence of her symptoms, she was referred to the local medical center for consultation with an adolescent gynecologist and consideration of a diagnostic laparoscopy.Dysmenorrhea is defined as painful menstruation; the word is derived from the Greek words dys, meaning difficult/painful/abnormal, meno, meaning month, and rrhea, meaning flow.;Primary dysmenorrhea typically begins during adolescence with ovulatory cycles and is not due to any pelvic disease; secondary dysmenorrhea is uncommon during adolescence and is due to the presence of pelvic disease. Previous attempts to categorize dysmenorrhea as “spasmodic” or “congestive” largely have been abandoned.Dysmenorrhea is the most common gynecologic condition of adolescence, occurring in 60% to 93% of adolescents. However, many do not seek medical care. One study reported that only 14% of adolescents ages 12 to 17 years who had dysmenorrhea and only 29% of those who reported severe dysmenorrhea had seen a physician. Many teens are unaware of effective medications that are available over-the-counter, others do not know where to get gynecologic care, and many fear a pelvic examination.Dysmenorrhea and other menstrual molimina typically are associated with ovulatory cycles. Because the hypothalamic-pituitary-ovarian axis requires time to mature, the incidence of ovulatory cycles increases with increasing gynecologic age; as many as one third of adolescents continue to experience anovulatory cycles in the fifth year after menarche. Thus, in the first several gynecologic years, dysmenorrhea often is absent or infrequent. It is not unusual for an adolescent to present to the emergency department because of pelvic cramping, experiencing her first episode of dysmenorrhea, and not recognizing that the pain is associated with her menses. Disability associated with dysmenorrhea is common; many teens report modifying their sports, work, and social activities around the time of their menses because of pain, and many miss school frequently. It has been reported that 14% of girls frequently miss work or school because of dysmenorrhea, and nearly 50% of those who have pain describe their pain as moderate or severe. One report in the mid-1980s estimated the economic loss in the United States due to dysmenorrhea among all women to be approximately $2 billion, with more than 600 million lost work hours.Dysmenorrhea statistically is more likely among adolescents who have early menarche, heavy menstrual flow, and a family history of dysmenorrhea. There is no association with height, body weight or body mass index, or history of abortion. Most studies suggest that adolescents who exercise regularly or who smoke are less likely to experience dysmenorrhea. Although the cause of these associations is speculative, it may relate to relative hypoestrogenism and anovulatory cycles.Until the early to mid-1960s, psychological factors were suggested as the major cause of primary dysmenorrhea; more recent studies suggest that emotional distress is not a major etiologic factor. In the 1970s, the pathophysiology of dysmenorrhea was elucidated and linked to the prostaglandin pathway. The physiologic basis of primary dysmenorrhea relates to cell membrane phospholipids, endomyometrial prostaglandins, and leukotrienes. After ovulation, in response to the production of progesterone, fatty acids build up in cell membrane phospholipids. Arachidonic acid and other omega-7 fatty acids are released and initiate a cascade of prostaglandins and leukotrienes in the uterus. These, in turn, mediate an inflammatory response, leading to menstrual cramps and other menstrual molimina. Prostaglandin (PG) F2-alpha is a cyclooxygenase metabolite of arachidonic acid that causes myometrial hypertonus and vasoconstriction, with resultant ischemia and pain. Individuals who have primary dysmenorrhea produce an excess of endometrial PGs compared with those who have no pain, including, most notably, PGF2-alpha. An abnormal PGF2-alpha:PGE2 ratio also has been reported in association with primary dysmenorrhea. Elevated endometrial levels of PGs have been found to correlate with the degree of pain reported. Infusion of PGF2-alpha and PGE2 induces dysmenorrhea. Further support for this mechanism of action is provided by the relief of symptoms with PG synthetase (cyclooxygenase) inhibitor drugs.It has been suggested that leukotrienes heighten the sensitivity of uterine pain fibers. High concentrations of leukotriene have been found in adult women who have dysmenorrhea; an increase in urinary leukotrienes also has been shown in adolescent girls who have dysmenorrhea. These substances are potent vasoconstrictors and inflammatory mediators, although the specifics of the mechanisms by which they are involved in causing dysmenorrhea are not well established.Low back pain occurring in association with dysmenorrhea is due to referred pain from spinal nerves. Bloating may result from sensitivity to progesterone, a smooth muscle relaxant, produced in the second half of the cycle. Subsequent loose stools are a PG-mediated symptom. Migraine or other headaches may be triggered by declining levels of estrogen in the immediate premenstrual phase of the cycle. Mood lability or “premenstrual syndrome (PMS)” is more complex in etiology; cyclic hormonal fluctuations and hormonally mediated fluctuations in neurotransmitters likely are causative, although the specifics of these pathways are not well established. Elimination of hormonal cycling with gonadotropin-releasing hormone (GnRH) agonists has been effective in treating severe PMS and premenstrual dysphoric disorder. Their use is limited by both cost and adverse effects.The pathologic mechanisms of pain associated with such causes of secondary dysmenorrhea as uterine fibroids, endometriosis, adenomyosis, and other pelvic pathologies may be somewhat more specific to the pathologic entity. Table 1 lists causes of secondary dysmenorrhea or conditions that may need to be considered in adolescents who experience pelvic pain.Endometriosis has been found to occur more frequently in first-degree relatives of women whose endometriosis has been confirmed surgically (7%) compared with first-degree relatives of their husbands (1%), suggesting a genetic component to this condition. Polygenic/multifactorial inheritance appears most likely. The defining symptom of primary dysmenorrhea is crampy midline lower abdominal pain that begins with menstrual flow or a short time before. Typically, the cramps are most intense on the first or second day of flow and resolve before the end of the menstrual flow. The pain may be referred and experienced as lower back or anterior thigh pain. Nausea or vomiting may occur in some individuals. Near-syncope or “dizziness” (not true vertigo) and complaints of “weakness” also can occur. Other premenstrual or menstrual molimina, including breast tenderness, bloating, headache, and mood changes, also may be troublesome or disabling. Secondary dysmenorrhea is more likely to begin several days or even 1 to 2 weeks prior to the onset of bleeding and to persist through the end of menstrual flow. Associated symptoms, including heavy bleeding, may suggest uterine fibroids as a cause.An abdominal examination is important to rule out nongynecologic causes of pain such as irritable bowel syndrome or even gastroesophageal reflux or gastritis. A periumbilical location argues for these latter conditions and against a pelvic/gynecologic etiology. Left lower quadrant fullness over the left colon is common with irritable bowel syndrome. The examiner must take care not to mistake the enlarged uterus associated with vaginal outlet obstruction and hematometra for obesity. Abdominal examination findings in primary dysmenorrhea include only mild suprapubic tenderness with normal bowel sounds, no upper abdominal tenderness, and no rebound tenderness.An abdominal examination can determine abdominal wall trigger-points associated with musculoskeletal pain, which is a common concomitant of dysmenorrhea. An evaluation for signs of musculoskeletal pain (Carnett sign) can be helpful. A bimanual examination during menses may reveal mild diffuse uterine tenderness without cervical motion or adnexal tenderness. Although a complete gynecologic/pelvic examination is not mandatory for evaluation of classic dysmenorrhea, inspection of the external genitalia is important to reveal an imperforate hymen or distal uterine septum. Other congenital anomalies such as a didelphic uterus with unilateral obstruction, a longitudinal vaginal septum with hemi-obstruction, cervical agenesis, cervical stenosis, or a partially obstructing uterine septum may not be elucidated completely by pelvic examination; imaging with pelvic ultrasonography or, if this is inconclusive, magnetic resonance imaging may be required.For adolescents whose external genitalia are normal and who have classic symptoms of dysmenorrhea, a pelvic examination is not required initially. If initial therapy is ineffective, a bimanual examination can be helpful; endometriosis can be associated with mild posterior uterine/cul-de-sac tenderness. The cul-de-sac (pouch of Douglas) posterior to the uterus is the most dependent portion of the pelvis and, thus, the most likely site for pelvic endometriosis. In adolescents, the classic findings of uterosacral nodularity are rare. The absence of posterior uterine tenderness argues against endometriosis.Laboratory testing typically is not required for the diagnosis of primary dysmenorrhea. If gastrointestinal (GI) disease is suspected, a rectal examination that includes testing for occult blood may be helpful. An erythrocyte sedimentation rate, while nonspecific, may be abnormal in conditions such as inflammatory bowel disease, but typically is normal with primary dysmenorrhea. Transabdominal or transvaginal ultrasonography can rule out ovarian pathology or an obstructive uterine or vaginal lesion. Transvaginal ultrasonography provides a more definitive picture of the internal pelvic organs. Adolescents who are sexually active usually tolerate this examination well, as can many appropriately informed mid- to older adolescents who have been using tampons successfully. Transvaginal ultrasonography should not be attempted in a virginal younger teen without an assessment of her ability to tolerate this approach and a discussion of what should be expected with the examination.The diagnosis of primary dysmenorrhea rests on a classic pain history, with attention to the timing and onset of symptoms (typically a few hours before onset of bleeding and lasting for 1 to 3 d), the nature and location of the complaints (crampy pelvic pain), the presence of moliminal symptoms associated with ovulation, and the lack of other signs or symptoms that suggest a secondary cause. The pain of secondary dysmenorrhea often begins 1 to 2 weeks prior to menses, may be more constant, and often persists throughout the duration of menstrual flow. A bimanual examination is indicated if signs or symptoms suggest secondary dysmenorrhea. Findings on examination that suggest endometriosis or uterine fibroids may prompt further study, including pelvic ultrasonography or laparoscopy.The management of primary dysmenorrhea involves the use of NSAIDs, which are cyclooxygenase inhibitors that reduce the production of PGs. Some NSAIDS, in particular meclofenamic acid, inhibit both cyclooxygenase and lipoxygenase pathways, inhibiting the production of leukotrienes as well. This theoretical advantage has not been shown to result in a clear-cut advantage of one NSAID over another. Cyclooxygenase type 2 (COX-2) inhibitors are approved by the United States Food and Drug Administration (FDA) for the treatment of primary dysmenorrhea in adults; pediatric use has not been evaluated. The FDA defines the adolescent subpopulation of pediatrics as including ages 13 to 21 years. Until recently raised questions of the safety of the COX-2 inhibitors have been answered satisfactorily, their use is not recommended for first-line therapy of dysmenorrhea.Over-the-counter pain medications frequently are used for dysmenorrhea; such use has been reported in 30% to 70% of adolescents. However, many adolescents are unaware of the differences in the mechanism of action of over-the-counter analgesics and often do not distinguish between those that have effective components and those that do not. Several medications that are marketed heavily for dysmenorrhea in teens do not contain components that have any proven efficacy. In addition, so many different formulations of these over-the-counter drugs exist (Table 2) that even when some of the formulations contain NSAIDs, it is difficult for teens to decipher this from merely knowing the names of the drugs.Teens commonly take medications for dysmenorrhea that are ineffective. In addition, most lay persons do not understand pharmacology, that is, concepts of loading dose, duration of action, half-life, and sustained serum levels of drugs. They rarely take NSAIDs often take at and even may a dose of of over-the-counter to last throughout the duration of their cramps. relief of primary dysmenorrhea can be with NSAIDs in up to of teens when in and A that are an effective treatment for although women using need to be of the significant of adverse and that is to determine which NSAID is the most and effective for the treatment of have been shown in to be effective for dysmenorrhea. of these and spinal have been in a of with of for primary dysmenorrhea. appears to work by pain in the of a or or may be effective and is associated with A that spinal therapy for primary dysmenorrhea was no more effective than such as of and have been but the to support their use and safety are oral contraceptives have been prescribed in the last years for dysmenorrhea in those who have not experienced relief with NSAIDs or who also contraceptives reduce PG by inhibiting and, thus, the increase in PG in both PGs and leukotrienes have been in the menstrual of women oral contraceptives compared with contraceptives are well in adolescents and provide additional benefits, such as in Adolescents who experience relief of dysmenorrhea are more likely to use oral contraceptives and oral contraceptives for management of dysmenorrhea are an therapy if no significant medical or family history their Some or parents may be to begin oral contraceptives for the management of dysmenorrhea in the that they the of sexual contraceptives should be considered for adolescents who have not experienced relief of dysmenorrhea with The and a support the use of older oral contraceptives; the for oral The that no can be the use of oral contraceptives for dysmenorrhea. Thus, a or may be to a FDA the pelvic examination prior to oral contraceptives in adolescents. However, adolescents who have a history of sexual should sexually disease testing may be performed by using acid and may be for cervical testing on the age of of sexual as recommended by therapy for adolescents who do not have endometriosis but who have dysmenorrhea in of oral contraceptives and NSAIDS is the cycling of oral A recently marketed combination oral has been with days of hormonally active by days of than the but dysmenorrhea an for use of oral contraceptives in this because menstrual periods and, thus, dysmenorrhea occur less frequently. The of this oral and use more likely. using oral contraceptives in this must be that or bleeding is not in the early cycles. Other oral formulations are and can be used in an or by for should be considered to determine the of endometriosis in who have dysmenorrhea in of adequate and frequency of NSAIDs and combination oral 2) who have a first-degree relative who has endometriosis, who have pelvic findings of posterior uterine or cul-de-sac tenderness on pelvic who have a history of significant due to pain, who have had previous medical or whose mother or family who have a of who are of having and not for without or and who are other such as or Although the of and on that treatment with agonists without be considered as an approach to treatment in this that differences between and adolescents are that is in adolescents. The of an adolescent to a diagnosis of endometriosis more potential for given their In addition, many adolescents are their and may be less able than to understand the of endometriosis on the potential to of therapy with agonists during a time of adolescent and are of One study the of therapy for endometriosis on adolescent and found no significant on loss with a but the in the use of such therapy prior to the patient to In of has been shown and is with However, nearly of teens do not have an adequate and adolescent are than adult such therapy may be indicated, but should be by a gynecologist who has experience in pelvic pain and dysmenorrhea in adolescents and in endometriosis The early of endometriosis may not have the classic that they have in adults; they may as or that are If endometriosis is not seen and confirmed by the teen and her family should be assured that this information is and that the clinician continue to work with the family to provide adequate pain use of NSAIDS with and duration is for the relief of primary dysmenorrhea. When NSAIDS provide relief of dysmenorrhea and secondary causes are not suspected, oral contraceptives can provide cost and are likely to efficacy. When of is an the of missed hours of school and work due to dysmenorrhea can be for oral contraceptives is Some do not oral even when prescribed for others may provide for dysmenorrhea if a of medical is provided by the when these medications are not by benefits, many that such as NSAIDS and combination oral contraceptives provide a that is the