Paula K. Braverman
More than 50% of female adolescents experience menstrual dysfunction, including dysfunctional uterine bleeding, amenorrhea, dysmenorrhea, and the premenstrual syndrome. Many of the problems are minor, including mild dysmenorrhea and minor variations in cycle length or amount of flow. However, the dysfunction can become more severe when amenorrhea, debilitating dysmenorrhea, or severe dysfunctional bleeding occurs. This chapter and the next several chapters deal with the evaluation of common adolescent menstrual dysfunctions. Dysmenorrhea, the most prevalent of these, is considered first.
The term primary dysmenorrhea refers to pain associated with the menstrual flow, with no evidence of organic pelvic disease. Secondary dysmenorrhea refers to pain associated with menses secondary to organic disease such as endometriosis, outflow tract obstruction, or pelvic inflammatory disease.
Psychosocial factors may play a role in dysmenorrhea.
Pain is caused by myometrial contractions induced by prostaglandins from the secretory endometrium.
Prostaglandins are formed in the secretory endometrium. Phospholipids from cell membranes are converted into arachidonic acid, the fatty acid precursor for prostaglandin synthesis. Prostaglandin E2 (PGE2) and PGF2α are the key prostaglandins involved in dysmenorrhea, although PGF2α is considered the most important. They are formed through the cyclooxygenase pathway, which also produces thromboxanes and prostacyclin. PGF2α induces myometrial contractions, vasoconstriction, and ischemia and mediates pain sensation, whereas PGE2 causes vasodilation and platelet disaggregation. There are two enzymes in the cyclooxygenase system. The COX-1 enzyme has homeostatic functions including gastrointestinal mucosal integrity, renal and platelet function, and vascular hemostasis. COX-2 is induced by inflammation. It has been noted that:
From this evidence it has been presumed that primary dysmenorrhea is related to prostaglandins released during menses, which seems to be increased during ovulatory cycles. It is postulated that women with dysmenorrhea may be more sensitive to prostaglandins. Prostaglandin levels have also been shown to be locally elevated in cases
of secondary dysmenorrhea such as endometriosis (Koike et al., 1992).
Dysmenorrhea is the greatest single cause of lost work and school hours in females, with>140 million hours lost per year (Ylikorkala and Dawood, 1978). Various studies worldwide have shown the following:
The prevalence of dysmenorrhea increases with age and pubertal stage.
Primary dysmenorrhea usually begins within 1 to 3 years of menarche and is associated with the establishment of ovulatory cycles. Although the pain usually begins within a few hours of starting menses, it may also start several days before the onset of menses. Local symptoms include pain that is spasmodic in nature and is strongest in the lower abdomen, with radiation to the back and anterior aspects of the thighs. In most cases, the pain resolves within 24 to 48 hours but sometimes the symptoms may persist further into the menstrual cycle. Associated systemic symptoms can include nausea or vomiting, fatigue, mood change, dizziness, diarrhea, backache, and headache.
It may be useful to grade dysmenorrhea as follows:
The symptoms of endometriosis in adolescents include chronic pelvic pain, which may be cyclic or acyclic. Cyclic pain alone is found in only 9.4% of adolescents (American College of Obstetrics and Gynecology, 2005). This is in contrast to adults who are more likely to have cyclic pain. Other associated symptoms can include dyspareunia; irregular menses; bowel symptoms such as rectal pain, nausea, constipation, diarrhea, and pain on defecation; and urinary symptoms such as dysuria, urgency, and frequency.
On examination, a tender or nodular cul-de-sac or tender uterosacral ligaments may be found. However, adolescents may not have the classic thickened nodular sacrouterine ligaments. Ovarian endometriomas are not usually found before the mid-twenties. Goldstein et al. (1980) found pelvic tenderness in 76% of adolescents with endometriosis whereasReese et al. (1996) found diffuse tenderness in 95% of patients and localized tenderness in 77.6%.
Endometriosis should by considered in patients with dysmenorrhea who do not respond to a combination of OCP and NSAID, as well as those with associated bowel or urinary function symptoms. This diagnosis is also more common when there is a positive family history for endometriosis.
Examine the pelvis for evidence of endometriosis, endometritis, fibroids, uterine or cervical abnormalities, or adnexal masses and tenderness. However, if the teen is not sexually active and the history is typical for dysmenorrhea, a pelvic examination is indicated only if the symptoms do not respond to standard medical therapy. Examination limited to a cotton swab inserted into the vagina can help rule out a hymenal abnormality or vaginal septum without performing a speculum examination. The musculoskeletal examination should focus on range of motion of the hips and spine to assess for tenderness and limitation in motion.
A complete blood count and a determination of the erythrocyte sedimentation rate should be done if pelvic inflammatory disease or inflammatory bowel disease is suspected. Sexually active adolescents should be tested for sexually transmitted diseases and pregnancy. A urinalysis and urine culture will help diagnose urinary tract problems. If a müllerian abnormality is suspected, ultrasonography or magnetic resonance imaging will define the anatomy. If evaluation of the genitourinary, gastrointestinal, and musculoskeletal systems fail to reveal a cause of the pain and if the pain is severe and intractable despite treatment with antiprostaglandins and oral contraceptives, laparoscopy should be considered.
The two most effective treatments for primary dysmenorrhea are with NSAIDs and oral contraceptives.
The patient should be educated and reassured that the problem is physiological and can be helped. The importance of education has been demonstrated repeatedly in studies demonstrating that adolescents have a knowledge deficit about available treatment modalities and how to use them most effectively (Johnson, 1988; Wilson and Keye, 1989;Campbell and McGrath, 1997; Hillen et al., 1999).
Nonsteroidal Anti-inflammatory Drugs
NSAIDs are the primary modality of therapy; 80% of dysmenorrhea can be relieved with these medications. Because much of primary dysmenorrhea is secondary to prostaglandin-mediated uterine hyperactivity, prostaglandin inhibitors can alleviate menstrual cramps and associated systemic symptoms. Many NSAIDs have been found effective in alleviating menstrual cramps. They are divided into two classes—carboxylic acids and enolic acids. Carboxylic acids are more widely used and are divided into four subgroups: (a) salicylic acids (aspirin), (b) acetic acids (indomethacin), and the two most useful sub-groups—(c) propionic acids such as ibuprofen (Motrin), naproxen (Naprosyn), and naproxen sodium (Anaprox), and the (d) fenamates such as mefenamic acid (Ponstel). Of the propionic acids, naproxen sodium may have a shorter onset of action because it is more rapidly absorbed. Mefenamic acid has an additional mechanism of action: It competes with prostaglandin-binding sites and antagonizes existing prostaglandins in addition to inhibiting prostaglandin synthesis. Some of these drugs and their typical doses are as follows:
Over-the-counter ibuprofen is available in preparations such as Advil and Nuprin. Naproxen is available as Aleve. Because these over-the-counter medications come in lower doses than the prescription formulations, a larger number of tablets may be needed for effectiveness. The medications should be started either as soon as possible when the symptoms of dysmenorrhea occur or to coincide with the first sign of menstruation. It is not necessary to start before the onset of menses. Usually, these medications are needed only for 1 to 3 days. After one of the NSAIDs is started, it should be tried for two or three menstrual cycles before being judged ineffective. At that time, a trial of a different prostaglandin inhibitor should be performed with a minimum trial of at least 6 months for this mode of therapy.
With the outlined doses used for short periods, side effects are usually minimal, but they include the following in more than 1% of patients:
The NSAIDs discussed in the preceding text inhibit both the COX-1 and COX-2 enzymes. However, selective COX-2 inhibitors will have less gastrointestinal side effects and may also be preferred in patients with coagulation disorders related to platelet function. Multiple studies have evaluated various drugs in this class and have found that they are equivalent to naproxen in relieving dysmenorrhea symptoms. Because of recent drug recalls, the only COX-2 inhibitor available at the time of this printing is celecoxib. The dosing is 400 mg as a loading dose followed by 200 mg every 12 hours (Harel, 2005). These medications are more expensive, potentially more toxic and not necessarily superior in efficacy to less expensive, nonselective NSAIDs.
If the patient wishes contraception or the pain is severe and not responsive to NSAIDs, oral contraceptives can be tried. The maximal effect may not become apparent for several months.
A 2001 Cochrane review (Proctor et al., 2001) conducted a meta-analysis of randomized clinical trials and concluded that OCPs with older first and second generation progestins and higher hormone doses than current OCPs were more effective than placebo for primary dysmenorrhea. However, they commented on the small size of the studies and poor quality. Two more recent studies address this knowledge deficit:
If cyclic hormonal contraception is ineffective then continuous combination hormonal therapy can be tried. Monophasic OCPs can be used by skipping the placebo pills. An extended cycling OCP, Seasonale, is currently available as a 91-pill regimen containing 84 hormonal pills before the week of placebo with 30 µg of ethinyl estradiol and 150 µg of levonorgestrel. Extended cycling may be particularly helpful in endometriosis (American College of Obstetrics and Gynecology, 2005; Vercellini et al., 2003a; Sulak et al., 2002). Theoretically, the contraceptive patch and vaginal ring could be used in the same manner. However, one study showed that cycling with OCPs provided better relief of dysmenorrhea than cycling with the patch (Audet et al., 2001). Injectable depot medroxyprogesterone acetate has also been effective.
Other Hormonal Modalities
Other Nonhormonal Modalities
Likely to be beneficial
The term premenstrual syndrome (PMS) is used to describe an array of predictable physical, cognitive, affective, and behavioral symptoms that occur cyclically during the luteal phase of the menstrual cycle and resolve quickly at or near the onset of menstruation. It is characterized by a broad spectrum of symptoms and until recently had confusing definitions. The etiology of PMS is currently unknown, but there is some evidence that reduced serotonergic function during the luteal phase and alterations in the γ aminobutyric acid (GABA) receptor complex response, may be responsible, among other mechanisms (Johnson, 2004; Freeman et al., 2004).
In the mid 1980s, more specific criteria were defined, and studies evaluating both the pathophysiology and treatment modalities were designed according to strict scientific standards. Evidence is accumulating that PMS is not a single condition but a set of interrelated symptom complexes, with multiple phenotypes of subtypes, and pathophysiological events that begin with ovulation (Johnson, 2004; Halbreich, 2004).
In the mental health field, criteria have been developed to define a syndrome called premenstrual dysphoric disorder (PMDD) as a distinct clinical entity. Although the PMS and PMDD overlap, in PMDD the focus is more on problems
with mood and symptoms are more severe. There is a higher level of dysfunction before the onset of menses. Both Johnson (2004); Speroff and Fritz (2005) conclude that it is not useful to differentiate PMS from PMDD, and agree that there is a broad spectrum of severity. Johnson suggests characterizing PMDD as severe PMS with impairment.
The exact prevalence is unknown, but estimates are that up to 85% of menstruating women have some degree of symptoms before menses, and that 3% to 8% are so severely afflicted that daily activities are hindered. This smaller subset of women meet criteria for PMDD (Chakmakjian, 1983; Singh et al., 1998; American College of Obstetrics and Gynecology, 2000;Grady-Weliky, 2003). As noted by Johnson (2004), approximately 50% of women have only a few mild symptoms for several days during the luteal phase and probably should not be diagnosed as having PMS. Some selected studies in adolescents have shown the following:
Risk factors for PMS include advancing age (beyond 30 years) and genetic factors. Some studies suggest that women whose mothers report PMS are more likely to develop PMS (70%, versus 37% of daughters of unaffected mothers) (Van der Akker et al., 1987; Dalton, 1987). In addition, concordance rates for PMS are significantly higher in monozygotic twins (93%) compared with dizygotic twins (44%) (Dalton, 1987). There are no significant differences in personality profile or level of stress in women with PMS compared with asymptomatic women. However, women with PMS may not handle stress as well. One recent article prospectively evaluating a community cohort of 1,488 women aged 14 to 24 over a 42-month period found that traumatic events such as a physical threat, childhood sexual abuse, and severe accidents increased the odds of developing PMDD (Perkonigg et al., 2004).
The exact mechanism of PMS is unknown, but is probably the result of an interaction between sex steroids and central neurotransmitters (Mortola, 1998).
More than 150 symptoms have been described in literature, ranging from mild symptoms to those severe enough to interfere with normal activities.
The diagnosis relies on the history of cyclic symptoms. No specific physical findings or laboratory tests have proved useful. Although there are no universally accepted specific diagnostic criteria among the various sources defining PMS including the World Health Organization's International Classification of Diseases, ACOG, the National Institute of Mental Health, and the Diagnostic and Statistical Manual of Mental Disorders, (Halbreich, 2004), three important findings are usually needed to make a diagnosis of PMS:
A calendar such as the one shown in Figure 50.1 can be helpful in the diagnosis and in monitoring teens after the start of any therapy. Prospective recording should be done for at least 2 to 3 months to document that symptoms are occurring cyclically in the luteal phase. Other assessment tools include the Self-Assessment Disk (Magos and Studd, 1988), the Premenstrual Assessment Form (Halbreich et al., 1982), Calendar of Premenstrual Experience (COPE) (Mortola et al., 1990), the Prospective Record of the Impact and Severity of Menstrual Symptoms (PRISM) (Reid, 1985), Premenstrual Syndrome Diary (Thys-Jacobs et al., 1995), Daily Record of Severity of Problems (Endicott and Harrison, 1990), and the Penn Daily Symptom Rating (Freeman et al., 1996).
The National Institute of Mental Health (NIMH) criteria require a change of 30% in intensity of symptoms, as measured with the use of an instrument, comparing days 5 through 10 of the cycle with the 6 days before menses. These changes must be documented for at least two consecutive cycles (American College of Obstetrics and Gynecology, 2000).
The Diagnostic and Statistical Manual of Mental Health Disorders, 4th edition text revision (American Psychiatric Association, 2000) lists similar criteria for PMDD (Table 50.1). It is important to remember that the symptoms cannot represent exacerbation of an existing disorder such as major depression, anxiety disorders, panic, dysthymic disorder, or personality disorder, but they may be superimposed on one of these psychiatric disorders. Women may have psychiatric disorders that become exacerbated during menstruation (menstrual magnification). Certain medical disorders can also become worse during menses, including seizures, migraine headaches, irritable bowel syndrome, asthma, and allergies.
No single treatment is universally accepted as effective. Studies have yielded conflicting results with most therapies, and most trials have not been well controlled. Treatments include the following:
; Girman et al., 2003; Johnson, 2004).
FIGURE 50.1 Premenstrual symptom calendar.
Possible reasons for efficacy of this new formulation include the lower estrogen dose, as well as improved follicular suppression. The maintenance of a more stable hormonal environment due to the longer number of days on hormone may also be helpful (e.g., 24 rather than 21 days) (Yonkers et al., 2005). The current thinking is that OCP should be considered if the symptoms are primarily physical and not mood related because they appear to be better for the physical symptoms. However, the 24/4 formulation OCP appears to be effective for both types of symptoms.
Summary: Steps in the Treatment of Symptoms of Premenstrual Syndrome
The following successive steps were outlined in an American College of Obstetrics and Gynecology (2000) and in a recent review by Johnson (2004):
For Teenagers and Parents
http://kidshealth.org/teen/sexual_health/girls/menstruation.html. Teen site on dysmenorrhea.
http://www.aafp.org/afp/990800ap/489.html. American Academy of Family Physicians (AAFP) article on primary dysmenorrhea.
http://www.obgyn.upenn.edu/mudd/PMSarticle.html. Information on PMS from University of Pennsylvania Obstetrics and Gynecology Department.
http://www.youngwomenshealth.org/menstrual.html. Information from Children's Hospital Boston on dysmenorrhea and PMS.
http://www.nlm.nih.gov/medlineplus/ency/article/001505. htm. Medical encyclopedia from the U.S. National Library of Medicine and National Institutes of Health. Information on PMS and dysmenorrhea.
For Health Professionals
http://www.emedicine.com/emerg/topic156.htm. E-medicine site on dysmenorrhea.
http://vh.org/navigation/vh/topics/menstruation.html. Information from the University of Iowa on dysmenorrhea and PMS.
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