Johannes Bitzer1
(1)
Department of Obstetrics and Gynaecology, Women’s Hospital, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland
Johannes Bitzer
Email: JBitzer@uhbs.ch
3.1 Dysmenorrhea
Dysmenorrhea is the most common gynecologic complaint among adolescent and young adult females.
Primary dysmenorrhea refers to recurrent, crampy lower abdominal pain that occurs during menstruation in the absence of pelvic pathology.
· It is the most common gynecologic complaint among adolescent females.
· Nausea, vomiting, diarrhea, headache, dizziness, or back pain may accompany the crampy abdominal pain.
· The pain and associated symptoms typically begin several hours prior to the onset of menstruation and continue for 1–3 days.
· Dysmenorrhea generally is linked to ovulatory cycles:
· Approximately 18–45 % of teens have ovulatory cycles 2 years postmenarche, 45–70 % by 2–4 years, and 80 % by 4–5 years.
· Dysmenorrhea rarely occurs in anovulatory cycles (mainly with hypermenorrhea with clots).
· Dysmenorrhea in adolescents and young adults is usually primary (functional) and is associated with normal ovulatory cycles and with no pelvic pathology.
· Secondary dysmenorrhea is caused by pelvic pathology. In approximately 10 % of adolescents and young adults with severe dysmenorrhea symptoms, pelvic abnormalities such as endometriosis or uterine anomalies may be found.
There is some controversy whether dysmenorrhea is a natural variation or “real clinical condition”. On the one hand, dysmenorrhea is a recurrent benign event, self-limiting condition, there is no threat to health or life, there are no long-term consequences. There is no objective pathology, but a patient reported outcome. On the other hand, it is a chronic recurrent pain condition leading to distress and having a negative impact on quality of life and it is contributing to losses and restrictions in personal and professional performance.
3.1.1 Prevalence
· The prevalence of dysmenorrhea among adolescent females ranges from 60 to 93 %.
· Most adolescent girls in varied populations report experiencing dysmenorrhea, and approximately 15 % describe the pain as severe.
· Many adolescents report limitations on daily activities, such as missing school, sporting events, and other social activities, because of dysmenorrhea.
· Morbidity due to dysmenorrhea represents a substantial public health burden. Based on estimates from the U.S. Census, approximately two million adolescents, or 15 % of the total females aged 13–19 years, experience severe dysmenorrhea.
· It was estimated that dysmenorrhea is the single greatest cause of lost working hours and school absence in adolescent girls.
· 15 % of females seek medical advice for menstrual pain, signifying the importance of screening all adolescent females for dysmenorrhea.
· Klein and Litt reported that only 14 % of US adolescents with dysmenorrhea sought help from a physician, including only 29 % of those reporting severe dysmenorrhea.
· Of those who experienced dysmenorrhea, 25.9 % consulted a physician, and 61.7 % practiced self-medication (SM) [1–4].
3.1.2 The Diagnosis
Verbal multidimensional scoring system for assessment of dysmenorrhea
|
Grade |
Working ability |
Systematic symptoms |
Analgesics |
|
Grade 0: Mensuration is not painful and daily activity is unaffected |
Unaffected |
None |
None required |
|
Grade 1: Mensuration is painful but seldom inhibits normal activity; analgesics are seldom required; mild pain |
Rarely affected |
None |
Rarely required |
|
Grade 2: Daily activity is affected; analgesics required and give sufficient relief so that absence from school is unusual; moderate pain |
Moderately affected |
Few |
Required |
|
Grade 3: Activity clearly inhibited; poor effect of analgesics; vegetative symptoms(headache, fatigue,vomiting, and diarrhea |
Clearly inhibited |
Apparent |
Poor effect |
3.1.3 The Differential Diagnosis
A history of painful menses occurring at menarche is unlikely to be primary dysmenorrhea, because most females are anovulatory for several months to several years after menarche. The presence of pelvic pain unrelated to menses also suggests secondary dysmenorrhea.
Menstrual pain that has become progressively worse over time is characteristic of endometriosis, which may present as cyclic or noncyclic pain.
Adolescents who have had pelvic infections (e.g., gonorrhea and chlamydia) may develop adhesions that result in pelvic pain, especially during menstruation.
The most important differential diagnosis is endometriosis which for definitive diagnosis still needs laparoscopy. Rare causes are obstructive disease, irritable bowel syndrome, and pelvic congestion syndrome.
3.1.4 Etiology and Risk Factors
The majority of women with primary dysmenorrhea do not have any risk factors for the disorder [5].
In a systematic review that evaluated risk factors for dysmenorrhea, multiple demographic, environmental, gynecological, and psychological factors appeared to be associated with the disorder, including age <30 years, body mass index <20 kg/m2 , smoking, menarche before age 12, longer menstrual cycles/duration of bleeding, irregular or heavy menstrual flow, and history of sexual assault.
Younger age at first childbirth and higher parity were associated with a reduced risk.
There appears to be a familial predisposition to primary dysmenorrhea.
3.1.5 Pathophysiology
3.1.5.1 Prostaglandin Hypothesis
Some basic observations indicate the pivotal role of prostaglandins in the pathophysiology of dysmenorrhea as:
· Endometrial concentrations of prostaglandin E2 and prostaglandin F2 alpha are elevated in primary dysmenorrhea and correlate with the severity of pain.
· Exogenous administration of prostaglandins reproduces the symptoms of primary dysmenorrhea.
Other observations indicate the importance of the contraction of the myometrium. The cascade of events can be described in the following way:
Phospholipids are part of the cell wall and after the onset of progesterone decline before menstruation, phospholipase A2 leads to the production of arachidonic acid, which can be either metabolized towards PGI prostaglandins (which have a relaxation effect) or through COX2 enzymes versus PGF2 alpha. PGF2 alpha causes potent vasoconstriction and myometrial contractions, leading to ischemia and pain [6, 7].
3.1.6 Treatment of Primary Dysmenorrhea
3.1.6.1 NSAIDs
· First-line treatment—NSAIDs are considered the first line of therapy. In randomized trials of NSAIDs, approximately 70–90 % of patients have effective pain relief, a value that is greater than that with placebo.
· NSAIDs should be started at the onset of menses and continued for the first 1 to 2 days of the menstrual cycle or for the usual duration of crampy pain. Patients with severe symptoms should begin taking NSAIDs 1–2 days prior to the onset of menses. They should be taken with food to minimize side effects such as gastrointestinal irritation or bleeding.
· Preferable use of NSAIDs that are COX-1 inhibitors, because of the uterotonic effects reported with COX-2 inhibitors and possible associations with serious adverse events.
Ibuprofen and naproxen are used commonly for the treatment of dysmenorrhea in clinical practice. Mefenamic acid is unique in that it both inhibits prostaglandin synthase and blocks the action of the prostaglandins that are already formed.
A trial of mefenamic acid should be considered for patients who do not respond to the propionic acid group of medications [8, 9].
3.1.6.2 Hormonal Contraceptives
A review and meta-analysis by the Cochrane Collaboration concluded that OCs may be more effective than placebo based on 5 controlled trials of OCs compared with placebo [10].
· In a randomized double-blind, placebo-controlled clinical trial of 76 healthy adolescents aged 19 years or younger reporting moderate or severe dysmenorrhea subjects were randomly allocated to receive either an OC (ethinyl estradiol 20 μg and levonorgestrel 100 μg) or a matching placebo for 3 months.
· At baseline, 42 % of participants described their dysmenorrhea as moderate, and 58 % described it as severe.
· Of those currently enrolled in school, 39 % reported usually missing 1 school day monthly, and an additional 14 % usually missed 2 or more days because of dysmenorrhea.
· This trial demonstrated that a low-dose oral contraceptive was more effective than placebo for moderate or severe primary dysmenorrhea in adolescents.
· A survey from the Netherlands revealed that almost one-third of young women reported that their primary reason for using birth control pills was for relief of menstrual pain rather than contraception.
Other options are:
· 150 mg MPA (Depo Provera)
· LNG IUD (Mirena)
· Desogestrel 75 μg/day (Cerazette)
· Desogestrel Implant (Implanon)
· Dienogest
3.2 Premenstrual Syndrome: Premenstrual Dysphoric Disorder
Different names like menstrual complaints, late luteal phase disorder, and premenstrual dysphoric disorder (PMDD) are used to define a syndrome which has already been described by Hippokrates as a cyclic disorder which renders women irritable and causes physical and psychological discomfort.
A large number of these symptoms have been described and reported by women:
3.2.1 Physical Symptoms
Breast tension, headache, bloatedness, weight gain, edema, back and lower abdominal pain, fatigue, sleeping disorders, and craving for sweets.
3.2.2 Psychological Symptoms
Irritability, mood swings, depression, concentration difficulties, memory problems, anxiety, aggressive behavior, withdrawal, and crying spells.
For practical purposes, two different clinical conditions should be differentiated.
3.2.3 Premenstrual Syndrome
PMS is defined as a condition with recurrent physical, psychological, and behavioral symptoms which occur during the luteal phase of the cycle (days 14–28) and which are usually relieved by menstruation with a symptom free week (usually days 1–7). The symptoms have a negative impact on the quality of life of the woman.
The most frequent physical symptoms are:
· Swelling, breast tenderness, aches, headache, and bloating
The most frequent behavioral symptoms are:
· Sleep disturbances, appetite changes, poor concentrations, decreased interest, and social withdrawal.
The most frequent mood symptoms are:
· Irritability, mood swings, anxiety, tension, depression, and feeling out of control.
3.2.3.1 Premenstrual Dysphoric Disorder
The following symptoms constitute the syndrome:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
PMDD symptoms are present for most of the time in the week before menses, diminish with the onset of menses, and are absent in the week following menses. At least 5 PMDD symptoms occur in most menstrual cycles for at least 1 year.
At least one of the five symptoms must be one of the first four on this list:
· Feeling sad, hopeless, or self-deprecating
· Feeling tense, anxious, or “on edge”
· Marked lability of mood interspersed with frequent tearfulness
· Persistent irritability, anger, and increased interpersonal conflicts
3.2.4 Etiology and Pathogenesis
PMS and PMDD depend on ovarian function. Before menarche, after menopause, during pregnancy, or after bilateral ovariectomy, there is no PMS but after hysterectomy women may still suffer from cyclic symptoms.
Another proof of the pivotal role of cyclic ovarian function or ovarian hormones is a study in which the application of a GnRH agonist leading to the suppression of ovarian function resulted in the disappearance of symptoms in women suffering from PMS. In the same study, it could be shown that giving ovarian steroids to these women made the symptoms reappear.
On the other hand, there is no difference in ovarian steroid production and concentration in women with and without PMS 18. This is also true for differences in metabolites of progesterone (like allopregnanolone). Furthermore, the use of antiprogestins in the second half of the menstrual cycle did not improve the symptoms.
This means that ovarian steroids are a necessary but not a conclusive condition for PMS and PMDD.
Based on laboratory and animal studies, the hypothesis focus on the observation that fluctuations in estrogen and progesterone lead to various changes in the Opioid, GABA, and Serotonin systems.
In earlier studies, beta endorphin concentrations were lower in patients suffering from PMS indicating the important role of opioids. There was however a lack of confirmation in later studies.
The GABA hypothesis was based on the therapeutic effect of Alprazolam. But again measurements of progesterone metabolites like Allopregnanolone did not show differences between patients and controls.
For the moment, the most promising concept seems to be the central role of serotonin in the pathogenesis of PMS and PMDD.
Women with PMS have lower levels of serotonin in plasma and less uptake of serotonin in platelets.
Another indicator for the important role of serotonin is that SSRIs reduce the symptoms, whereas lack of tryptophan, a serotonin precursor, increases the symptomatology.
The role of psychosocial factors is still under investigation.
On the one hand, it is remarkable that help seeking behavior because of symptoms differs considerably between countries. In the USA, Canada, and Australia more women consult physicians than in Germany, France, or Switzerland. This may be an indirect sign of psychological factors like attributional style, body perception and body image, etc.
Stress seems to increase the symptoms, but it is sometimes difficult to distinguish between stress as a cause or a consequence of PMS.
3.2.5 Diagnosis
The most important feature of both PMS and PMDD is the cyclicity of symptoms and the typical symptom free phase at the beginning of a new cycle. As women may experience many different symptoms and each patient has its own cluster of symptoms, it is important to use prospective symptoms inventories.
Based on the most commonly reported symptoms, the Calendar of Premenstrual Experiences (COPE) was constructed. It includes a four-point Likert scale for each of the ten most commonly reported physical and 12 most commonly reported behavioral symptoms rated daily throughout the menstrual cycle.
A total score on this inventory of less than 40 during days 3–9 of the menstrual cycle combined with a score greater than 42 during the last 7 days of the menstrual cycle has been shown to be an excellent predictor of women who meet inclusion criteria for PMDD.
In addition to the COPE, other commonly used scales for the assessment of PMS are the prospective forms of the Moos Menstrual Distress Questionnaire (MDQ) and the Premenstrual Assessment Form (PAF).
3.2.6 Differential Diagnosis
The differential diagnosis of PMS and PMDD includes:
Cyclic exacerbation of chronic conditions like mastodynia, chronic pelvic pain, dysmenorrhea, hormone withdrawal symptoms, migraine, irritable bowel syndrome, chronic fatigue syndrome, and various affective disorders.
An important differential diagnosis in women over 40 years is perimenopausal depression.
Another medical condition which has to be excluded is hyper- or hypothyroidism.
There is a close link between PMS/PMDD and the risk for psychiatric morbidity.
· The lifetime incidence of significant psychiatric disorder in women with PMS is between 50 and 78 %.
· Women who present with PMS have a much higher incidence of major depression in the past and appear to be at greater risk for major depression in the future.
3.2.7 Treatment
A treatment plan should be established according to the following criteria:
· Predominant symptoms (physical, psychological, and behavioral)
· Impact on quality of life
· Patient preferences
There is a large variety of treatment options, which can be grouped according to the scientific evidence of efficacy on one hand and treatment risks on the other.
3.2.7.1 Basic Therapy
· Physical exercise, relaxation techniques, and other body centered interventions lack scientific evidence but have proven in clinical practice to have some therapeutic effect in some women. These interventions have no risk.
· In addition, cognitive interventions, which help patients to interpret bodily sensations in a different way (knowing where the symptoms come from, dedramatising the symptoms, reducing catastrophizing thoughts, etc.), have shown some efficacy although well-designed studies are lacking.
· It is important in this context to note that in all clinical trials in patients with PMS and PMDD there is a strong positive effect in the placebo group pointing to the importance of care and positive expectations.
3.2.7.2 Low-Risk Interventions with Some Scientific Evidence
· Vitex agnus castus has proven in one placebo-controlled trial to reduce symptoms like irritability, anger, headache, and breast tension significantly more than placebo.
· Different vitamins, calcium and magnesium have shown some therapeutic effect, but all need further studies. This is also true for cyclic progesterone, Cimicifuga, essential fatty acids, and Gingko biloba.
· Light therapy may be a promising alternative, but there is also a lack of studies.
3.2.7.3 Interventions with Robust Scientific Evidence and Some Risks and Side Effects
Combined Oral Contraceptives
Combined oral contraceptives applied as long cycle (no pill free interval) have proven to be partially effective. The combination of EE with the progestogen drospirenone in a 24/4 regimen has shown in a randomized cross-over trial superiority over placebo. There is an increased risk in of thromboembolic complications compared to one user. But the risk is small in absolute terms.
Serotonin Reuptake Inhibitor
Systematic reviews indicate the efficacy of Serotonin Reuptake Inhibitor (SSRI) (Fluoxetine, Sertraline, Paroxetine, and Citalopram). The response rate is between 60 and 75 %. Typical side effects are headache, nausea, anxiety feelings, and loss of libido in about 15 % of patients.
Other antidepressants like Clomipramine, Nefazodone, and Venlafaxine can also be used.
It is important to note that the treatment regimen can differ from the treatment of depression. Taking the drugs only during the luteal phase was effective although a little less effective than continuous treatment.
Hormonal Therapies (other than COCs)
GnRH Analog and Danazol suppress ovarian activity and thus reduce PMS and PMDD symptoms. The efficacy of GnRH was proven in several studies, especially regarding irritability and physical symptoms, less so for depressive symptoms.
GnRH is rarely used because of the short-term and long-term side effects due to lack of estrogen (hot flushes, osteoporosis, etc.). If used it should be used with an add-back therapy replacing estrogen if necessary with a progestogen. It has been shown that low-dose add-back therapy does not reduce the efficacy of GnRH treatment.
Danazol is rarely used because of androgenic side effects.
References
1.
Wilson CA, Keye WR Jr (1989) A survey of adolescent dysmenorrhea and premenstrual symptom frequency. A model program for prevention, detection, and treatment. J Adolesc Health Care 10:317PubMedCrossRef
2.
Klein JR, Litt IF (1981) Epidemiology of adolescent dysmenorrhea. Pediatrics 68:661PubMed
3.
Census 2000 data for the United States. Sex by single years of age. Available at: http://www.census.gov/census2000/states/us.html. Retrieved 5 Nov 2004
4.
Johnson J (1988) Level of knowledge among adolescent girls regarding effective treatment for dysmenorrhea. J Adolesc Health Care 9:398PubMedCrossRef
5.
Klein JR, Litt IF (1981) Epidemiology of adolescent dysmenorrhea. Pediatrics 68:661PubMed
6.
Ylikorkala O, Dawood MY (1978) New concepts in dysmenorrhea. Am J Obstet Gynecol 130:833PubMed
7.
Dawood MY (2006) Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol 108:428PubMedCrossRef
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Chan WY, Dawood MY, Fuchs F (1979) Relief of dysmenorrhea with the prostaglandin synthetase inhibitor ibuprofen: effect on prostaglandin levels in menstrual fluid. Am J Obstet Gynecol 135:102PubMed
9.
Marjoribanks J, Proctor M, Farquhar C, Derks RS (2010) Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev: CD001751.
10.
Proctor ML, Roberts H, Farquhar CM (2001) Combined oral contraceptive pill (OCP) as treatment for primary dysmenorrhoea. Cochrane Database of Syst Rev 4, CD002120