Continuing Education Activity

Dysmenorrhea can be classified as primary and secondary dysmenorrhea. Primary dysmenorrhea is a lower abdominal pain happening during the menstrual cycle which is not associated with other diseases or pathology. This activity reviews the evaluation and management of dysmenorrhea. It highlights the role of the interprofessional team in evaluating and treating primary dysmenorrhea, as well as to correctly identify secondary dysmenorrhea and appropriately refer to subspecialty care in a timely fashion.

Objectives:

• Identify the etiology of primary and secondary dysmenorrhea.
• Describe the evaluation of primary and secondary dysmenorrhea.
• Outline the management options available for primary and secondary dysmenorrhea.

Introduction

Dysmenorrhea is a Greek term for “painful monthly bleeding.”[1] Dysmenorrhea can be classified as primary and secondary dysmenorrhea. Primary dysmenorrhea is a lower abdominal pain happening during the menstrual cycle, which is not associated with other diseases or pathology.[2] In contrast, secondary dysmenorrhea is usually associated with other pathology inside or outside the uterus.[3] Dysmenorrhea is a common complaint among women during their reproductive age. Dysmenorrhea is associated with significant emotional, psychological, and functional health impacts.[4]

Etiology

Many theories have explained the etiology of dysmenorrhea since the 1960s. This includes psychological, biochemical, and anatomical etiologies. The anatomical theory included abnormal uterine positions and abnormalities in shape or the length of the cervix. Zebitay et al., in their study, proposed a positive correlation between the cervical length and the volume and intensity of dysmenorrhea.[5] However, the biochemical theory has proven to be stronger than others according to several homogenous studies.[6] 

Associated risk factors are

• Age ()
• Smoking 
• Attempts to lose weight
• Higher body mass index
• Depression/anxiety
• Earlier age at menarche
• Nulliparity
• longer and heavier menstrual flow
• Family history of dysmenorrhea
• Disruption of social networks[7]

Primary dysmenorrhea: Prostaglandin F (PGF) is the main contributor to the cause of dysmenorrhea.[8][9] The time of the endometrial shedding during the beginning of menstruation is when the endometrial cells release PGF. Prostaglandin (PG) causes uterine contractions, and the intensity of the cramps is proportionate to the amount of PGs released after the sloughing process that started due to dropping hormonal surge.[10][11]

Secondary dysmenorrhea:  Secondary dysmenorrhea presentation is a clinical situation where menstrual pain can be due to an underlying disease, disorder, or structural abnormality either within or outside the uterus.[12] There are many common causes of secondary dysmenorrhea, which include endometriosis, fibroids (endometriomas), adenomyosis, endometrial polyps, pelvic inflammatory disease, and maybe even the use of an intrauterine contraceptive device.[8]

Epidemiology

Dysmenorrhea is one of the common gynecological problems among all women regardless of age or race. It is one of the most frequently identified etiology of pelvic pain in females. The prevalence of dysmenorrhea can vary between 16% and 91% in women of reproductive age, with severe pain observed in 2% to 29%.[7]  Agarwal et al. showed the prevalence of dysmenorrhea to be 80% in adolescents. Of that, approximately 40% had severe dysmenorrhea.[13]

The symptoms associated with dysmenorrhea include gastrointestinal symptoms such as nausea, bloating, diarrhea, constipation, or both, along with vomiting and indigestion. Also, irritability, headache, and low back pain are prevalent among women presenting with primary dysmenorrhea. Tiredness and dizziness are also associated with dysmenorrhea.[14] Dysmenorrhea is associated with significant impairment in quality of life between 16% to 29% of women.[7] Furthermore, 12% of the monthly school and work activities are lost due to absenteeism because of dysmenorrhea.[15][7]

Pathophysiology

The pathophysiology of primary dysmenorrhea is not well understood. Nevertheless, the identified cause is due to the hypersecretion of the prostaglandins from the uterine inner lining. Prostaglandin F2alpha (PGF-2a) and Prostaglandin PGF 2 increases the uterine tone, and also causes high-amplitude contractions of the uterus.[16] Also, vasopressin has been linked to primary dysmenorrhea. Vasopressin increases the uterine contractility and can cause ischemic pain due to its vasoconstriction effects.[3][17] 

The uterine contractility is observed to be more prominent in the first two days of the menstrual period. Progesterone levels drop before menstruation, which leads to increased production of PGs' triggering dysmenorrhea.[18] Endometriosis and adenomyosis are the most common causes of secondary dysmenorrhea in premenopausal women.[18]

History and Physical

A comprehensive history, along with adequate physical examination, is important to establish the diagnosis. History of the location of pain, onset, characteristics, and duration, along with associated symptoms like fatigue, headache, diarrhea, nausea, and vomiting, could be helpful to establish a diagnosis.[14]

For primary dysmenorrhea, the physical examination is usually normal. A pelvic examination is not necessary for adolescents and women with characteristics of primary dysmenorrhea/ Pelvic examination is indicated in adolescents and women who have previously been sexually active and when the secondary cause is suspected or if there is a lack of response to treatment. The common findings that indicate secondary dysmenorrhea are:

• Young age (around menarche) primary dysmenorrhea vs. older age > 25 years old (secondary dysmenorrhea)
• Fluid in the vaginal vault of foul odor or whitish grayish in color. (Pelvic Inflammatory Disease)
• Associated dysuria, dyspareunia, dyschezia, infertility, nodularity, adnexal masses, tenderness (endometriosis, non-gynecological etiology)[19]
• Abnormal bleeding with the enlarged symmetrical uterus (Adenomyosis)
• Abnormal bleeding with the enlarged asymmetrical uterus (Fibroids)
• Obstructive anatomical abnormalities and history of other congenital anomalies
• Pelvic masses (fibroids, neoplasms, ovarian cysts)[20][21]

Evaluation

Primary dysmenorrhea is diagnosed, depending upon the history and physical examination.

1. A pelvic examination is important for evaluating dysmenorrhoea if the history of onset and duration of lower abdominal pain suggests secondary dysmenorrhoea or if the dysmenorrhea is not responding to medical treatment.[21]
2. The use of ultrasound in the evaluation of primary dysmenorrhea has little significance. However, ultrasound can be useful in differentiating secondary dysmenorrhea and causes that include endometriosis and adenomyosis.[8][21] Secondary dysmenorrhoea affects all women any time after menarche, while it can happen as a new symptom for females in their 30s or 40s. It can be associated with different intensity of pain and other symptoms such as dyspareunia, menorrhagia, intermenstrual, postcoital bleeding. 
3. The pregnancy tests using urinary human chorionic gonadotropin (B-HCG) are useful in history suggestive of suspected pregnancy.
4. Patients who are at risk of sexually transmitted infections (STIs) or when pelvic inflammatory disease (PID) is suspected will need endocervical or vaginal swabs.[8][21]
5. If indicated by clinical examination and history, to rule out suspected malignancy cervical cytology samples may be required.
6. Magnetic resonance imaging (MRI) or Doppler ultrasonography may be required if torsion of adnexa, adenomyosis, or deep pelvic endometriosis is suspected or if there are inconclusive findings on the transvaginal ultrasonography.[21]
7. Laparoscopy may be indicated when all the non-invasive investigations have been carried out and the cause remains unknown.

Treatment / Management

Pharmacological Treatment

Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered to be the first line of treatment for dysmenorrhea. NSAIDs are very effective in the treatment of dysmenorrhea in comparison to placebo or other therapy.[22] NSAIDs exert their benefit in the treatment of dysmenorrhea by inhibiting cyclooxygenase enzyme, thereby blocking prostaglandin productions.[23] In a systematic review comparing different NSAIDs to placebo in the treatment of dysmenorrhoea, Marjoribanks et al. concluded that no NSAIDs are safer or more effective than others.[24] However, there is evidence that around 20 percent of patients with dysmenorrhea do not respond to treatment with NSAIDs.[25] Fenamates (mefenamic acid) may have slightly better efficacy than the phenyl propionic acid derivatives (ibuprofen, naproxen) because fenamates have a dual action of blocking the production of PGs and inhibiting their action. [26][27] One study recommended ibuprofen and fenamates to be preferred in terms of safety and efficacy.[28] NSAIDs are still more effective compared to paracetamol. However, paracetamol is still a valid alternative where NSAIDs are contraindicated. Paracetamol with Caffeine and/or Pamabrom (short-acting diuretic) showed reduced pain.[29][30][31] COX-2 selective NSAIDs can be used, taking into consideration its cardiovascular side effects; besides, they are not more effective or tolerable than NSAIDs.[32] COX-2 selective NSAIDs and its PGs inhibition mechanism have been linked to delayed ovulation [33][34]

Oral contraceptive pills (OCPs)are reported effective in reducing the dysmenorrheic pain compared to placebo among adolescents.[35][36][37][38] Many other studies argued against the effectiveness of OCPs as a treatment for dysmenorrhea due to small sample sizes and limited comparative data.[39][40] OCPs have a mechanism by limiting endometrial lining growth. It decreases the production of prostaglandins.[22] Low levels of PGs are noted in the menstrual fluid of women on OCPs. Contraceptive pills users appeared to have significantly lower rates of dysmenorrhea and needed less additional analgesics.[10]

Progestin-only pills (POPs) are suitable more for patients with secondary dysmenorrhea related to endometriosis, whereas their effectiveness as a treatment for primary dysmenorrhea is not evident.[41][42][43] POPs mainly works by causing atrophy of the endometrial lining and by inhibiting ovulation.

Non-pharmacological Treatment

Maintaining an active lifestyle and a balanced diet that is rich in vitamins and minerals are generally recommended for better health outcomes. In particular, such diet and lifestyle are useful to reduce the intensity of the dysmenorrhea.[44][45][46]  

Though different types of exercise are generally recommended due to several health benefits and low or no risk, it also helps reduce the intensity of dysmenorrhea. No clear evidence about certain exercise activity or specific duration but moderate exercise is recommended, especially in obese women.[47]

Heat is effective compared to NSAIDs and seems to be preferred easy therapy option by many patients with no side effects. Still, high-quality studies needed.[48][49]

Food supplements, complementary or alternative medicine such as plant-based therapy, Chinese medicine, and supplements are being used for dysmenorrhea. Further, they are not regulated by the FDA. Overall there is insufficient evidence to recommend the use of any of the other herbal and dietary therapies.[50] The effectiveness of acupuncture is supported by a few studies which lack active comparisons and lack sound methodological techniques.[51][52][53]

Differential Diagnosis

Differential diagnosis of dysmenorrhea is broad, and it can be listed as gynecological conditions and non-gynecological conditions:[54] 

Gynecological conditions:

• Endometriosis
• Obstruction of the reproductive tract: Imperforate hymen, transverse vaginal septum, vaginal agenesis, OHVIRA syndrome (uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis), cervical stenosis.
• Functional and nonfunctional adnexal cysts: Nonfunctional adnexal cysts include para tubal and para ovarian cysts, endometrioma, benign ovarian cysts such as benign cystic teratoma and benign serous or mucinous cystadenoma, and the rare cases of ovarian borderline or malignant tumors (germ cell, granulosa cell, or epithelial tumors).
• Adnexal torsion
• Adenomyosis
• Pelvic inflammatory disease / sexual transmitted infections
• Endometrial polyps
• Asherman syndrome
• Ectopic pregnancy
• Chronic pelvic pain
• Membranous dysmenorrhea

Non-Gynecological conditions: (gastrointestinal, urological, and musculoskeletal)

• Irritable bowel syndrome
• Urinary tract Infections
• Interstitial cystitis
• Musculoskeletal causes: abdominal wall muscles, the abdominal wall fascia, the pelvic and hip muscles, the sacroiliac joints, and the lumbosacral muscles

Prognosis

Dysmenorrhea has been associated with a major impact on woman's day to day life. Such impact is reflected in the rates of absenteeism from school or work. Dysmenorrhea could also limit women's participation in sports or social events. Furthermore, there are associated emotional stressors associated with dysmenorrhea. Dysmenorrhea is a public health matter that has an economic impact. Only in the United States, it is estimated to be around 140 million working hours per year.[55] However, with the recommended treatment options, the prognosis for primary dysmenorrhea is generally good. Mild and moderate dysmenorrhea usually responds well to NSAIDs. Severe dysmenorrhea still responds to NSAIDs but may require higher doses or using combination/adjuvant therapy. In the case of persistent dysmenorrhea, the secondary causes of dysmenorrhea should be investigated. Prognosis of secondary dysmenorrhea will depend on the type, location, and severity of the cause.

Complications

Primary dysmenorrhea complications can be summarized by the intensity of the pain affecting the women's wellbeing and their daily activities. Since primary dysmenorrhea is not linked to any pathology or disease, there are no known complications. In contrast, secondary dysmenorrhea complication varies depending on the etiology. Complications may include infertility, pelvic organ prolapse, heavy bleeding, and anemia.[18][56]

Deterrence and Patient Education

Balanced, healthier nutrition reduces the severity of dysmenorrhea.[57] Therefore, it is important to educate and create awareness among young women about the importance of proper balanced nutrition to prevent and reduce dysmenorrhea complications. Vitamins and dietary modifications have been associated with reduced menstrual pain.[45][58][59][58] 

More regular physical activity is effective in reducing dysmenorrhea complications. Exercise acts as non-specific analgesia by improving pelvic blood circulation and stimulating the release of beta-endorphins. The primary goal of treatment is to reduce the pain and improve the quality of life of patients suffering from dysmenorrhea. Hence analgesics should be given appropriately to allow women to perform there day to day chores. For those patients having dysmenorrhea along with heavy menstrual bleeding, endometrial ablation may be an option. Patients should be asked to follow up with their clinicians when dysmenorrheic symptoms are uncontrollable and bothersome.

Enhancing Healthcare Team Outcomes

The patient should be counseled appropriately regarding primary dysmenorrhea and complications associated with secondary dysmenorrhoea. The management of a patient with dysmenorrhea depends on the severity and will require an interprofessional team. The management should focus on making the patient comfortable with the treatment so that they can continue without restrictions there day to day activities.

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

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