Approach to dysmenorrhoea in primary care

Opening Vignette

Ms. Lim is a 14-year-old girl who visited your clinic with her mother. She complained of lower abdominal cramps that were worse at the start of her menstrual cycle. She is a cross-country runner, but the pain has been limiting her participation in sports activities. Additionally, she has had to take sick leave from school almost every month due to the pain. She has tried heat therapy and paracetamol with minimal symptomatic improvement. Her mother asked if there were any other treatments available, as she was concerned that her daughter’s grades would be affected owing to the frequent absenteeism. She was also worried this might impact her daughter’s future fertility.

WHAT IS DYSMENORRHOEA?

Dysmenorrhoea refers to recurrent pelvic pain related to menstruation. It can be categorised into two groups: primary and secondary. Primary dysmenorrhoea occurs without any pathological cause whilst secondary dysmenorrhoea occurs as a result of a pelvic pathology or medical condition.[1]

Dysmenorrhoea occurs when there is excessive secretion of endometrial prostaglandin F2 alpha.[2] This results in uterine hypercontractility with consequent uterine muscle hypoxia and ischaemia.[3] Central sensitisation may also play a role in primary dysmenorrhoea. This occurs when repeated episodes of dysmenorrhoea result in an increased pain response within the central nervous system.[3]

HOW COMMON IS THIS IN MY PRACTICE?

Dysmenorrhoea is the most common gynaecological condition in women of childbearing age[1] and can be associated with significant morbidity. The prevalence of dysmenorrhoea varies from 45% to 95%, worldwide.[3] In Singapore, it was reported by 83.5% of adolescent females aged 12–19 years.[4]

Dysmenorrhoea has been found to have a significant negative impact on schooling, work life and interpersonal relationships, resulting in poorer quality of life.[3] It is the main reason for repeated short periods of school and work absenteeism.[3] In Singapore, almost one in four girls reported time-off from school.[4] This is similar abroad, where 10%–30% of women who are working or studying lose 1–2 days a month due to dysmenorrhoea.[3] It has also been associated with poorer mental health, including depression and anxiety.[5]

Despite the high prevalence and significant impact of dysmenorrhoea, many individuals either do not seek medical attention or undertreat with over-the-counter medications.[2,4] Adolescent patients and their caregivers may feel that pain is ’normal’ and medications are unnecessary.[4] Some reasons for this include a lack of knowledge on dysmenorrhoea and its available treatments, misconception regarding what is normal and a lack of awareness of the potential consequences of non-diagnosis and treatment.[4,6] Primary care physicians are well positioned to explore and provide evidence-based education and management for this condition, as many patients present to primary care clinics.

WHAT CAN I DO IN MY PRACTICE?

Given the potential implications of dysmenorrhoea, it is necessary to adopt a holistic approach. This includes exploring for associated symptoms, taking a complete menstrual and sexual history and performing a focused physical examination. This is then followed by patient education, investigations to rule out secondary causes and management that addresses the impact dysmenorrhoea has on the patient's life.

The initial step would be to determine if there is an underlying cause for the patient's symptoms. History taking should include evaluation of the menstrual symptoms and other systemic symptoms, impact on day-to-day living and quality of life, previous analgesia use and its effectiveness and any family history of dysmenorrhoea. Risk factors associated with dysmenorrhoea include a younger age at menarche, nulliparity and a positive family history of dysmenorrhoea.[1,7] Further details on history evaluation are illustrated in Box 1.

Box 1.

Medical history to evaluate patients with dysmenorrhoea.[7]

Menstrual history

Onset of menarche

Onset and characteristics of dysmenorrhoea (including timing of pain during menstrual cycle, radiation and frequency of pain)

Duration of menstruation

Amount of bleeding

Irregular or regular pattern of menstruation

Previous treatment methods and response

This includes any analgesia, heat therapy, massage, exercises, complementary treatments

Sexual history

History of sexual activity

History of sexually transmitted disease

Number of sexual partners

Use of contraception

History of sexual abuse or assault

Associated symptoms

Fever, mucopurulent vaginal discharge

Deep dyspareunia

Urinary: dysuria, haematuria, frequency, urgency

Gastrointestinal: vomiting, diarrhoea, bloody stools, weight loss, constipation

Musculoskeletal: focal abdominal tenderness, recent strain or participation in sports

Family history of endometriosis/adenomyosis

Impact of dysmenorrhoea

Extent of impairment on work, school and activities

Psychosocial history.

Mental health (anxiety, depression), substance abuse

Patients with a history suggestive of primary dysmenorrhoea but have never been sexually active should not undergo a vaginal examination.[1,7] However, a rectal examination can elicit general tenderness, tender nodules along the uterosacral ligaments or recto-vaginal septum or pelvic masses. For those who are or have been sexually active, both vaginal and rectal examination should be performed. A bimanual examination of the uterus should be performed to identify its size, texture, position, presence of tenderness, masses and whether it is fixed or mobile. The adnexa and uterosacral ligaments should also be examined for any tenderness or nodularity.[7] A speculum examination may identify a nodule, vaginal or cervical discharge as well as uncommon anatomical abnormalities such as a vaginal septum, which can cause partial outflow tract obstruction. Most patients with primary dysmenorrhoea, however, will have a normal pelvic examination.

Figure 1 illustrates the evaluation process for patients who present with dysmenorrhoea.

Figure 1.

Flowchart summarises the evaluation and management of a patient with dysmenorrhoea. ^aAntibiotic regimen: Intramuscular ceftriaxone 500 mg once, with oral doxycycline 100 mg twice a day and oral metronidazole 400 mg twice a day for 14 days. ^bPatients not suitable for outpatient antibiotics include those with suspected pelvic abscess, those with inability to take oral medications due to nausea and vomiting, immunosuppressed individuals, those with a poor response to previous antibiotics and those who have inability to arrange for review 72 h after initiation of treatment. COCPs: combined oral contraceptive pills, ED: emergency department, NSAIDs: nonsteroidal anti-inflammatory drugs

WHAT RED FLAGS TO LOOK OUT FOR?

Patients with the following red flags should undergo prompt evaluation for secondary causes of dysmenorrhoea.

1. Dysmenorrhoea with poor response to nonsteroidal anti-inflammatory drugs (NSAIDs) or hormonal contraception after three cycles[2]

2. Patients in whom dysmenorrhoea started more than 2 years after the onset of menarche or who present with progressively worsening dysmenorrhoea[8]

3. Pelvic mass or abnormal vaginal or rectal examination

4. Symptoms suggestive of secondary dysmenorrhoea, such as abnormal uterine bleeding (menorrhagia and intermenstrual bleeding), mid-cycle or acyclic pain, deep dyspareunia, subfertility and mucopurulent vaginal discharge

5. Family history of endometriosis or adenomyosis

6. Renal, spine, cardiac or gastrointestinal anatomical anomalies, as these can be associated with gynaecological structural anomalies[8]

PRIMARY DYSMENORRHOEA

Primary dysmenorrhoea frequently begins 6–12 months after menarche, when cycles become ovulatory.[3] The pain in primary dysmenorrhoea is typically worse on the first day of the menstrual cycle and usually subsides within 2–3 days. It may radiate to the back or down the legs. Other associated symptoms include nausea, vomiting, abdominal bloating and migraine.[3] The patient with primary dysmenorrhoea will typically have normal physical examination and tend to respond to NSAIDs.

TREATMENT

Treatment for primary dysmenorrhoea includes non-pharmacological, pharmacological and surgical methods. The patient's mood should also be explored.

Non-pharmacological or complementary therapies

While there is limited high-quality evidence for non-pharmacological management of patients with primary dysmenorrhoea, several options can still be considered. These methods may also encourage self-empowerment. It is also necessary to educate the patients to equip them with medical knowledge associated with their symptoms, which may in turn improve adherence to medication and decrease pain.[8]

Heat therapy

Topical heat applied to the lower abdomen has been shown to reduce pain intensity, compared to placebo.[9] This is easily available as heat packs or heated water bottles.[1] It is thought that the topical heat activates thermoreceptors and reduces the response to nociceptors, consequently reducing pain signals to the brain.

Exercise

While there is limited quality evidence for exercise, it is unlikely to be harmful and can benefit physical health. Of the different exercise intensities, low-intensity exercise has been shown to have the greatest benefit in reducing dysmenorrhoea and improving overall quality of life.[9] Such exercises include yoga and stretching.

Transcutaneous electrical nerve stimulation/acupuncture/traditional Chinese medicine

There is some evidence for the use of transcutaneous electrical nerve stimulation and acupuncture in improving dysmenorrhoea. However, the trial findings are limited by small numbers.[7,8,10] Similarly, traditional Chinese medicine has also been shown to have some benefit in small studies. However, evidence evaluating the adverse effects of these medications is limited.[11] Cautionary advice should be given to patients who wish to try these options, as there is limited data regarding their efficacy and adverse effects.

Diet

There may be a potential for certain supplements such as ginger, fish oil, magnesium and vitamin B1 in improving dysmenorrhoea.[12] However, the evidence is limited to small studies.

Behavioural interventions

Behavioural techniques such as biofeedback, as well as cognitive behavioural therapy such as relaxation training and desensitisation, may be used as adjuncts to pharmacological treatments.[1]

Pharmacological treatment

Nonsteroidal anti-inflammatory drugs

NSAIDs are the first-line treatment and have been shown to be more effective than paracetamol.[13] They inhibit the cyclooxygenase pathway, preventing the formation of prostaglandins.[2] A Cochrane review found no superiority between the different NSAIDs; therefore, doctors are encouraged to opt for the most cost-effective option, usually ibuprofen or mefenamic acid.[13] To be most effective, patients should take NSAIDs 1–2 days before the start of the menstrual cycle. If a patient has irregular cycles and is unable to predict the start date, NSAIDs should be taken on the first day of their menstrual cycle and stopped when symptoms resolve, typically around day 2 or 3.[2] Patients can be advised to take a loading dose followed by regular dosing, as this has been shown to improve dysmenorrhoea to a greater extent compared to only a regular dose regimen [Table 1].[2] NSAIDs should be taken with meals to reduce the risk of adverse gastric side effects. Avoid use of NSAIDs in patients with comorbidities such as asthma, peptic ulcer disease, cardiovascular diseases or renal impairment. Specific cyclooxygenase isoform 2 (COX-2) inhibitors may be used in those with known peptic ulcer disease. If one agent does not work, consider trying a different one.[8]

Table 1.

Suggested nonsteroidal anti-inflammatory drugs dosing regimen for primary dysmenorrhoea.[2]

Medication	Dosage
Ibuprofen	Loading dose 800 mg, followed by 400–800 mg every 8 h as needed
Naproxen sodium	Loading dose 440–550 mg, followed by 220–550 mg every 12 h as needed
Mefenamic acid	Loading dose 500 mg, followed by 250 mg every 6 h as needed
Celecoxib	Loading dose 400 mg, followed by 200 mg every 12 h as needed

Hormonal treatment

Hormonal treatments that can be considered include combined hormonal contraception (CHC) and progestin-only contraceptives, including depot medroxyprogesterone acetate (DMPA), etonogestrel subdermal implant (Nexplanon^®) and the levonorgestrel-releasing intrauterine system (Mirena^®).

Combined hormonal contraception, which includes combined oral contraceptive pill and patch, may be used as the second-line treatment in those who fail to respond or are unable to tolerate NSAIDs. However, this can be the first-line treatment for those requiring concomitant contraception. The hormones released suppress ovulation and reduce endometrial growth, thereby reducing prostaglandin secretion.[2,14] CHC has been shown to improve pain, with no difference found between the different preparations.[14] When used in continuous or extended regimens (more than 28 days of active hormone), CHC may result in improved pain control compared to the traditional cyclical regimen (21 days of active hormone with seven hormone-free days).[1,15] It is, therefore, reasonable to consider switching a patient to a continuous or extended regimen if she does not show improvement in her symptoms while on cyclical therapy.[15]

Progestin-only contraceptives may provide pain relief by inducing endometrial atrophy. This option is particularly useful in patients with contraindications to the oestrogen component of CHCs, such as high body mass index (BMI) or the risk of thrombosis. There is evidence that DMPA, Nexplanon and Mirena may alleviate dysmenorrhoea.[1,2] These methods may be considered in patients who desire long-term reversible contraception, have contraindications to oestrogen or desire the convenience of long-acting treatment.

Surgical options

Most women will experience improvement in symptoms with either non-pharmacological or pharmacological treatment. However, those who show no improvement should be referred to a gynaecologist for further evaluation. If primary dysmenorrhoea continues, the patient may be referred to a chronic pain team for a multidisciplinary approach to optimise analgesia through a biopsychosocial model. Two main surgical techniques have been reported: uterosacral nerve ablation and presacral neurectomy. While both can be performed laparoscopically, they are not common procedures. Evidence to support these approaches in the long term is limited, with adverse effects reported.[1,8] If symptoms remain refractory, patients who have completed their family or do not desire to have children may be offered hysterectomy after a successful trial of a gonadotropin-releasing hormone agonist.

FOLLOW-UP MANAGEMENT FOR PRIMARY DYSMENORRHOEA

Patients with presumed primary dysmenorrhoea should be monitored for response to treatment, as this would support the diagnosis. If there is no improvement in symptoms within 3–6 months of treatment, the clinician should evaluate for treatment adherence and secondary causes of dysmenorrhoea, such as obstructive structural causes.[8] Pelvic imaging is recommended.

DYSMENORRHOEA AND MOOD

Dysmenorrhoea has also been shown to be associated with psychological disorders such as depression and anxiety.[5] This relationship can be bidirectional.[3] Dysmenorrhoea may contribute to the development of psychological disorders due to the pain experienced. Conversely, patients with concomitant psychological disorders may have greater sensitivity to pain, exacerbating dysmenorrhoea. It is, therefore, important to explore the impact of dysmenorrhoea on the patient's mental well-being, with appropriate follow-up and psychologist support.

SECONDARY DYSMENORRHOEA

Secondary dysmenorrhoea usually begins a number of years after menarche.[3] It can be further subdivided into gynaecological and non-gynaecological causes [Table 2]. Endometriosis and adenomyosis are the most common gynaecological causes. This is also more likely to occur in societies where childbearing is delayed and eschewed. A quick reference guide to the diagnosis and management of endometriosis can be found here: https://virtual.miceneurol.com/protocol.pdf. Non-gynaecological causes may arise from the genitourinary, gastrointestinal or musculoskeletal systems.

Table 2.

Causes of secondary dysmenorrhoea and their characteristics.[1,7]

Condition	History	Examination	Evaluation
Endometriosis	Cyclical or non-cyclical pain Associated with deep dyspareunia, dyschezia (rectal pain during defaecation), haematochezia, dysuria, fertility issues Risk factor: family history of endometriosis	Fixed or retroverted uterus, adnexal mass Uterosacral nodularity Vaginal nodules	Transvaginal or pelvic ultrasound Diagnostic laparoscopy with biopsy (gold standard)
Adenomyosis	Associated with menorrhagia, intermenstrual bleeding	Enlarged, bulky uterus with possible tenderness	Pelvic ultrasound
Leiomyoma	Submucous type associated with menorrhagia Rarely causes urinary retention	Enlarged, irregular, mobile uterus	Pelvic ultrasound
Pelvic inflammatory disease	More likely to present with chronic pain as a result of pelvic adhesions and consequent subfertility Acute cases can be associated with fever, abnormal mucopurulent vaginal discharge but may be asymptomatic Risk factors include sexually active individuals, multiple sexual partners, history of STDs	Uterine and/or adnexal tenderness Cervical motion tenderness	Vaginal swab to evaluate for Chlamydia trachomatis or Neisseria gonorrhoeae infection Pelvic ultrasound (may be associated with infected endometrioma)
Reproductive tract anomalies (Mullerian obstructive anomalies)	Cyclical pelvic pain close to menarche May have irregular menstrual cycles Associated with urinary retention, constipation, back pain, urinary frequency	Abdominal mass Duplicated vagina and cervix	Pelvic ultrasound or MRI
Interstitial cystitis	Associated with urinary symptoms, for example, urgency, frequency	Pelvic examination is normal	Urinalysis Cystoscopy
Gastrointestinal diseases, e.g. IBD, constipation	Associated with gastrointestinal symptoms, for example, bloody stools, constipation, weight loss	Pelvic examination is normal	Colonoscopy
Musculoskeletal	Active participation in sports	Focal tenderness on abdominal wall Carnett’s test may be positive	None required

IBD: inflammatory bowel disease, MRI: magnetic resonance imaging, STDs: sexually transmitted diseases

Pelvic imaging with ultrasonography is the initial imaging modality of choice to evaluate for gynaecological causes of secondary dysmenorrhoea.[8] Transvaginal ultrasound is less influenced by body habitus and bowel shadows, and can identify pelvic pathology better than transabdominal ultrasound. However, the former is not suitable for patients with an intact hymen. Ultrasound scans done on day 2 or 3 of the menstrual cycle may avoid physiological changes that may be interpreted as pathology such as follicle development.

TAKE-HOME MESSAGES

1. Dysmenorrhoea may negatively affect women's quality of life. Primary care physicians are well positioned to proactively explore the symptoms and provide appropriate education and management.

2. In the initial evaluation of dysmenorrhoea, it is important to determine if it is primary or secondary in nature. If secondary dysmenorrhoea is suspected, the patient should be referred to a gynaecologist for further evaluation.

3. Holistic approach of patients with dysmenorrhoea includes symptomatic treatment as well as consideration of the psychosocial issues that often accompany the disorder.

4. NSAIDs are the recommended first-line treatment for primary dysmenorrhoea. Combined hormonal or progesterone-only contraceptives can be used in those who desire contraception.

5. Most adolescents will have primary dysmenorrhoea. Referral to a gynaecologist should be considered if symptoms do not improve with treatment after three menstrual cycles, as these patients are more likely to be diagnosed with an organic cause.

Closing Vignette

You evaluated Ms. Lim further and found no history or risk factors suggestive of secondary dysmenorrhoea. A patient health questionnaire-2 screen for depression was negative. You prescribed her with mefenamic acid (500 mg initial dose, followed by 250 mg every 6 h) and advised her to start the tablets 1–2 days before her menstrual cycle. She asked if there was anything else she could do besides medications to improve her pain. You advised her to continue heat therapy and exercise and guided her through some relaxation techniques that can be used for self-management. You reviewed her again 2 months later, and she reported significant improvement of her menstrual pain and she had not had to miss a day of school in the past 2 months. You advised her to continue with the current treatment and to return in the event of any recurrence or worsening dysmenorrhoea.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 10 April 2023

Question	True	False
1. Dysmenorrhoea can be subdivided into two main categories, primary and secondary.
2. Excessive secretion of endometrial prostaglandin causes dysmenorrhoea.
3. Initial approach to dysmenorrhoea involves determining if it is likely primary or secondary in nature.
4. Patients who have never been sexually active should undergo a vaginal examination for evaluation of dysmenorrhoea.
5. Most patients with primary dysmenorrhoea will have a normal pelvic examination.
6. A holistic approach including symptomatic management, patient education and addressing the impact on the patient’s quality of life is required in managing dysmenorrhoea.
7. Heat therapy has not been shown to improve dysmenorrhoea.
8. Patients who have previously tried nonsteroidal anti-inflammatory drugs (NSAIDs) or hormonal contraception for at least three menstrual cycles with no signs of improvement of dysmenorrhoea should continue to trial other methods of treatment.
9. A patient who presents with dysmenorrhoea 10 years after menarche with no family history is likely to have primary dysmenorrhoea.
10. Menstrual cycle abnormalities suggestive of secondary dysmenorrhoea include abnormal uterine bleeding such as menorrhagia or intermenstrual bleeding, as well as mid cycle or acyclic pain.
11. The first line pharmacological treatment for primary dysmenorrhoea is NSAIDs.
12. Celecoxib is superior compared to other NSAIDs in the management of dysmenorrhoea.
13. Combined hormonal contraception can be used as the first line treatment in primary dysmenorrhoea in those who also require contraception.
14. A patient with a history of a previous thrombotic event can be trialled on combined hormonal contraception for management of dysmenorrhoea.
15. Relaxation training may be used as an adjunct to pharmacological treatment of dysmenorrhoea.
16. The relationship between dysmenorrhoea and psychological disorders may be bidirectional.
17. Reproductive tract anomalies are the most common gynaecological cause of secondary dysmenorrhoea.
18. Pelvic imaging with ultrasonography can be used as the initial imaging to evaluate for gynaecological causes of secondary dysmenorrhoea.
19. Endometriosis may present with deep dyspareunia, dyschezia and subfertility.
20. Endometriosis and adenomyosis are the most common causes of secondary dysmenorrhoea.