Dysmenorrhea - Guidelines for Prescribing NSAIDs

Description of Dysmenorrhea
  • Dysmenorrhea is painful cramping, usually in the lower abdomen, occurring shortly before and/or during menstruation.
    • Primary dysmenorrhea occurs in the absence of any identifiable underlying pelvic pathology.
    • Secondary dysmenorrhea is associated with underlying pelvic pathology (such as endometriosis, fibroids, or endometrial polyps).
  • Dysmenorrhea occurs in ovulatory cycles.  Prostaglandins are released during endometrial cell lysis, which occurs just prior to menstruation, and have a direct effect on the endometrium  and surrounding tissues, resulting in the signs and symptoms of dysmenorrhea. 
  • Women with dysmenorrhea generally have a higher concentration of PGF2 alpha and PGE2  in their menstrual fluid than women who do not complain of pain on menstruation. Women with dysmenorrhea have increased uterine activity, resulting in increased resting tone, increased strength and frequency of contractions and /or dysrhythmic contractions. 
  • Dysmenorrhea usually begins 6 to 12 months after menarche and only occurs with ovulatory cycles.
  • Primary dysmenorrhea is most common in young women and less so in women beyond their late 20's.  This decrease in incidence and severity may be related to pregnancy because, during late pregnancy, uterine adrenergic nerves virtually disappear and only a portion regenerate after childbirth.
  • Secondary dysmenorrhea is painful menstruation caused by another condition, such as endometriosis, pelvic inflammatory disease, fibroids, or incorrect IUD insertion.
  • Dysmenorrhea is the most common gynaecological symptom reported by women. It affects between 50% and 90% of menstruating women. The wide variation in reported prevalence rates is probably due to differences in definition.
    • In a longitudinal survey of 404 nurses with primary dysmenorrhea, mild symptoms were present in 53%, moderate symptoms in 20%, and severe symptoms in 2%.
    • May cause absence from school or work; 13-51% of women report ever having been absent and 5–14% report being frequently absent because of dysmenorrhea.
  • Despite the high prevalence of dysmenorrhea and the impact it has on quality of life and general well-being few women seek medical treatment for dysmenorrhea.
  • For more information, go to:
    • e-therapeutics+ . Sexual Health: Dsymenorrhea. Available at SHIRP.
    • Emedicine - Dysmenorrhea
Signs and Symptoms
  • Lower midabdominal or suprapubic pain, which is cramping in nature.
    • Pain may radiate to the lower back and upper thighs.
    • Primary dysmenorrhea pain lasts from a few hours to between 48 and 72 hours
  • Associated symptoms include nausea and vomiting, fatigue, diarrhea and headache.
  • Risk factors for primary dysmenorrhea:
    • Age <30
    • BMI <20
    • Early menarche (<12 years)
    • Longer cycles and duration of bleeding
    • Heavy or irregular menstrual flow
    • Smoking
Differential Asssessment

DIFFERENTIATE PRIMARY AND SECONDARY DYSMENORRHEA

  • Primary dysmenorrhea
    • Usually starts 6 to 12 months after menarche, once cycles are regular.
    • Pain often starts shortly before onset of menstruation and lasts for up to 72 hours, improving as the menses progresses.
    • Other gynaecological symptoms are not usually present.
    • Non-gynaecological symptoms, such as fever, nausea, vomiting, fatigue, diarrhea or headache, may be present.

  • Secondary dysmenorrhea:
    • Menstrual pain appearing after two years or more of painless periods.
      • Can rarely occur right after menarche, due to uterine outlet obstruction.
    • Pain persisting after menstruation finishes; or present throughout the menstrual cycle, but exacerbated by menstruation.
    • Other gynaecological symptoms present (for example, dyspareunia , menorrhagia, intermenstrual bleeding, vaginal discharge, postcoital bleeding)
    • Common causes: endometriosis, fibroids, pelvic inflammatory disease
    • Insertion of intrauterine device within last 6 months
    • Rectal pain or bleeding may indicate recto-vaginal endometriosis.

  • Rule out pregnancy
    • Miscarriage  and ectopic pregnancy can present with new onset of pain and bleeding

OTHER CONDITIONS WHICH CAN CAUSE SIMILAR PAIN

  • Abnormal uterine structure
    • Unilateral or non-midline pain occuring around time of menses.  This is usually benign, but should be investiaged by a physician
  • Adenomyosis
    • A condition causing dysmenorrhea, menorrhagia, and an enlarged uterus.  This is possible if there is unusual heavy bleeding, and is more common in older women (40-50) 
  • Cystitis
    • A bladder infection which can cause pain similar to dysmenorrhea, but there will urinary symptoms as well, such as urinary frequnecy, urgency, pain or blood in the urine.  Symptoms will not be related to the timing of menstruation.
  • Ectopic pregnancy or miscarriage
    • Unexpected cramping or abdonrmal vaginal bleeding could indicate an ectopic pregnancy or miscarriage.  This would also present with recent menstrual irregularities.
  • Endometriosis
    • Causes menstural pelvic pain, similar to dysmenorrhea, but also occurs outside of menstruation.  Dyspareunia, dyschezia (difficult or painful defication), progressively worsening symptoms, or non-response to NSAIDs are clues for this.
  • Uterine fibroids
    • May cause mild dysmenorrhea, but also dyspareunia and non-cyclic pelvic pain.
  • Inflammatory bowel disease
    • May cause abdominal cramping similar to dysmenorrhea, but will also present with diarrhea and be non-cyclical.
  • Irritable bowel syndrome
    • May cause abdominal pain similar to dysmenorrhea, but will not be cyclical and will also present with diarrhea or constipation.
  • Pelvic inflammatory disease
    • Pain is similar to dysmenorrhea and occurs around time of menses.  However, there will be other symptoms: abnormal uterine bleeding, vaginal discharge, fever or chills, and symptoms that worsen with motion, exercise or intercourse.
When to Refer

Patients with symptoms and history typical of dysmenorrhea often do not require further investigation, however a physician assessment should be recommended in the following situations:

  • Secondary dysmenorrhea suspected
  • Red flag symptoms
    • New onset of pain with bleeding in patient with history of pain-free periods, especially if over age 25.
    • Persistent bleeding between periods
    • Patient reports palpable abdominal or pelvic lump
    • Pain occurs outside first 3 days of menses
    • Changes in severity or pattern of the pain and menstrual fluid (flow, odour, colour)
    • Non-midline pain, or unilateral pain

  • Previous trial of proven therapy has failed (ensure it was taken optimally)
  • Comorbidities such as GI disorders, renal or hepatic disease if NSAID therapy is being considered.
Treatment

Non-pharmacological Measures:

  • Regular aerobic exercise
  • Yoga
  • Application of local heat to the lower back or abdomen
  • Smoking cessation

OTC Options:

  • Vitamin B1 100 mg/day for 3 months shown to be effective for reducing pain (1 large randomized trial only).
  • Magnesium has 3 small trials demonstrating modest benefits over placebo, but optimal dosing is unknown.  360mg starting three days before the period has been used.
  • Fish oils, with a total daily dose of 1000mg of EPA and 720mg DHA, has some evidence for effectiveness.  Takes up to 3 months of treatment to gauge effect.
  • Calcium and Vitamin E are not effective.
  • Acetaminophen may be helpful for mild symptoms but is not as effective as NSAIDs (other than ASA) (low quality evidence).
  • ASA is not as effective as other NSAIDs (low quality evidence).
  • OTC NSAIDs can be recommended for dysmenorrhea which does not restrict normal activities.

Prescription Drug Options:

  • NSAIDS are first choice for dysmenorrhea, effective in about 80% of cases.(Level 2 [mid-level] evidence.) See Products - Table 1.
    • NSAIDS have anti-inflammatory and analgesic activity. They inhibit the cyclo-oxygenase (COX) enzymes responsible for prostaglandin synthesis.
      • NSAIDs at prescription strengths are appropriate for moderate to severe symptoms which necessitate absence from school or work.
      • Insufficient evidence to indicate whether any individual NSAID is more effective than any others.
      • Mefenamic acid may have an advantage, as it not only inhibits the formation of prostaglandins but can also block prostaglandins at the receptor site, however the clinical significance of this has been questioned.

  • Choice of an NSAID can be based off what a patient has successfully used before
  • With short term use side effects of all NSAIDS are generally minor in patients without contraindications.
  • An initial loading dose of (one and one-half to double the usual single dose may provide faster relief. The loading dose should be followed by the usual recommended dose until symptoms resolve.
  • An alternative recommendation is to begin the NSAID at the onset of menses or perhaps even the day before and continue treatment around the clock for 2 to 3 days instead of waiting until symptom onset. 
  • Patient should experience reduction in or absence of pelvic pain related to menses within three menstrual cycles of therapy. 
  • If pain relief is inadequate a second NSAID of a different class can be substituted and reviewed after three cycles.
  • In refractory cases a combination of NSAID and oral contraceptive may be effective. Review after 2 - 3 cycles.  Around 10% of patients may not respond to combination treatment with NSAIDS and oral contraceptives.
  • Oral contraceptives are up to 90% effective in relieving dysmenorrhea symptoms; consider referral to MD if this is a more desirable option for the patient

  • Lactation: Ibuprofen is first choice because it has very low levels in breast milk, a short half-life and is officially indicated as a treatment for fever and pain in infants. There is limited safety data on the use of other NSAIDs during lactation.

  • Cardiovascular and/or Cerebrovascular disease:

    • Treatment with NSAIDs must be undertaken with caution in patients with pre-existing cardiovascular disease (CVD) or cerebrovascular disease, or presenting risk factors for CVD. For these patients, treatment options other than non-steroidal anti-inflammatory drugs (NSAIDs) should be considered first.

      • CVD includes:
        • Myocardial infarction, angina, heart failure
        • Peripheral artery disease (eg. intermittent claudication)
        • Atherosclerosis

      • Cerebrovascular disease includes:
        • Stroke or transient ischemic attack

      • Risk factors include:
        • Age >65
        • Family history of premature cardiovascular disease
        • Uncontrolled hypertension
          • NSAIDs may raise blood pressure to a small degree and should be monitored during therapy, even if patient has controlled hypertension
        • Uncontrolled dyslipidemia
        • Diabetes
        • Kidney disease

      • Diclofenac and celecoxib are the highest risk NSAIDs and should never be recommendation in this population.
      • Naproxen has been found to be the lowest risk NSAID in patients with cardiovascular or cerebrovascular concerns.
      • Short-term use of NSAIDs still carries risk in this population.
  • Prescribe a quantity sufficient for 3-5 days of treatment, and may give up to three treatment cycles.  This would be an adequate trial duration.  May prefer to give enough for only one treatment cycle if concerned about adverse effects.
    • May also provide one refill (thus a total of 6 cycles of treatment)
Advice / Monitoring
  • Recommend appropriate non-pharmacological measures for all patients.
  • NSAIDs should be taken with a full glass of water to facilitate dissolution.
  • Encourage patients on NSAIDs to drink adequate fluids to maintain hydration (to prevent kidney dysfunction).
  • Taking NSAIDs with food is often recommended to prevent GI symptoms although there is no evidence this reduces the incidence of dyspepsia or ulceration.
  • If NSAIDS are used an improvement in pain should be observed within an hour of the first dose; if pain does not improve or worsens, consult your pharmacist or physician.
  • If patient not responding after 3 cycles, refer to physician for evaluation and consideration of hormonal therapy (e.g. oral contraceptive).

Assess Benefit

  • To gauge efficacy, see if these goals have been achieved:
    • Pain level tolerable?
    • No longer missing work or school (if applicable)?
    • Any general improvement?
  • If good response to prescription NSAIDs, advise patient to continue therapy for first few days of each cycle. Contact physician for authorization of refills or refer the patient to physician.
  • Remind patient to pre-dose the NSAIDs and use loading doses if appropriate.
  • Treatment should be continued for a 3-cycle trial before declaring non-response.
  • Non-responders should be referred for investigation of a secondary cause of dysmenorrhea such as endometriosis.
  • If only partial relief of symptoms, recommend / prescribe an NSAID from a different class or refer patient to physician for consideration of alternate or additional therapy (e.g. oral contraceptives).

Assess for Adverse Effects:

  • NSAIDs are generally well-tolerated for short-term therapy in young adults.
  • Mild GI upset - suggest small frequent meals, chewing gum or sucking lozenges.
  • Discontinue if persistent nausea / vomiting, ringing in ears, shortness of breath; unusual bruising or bleeding (mouth, urine, stool), skin rash, swelling of limbs; chest pain, or palpitations. Refer to physician.

 

Products

Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in the CPS (e-CPS), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).
This information should be routinely consulted before prescribing.

TABLE 1: NSAIDS COMMONLY USED FOR DYSMENORRHEA

DRUG

RECOMMENDED DOSE

MAXIMUM

Ibuprofen

200 – 400 mg every 4 to 6 hours
OR 600 – 800 mg three times daily as required

3200 mg/day

Mefenamic acid

500 mg initially , then 250 mg every 6 hours for 3-5 days. Not indicated for children < 14 years of age.

1250 mg/day with loading dose;
1000 mg/day subsequent days;
Max of 1 week therapy

Naproxen base*

500 mg initially, then 250 mg every 6 to 8 hours

1250 mg/day

Naproxen sodium DS*
(long acting)

220 - 540mg BID

1110 mg/day

Ketoprofen

25 – 50 mg TID-QID

300 mg/day

Diclofenac potassium§
  - Diclofenac K
  - Apo-Diclo Rapide 50
  - Voltaren Rapide
  - Teva-Diclofenac-K 

100mg loading dose, followed by 50mg every 6-8 hours

Max of 200mg on the first day which includes a loading dose; max of 100mg  per subsequent day

Flurbiprofen

50mg QID

200 mg/day


*220mg of naproxen sodium = 200mg naproxen base
§ Diclofenac sodium is NOT approved for dysmenorrhea

Prescribing and Billing Details
  • pseudoDIN: 00951095
    • Max of 2 claims per 365 days per patient

  • May prescribe sufficient quantity to treat up to three episodes of dysmenorrhea (three consecutive menstrual cycles).  Include a loading dose (if appropriate for chosen medication) and 5 days of treatment per menstrual cycle.  One refill can be given, for a total of six cycles of treatment per assessment.  
    • Example:  Diclofenac potassium 50mg, two tabs stat, then 1 tab q8h for 5 days.  Prescribe a total of 48 tablets with one refill (one cycle = 16 tablets. 4 tablets on day 1 (2 tablets for loading dose then 2 more tablets on day 1), then 12 tablets for remaining 4 days of q8h treatment; give three cycles).
    • If tolerability of chosen treatment is uncertain, may prefer to give only enough for one treatment cycle, then assess

  • If an OTC strength of ibuprofen is chosen (200mg or 400mg), it will NOT be eligible for the assessment fee.

  • Only products with an official indication from Health Canada for dysmenorrhea are considered for these guidelines.  Only the active ingredients in the "products" section are approved for pharmacist prescribing.  
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Mulherin, K.  Condition: Dysmenorrhea.  In: Minor Ailments. e-Therapeutics Complete [Internet]. Canadian Pharmacists Association. Available from: http://www.e-therapeutics.ca. (In Saskatchewan available through www.shirp.ca.)
  2. Burnett, M. Sexual Health: Dysmenorrhea. In: Therapeutic Choices. e-Therapeutics Complete [Internet]. Canadian Pharmacists Association. Available from: http://www.e-therapeutics.ca. (In Saskatchewan available through www.shirp.ca.)
  3. Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.: CD001751. DOI: 10.1002/14651858.CD001751.pub3.
  4. Latthe PM1, Champaneria R. Dysmenorrhoea. BMJ Clin Evid. 2014 Oct 21;2014. pii: 0813. http://www.ncbi.nlm.nih.gov/pubmed/25338194
  5. Smith, R. Treatment of primary dysmenorrhea in adult women. In: UpToDate. Available at www.uptodate.com by subscription.
  6. Dysmenorrhea. In: Mayo Clinic. www.mayoclinic.org. (Free access)
  7. Rx Files 9th edition – NSAIDS, COXIB and other analgesics comparison chart. Available at www.rxfiles.ca
  8. Lefebvre G, Pinsonneault O, Antao V et al. Primary dysmenorrhea consensus guideline. J Obstet Gynaecol Can 2005;27:1117-46.
  9. Kalis K, Rivlin M. Dysmenorrhea. In Emedcine online. Available at http://emedicine.medscape.com/article/253812-overview, Accessed November 2015.

Prepared by the medSask.
Reviewed by Dr. D.G. Bishop, Family Physician and Loren Regier, Pharmacist, RxFiles Academic Detailing Program
Funded by the Saskatchewan College of Pharmacists.
Posted May, 2010. Updated Feb 2016.