Every month, many women face an unexpected challenge - menstrual pain.
Apart from causing physical discomfort, it significantly influences daily life.
In this article, we will delve into the relevant knowledge and principles of menstrual pain, outlining effective treatments and support methods to provide comprehensive medical advice for patients.
I. Classification of Menstrual Pain:
Clinically, menstrual pain is divided into two main types: primary dysmenorrhea and secondary dysmenorrhea:
1. Primary Dysmenorrhea: Recurring, crampy lower abdominal pain during menstruation, not attributed to any identifiable disease. Common among teenagers and young women.
2. Secondary Dysmenorrhea: Similar pain symptoms occurring in women with conditions such as endometriosis, adenomyosis, or uterine fibroids. These conditions exhibit distinct clinical features like enlarged uterus, pain during intercourse, and resistance to medical treatments.
Caution is needed for individuals with the following medical history, as they might be at risk for secondary dysmenorrhea:
1. Onset of menstrual pain after the age of 25.
2. Abnormal uterine bleeding (excessive, irregular, or intermenstrual bleeding).
3. Non-midline pelvic pain.
4. Absence of nausea, vomiting, diarrhea, back pain, dizziness, or headaches during menstruation.
5. Experience of dyspareunia (painful intercourse) or dyschezia (painful defecation).
6. Progressive worsening of symptom severity.
II. Epidemiology and Physiology:
a. Prevalence and Impact:
Studies indicate that 50-90% of reproductive-age women globally experience painful menstrual periods.
This predominantly affects young women, with the prevalence of primary dysmenorrhea decreasing with age, while secondary dysmenorrhea tends to appear in older age.
Menstrual pain significantly impacts the education and work efficiency of young women, with an estimated global school absenteeism rate of 10-20% or higher due to menstrual pain.
A survey of over 32,000 Dutch women aged 15 to 45 revealed an average annual absenteeism of 1.3 days due to menstrual pain, leading to a decrease in productivity by an average of 23.2 days per year.
Insufficient diagnosis and treatment of menstrual pain underscore the importance of clinicians actively inquiring about this common condition.
b. Risk Factors:
Younger age (especially in teenagers), smoking, and stress are associated with primary dysmenorrhea.
There appears to be a familial tendency for primary dysmenorrhea.
Risk reduction is linked to a younger age at first childbirth, higher parity, and the use of hormonal contraceptives.
c. Pathophysiology:
Menstruation
-> Endometrial sloughing
-> Release of prostaglandins
-> Induction of uterine contractions
-> Increase in uterine pressure
-> Uterine pressure exceeding arterial pressure
-> Uterine ischemia
-> Accumulation of anaerobic metabolites
-> Stimulation of C-type pain neurons
-> Menstrual pain.
The activation of stretch receptors and central sensitization of pain-sensitive neurons may play a role in pain perception.
A case-control study with 60 participants indicated that individuals with severe menstrual pain have lower pain thresholds (abdomen, buttocks, and arms) and larger pain distribution areas during menstruation compared to those with mild or pain-free menstruation.
This observation suggests that, similar to patients with chronic pain, central sensitization may lead to heightened overall pain sensitivity, resulting in severe menstrual pain.
Multiple pieces of evidence support these hypotheses:
⁃ Higher concentrations of prostaglandin E2 and prostaglandin F2α in menstrual fluid and uterine tissue of primary dysmenorrhea patients correlate with pain severity.
⁃ Doppler ultrasound studies show increased uterine artery resistance indices (indicating higher uterine artery blood flow resistance) in primary dysmenorrhea compared to pain-free individuals during menstruation.
⁃ Patients with primary dysmenorrhea treated with nonsteroidal anti-inflammatory drugs (NSAIDs) show improvements over time, with decreases in uterine pressure/contraction force and prostaglandins in menstrual blood.
III. Treatment:
a. Baseline Intervention:
Firstly, we discuss self-care methods for pain relief, especially for those wishing to avoid drug treatments.
a1. Exercise:
A substantial body of evidence supports the role of regular exercise in alleviating menstrual pain. However, the optimal type, duration, and frequency of exercise for symptom relief remain unclear. Integrated analysis shows that exercise can reduce pain intensity and duration. The principle may involve increased progesterone and decreased pain mediators.
Given the various health benefits of exercise and low injury risks, increasing physical activity is a reasonable approach to reducing menstrual pain.
a2. Heat Therapy:
In randomized trials, applying heat to the lower abdomen effectively relieves menstrual pain. Heat exhibits effects similar to the pain reliever ibuprofen and is more effective than acetaminophen. While some may find heat therapy more cumbersome than oral medications, it has no side effects and can enhance the effectiveness of other treatments.
b. First-line Treatment
Nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen (Paracetamol), and hormonal contraceptives are the main methods of pharmacological treatment.
There are no randomized trials comparing the efficacy of NSAIDs and hormonal contraceptives in treating primary dysmenorrhea.
If the treatment with one medication fails after two to three months, we recommend trying another medication.
For patients who still experience symptoms with a single medication, the combination of hormonal contraceptives and NSAIDs may be effective. Additionally, if the treatment does not achieve the expected response, a reevaluation of the initial diagnosis is necessary.
b1. Non-hormonal Therapy
For patients who do not want to use hormonal contraceptives or wish to avoid hormonal treatment, we recommend nonsteroidal anti-inflammatory drug (NSAID) therapy. Acetaminophen (Paracetamol) is an alternative treatment for patients intolerant to NSAIDs.
b1.1. Nonsteroidal Anti-Inflammatory Drugs
Compared to placebo, NSAIDs are more effective in treating pain associated with dysmenorrhea.
Although concerns about side effects may arise, most side effects are mild.
• Choice of Medication: While meta-analysis and other studies have not reported significant differences in the efficacy of non-specific NSAIDs, a few researches suggest that fenamates (mefenamic acid, tolfenamic acid, flufenamic acid, meclofenamate, bromfenac) may be slightly more effective than phenylpropionic acid derivatives (ibuprofen, naproxen). Fenamates and phenylpropionic acid derivatives both inhibit the synthesis of prostaglandins, but fenamates also block the action of prostaglandins, which could explain their stronger effectiveness in some studies. A comprehensive analysis suggests that, compared to aspirin, fenamates and phenylpropionic acid derivatives can better alleviate pain.
b1.2. Acetaminophen (Paracetamol)
For patients intolerant to or unable to use NSAIDs but still wish to alleviate pain through medication, acetaminophen is a reasonable alternative.
Although NSAID therapy seems to be more effective in reducing pain, acetaminophen generally does not cause adverse gastrointestinal effects.
b2. Hormonal Contraceptives
For patients desiring contraception or willing to use contraceptive methods, we recommend using combined estrogen-progestin hormonal contraceptives (e.g., combined oral contraceptives, transdermal patches, or vaginal rings) or placing a levonorgestrel-releasing intrauterine device as the first-line choice. The choice of method ultimately depends on patient preferences related to dosage, cycle control, cost, availability, and side effects.
b2.1. Estrogen-Progestin Methods
Combined estrogen-progestin contraceptives containing synthetic progestin can inhibit ovulation and thin the endometrium over time.
A thinner endometrium contains less arachidonic acid, a precursor to most prostaglandins.
Due to these changes in the endometrium, estrogen-progestin contraceptives can reduce menstrual bleeding and uterine contractions, thus alleviating dysmenorrhea.
b2.2. Progestin-Only Methods
Pure progestin contraceptives may be an effective treatment since progestin induces endometrial atrophy, relieving dysmenorrhea.
However, this approach has not been as extensively studied as combined estrogen-progestin contraceptives.
The advantages of progestin-only contraceptives are their safe use in individuals with contraindications to estrogen contraceptives.
However, compared to combined contraceptives, progestin-only methods are more likely to cause side effects, especially irregular bleeding, and may not consistently suppress ovulation, which could be important in treating dysmenorrhea.
c. Second-line Treatment
c1. Transcutaneous Electrical Nerve Stimulation (TENS)
For patients who continue to experience pain despite the above measures, TENS is a reasonable option.
TENS is an alternative method for patients who cannot or do not want to use medications.
While TENS alone provides less pain relief compared to medications, combining TENS with other treatments can help reduce the dosage of pain medication.
It can also be combined with local heat therapy for optimal effectiveness.
Percutaneous Tibial Nerve Stimulation (PTNS) is a minimally invasive electrical stimulation therapy requiring weekly treatments for 12 consecutive weeks.
TENS is speculated to work through two possible mechanisms:
(1) sending a volley of afferent impulses through large-diameter sensory fibers of the same nerve root
—> raising the threshold for pain signals from uterine hypoxia and hypercontractility
—> lowering the perception of painful uterine signals;
(2) stimulating peripheral nerves and the spinal cord to release endorphins.
Research indicates that TENS therapy does not affect uterine contraction activity.
c2. Empiric GnRH Analog Therapy
GnRH analog therapy is generally used in patients diagnosed with endometriosis (usually confirmed by laparoscopy).
However, it can also be considered for:
• Patients with persistent dysmenorrhea who wish to avoid surgery, even if laparoscopic examination has not been performed but endometriosis is suspected.
• Patients with ongoing pain and negative laparoscopic findings. If both oral contraceptives and NSAIDs fail and laparoscopic examination results are negative, a three-month course of GnRH agonist therapy can be attempted. This is because even in the hands of experienced laparoscopic surgeons, the accurate diagnosis of endometriosis is challenging due to its microscopic nature and varied atypical presentations.
For patients intolerant or unwilling to use GnRH agonist therapy, the use of GnRH antagonist is a reasonable choice, although supporting data are limited due to being a newer treatment method.
Limitations of GnRH analog therapy include menopause-like side effects, cost, and bone density loss with long-term use.
Therefore, it is usually reserved for patients definitively diagnosed with endometriosis.
d. Supportive Therapies
d1. Behavioral Counseling
Behavioral counseling teaches patients strategies to change their perception of pain (e.g., desensitization-based procedures, hypnotherapy, imagery, coping strategies) and attempts to alter their response to pain (e.g., biofeedback, electromyographic training, Lamaze exercises, relaxation training).
There is no high-quality evidence supporting or opposing the use of these methods, and some patients may find them beneficial.
Behavioral counseling can be an effective adjunct for proactive patients alongside exercise and drug therapy.
d2. Physiotherapy Treatment
Physiotherapy and activity-based treatment may be helpful with minimal risks. An integrated analysis assessed isometric exercises, massage therapy, yoga, electrotherapy, connective tissue manipulation, stretching, kinesiology tape, progressive relaxation exercises, and aerobic dance, supporting their use, although with low-quality evidence.
Given the lack of high-quality data, these methods are considered supplemental therapies for interested patients.
d3. Complementary or Alternative Medicine
Evidence for complementary or alternative interventions is limited, but since these interventions have low risks, interested patients may reasonably use them.
d3.1. Acupuncture or Acupressure
Although several studies have been published on acupuncture for dysmenorrhea, the generally low quality and substantial design differences make it challenging to determine its effectiveness.
Due to the heterogeneity of research, a meta-analysis in 2016 of 42 acupuncture or acupressure trials could not conclusively determine its effectiveness in treating primary dysmenorrhea.
Another meta-analysis in 2018 of 49 trials, despite mostly low-quality data, concluded that acupuncture might alleviate menstrual pain symptoms when compared to no treatment or nonsteroidal anti-inflammatory drug therapy.
An experiment involving 221 women compared a smartphone app acupressure self-treatment with usual care.
The report indicated that self-acupressure could alleviate menstrual pain and showed improvement over time (three to six months).
Small but significant improvements were noted in the worst pain intensity, number of days with pain, and proportion of patients using pain medication.
d4. Diet and Vitamins -
Some small studies suggest that dietary changes and vitamins may reduce the severity of dysmenorrhea, but the data is limited.
Further trials are needed to support these interventions.
Interventions to some extent reduce dysmenorrhea include:
• Low-fat vegetarian diet.
• Increased dairy intake.
• Vitamin E (500 units per day or 200 units twice per day, beginning two days before menses and continuing through the first three days of bleeding).
• Vitamin B1 (100 mg per day), Vitamin B6 (200 mg per day), and fish oil supplements [1080 mg eicosapentaenoic acid (EPA), 720 mg docosahexaenoic acid (DHA), and 1.5 mg Vitamin E] are more effective in relieving pain than placebo.
• A single high-dose of Vitamin D3 (oral, 300,000 international units/1mL) given five days before the expected start of the menstrual cycle, although the safety of this method is unclear.
• Consumption of 750 to 2000 mg of ginger powder on days 1 to 3 of the menstrual cycle.
• Dietary supplementation with omega-3 polyunsaturated fatty acids has limited efficacy, and paradoxically, its effectiveness decreases with increasing dosage and patient age.
e. Surgery for Refractory Dysmenorrhea
e1. Endometrial Ablation -
Endometrial ablation is beneficial for certain patients who do not wish to conceive and experience significant pain and excessive menstrual bleeding.
In a retrospective study involving 144 patients who underwent endometrial ablation, nearly half (48 out of 100) of the preoperative dysmenorrheal women experienced symptom relief after ablation.
Patients with reduced menstrual volume after ablation were more likely to report relief from dysmenorrhea.
e2. Hysterectomy -
For patients who have completed childbirth and have had an inadequate response to the above treatments, hysterectomy may be considered.
Summary:
In the above article, we discussed the causes and treatment options for dysmenorrhea, exploring risk factors associated with primary dysmenorrhea and pelvic pathology related to secondary dysmenorrhea.
In terms of treatment, nonsteroidal anti-inflammatory drugs, hormonal contraceptives, and other emerging methods are considered primary pharmacological approaches.
Lifestyle adjustments, behavioral therapy, and other novel approaches offer additional choices for patients.
Despite certain limitations and challenges, these research findings provide a variety of treatment options and potential future developments.
It is hoped that this information will offer a comprehensive understanding and better treatment choices for women suffering from dysmenorrhea, allowing each patient to achieve a better quality of life throughout the menstrual cycle.
References:
Uptodate:
Dysmenorrhea in adult females: Clinical features and diagnosis
Dysmenorrhea in adult females: Treatment
Postscript: This document is dedicated to my dearest Y.W.
