Background Primary dysmenorrhea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynecological condition that affects between 45 and 95% of menstruating women. Despite the high prevalence, dysmenorrhea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. This review reports on current knowledge, particularly with regards to the impact and consequences of recurrent menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhea. Methods Comprehensive literature searches on primary dysmenorrhea were performed using the electronic databases PubMed, Google Scholar and the Cochrane Library. Full-text manuscripts published between the years 1944 and 2015 were reviewed for relevancy and reference lists were cross-checked for additional relevant studies. In combination with the word 'dysmenorrhea' one or more of the following search terms were used to obtain articles published in peer-reviewed journals only: pain, risk factors, etiology, experimental pain, clinical pain, adenomyosis, chronic pain, women, menstrual cycle, hyperalgesia, pain threshold, pain tolerance, pain sensitivity, pain reactivity, pain perception, central sensitization, quality of life, sleep, treatment, non-steroidal anti-inflammatory drugs. Results Women with dysmenorrhea, compared with women without dysmenorrhea, have greater sensitivity to experimental pain both within and outside areas of referred menstrual pain. Importantly, the enhanced pain sensitivity is evident even in phases of the menstrual cycle when women are not experiencing menstrual pain, illustrating that long-term differences in pain perception extend outside of the painful menstruation phase. This enhanced pain sensitivity may increase susceptibility to other chronic pain conditions in later life; dysmenorrhea is a risk factor for fibromyalgia. Further, dysmenorrheic pain has an immediate negative impact on quality of life, for up to a few days every month. Women with primary dysmenorrhea have a significantly reduced quality of life, poorer mood and poorer sleep quality during menstruation compared with their pain-free follicular phase, and compared with the menstruation phase of pain-free control women. The prescribed first-line therapy for menstrual pain remains non-steroidal anti-inflammatory drugs, which are effective in relieving daytime and night-time pain. Conclusion Further study is needed to determine whether effectively blocking dysmenorrheic pain ameliorates risk for the development of chronic pain disorders and to explore whether it is possible to prevent the development-and not just treat-severe dysmenorrheic pain in adolescent girls. In conclusion, we demonstrate the extensive multi-factorial impact of dysmenorrhea and we encourage and direct researchers to necessary future studies.

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What we know about primary dysmenorrhea today: a critical review

Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. This disease should be viewed as a public health problem with a major effect on the quality of life of women as well as being a substantial economic burden. In light of the considerable progress with diagnostic imaging (for example, transvaginal ultrasound and MRI), exploratory laparoscopy should no longer be used to diagnose endometriotic lesions. Instead, diagnosis of endometriosis should be based on a structured process involving the combination of patient interviews, clinical examination and imaging. Notably, a diagnosis of endometriosis often leads to immediate surgery. Therefore, rethinking the diagnosis and management of endometriosis is warranted. Instead of assessing endometriosis on the day of the diagnosis, gynaecologists should consider the patient's 'endometriosis life'. Medical treatment is the first-line therapeutic option for patients with pelvic pain and no desire for immediate pregnancy. In women with infertility, careful consideration should be made regarding whether to provide assisted reproductive technologies prior to performing endometriosis surgery. Modern endometriosis management should be individualized with a patient-centred, multi-modal and interdisciplinary integrated approach.

Rethinking mechanisms, diagnosis and management of endometriosis

Background
Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs that act by blocking prostaglandin production. They inhibit the action of cyclooxygenase (COX), an enzyme responsible for the formation of prostaglandins. The COX enzyme exists in two forms, COX-1 and COX-2. Traditional NSAIDs are considered 'non-selective' because they inhibit both COX-1 and COX-2 enzymes. More selective NSAIDs that solely target COX-2 enzymes (COX-2-specific inhibitors) were launched in 1999 with the aim of reducing side effects commonly reported in association with NSAIDs, such as indigestion, headaches and drowsiness.

Objectives
To determine the effectiveness and safety of NSAIDs in the treatment of primary dysmenorrhoea.

Search methods
We searched the following databases in January 2015: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, November 2014 issue), MEDLINE, EMBASE and Web of Science. We also searched clinical trials registers (ClinicalTrials.gov and ICTRP). We checked the abstracts of major scientific meetings and the reference lists of relevant articles.

Selection criteria
All randomised controlled trial (RCT) comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea.

Data collection and analysis
Two review authors independently selected the studies, assessed their risk of bias and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). We used inverse variance methods to combine data. We assessed the overall quality of the evidence using GRADE methods.

Main results
We included 80 randomised controlled trials (5820 women). They compared 20 different NSAIDs (18 non-selective and two COX-2-specific) versus placebo, paracetamol or each other.

NSAIDs versus placebo

Among women with primary dysmenorrhoea, NSAIDs were more effective for pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I2 = 53%, low quality evidence). This suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so.

However, NSAIDs were associated with more adverse effects (overall adverse effects: OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, I2 = 0%, low quality evidence; gastrointestinal adverse effects: OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs, I2 = 30%; neurological adverse effects: OR 2.74, 95% CI 1.66 to 4.53, seven RCTs, I2 = 0%, low quality evidence). The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so.

NSAIDs versus other NSAIDs

When NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety. However, the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials.

Non-selective NSAIDs versus COX-2-specific selectors

Only two of the included studies utilised COX-2-specific inhibitors (etoricoxib and celecoxib). There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs; however data were very scanty.

NSAIDs versus paracetamol

NSAIDs appeared to be more effective for pain relief than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, three RCTs, I2 = 0%, low quality evidence). There was no evidence of a difference with regard to adverse effects, though data were very scanty.

Most of the studies were commercially funded (59%); a further 31% failed to state their source of funding.

Authors' conclusions
NSAIDs appear to be a very effective treatment for dysmenorrhoea, though women using them need to be aware of the substantial risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods.

/pdf/nonsteroidal-anti-inflammatory-drugs-for-dysmenorrhoea-39n1f1htcu.pdf

Nonsteroidal anti‐inflammatory drugs for dysmenorrhoea

Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force

STUDY QUESTION What is the relationship between endometriosis phenotypes superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic resonance imaging (MRI)? SUMMARY ANSWER Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype WHAT IS KNOWN ALREADY An association between endometriosis and adenomyosis has been reported previously, although data regarding the association between MRI appearance of adenomyosis and the endometriosis phenotype are currently still lacking STUDY DESIGN, SIZE, DURATION This was an observational, cross-sectional study using data prospectively collected from non-pregnant patients who were between 18 and 42 years of age, and who underwent surgery for symptomatic benign gynecological conditions between January 2011 and December 2014 For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery Only women with preoperative standardized uterine MRIs were retained for this study PARTICIPANTS/MATERIALS, SETTING, METHODS Surgery was performed on 292 patients with signed consent and available preoperative MRIs After a thorough surgical examination of the abdomino-pelvic cavity, 237 women with histologically proven endometriosis were allocated to the endometriosis group and 55 symptomatic women without evidence of endometriosis to the endometriosis free group The existence of diffuse or FAOM was studied in both groups and according to surgical endometriosis phenotypes (SUP, OMA and DIE) MAIN RESULTS AND THE ROLE OF CHANCE Adenomyosis was observed in 599% (n = 175) of the total sample population (n = 292) Based on MRI, the distribution of adenomyosis was as follows: isolated diffuse adenomyosis (53 patients; 182%), isolated FAOM (74 patients; 253%), associated diffuse and FAOM (48 patients; 164%) Diffuse adenomyosis (isolated and associated to FAOM) was observed in one-third of the patients regardless of whether they were endometriotic patients or endometriosis free women taken as controls (342% (81 cases) versus 364% (20 cases)); P = 0764 Among endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed to reach significant correlation with the endometriosis phenotypes (SUP, 200% (8 cases); OMA, 452% (14 cases) and DIE, 355% (59 cases); P = 0068) In striking contrast, there was a significant increase in the frequency of FAOM in endometriosis-affected women than in controls (119 cases (502%) versus 54% (3 cases); P < 0001) FAOM correlated with the endometriosis phenotypes, significantly with DIE (SUP, 75% (3 cases); OMA, 193% (6 cases) and DIE, 663% (110 cases); P < 0001) LIMITATIONS, REASONS FOR CAUTION There was a possible selection bias due to the specificity of the study design, as it only included surgical patients in a referral center that specializes in endometriosis surgery Therefore, women referred to our center may have suffered from particularly severe forms of endometriosis This could explain the high number of women with DIE (166/237-70%) in our study group This referral bias for women with severe lesions may have amplified the difference in association of FAOM with the endometriosis-affected patients compared to women without endometriosis Furthermore, according to inclusion criteria, women in the endometriosis free group were symptomatic women This may introduce some bias as symptomatic women may be more prone to have associated adenomyosis that in turn could have been overrepresented in the endometriosis free group Whether this selection could have introduced a bias in the relationship between endometriosis and adenomyosis remains unknown WIDER IMPLICATIONS OF THE FINDINGS This study opens the door to future epidemiological, clinical and mechanistic studies aimed at better characterizing diffuse and focal adenomyosis Further studies are necessary to adequately determine if diffuse and focal adenomyosis are two separate entities that differ in terms of pathogenesis STUDY FUNDING/COMPETING INTEREST(S) No funding supported this study The authors have no conflict of interest to declare

Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes.

Primary dysmenorrhea is the most common gynecological condition among women of reproductive age. Although dysmenorrhea has been reported to affect the ability of women to carry out daily activities, the impact of primary dysmenorrheic pain specifically on quality of life (QoL), has yet to be elucidated. We investigated whether QoL varies between women with and without severe primary dysmenorrhea, and whether QoL is impaired only during menstruation or also during pain-free phases of the menstrual cycle. Twelve women with severe primary dysmenorrhea and nine control women completed the quality of life enjoyment and satisfaction questionnaire (Q-LES-Q-SF) during menstruation and during the late follicular phase. Women with dysmenorrhea had a significant reduction in Q-LES-Q-SF scores (mean ± SD: 54 ± 18%, percentage of the total maximum possible score) when they were experiencing severe menstrual pain compared with their own pain-free follicular phase (80 ± 14%, p < 0.0001) and compared with controls during menstruation (81 ± 10%, p < 0.0001). They also rated their overall life satisfaction and contentment as poorer during menstruation. Severe menstrual pain associated with primary dysmenorrhea, therefore, impacts health-related of QoL.

https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1111/aogs.12287

Stella Iacovides

Papers

What we know about primary dysmenorrhea today: a critical review

Reduced quality of life when experiencing menstrual pain in women with primary dysmenorrhea

Does pain vary across the menstrual cycle? A review

Women With Dysmenorrhea Are Hypersensitive to Experimental Deep Muscle Pain Across the Menstrual Cycle

Sleep Fragmentation Hypersensitizes Healthy Young Women to Deep and Superficial Experimental Pain.