Дисменорея: генетические факторы и фенотипы боли при менструации.

Pain during and sometimes before menstruation
Dysmenorrhea is associated with increased pain sensitivity and heavy menstrual bleeding. For many women, primary dysmenorrhea gradually subsides in late second generation. Pregnancy has also been demonstrated to lessen the severity of dysmenorrhea, when menstruation resumes. However, dysmenorrhea can continue until menopause. 5–15% of women with dysmenorrhea experience symptoms severe enough to interfere with daily activities.

Genetic factors, stress and depression are risk factors for dysmenorrhea. Risk factors for primary dysmenorrhea include: early age at menarche, long or heavy menstrual periods, smoking, and a family history of dysmenorrhea. There is strong evidence of familial predisposition and genetic factors increasing susceptibility to dysmenorrhea. There have been multiple polymorphisms and genetic variants in both metabolic genes and genes responsible for immunity which have been associated with the disorder. Three distinct possible phenotypes have been identified for dysmenorrhea which include "multiple severe symptoms", "mild localized pain", and "severe localized pain". While there are likely differences in genotypes underlying each phenotype, the specific correlating genotypes have not yet been identified. These phenotypes are prevalent at different levels in different population demographics, suggesting different allelic frequencies across populations (in terms of race, ethnicity, and nationality). Polymorphisms in the ESR1 gene have been commonly associated with severe dysmenorrhea. The occurrence and frequency of secondary dysmenorrhea (SD) has been associated with different alleles and genotypes of those with underlying pathologies, which can affect the pelvic region or other areas of the body. Individuals with disorders may have genetic mutations related to their diagnoses which produce dysmenorrhea as a symptom of their primary diagnosis. It has been found that those with fibromyalgia who have the ESR1 gene variation Xbal and possess the Xbal AA genotype are more susceptible to experiencing mild to severe menstrual pain resulting from their primary pathology. Commonly, genetic mutations which are a hallmark of or associated with specific disorders can produce dysmenorrhea as a symptom which accompanies the primary disorder. In contrast with secondary dysmenorrhea, primary dysmenorrhea (PD) has no underlying pathology. Genetic mutation and variations have therefore been thought to underlie this disorder and contribute to the pathogenesis of PD. There are multiple single nucleotide polymorphisms (SNP) associated with PD. Two of the most well studied include an SNP in the promoter of MIF and an SNP in the tumor necrosis factor (TNF α) gene. When a cytosine 173 base pairs upstream of macrophage migration inhibitory factor (MIF) promoter was replaced by a guanine there was an associated increase in the likelihood of the individual experiencing PD. While a CC/GG genotype led to an increase in likelihood of the individual experiencing severe menstrual pain, a CC/GC genotype led to a more significant likelihood of the disorder impacting the individual overall and increasing the likelihood of any of the three phenotypes. A second associated SNP was located 308 base pairs upstream from the start codon of the TNF α gene, in which guanine was substituted for adenine. A GG genotype at the loci is associated with the disorder and has been proposed as a possible genetic marker to predict PD. The phenotypes associated with these mutations in the MEFV genes have been better studied; individuals who are heterozygous for these mutations are more likely to be affected by PD which presents as a severe pain phenotype. Release of prostaglandins and other inflammatory mediators in the uterus cause the uterus to contract and can result in systemic symptoms such as nausea, vomiting, bloating and headaches or migraines. When the uterine muscles contract, they constrict the blood supply to the tissue of the endometrium, which, in turn, breaks down and dies. These uterine contractions continue as they squeeze the old, dead endometrial tissue through the cervix and out of the body through the vagina. These contractions, and the resulting temporary oxygen deprivation to nearby tissues, are thought to be responsible for the pain or cramps experienced during menstruation. Compared with non dysmnenorrhic individuals, those with primary dysmenorrhea have increased activity of the uterine muscle with increased contractility and increased frequency of contractions.

The diagnosis of dysmenorrhea is usually made simply on a medical history of menstrual pain that interferes with daily activities. However, there is no universally accepted standard technique for quantifying the severity of menstrual pains.

Once a diagnosis of dysmenorrhea is made, further workup is required to search for any secondary underlying cause of it, in order to be able to treat it specifically and to avoid the aggravation of a perhaps serious underlying cause. Further work up includes a specific medical history of symptoms and menstrual cycles and a pelvic examination. These drugs are typically more effective than treatments that do not target the source of the pain (e. g. acetaminophen).

Nonsteroidal anti inflammatory drugs (NSAIDs) such as ibuprofen and naproxen are effective in relieving the pain of primary dysmenorrhea. They can have side effects of nausea, dyspepsia, peptic ulcer, and diarrhea. A 2009 systematic review (updated in 2023) found evidence that the low or medium doses of estrogen contained in the birth control pill reduces pain associated with dysmenorrhea. In addition, no differences between different birth control pill preparations were found. and Depo provera are also effective, since these methods often induce amenorrhea. The intrauterine system (Mirena IUD) may be useful in reducing symptoms.

A review indicated the effectiveness of transdermal nitroglycerin. Reviews indicated magnesium supplementation seemed to be effective. Heat is effective compared to NSAIDs and is a preferred option by many patients, as it is easy to access and has no known side effects. There is some evidence that exercises performed 3 times a week for about 45 to 60 minutes, without particular intensity, reduces menstrual pain.

There is insufficient evidence to recommend the use of many herbal or dietary supplements for treating dysmenorrhea, including melatonin, vitamin E, fennel, dill, chamomile, cinnamon, damask rose, rhubarb, guava, and uzara. Further research is recommended to follow up on weak evidence of benefit for: fenugreek, ginger, valerian, zataria, zinc sulphate, fish oil, and vitamin B1.<! One review found thiamine and vitamin E to be likely effective. Reviews found tentative evidence that ginger powder may be effective for primary dysmenorrhea. Reviews have found promising evidence for Chinese herbal medicine for primary dysmenorrhea, but that the evidence was limited by its poor methodological quality. A 2016 Cochrane review of acupuncture for dysmenorrhea concluded that it is unknown if acupuncture or acupressure is effective. There were also concerns of bias in study design and in publication, insufficient reporting (few looked at adverse effects), and that they were inconsistent. Spinal manipulation does not appear to be helpful. a 2006 systematic review found that overall no evidence suggests that spinal manipulation is effective for treatment of primary and secondary dysmenorrhea. Valerian, Humulus lupulus and Passiflora incarnata may be safe and effective in the treatment of dysmenorrhea.

Dysmenorrhea is one of the most common gynecological problems, regardless of age or race. It is one of the most frequently identified causes of pelvic pain in those who menstruate. Dysmenorrhea is estimated to affect between 50% and 90% of female adolescents and women of reproductive age. Reports of dysmenorrhea are greatest among individuals in their late teens and 20s, with reports usually declining with age. The prevalence in adolescent females has been reported to be 67.2% by one study and 90% by another. It has been stated that there is no significant difference in prevalence or incidence between races, Another study indicated that dysmenorrhea was present in 36.4% of participants, and was significantly associated with lower age and lower parity. Childbearing is said to relieve dysmenorrhea, but this does not always occur. One study indicated that in nulliparous individuals with primary dysmenorrhea, the severity of menstrual pain decreased significantly after age 40. A survey in Norway showed that 14 percent of females between the ages of 20 to 35 experience symptoms so severe that they stay home from school or work. Among adolescent girls, dysmenorrhea is the leading cause of recurrent short term school absence.