Primary Dysmenorrhea/Dysmenorrhea also knew as painful periods or menstrual cramps is pain during menstruation. Its usual onset occurs around the time that menstruation begins.[rx] Symptoms typically last less than three days.[rx] The pain is usually in the pelvis or lower abdomen.[rx] Other symptoms may include back pain, diarrhea, or nausea.[rx]
Dysmenorrhea is a Greek term for “painful monthly bleeding.”[rx] Dysmenorrhea can be classified as primary and secondary dysmenorrhea. Primary dysmenorrhea is a lower abdominal pain happening during the menstrual cycle, which is not associated with other diseases or pathology.[rx] In contrast, secondary dysmenorrhea is usually associated with other pathology inside or outside the uterus.[rx] Dysmenorrhea is a common complaint among women during their reproductive age. Dysmenorrhea is associated with significant emotional, psychological, and functional health impacts.[rx]
Dysmenorrhea is called “primary” when there is no specific abnormality, and “secondary” when the pain is caused by an underlying gynecological problem. It is believed that primary dysmenorrhea occurs when hormone-like substances called “prostaglandins” produced by uterine tissue trigger strong muscle contractions in the uterus during menstruation. However, the level of prostaglandins does not seem to have anything to do with how strong a woman’s cramps are. Some women have high levels of prostaglandins and no cramps, whereas other women with low levels have severe cramps. This is why experts assume that cramps must also be related to other things (such as genetics, stress, and different body types) in addition to prostaglandins. The first year or two of a girl’s periods are not usually very painful. However, once ovulation begins, the blood levels of the prostaglandins rise, leading to stronger contractions.
Types of Dysmenorrhea
Dysmenorrhea can be classified as either primary or secondary based on the absence or presence of an underlying cause. Primary dysmenorrhea occurs without an associated underlying condition, while secondary dysmenorrhea has a specific underlying cause, typically a condition that affects the uterus or other reproductive organs.[rx]
- Primary dysmenorrhea – Prostaglandin F (PGF) is the main contributor to the cause of dysmenorrhea.[rx][rx] The time of the endometrial shedding during the beginning of menstruation is when the endometrial cells release PGF. Prostaglandin (PG) causes uterine contractions, and the intensity of the cramps is proportionate to the amount of PGs released after the sloughing process that started due to dropping hormonal surge.[rx][rx]
- Secondary dysmenorrhea – Secondary dysmenorrhea presentation is a clinical situation where menstrual pain can be due to an underlying disease, disorder, or structural abnormality either within or outside the uterus.[rx] There are many common causes of secondary dysmenorrhea, which include endometriosis, fibroids (endometriomas), adenomyosis, endometrial polyps, pelvic inflammatory disease, and maybe even the use of an intrauterine contraceptive device.[rx]
Differential diagnosis of primary and secondary dysmenorrhoea
| Primary dysmenorrhoea | Secondary dysmenorrhoea |
|---|---|
| Onset shortly after menarche | Onset can occur at any time after menarche (typically after 25 years of age) |
| Lower pelvic or abdominal pain is usually associated with the onset of menstrual flow and lasts 8-72 hours | Women may complain of change in time of pain onset during the menstrual cycle or in the intensity of pain |
| Back and thigh pain, headache, diarrhea, nausea, and vomiting may be present | Other gynecological symptoms (such as dyspareunia, menorrhagia) may be present |
| No abnormal findings on examination | Pelvic abnormality on physical examination |
Causes of Dysmenorrhea
Many theories have explained the etiology of dysmenorrhea since the 1960s. This includes psychological, biochemical, and anatomical etiologies. The anatomical theory included abnormal uterine positions and abnormalities in shape or the length of the cervix. Zebitay et al., in their study, proposed a positive correlation between the cervical length and the volume and intensity of dysmenorrhea.[rx] However, the biochemical theory has proven to be stronger than others according to several homogenous studies.[rx]
- When laparoscopy is used for diagnosis, the most common cause of dysmenorrhea is endometriosis, in approximately 70% of adolescents.[rx]
- Other causes of secondary dysmenorrhea include leiomyoma,[rx] adenomyosis,[rx] ovarian cysts, pelvic congestion,[rx] and cavitated and accessory uterine mass.[rx]
Associated risk factors are
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Age ()
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Smoking
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Attempts to lose weight
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Higher body mass index
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Depression/anxiety
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Earlier age at menarche
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Nulliparity
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longer and heavier menstrual flow
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Family history of dysmenorrhea
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Disruption of social networks[rx]
Symptoms of Dysmenorrhea
- menstrual periods at intervals of more than 35 days
- irregular menstrual periods with unpredictable flow
- some women with oligomenorrhea may have difficulty conceiving.
- Aching pain in the abdomen (pain may be severe at times).
- Feeling of pressure in the abdomen.
- Pain in the hips, lower back, and inner thighs.
- Symptoms often co-occurring with menstrual pain include nausea and vomiting, diarrhea, headache, dizziness, disorientation, fainting, and fatigue.[rx] Symptoms of dysmenorrhea often begin immediately after ovulation and can last until the end of menstruation. This is because dysmenorrhea is often associated with changes in hormonal levels in the body that occur with ovulation.
- In particular, prostaglandins induce abdominal contractions that can cause pain and gastrointestinal symptoms.[rx][rx] The use of certain types of birth control pills can prevent the symptoms of dysmenorrhea because they stop ovulation from occurring.
- Dysmenorrhea is associated with increased pain sensitivity and heavy menstrual bleeding.
- Oligomenorrhea that occurs in adolescents is often caused by immaturity or lack of synchronization between the hypothalamus, pituitary gland, and ovaries. The hypothalamus is part of the brain that controls body temperature, cellular metabolism, and basic functions such as eating, sleeping, and reproduction. It secretes hormones that regulate the pituitary gland.
- The pituitary gland is then stimulated to produce hormones that affect growth and reproduction. At the beginning and end of a woman’s reproductive life, some of these hormone messages may not be synchronized, causing menstrual irregularities.
- In PCOS, oligomenorrhea is probably caused by inappropriate levels of both female and male hormones. Male hormones are produced in small quantities by all women, but in women with PCOS, levels of male hormone (androgens) are slightly higher than in other women. More recently, however, some researchers are hypothesizing that the ovaries of women with PCOS are abnormal in other respects. In 2003, a group of researchers in London reported that there are fundamental differences between the development of egg follicles in normal ovaries and follicle development in the ovaries of women with PCOS.
Diagnosis of Dysmenorrhea
History and Physical
A comprehensive history, along with adequate physical examination, is important to establish the diagnosis. History of the location of pain, onset, characteristics, and duration, along with associated symptoms like fatigue, headache, diarrhea, nausea, and vomiting, could be helpful to establish a diagnosis.[rx]
For primary dysmenorrhea, the physical examination is usually normal. A pelvic examination is not necessary for adolescents and women with characteristics of primary dysmenorrhea/ Pelvic examination is indicated in adolescents and women who have previously been sexually active and when the secondary cause is suspected or if there is a lack of response to treatment. The common findings that indicate secondary dysmenorrhea are:
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Young age (around menarche) primary dysmenorrhea vs. older age > 25 years old (secondary dysmenorrhea)
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Fluid in the vaginal vault of foul odor or whitish grayish in color. (Pelvic Inflammatory Disease)
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Associated dysuria, dyspareunia, dyschezia, infertility, nodularity, adnexal masses, tenderness (endometriosis, non-gynecological etiology)[rx]
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Abnormal bleeding with the enlarged symmetrical uterus (Adenomyosis)
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Abnormal bleeding with the enlarged asymmetrical uterus (Fibroids)
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Obstructive anatomical abnormalities and history of other congenital anomalies
Evaluation
Primary dysmenorrhea is diagnosed, depending upon the history and physical examination.
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A pelvic examination is important for evaluating dysmenorrhoea if the history of onset and duration of lower abdominal pain suggests secondary dysmenorrhoea or if the dysmenorrhea is not responding to medical treatment.[rx]
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The use of ultrasound in the evaluation of primary dysmenorrhea has little significance. However, ultrasound can be useful in differentiating secondary dysmenorrhea and causes that include endometriosis and adenomyosis.[rx][rx] Secondary dysmenorrhoea affects all women any time after menarche, while it can happen as a new symptom for females in their 30s or 40s. It can be associated with different intensity of pain and other symptoms such as dyspareunia, menorrhagia, intermenstrual, postcoital bleeding.
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The pregnancy tests using urinary human chorionic gonadotropin (B-HCG) are useful in history suggestive of suspected pregnancy.
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If indicated by clinical examination and history, to rule out suspected malignancy cervical cytology samples may be required.
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Magnetic resonance imaging (MRI) or Doppler ultrasonography may be required if torsion of adnexa, adenomyosis, or deep pelvic endometriosis is suspected or if there are inconclusive findings on the transvaginal ultrasonography.[rx]
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Laparoscopy may be indicated when all the non-invasive investigations have been carried out and the cause remains unknown.
Treatment of Dysmenorrhea
Pharmacological Treatment
- Simple analgesics – Simple analgesics, such as aspirin and paracetamol, may be useful as a starting point especially when NSAIDs are contraindicated. Two systematic reviews (one of eight RCTs, the other of two such trials) found no significant difference in pain relief between paracetamol and placebo, aspirin, or naproxen, although some of the trials may have been too small to detect clinically important differences.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) – are considered to be the first line of treatment for dysmenorrhea. [rx] NSAIDs exert their benefit in the treatment of dysmenorrhea by inhibiting cyclooxygenase enzyme, thereby blocking prostaglandin productions.[rx] [rx] Fenamates (mefenamic acid) may have slightly better efficacy than the phenyl propionic acid derivatives (ibuprofen, naproxen) because inmates have a dual action of blocking the production of PGs and inhibiting their action. [rx][rx] One study recommended ibuprofen and inmates to be preferred in terms of safety and efficacy.[rx] NSAIDs are still more effective compared to paracetamol. However, paracetamol is still a valid alternative where NSAIDs are contraindicated. Paracetamol with Caffeine and/or Pamabrom (short-acting diuretic) showed reduced pain.[rx][rx][rx]
- COX 2 specific inhibitors – A review of the newest generation of anti-inflammatories has shown that COX 2 (cyclooxygenase-2) specific inhibitors are effective for dysmenorrhoea.w9 Questions about the cardiovascular and cardioprotective safety of COX 2 inhibitorsw10 remain unresolved, however, and these drugs have been withdrawn from use in many countries.
- Tamoxifen – has been used effectively to reduce uterine contractility and pain in dysmenorrhea patients.[rx]
- Oral contraceptive pills (OCPs) – are reported effective in reducing dysmenorrheic pain compared to placebo among adolescents.[rx][rx][rx][rx] Many other studies argued against the effectiveness of OCPs as a treatment for dysmenorrhea due to small sample sizes and limited comparative data.[rx][rx] OCPs have a mechanism by limiting endometrial lining growth. It decreases the production of prostaglandins.[rx] Low levels of PGs are noted in the menstrual fluid of women on OCPs. Contraceptive pill users appeared to have significantly lower rates of dysmenorrhea and needed fewer additional analgesics.[rx]
- Hormonal birth control – use of hormonal birth control may improve symptoms of primary dysmenorrhea.[rx][rx] A 2009 systematic review found limited evidence that the low or medium doses of estrogen contained in the birth control pill reduce pain associated with dysmenorrhea.[rx] In addition, no differences between different birth control pill preparations were found.[rx] Norplant[rx] and Depo-provera[rx][rx] are also effective since these methods often induce amenorrhea. The intrauterine system (Mirena IUD) may be useful in reducing symptoms.[rx]
- Progestin-only pills (POPs) – are suitable more for patients with secondary dysmenorrhea related to endometriosis, whereas their effectiveness as a treatment for primary dysmenorrhea is not evident.[rx][rx][rx] POPs mainly works by causing atrophy of the endometrial lining and by inhibiting ovulation.
- Progestins – Hormonal progestins-only treatment produces a benefit on menstrual pain, causing endometrial atrophy and inhibiting ovulation. Several long-acting reversible progestin contraceptives have been found to be effective treatments for primary dysmenorrhea. These include 52-mg (20 µg/day) levonorgestrel-releasing intrauterine system, the etonogestrel-releasing subdermal implant, and depot medroxyprogesterone [rx].
- Levonorgestrel releasing intrauterine system – The levonorgestrel-releasing intrauterine system releases levonorgestrel (20 μ/day) into the uterine cavity for at least five years, thus preventing the thickening of the lining of the uterus. Up to 50% of women using it become amenorrhoeic after 12 months and reduction in dysmenorrhoea was spontaneously reported by women in non-randomized studies.[rx] The levonorgestrel-releasing intrauterine system has also been shown to be effective in reducing dysmenorrhoea in an RCT of women with endometriosis after one year.[rx] It should be noted that non-hormone intrauterine devices may result in dysmenorrhoea and may require removal if adequate pain relief is not provided with analgesics.
- Combined drug treatments and less common drug treatments – A combination of analgesics and the oral contraceptive or the Mirena intrauterine device is also an option in cases that do not respond to a single treatment. For the small percentage of patients who do not respond to these treatments or to combination treatment, other options exist.
- Thiamine and Vitamin E – One study has shown that 100 mg of thiamine (vitamin B-1) taken daily may be an effective cure for dysmenorrhoea: 87% of patients were cured up to two months after treatment. Thiamine and vitamin E may reduce pain compared with placebo in young women with primary dysmenorrhoea. One review found thiamine and vitamin E to be likely effective.[rx] It found the effects of fish oil and vitamin B12 to be unknown.[rx] Reviews found tentative evidence that ginger powder may be effective for primary dysmenorrhea.[rx] Reviews have found promising evidence for Chinese herbal medicine for primary dysmenorrhea, but that the evidence was limited by its poor methodological quality.[rx][rx]
- Pyridoxine and magnesium – Some evidence also exists that pyridoxine (vitamin B-6) supplements, taken alone or with magnesium, can reduce pain, but more research is needed to confirm this. Magnesium may also be an effective treatment. Women in some trials of magnesium experienced a reduction in period pain and a lowering of prostaglandins in their blood. The therapeutic dose is unclear, however, as magnesium supplements were used in several ways (daily or during pain). In addition, some women stopped taking magnesium during the trials, possibly owing to lack of benefit or due to adverse effects such as constipation.
- Fish oil – The use of fish oil capsules (omega 3 fatty acids) may also reduce pain, although more research is needed; adverse effects associated with fish oil treatment were mild and included nausea and worsening of acne.
- Progestogens and antiprogestogens – Progestogens such as medroxyprogesterone acetate and gestrinone induce anovulation with resulting amenorrhoea and therefore can successfully treat the symptoms of dysmenorrhoea in women with endometriosis.[rx,rx]
- Gonadotrophin releasing hormones and danazol – Gonadotrophin releasing hormones and danazol confer the same degree of pain relief.[rx] The side effect profiles of these treatments are different, however, with danazol having more androgenic side effects, while gonadotrophin-releasing hormones tend to produce more hypo-oestrogenic symptoms. Further studies are also required to establish the optimal supplementation or “add back” regimen of estrogen for limiting adverse effects.[rx]
- Calcium channel blockers – Calcium antagonists can reduce myometrial activity and relieve dysmenorrhoea by controlling the cytoplasmic concentration of free calcium and thereby the contractions of the uterine muscle. None, however, are licensed for this indication.[rx]
Alternative therapies
Food supplements, complementary or alternative medicine such as plant-based therapy, Chinese medicine, and supplements are being used for dysmenorrhea. Further, they are not regulated by the FDA. Overall there is insufficient evidence to recommend the use of any of the other herbal and dietary therapies.[rx] The effectiveness of acupuncture is supported by a few studies which lack active comparisons and lack sound methodological techniques.[rx][rx][rx]
In all, 10-20% of women with primary dysmenorrhoea do not respond to treatment with NSAIDs or oral contraceptives. In addition, some women have contraindications to these treatments. Consequently, researchers have investigated many alternatives to drug treatments.
Topical heat (about 39 °C) may be as effective as ibuprofen and more effective than paracetamol at reducing pain.
- High-frequency transcutaneous electrical nerve stimulation (TENS) may reduce pain compared with sham TENS, but seems to be less effective than ibuprofen.
- Acupressure may be more effective than sham acupressure or no treatment at relieving dysmenorrhoea.
- Spinal manipulation may be no more effective than placebo at reducing pain after 1 month in women with primary dysmenorrhoea.
- Relaxation may be better than no treatment at relieving dysmenorrhoea.
- We don’t know whether acupuncture, fish oil, vitamin B12, magnets, or intrauterine progestogens reduce dysmenorrhoea.
Herbal products or medicines, and dietary supplements
Herbal and dietary therapies are popular as they can be self-administered and are available from health shops, chemists, and supermarkets. This availability, although helpful, can create problems with the control of dosage, quality, and drug interactions. Systematic reviews and RCTs of herbal and dietary supplements have shown that thiamine, pyridoxine, magnesium, and fish oil may be effective in relieving pain, although some of these may be associated with adverse effects (see box). A Bandolier review found evidence from three small RCTs that vitamin E was effective in treating dysmenorrhoea, but it advises caution in use owing to potential adverse effects when used in high doses.[rx]
Dietary changes
One RCT has shown a significant association between a low fat vegetarian diet and a reduction in symptoms (perhaps by influencing prostaglandin metabolism), but the trial was too small (33 women) to give conclusive results.[rx]
Exercise
Physical exercise may reduce dysmenorrhoea. Current studies have too many methodological flaws, however, to be able to confirm results.w14 It is hypothesised that exercise works by improving blood flow at the pelvic level as well as stimulating the release of β endorphins, which act as non-specific analgesics.
Transcutaneous electrical nerve stimulation
Transcutaneous electrical nerve stimulation (TENS) involves stimulation of the skin using current at various pulse rates (frequencies) and intensities to provide pain relief. A Cochrane systematic review found limited evidence from small trials that high frequency transcutaneous electrical nerve stimulation reduces pain[rx]; 42-60% of patients had at least moderate relief, and less use of additional analgesics was needed in one RCT. A 2011 review stated that high-frequency transcutaneous electrical nerve stimulation may reduce pain compared with sham TENS, but seems to be less effective than ibuprofen.[rx]
Acupuncture
Acupuncture excites receptors or nerve fibres, which, through a complicated interaction with serotonin and endorphins, block pain impulses. A Cochrane systematic review found one RCT showing that acupuncture significantly reduces pain, but more research is needed to confirm this finding.[rx]
Heat
Heat is effective compared to NSAIDs and seems to be the preferred easy therapy option by many patients with no side effects. Still, high-quality studies needed.[rx][rx] Heat therapy has been a traditional home remedy for dysmenorrhoea. One RCT has compared its use with the NSAID ibuprofen.[rx] The heat patch (39°C) used for 12 hours a day was found to be as effective as ibuprofen (400 mg three times a day) and more effective than placebo in reducing pain. Women using both the heat patch and ibuprofen experience the most pain relief. Another RCT found a heat wrap was better than paracetamol for pain relief over an eight hour period.[rx]
Spinal manipulation
A Cochrane systematic review of five RCTs found no significant difference between spinal manipulation and placebo manipulation.[rx]
Surgery
In recent years uterine nerve ablation and presacral neurectomy have been increasingly used when diagnostic laparoscopy has been indicated for dysmenorrhoea. These two surgical procedures interrupt most of the cervical sensory nerve fibers (thus diminishing uterine pain). However, a Cochrane systematic review of nine RCTs found insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhoea, regardless of cause.[rx]
What treatments can we expect in the future?
Current research into treatments for dysmenorrhoea includes vasopressin antagonists, nitroglycerin, and magnets.
- Vasopressin antagonists – Overproduction of vasopressin, a hormone that stimulates the contraction of muscular tissue, has been identified as a contributing factor to dysmenorrhoea. An RCT of vasopressin antagonist given as a dose of 300 mg/day starting between four hours to three days before the onset of pain and/or bleeding significantly reduced pain compared with placebo.[rx] No serious adverse effects were noted.
- Nitroglycerin – Nitric oxide can relax the uterine muscle. Nitroglycerin formulations are currently used to relax the uterus for various pregnancy problems, so it may have implications for dysmenorrhoea. One study, in patients with dysmenorrhoea, used 0.1-0.2 mg of nitroglycerin taken hourly during first few days of the menstrual cycle and found that pain was reduced in most patients.[rx] However, 20% of women reported headaches as an adverse effect and more research is needed.
- Magnets – An RCT of a static magnet of 0.27 T attached over the pelvic area, compared with a placebo magnet in women with primary dysmenorrhoea showed a significant reduction in pain and irritability symptoms.w15 A larger study to confirm results is planned.
- Current research – RCTs are ongoing or currently recruiting for the following interventions for dysmenorrhoea: vitamin K, antispasmodics (drotaverine hydrochloride), TENS, high-frequency TENS, extended-regimen oral contraceptives, low dose oral contraceptives, and sildenafil citrate.w16
Differential Diagnosis
Differential diagnosis of dysmenorrhea is broad, and it can be listed as gynecological conditions and non-gynecological conditions:[54]
Gynecological conditions
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Endometriosis
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Obstruction of the reproductive tract: Imperforate hymen, transverse vaginal septum, vaginal agenesis, OHVIRA syndrome (uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis), cervical stenosis.
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Functional and nonfunctional adnexal cysts: Nonfunctional adnexal cysts include para tubal and para ovarian cysts, endometrioma, benign ovarian cysts such as benign cystic teratoma and benign serous or mucinous cystadenoma, and the rare cases of ovarian borderline or malignant tumors (germ cell, granulosa cell, or epithelial tumors).
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Adnexal torsion
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Adenomyosis
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Pelvic inflammatory disease / sexual transmitted infections
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Endometrial polyps
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Asherman syndrome
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Ectopic pregnancy
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Chronic pelvic pain
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Membranous dysmenorrhea
Non-Gynecological conditions: (gastrointestinal, urological, and musculoskeletal)
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Irritable bowel syndrome
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Urinary tract Infections
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Interstitial cystitis
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Musculoskeletal causes: abdominal wall muscles, the abdominal wall fascia, the pelvic and hip muscles, the sacroiliac joints, and the lumbosacral muscles
Glossary
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