Dysmenorrhea

Article Author:
Hassan Nagy
Article Editor:
Moien AB Khan
Updated:
7/21/2020 8:34:49 PM
For CME on this topic:
Dysmenorrhea CME
PubMed Link:
Dysmenorrhea

Introduction

Dysmenorrhea is a Greek term for “painful monthly bleeding.”[1] 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.[2] In contrast, secondary dysmenorrhea is usually associated with other pathology inside or outside the uterus.[3] Dysmenorrhea is a common complaint among women during their reproductive age. Dysmenorrhea is associated with significant emotional, psychological, and functional health impacts.[4]

Etiology

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.[5] However, the biochemical theory has proven to be stronger than others according to several homogenous studies.[6] 

Associated risk factors are

  • Age (13 to 15)
  • Smoking 
  • Attempts to lose weight
  • Higher body mass index
  • Depression/anxiety
  • Earlier age at menarche
  • Nulliparity
  • longer and heavier menstrual flow
  • Family history of dysmenorrhea
  • Disruption of social networks[7]

Primary dysmenorrhea: Prostaglandin F (PGF) is the main contributor to the cause of dysmenorrhea.[8][9] 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.[10][11]

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.[12] 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.[8]

Epidemiology

Dysmenorrhea is one of the common gynecological problems among all women regardless of age or race. It is one of the most frequently identified etiology of pelvic pain in females. The prevalence of dysmenorrhea can vary between 16% and 91% in women of reproductive age, with severe pain observed in 2% to 29%.[7]  Agarwal et al. showed the prevalence of dysmenorrhea to be 80% in adolescents. Of that, approximately 40% had severe dysmenorrhea.[13]

The symptoms associated with dysmenorrhea include gastrointestinal symptoms such as nausea, bloating, diarrhea, constipation, or both, along with vomiting and indigestion. Also, irritability, headache, and low back pain are prevalent among women presenting with primary dysmenorrhea. Tiredness and dizziness are also associated with dysmenorrhea.[14] Dysmenorrhea is associated with significant impairment in quality of life between 16% to 29% of women.[7] Furthermore, 12% of the monthly school and work activities are lost due to absenteeism because of dysmenorrhea.[15][7]

Pathophysiology

The pathophysiology of primary dysmenorrhea is not well understood. Nevertheless, the identified cause is due to the hypersecretion of the prostaglandins from the uterine inner lining. Prostaglandin F2alpha (PGF-2a) and Prostaglandin PGF 2 increases the uterine tone, and also causes high-amplitude contractions of the uterus.[16] Also, vasopressin has been linked to primary dysmenorrhea. Vasopressin increases the uterine contractility and can cause ischemic pain due to its vasoconstriction effects.[3][17] 

The uterine contractility is observed to be more prominent in the first two days of the menstrual period. Progesterone levels drop before menstruation, which leads to increased production of PGs' triggering dysmenorrhea.[18] Endometriosis and adenomyosis are the most common causes of secondary dysmenorrhea in premenopausal women.[18]

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.[14]

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:

  • Young age (around menarche) primary dysmenorrhea vs. older age > 25 years old (secondary dysmenorrhea)
  • Fluid in the vaginal vault of foul odor or whitish grayish in color. (Pelvic Inflammatory Disease)
  • Associated dysuria, dyspareunia, dyschezia, infertility, nodularity, adnexal masses, tenderness (endometriosis, non-gynecological etiology)[19]
  • Abnormal bleeding with the enlarged symmetrical uterus (Adenomyosis)
  • Abnormal bleeding with the enlarged asymmetrical uterus (Fibroids)
  • Obstructive anatomical abnormalities and history of other congenital anomalies
  • Pelvic masses (fibroids, neoplasms, ovarian cysts)[20][21]

Evaluation

Primary dysmenorrhea is diagnosed, depending upon the history and physical examination.

  1. 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.[21]
  2. 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.[8][21] 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. 
  3. The pregnancy tests using urinary human chorionic gonadotropin (B-HCG) are useful in history suggestive of suspected pregnancy.
  4. Patients who are at risk of sexually transmitted infections (STIs) or when pelvic inflammatory disease (PID) is suspected will need endocervical or vaginal swabs.[8][21]
  5. If indicated by clinical examination and history, to rule out suspected malignancy cervical cytology samples may be required.
  6. 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.[21]
  7. Laparoscopy may be indicated when all the non-invasive investigations have been carried out and the cause remains unknown.

Treatment / Management

Pharmacological Treatment

Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered to be the first line of treatment for dysmenorrhea. NSAIDs are very effective in the treatment of dysmenorrhea in comparison to placebo or other therapy.[22] NSAIDs exert their benefit in the treatment of dysmenorrhea by inhibiting cyclooxygenase enzyme, thereby blocking prostaglandin productions.[23] In a systematic review comparing different NSAIDs to placebo in the treatment of dysmenorrhoea, Marjoribanks et al. concluded that no NSAIDs are safer or more effective than others.[24] However, there is evidence that around 20 percent of patients with dysmenorrhea do not respond to treatment with NSAIDs.[25] Fenamates (mefenamic acid) may have slightly better efficacy than the phenyl propionic acid derivatives (ibuprofen, naproxen) because fenamates have a dual action of blocking the production of PGs and inhibiting their action. [26][27] One study recommended ibuprofen and fenamates to be preferred in terms of safety and efficacy.[28] 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.[29][30][31] COX-2 selective NSAIDs can be used, taking into consideration its cardiovascular side effects; besides, they are not more effective or tolerable than NSAIDs.[32] COX-2 selective NSAIDs and its PGs inhibition mechanism have been linked to delayed ovulation [33][34]

Oral contraceptive pills (OCPs)are reported effective in reducing the dysmenorrheic pain compared to placebo among adolescents.[35][36][37][38] Many other studies argued against the effectiveness of OCPs as a treatment for dysmenorrhea due to small sample sizes and limited comparative data.[39][40] OCPs have a mechanism by limiting endometrial lining growth. It decreases the production of prostaglandins.[22] Low levels of PGs are noted in the menstrual fluid of women on OCPs. Contraceptive pills users appeared to have significantly lower rates of dysmenorrhea and needed less additional analgesics.[10]

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.[41][42][43] POPs mainly works by causing atrophy of the endometrial lining and by inhibiting ovulation.

Non-pharmacological Treatment

Maintaining an active lifestyle and a balanced diet that is rich in vitamins and minerals are generally recommended for better health outcomes. In particular, such diet and lifestyle are useful to reduce the intensity of the dysmenorrhea.[44][45][46]  

Though different types of exercise are generally recommended due to several health benefits and low or no risk, it also helps reduce the intensity of dysmenorrhea. No clear evidence about certain exercise activity or specific duration but moderate exercise is recommended, especially in obese women.[47]

Heat is effective compared to NSAIDs and seems to be preferred easy therapy option by many patients with no side effects. Still, high-quality studies needed.[48][49]

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.[50] The effectiveness of acupuncture is supported by a few studies which lack active comparisons and lack sound methodological techniques.[51][52][53]

Differential Diagnosis

Differential diagnosis of dysmenorrhea is broad, and it can be listed as gynecological conditions and non-gynecological conditions:[54] 

Gynecological conditions:

  • Endometriosis
  • 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.
  • 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).
  • Adnexal torsion
  • Adenomyosis
  • Pelvic inflammatory disease / sexual transmitted infections
  • Endometrial polyps
  • Asherman syndrome
  • Ectopic pregnancy
  • Chronic pelvic pain
  • Membranous dysmenorrhea

Non-Gynecological conditions: (gastrointestinal, urological, and musculoskeletal)

  • Irritable bowel syndrome
  • Urinary tract Infections
  • Interstitial cystitis
  • Musculoskeletal causes: abdominal wall muscles, the abdominal wall fascia, the pelvic and hip muscles, the sacroiliac joints, and the lumbosacral muscles

Prognosis

Dysmenorrhea has been associated with a major impact on woman's day to day life. Such impact is reflected in the rates of absenteeism from school or work. Dysmenorrhea could also limit women's participation in sports or social events. Furthermore, there are associated emotional stressors associated with dysmenorrhea. Dysmenorrhea is a public health matter that has an economic impact. Only in the United States, it is estimated to be around 140 million working hours per year.[55] However, with the recommended treatment options, the prognosis for primary dysmenorrhea is generally good. Mild and moderate dysmenorrhea usually responds well to NSAIDs. Severe dysmenorrhea still responds to NSAIDs but may require higher doses or using combination/adjuvant therapy. In the case of persistent dysmenorrhea, the secondary causes of dysmenorrhea should be investigated. Prognosis of secondary dysmenorrhea will depend on the type, location, and severity of the cause.

Complications

Primary dysmenorrhea complications can be summarized by the intensity of the pain affecting the women's wellbeing and their daily activities. Since primary dysmenorrhea is not linked to any pathology or disease, there are no known complications. In contrast, secondary dysmenorrhea complication varies depending on the etiology. Complications may include infertility, pelvic organ prolapse, heavy bleeding, and anemia.[18][56]

Deterrence and Patient Education

Balanced, healthier nutrition reduces the severity of dysmenorrhea.[57] Therefore, it is important to educate and create awareness among young women about the importance of proper balanced nutrition to prevent and reduce dysmenorrhea complications. Vitamins and dietary modifications have been associated with reduced menstrual pain.[45][58][59][58] 

More regular physical activity is effective in reducing dysmenorrhea complications. Exercise acts as non-specific analgesia by improving pelvic blood circulation and stimulating the release of beta-endorphins. The primary goal of treatment is to reduce the pain and improve the quality of life of patients suffering from dysmenorrhea. Hence analgesics should be given appropriately to allow women to perform there day to day chores. For those patients having dysmenorrhea along with heavy menstrual bleeding, endometrial ablation may be an option. Patients should be asked to follow up with their clinicians when dysmenorrheic symptoms are uncontrollable and bothersome.

Enhancing Healthcare Team Outcomes

The patient should be counseled appropriately regarding primary dysmenorrhea and complications associated with secondary dysmenorrhoea. The management of a patient with dysmenorrhea depends on the severity and will require an interprofessional team. The management should focus on making the patient comfortable with the treatment so that they can continue without restrictions there day to day activities.


References

[1] Vlachou E,Owens DA,Lavdaniti M,Kalemikerakis J,Evagelou E,Margari N,Fasoi G,Evangelidou E,Govina O,Tsartsalis AN, Prevalence, Wellbeing, and Symptoms of Dysmenorrhea among University Nursing Students in Greece. Diseases (Basel, Switzerland). 2019 Jan 8     [PubMed PMID: 30626091]
[2] Burnett M,Lemyre M, No. 345-Primary Dysmenorrhea Consensus Guideline. Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC. 2017 Jul;     [PubMed PMID: 28625286]
[3] French L, Dysmenorrhea. American family physician. 2005 Jan 15;     [PubMed PMID: 15686299]
[4] Chauhan M,Kala J, Relation between dysmenorrhea and body mass index in adolescents with rural versus urban variation. Journal of obstetrics and gynaecology of India. 2012 Aug;     [PubMed PMID: 23904707]
[5] Zebitay AG,Verit FF,Sakar MN,Keskin S,Cetin O,Ulusoy AI, Importance of cervical length in dysmenorrhoea aetiology. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2016 May;     [PubMed PMID: 27012227]
[6] Dawood MY, Current concepts in the etiology and treatment of primary dysmenorrhea. Acta obstetricia et gynecologica Scandinavica. Supplement. 1986;     [PubMed PMID: 3548208]
[7] Ju H,Jones M,Mishra G, The prevalence and risk factors of dysmenorrhea. Epidemiologic reviews. 2014;     [PubMed PMID: 24284871]
[8] Proctor M,Farquhar C, Diagnosis and management of dysmenorrhoea. BMJ (Clinical research ed.). 2006 May 13;     [PubMed PMID: 16690671]
[9] Lundström V,Gréen K,Svanborg K, Endogenous prostaglandins in dysmenorrhea and the effect of prostaglandin synthetase inhibitors (PGSI) on uterine contractility. Acta obstetricia et gynecologica Scandinavica. Supplement. 1979;     [PubMed PMID: 111466]
[10] Coco AS, Primary dysmenorrhea. American family physician. 1999 Aug;     [PubMed PMID: 10465224]
[11] Ylikorkala O,Dawood MY, New concepts in dysmenorrhea. American journal of obstetrics and gynecology. 1978 Apr 1;     [PubMed PMID: 25021]
[12] Mrugacz G,Grygoruk C,Sieczyński P,Grusza M,Bołkun I,Pietrewicz P, [Etiopathogenesis of dysmenorrhea]. Medycyna wieku rozwojowego. 2013 Jan-Mar;     [PubMed PMID: 23749700]
[13] Agarwal AK,Agarwal A, A study of dysmenorrhea during menstruation in adolescent girls. Indian journal of community medicine : official publication of Indian Association of Preventive     [PubMed PMID: 20606943]
[14] Alsaleem MA, Dysmenorrhea, associated symptoms, and management among students at King Khalid University, Saudi Arabia: An exploratory study. Journal of family medicine and primary care. 2018 Jul-Aug;     [PubMed PMID: 30234051]
[15] Zannoni L,Giorgi M,Spagnolo E,Montanari G,Villa G,Seracchioli R, Dysmenorrhea, absenteeism from school, and symptoms suspicious for endometriosis in adolescents. Journal of pediatric and adolescent gynecology. 2014 Oct;     [PubMed PMID: 24746919]
[16] Word RA,Kamm KE,Casey ML, Contractile effects of prostaglandins, oxytocin, and endothelin-1 in human myometrium in vitro: refractoriness of myometrial tissue of pregnant women to prostaglandins E2 and F2 alpha. The Journal of clinical endocrinology and metabolism. 1992 Oct;     [PubMed PMID: 1400867]
[17] Ekström P,Akerlund M,Forsling M,Kindahl H,Laudanski T,Mrugacz G, Stimulation of vasopressin release in women with primary dysmenorrhoea and after oral contraceptive treatment--effect on uterine contractility. British journal of obstetrics and gynaecology. 1992 Aug;     [PubMed PMID: 1390475]
[18] Bernardi M,Lazzeri L,Perelli F,Reis FM,Petraglia F, Dysmenorrhea and related disorders. F1000Research. 2017;     [PubMed PMID: 28944048]
[19] Falcone T,Flyckt R, Clinical Management of Endometriosis. Obstetrics and gynecology. 2018 Mar     [PubMed PMID: 29420391]
[20] Agarwal SK,Chapron C,Giudice LC,Laufer MR,Leyland N,Missmer SA,Singh SS,Taylor HS, Clinical diagnosis of endometriosis: a call to action. American journal of obstetrics and gynecology. 2019 Apr     [PubMed PMID: 30625295]
[21] Osayande AS,Mehulic S, Diagnosis and initial management of dysmenorrhea. American family physician. 2014 Mar 1;     [PubMed PMID: 24695505]
[22] Doty E,Attaran M, Managing primary dysmenorrhea. Journal of pediatric and adolescent gynecology. 2006 Oct;     [PubMed PMID: 17060018]
[23] Dawood MY, Ibuprofen and dysmenorrhea. The American journal of medicine. 1984 Jul 13;     [PubMed PMID: 6380282]
[24] Marjoribanks J,Proctor M,Farquhar C,Derks RS, Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. The Cochrane database of systematic reviews. 2010 Jan 20;     [PubMed PMID: 20091521]
[25] Owen PR, Prostaglandin synthetase inhibitors in the treatment of primary dysmenorrhea. Outcome trials reviewed. American journal of obstetrics and gynecology. 1984 Jan 1;     [PubMed PMID: 6419611]
[26] Budoff PW, Use of mefenamic acid in the treatment of primary dysmenorrhea. JAMA. 1979 Jun 22;     [PubMed PMID: 376875]
[27] Milsom I,Minic M,Dawood MY,Akin MD,Spann J,Niland NF,Squire RA, Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies. Clinical therapeutics. 2002 Sep;     [PubMed PMID: 12380631]
[28] Feng X,Wang X, Comparison of the efficacy and safety of non-steroidal anti-inflammatory drugs for patients with primary dysmenorrhea: A network meta-analysis. Molecular pain. 2018 Jan-Dec;     [PubMed PMID: 29587566]
[29] Armour M,Parry K,Al-Dabbas MA,Curry C,Holmes K,MacMillan F,Ferfolja T,Smith CA, Self-care strategies and sources of knowledge on menstruation in 12,526 young women with dysmenorrhea: A systematic review and meta-analysis. PloS one. 2019;     [PubMed PMID: 31339951]
[30] Ali Z,Burnett I,Eccles R,North M,Jawad M,Jawad S,Clarke G,Milsom I, Efficacy of a paracetamol and caffeine combination in the treatment of the key symptoms of primary dysmenorrhoea. Current medical research and opinion. 2007 Apr;     [PubMed PMID: 17407641]
[31] Di Girolamo G,Sánchez AJ,De Los Santos AR,González CD, Is acetaminophen, and its combination with pamabrom, an effective therapeutic option in primary dysmenorrhoea? Expert opinion on pharmacotherapy. 2004 Mar;     [PubMed PMID: 15013925]
[32] Harel Z, Cyclooxygenase-2 specific inhibitors in the treatment of dysmenorrhea. Journal of pediatric and adolescent gynecology. 2004 Apr;     [PubMed PMID: 15050982]
[33] Pall M,Fridén BE,Brännström M, Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: a randomized double-blind study. Human reproduction (Oxford, England). 2001 Jul;     [PubMed PMID: 11425807]
[34] Bata MS,Al-Ramahi M,Salhab AS,Gharaibeh MN,Schwartz J, Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study. Journal of clinical pharmacology. 2006 Aug;     [PubMed PMID: 16855077]
[35] Oral contraceptives are effective for dysmenorrhea. The Journal of family practice. 2005 Oct;     [PubMed PMID: 16237849]
[36] Audet MC,Moreau M,Koltun WD,Waldbaum AS,Shangold G,Fisher AC,Creasy GW, Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA. 2001 May 9;     [PubMed PMID: 11343482]
[37] Petraglia F,Parke S,Serrani M,Mellinger U,Römer T, Estradiol valerate plus dienogest versus ethinylestradiol plus levonorgestrel for the treatment of primary dysmenorrhea. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2014 Jun;     [PubMed PMID: 24713413]
[38] Callejo J,Díaz J,Ruiz A,García RM, Effect of a low-dose oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel on dysmenorrhea. Contraception. 2003 Sep;     [PubMed PMID: 14561538]
[39] Wong CL,Farquhar C,Roberts H,Proctor M, Oral contraceptive pill as treatment for primary dysmenorrhoea. The Cochrane database of systematic reviews. 2009 Apr 15;     [PubMed PMID: 19370576]
[40] Proctor ML,Roberts H,Farquhar CM, Combined oral contraceptive pill (OCP) as treatment for primary dysmenorrhoea. The Cochrane database of systematic reviews. 2001;     [PubMed PMID: 11687142]
[41] Casper RF, Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills. Fertility and sterility. 2017 Mar;     [PubMed PMID: 28162779]
[42] Strowitzki T,Faustmann T,Gerlinger C,Seitz C, Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study. European journal of obstetrics, gynecology, and reproductive biology. 2010 Aug;     [PubMed PMID: 20444534]
[43] Al-Jefout M,Nawaiseh N, Continuous Norethisterone Acetate versus Cyclical Drospirenone 3 mg/Ethinyl Estradiol 20 μg for the Management of Primary Dysmenorrhea in Young Adult Women. Journal of pediatric and adolescent gynecology. 2016 Apr;     [PubMed PMID: 26342733]
[44] Hosseinlou A,Alinejad V,Alinejad M,Aghakhani N, The effects of fish oil capsules and vitamin B1 tablets on duration and severity of dysmenorrhea in students of high school in Urmia-Iran. Global journal of health science. 2014 Sep 18;     [PubMed PMID: 25363189]
[45] Barnard ND,Scialli AR,Hurlock D,Bertron P, Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. Obstetrics and gynecology. 2000 Feb;     [PubMed PMID: 10674588]
[46] Abdul-Razzak KK,Ayoub NM,Abu-Taleb AA,Obeidat BA, Influence of dietary intake of dairy products on dysmenorrhea. The journal of obstetrics and gynaecology research. 2010 Apr;     [PubMed PMID: 20492391]
[47] Matthewman G,Lee A,Kaur JG,Daley AJ, Physical activity for primary dysmenorrhea: a systematic review and meta-analysis of randomized controlled trials. American journal of obstetrics and gynecology. 2018 Sep;     [PubMed PMID: 29630882]
[48] Akin MD,Weingand KW,Hengehold DA,Goodale MB,Hinkle RT,Smith RP, Continuous low-level topical heat in the treatment of dysmenorrhea. Obstetrics and gynecology. 2001 Mar;     [PubMed PMID: 11239634]
[49] Akin M,Price W,Rodriguez G Jr,Erasala G,Hurley G,Smith RP, Continuous, low-level, topical heat wrap therapy as compared to acetaminophen for primary dysmenorrhea. The Journal of reproductive medicine. 2004 Sep;     [PubMed PMID: 15493566]
[50]     [PubMed PMID: 11957721]
[51] Witt CM,Reinhold T,Brinkhaus B,Roll S,Jena S,Willich SN, Acupuncture in patients with dysmenorrhea: a randomized study on clinical effectiveness and cost-effectiveness in usual care. American journal of obstetrics and gynecology. 2008 Feb;     [PubMed PMID: 18226614]
[52] Helms JM, Acupuncture for the management of primary dysmenorrhea. Obstetrics and gynecology. 1987 Jan;     [PubMed PMID: 3540764]
[53] Shetty GB,Shetty B,Mooventhan A, Efficacy of Acupuncture in the Management of Primary Dysmenorrhea: A Randomized Controlled Trial. Journal of acupuncture and meridian studies. 2018 Aug;     [PubMed PMID: 29654840]
[54] Smorgick N,As-Sanie S, Pelvic Pain in Adolescents. Seminars in reproductive medicine. 2018 Mar;     [PubMed PMID: 30566977]
[55] Habibi N,Huang MS,Gan WY,Zulida R,Safavi SM, Prevalence of Primary Dysmenorrhea and Factors Associated with Its Intensity Among Undergraduate Students: A Cross-Sectional Study. Pain management nursing : official journal of the American Society of Pain Management Nurses. 2015 Dec;     [PubMed PMID: 26328887]
[56] Femi-Agboola DM,Sekoni OO,Goodman OO, Dysmenorrhea and Its Effects on School Absenteeism and School Activities among Adolescents in Selected Secondary Schools in Ibadan, Nigeria. Nigerian medical journal : journal of the Nigeria Medical Association. 2017 Jul-Aug;     [PubMed PMID: 31057207]
[57] Bajalan Z,Alimoradi Z,Moafi F, Nutrition as a Potential Factor of Primary Dysmenorrhea: A Systematic Review of Observational Studies. Gynecologic and obstetric investigation. 2019;     [PubMed PMID: 30630172]
[58] Ziaei S,Zakeri M,Kazemnejad A, A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea. BJOG : an international journal of obstetrics and gynaecology. 2005 Apr;     [PubMed PMID: 15777446]
[59] Proctor ML,Murphy PA, Herbal and dietary therapies for primary and secondary dysmenorrhoea. The Cochrane database of systematic reviews. 2001;     [PubMed PMID: 11687013]