{"paper_id":"af849969-b663-4458-ba3e-567728e61c36","body_text":"Citation: Dawod LH, Mohmmed SJ and Seddiq WT. The Effect of Vitamin D on Dysmenorrheic Vitamin D \nDeficient Females (Single Centre Experiment). Austin J Obstet Gynecol. 2020; 7(2): 1159.\nAustin J Obstet Gynecol - Volume 7 Issue 2 - 2020\nSubmit your Manuscript | www.austinpublishinggroup.com \nDawod et al. © All rights are reserved\nAustin Journal of Obstetrics and Gynecology\nOpen Access\nAbstract\nAim: The aim of this study was evaluating the effect of vitamin D in the \ntreatment of dysmenorrhea in females who have vitamin D deficiency.\nMaterial and Methods: A total of 40 patients between 19 and 37 years \nof age who were diagnosed with dysmenorrhea were included in the study in \na randomized controlled manner. Cases were randomized into two groups of \n5000 IU vitamin D once a day and a group did not receive vitamin D starting at \nthe end of their menstrual cycle and continuing throughout two months study. \nSeverity of menstrual pain was measured with Visual Analogue Scale (VAS), \nas the primary outcome. Need for using Non-Steroidal Anti-Inflammatory Drugs \n(NSAIDs) during the study period was evaluated as the secondary outcome.\nResults: There were no significant difference in age, body mass index and \nbaseline VAS scores between groups. Pain severity of vitamin D group after \ntreatment was found significantly lower than the group did not receive vitamin D. \nMedian VAS scores of vitamin D group and the group did not receive vitamin D \nwere 2 (1-4) and 7 (6-9), respectively after treatment. Requirement of NSAIDs \nwas significantly less in vitamin D group than the group did not receive vitamin \nD.\nConclusion: Vitamin D has a clear effect in reducing the pain of \ndysmenorrhea in women with vitamin D deficiency.\nKeywords: Dysmenorrhea; Vitamin D; Vitamin D deficiency\nResearch Article\nThe Effect of Vitamin D on Dysmenorrheic Vitamin D \nDeficient Females (Single Centre Experiment)\nDawod LH*, Mohmmed SJ and Seddiq WT\nDepartment of Gynecology and Obstetrics, Al-Khanzaa \nTeaching Hospital, Iraq\n*Corresponding author: Lubna Hazim Dawod, \nDepartment of Gynecology and Obstetrics, Al-Khanzaa \nTeaching Hospital, Hay Nirkal, Mosul, Iraq\nReceived: November 15, 2020; Accepted: December \n21, 2020; Published: December 28, 2020\nIntroduction\nDysmenorrhea is pelvic or lower abdominal cyclic or recurrent \npain, associated with menstruation [1]. Systemic symptoms such \nas nausea, vomiting, diarrhea, fatigue and insomnia frequently \naccompany the pain [2-6]. Dysmenorrhea has a high prevalence \nranging from 45 to 93% of women of reproductive age [7]. \nDysmenorrhea is classified into primary dysmenorrhea, defined as \ncramps originating from the uterus during menstruation without any \nunderlying pelvic pathology, and secondary dysmenorrhea which is \nmenstrual pain resulting from underlying pelvic pathologies [4,7]. \nDysmenorrhea, when it is severe, can be associated with restriction \nof activity and absence from school or work [5]. Even with analgesics, \nmany women get unsatisfactory relief of pain and uptake self-care \nstrategies [9,10]. Pathogenesis of primary dysmenorrhea results from \nthe increased synthesis of prostaglandins PGs which play a significant \nrole in the development of uterine ischemia and hypoxia, resulting in \ndysrhythmic uterine contractions and decreased blood flow [11-14]. \nBoth pharmacological and non-pharmacological methods have been \nused to alleviate pain [9]. Pharmacological management involves the \nuse of analgesics (paracetamol & non-steroidal anti-inflammatory \ndrugs NSAIDs) [5]. NSAIDs are superior to paracetamol in pain \nrelief [3], they act through inhibition of prostaglandin synthesis [15] \nbut are associated with undesirable side effects that sometimes limit \ntheir use (e.g. gastro-intestinal discomfort and even bleeding) [16]. \nSelective COX-2 inhibitors are sometimes used as alternatives, still \nthey increase the risk of cardiovascular events with long term use [17].\nThe term “vitamin D” refers to both ergocalciferol (vitamin \nD2) and cholecalciferol (vitamin D3). Vitamin D3 is formed in the \nskin upon exposure to sunlight [18-20]. Vitamin D is enzymatically \nactivated. First, it is hydroxylated in liver to 25-hydroxy-cholicalciferol \n(25-(OH)D) (calcidiol), the major circulating form of vitamin D. \nThen it is converted in kidneys through 1α-hydroxylation to its \nmost active form, 1, 25-dihydroxycholecalciferol (1, 25-(OH)\n2D) \n(calcitriol) [21,22]. In tissues, 1, 25-(OH) 2D binds to intracellular \nVitamin D Receptors (VDR) [19]. The presence of the Vitamin D \nReceptor (VDR) and the expression of the 1α- hydroxylation enzyme \nin many cells and the large number of genes under the control of \n1,25-(OH)\n2D suggest a broader role of the vitamin D beyond bone \nand calcium homeostasis [23]. It was evidenced that 1,25-(OH) 2D \nmodulates cellular growth and differentiation. It also enhances the \nimmune system [19] and regulates the expression of several key genes \ninvolved in the PG pathway causing decreased biological activity \nof PGs [24]. The National Academy of Medicine considers a serum \n25-hydroxyvitamin D (25-(OH)D) level of 12 to 20 ng per mL (30 \nto 50 nmol per L) as the normal range. Individuals with levels less \nthan 12 ng per mL (30 nmol per L) will usually be deficient [25]. \nVitamin D deficiency has a high prevalence, about 50% in both \nnorthern and southern latitudes [26]. The main reason is inadequate \ncutaneous vitamin D synthesis (due to inadequate sun exposure) \n[21,26]. Our study is focusing on the effect of vitamin D deficiency on \ndysmenorrhea symptoms, which have been the subject of number of \nstudies in the last few years.\n\nAustin J Obstet Gynecol 7(2): id1159 (2020)  - Page - 02\nDawod LH Austin Publishing Group\nSubmit your Manuscript | www.austinpublishinggroup.com\nNO. Name Age BMI Serum 25-(OH)D3 before \ntreatment nmol/L VAS-1 Serum 25-(OH)D3 After 1 \nmonth treatment nmol/L VAS-2 Serum 25-(OH)D3 after 2 \nmonths treatment nmol/L VAS-3\n1 E. A 26 24 8.1 6 24 4 40 1\n2 S. H 26 23 8.1 8 25 5 43 4\n3 S. S 19 20.7 8.1 7 27 4 44 3\n4 R. K 29 30.2 8.1 9 23 6 45 4\n5 A. A 22 24.1 8.3 10 25 6 42 2\n6 M. K 21 26.5 8 7 26 4 41 1\n7 E. E 37 29 8 8 28 6 48 3\n8 S. R 30 24 9 8 27 7 46 3\n9 O. I 27 19.6 8 6 24 4 49 1\n10 N. M 36 27.3 8.2 9 22 6 42 2\n11 F. J 31 22.5 8.1 8 29 5 46 3\n12 A. G 28 20.7 8 7 24 5 44 2\n13 A. H 35 21.4 8 9 30 4 47 1\n14 S. F 33 28.4 8 6 22 4 48 1\n15 A. Ab 19 20.6 8.1 10 26 6 46 3\n16 Z. S 20 21.4 8.3 7 28 6 49 2\n17 S. A 21 20.7 8.1 7 25 6 44 4\n18 S. Ha 23 20.4 8 9 23 5 48 1\n19 R. A 34 19.6 8 7 26 5 48 3\n20 L. K 27 19.3 8 8 24 6 44 2\nMean Values 27.2 23.24 8.125 7.8 25.4 5.2 45.2 2.3\nTable 1: Results of participants in vitamin D group.\nNO. Name Age BMI Serum 25-(OH)D3 before \ntreatment nmol/L VAS-1 Serum 25-(OH)D3 After 1 \nmonth treatment nmol/L VAS-2 Serum 25-(OH)D3 after 2 \nmonths treatment  nmol/L VAS-3\n1 N. Z 21 19.7 8.2 9 9 7 8 7\n2 K. M 32 25 8.5 6 12 6 9 7\n3 A. G 32 20.7 9 10 8 8 9 7\n4 Z. R 30 21.4 8 8 14 9 12 8\n5 G. N 29 23.4 8 7 12 7 9 9\n6 R. A 26 22.2 8.3 9 8 9 8 8\n7 I. A 26 21.4 8.1 9 9 8 9 8\n8 F. Si 24 23 8.2 6 8 8 8 9\n9 M. M 30 25 7 7 9 7 8 7\n10 H. S 21 33.5 8.3 6 8.5 7 8 6\n11 A. N 34 32.8 8 8 12 6 9 7\n12 S. A 34 21.8 8 8 10 8 9 7\n13 J. J 20 20.7 8 8 12 8 11 8\n14 M. S 18 21.4 8.1 9 8 7 8 7\n15 H. B 20 23.5 8.3 7 9 7 8 7\n16 A. E 37 22.6 6 8 12 6 9 7\n17 R. M 31 24.9 8.3 9 8 8 9 7\n18 F. S 24 20.9 8 8 14 9 12 8\n19 R. K 18 19.9 8 7 12 7 9 9\n20 M. H 34 23.8 8 10 8 9 8 8\nMean Values 27.05 23.38 8.025 7.95 10.125 7.55 9 7.55\nTable 2: Results of participants in the group did not receive vitamin D.\n\nAustin J Obstet Gynecol 7(2): id1159 (2020)  - Page - 03\nDawod LH Austin Publishing Group\nSubmit your Manuscript | www.austinpublishinggroup.com\nObjective and Aim\nThe aim of this study was evaluating the effectiveness of two \nmonths treatment with 5000 IU of vitamin D in reducing symptoms \nof dysmenorrhea in women with vitamin D deficiency and \ndysmenorrhea.\nMaterials and Methods\nThis is a randomized single blind study. The participants were \nunaware of the study group. The study was conducted after approval \nof the ethics committee at Al-Khanzaa teaching hospital. A written \ninformed consent was obtained from 50 women aged between 19 and \n37 years complaining from dysmenorrhea. The study lasted for two \nmonths; started during March 2020 and ended in May 2020.\nInclusion criteria\n Eligible participants met the following inclusion criteria:\n1) Women had normal menstrual periods lasting 21 to 35 days, \nwith menstruation lasting 3 to 7 days.\n2) Women had to be healthy and taking no medications including \nvitamins, magnesium, calcium and oral contraceptives.\n3) Women had no history of gynecological disease.\n4) Current and previous use of intrauterine devices for \ncontraception within 6 months were not allowed.\nStudy design\nA total of 50 women were identified. Participants were randomly \nassigned to the treatment groups. Excluded members were eight \nwomen who were unwilling to continue and two women who became \npregnant. Finally, the analysis was conducted with 40 women; 20 \nin vitamin D group and 20 in the group did not receive vitamin D \n(Figure 1).\nList of results after randomization and throughout the study \nperiod. Severity of dysmenorrheic pain was determined based on \neach women’s self-perception of the pain (Table 1,2). Women were \nasked to mark on a 10 cm Visual Analogue Scale (VAS) anchored \nfrom zero “no pain at all” to 10 “the worst pain I have ever felt” to \nindicate the severity of dysmenorrheic pain. Use of NSAIDs was \nallowed and it had to be registrated. Participants were randomized \ninto 2 groups by simple randomization using random numbers \ntable. Twenty women were given 5000 IU of vitamin D once a day \nand 20 women did not receive vitamin D, beginning at the end of \ntheir menstrual cycle and continuing throughout two months study. \nThe primary aim was measuring the severity of menstrual pain by \na VAS. The secondary aim was the need to use NSAIDs during the \nstudy period. The severity of menstrual pain and serum 25-(OH)D\n3 \nlevels were measured monthly; at the beginning of study (baseline), \nafter one month and after two months of treatment. Serum 25-(OH)\nD3 was measured using electrochemiluminescence method. Statistical \nanalysis was performed using Microsoft Office Excel 2010 program. P \nvalue of <0.05 was considered significant.\nResults\nValues are shown in (Table 3). The median age was 27 (19-37) in \nvitamin D group and 27.5 (18-37) in the group did not receive vitamin \nD. The median Body Mass Index (BMI) was detected as 21.95 (19.3-\n30.2) in vitamin D group and 22.4 (19.7-33.5) in the group did not \nreceive vitamin D. The median baseline VAS scores were 8 (6-10) in \nvitamin D group and 8 (6-10) in the group did not receive vitamin D. \nThere were no significant difference in terms of age, BMI and baseline \nVAS scores between the two groups.\nThe treatment group showed significant difference in pain severity \nas measured on VAS score upon receiving vitamin D supplementation \ncompared to the group did not receive vitamin D where pain severity \nwas almost the same (Table 3,4). At the beginning of study baseline \nVAS score for participants in vitamin D group was (7.8±1.2SD), with \ntreatment VAS scores decreased to (5.2±0.95SD) after one month \nFigure 1: Study design.\nFigure 2: Average serum 25-(OH)D 3 of participants in vitamin D and the \ngroup did not receive vitamin D throughout the study.\nFigure 3: Average VAS scores of both groups throughout the study.\n\nAustin J Obstet Gynecol 7(2): id1159 (2020)  - Page - 04\nDawod LH Austin Publishing Group\nSubmit your Manuscript | www.austinpublishinggroup.com\ntreatment and then to (2.3±1.08SD) after two months treatment. As \nserum levels of 25-(OH)D 3 increased throughout treatment (Figure \n2) pain severity significantly decreased. The group of patients did \nnot receive vitamin D retained serum 25-(OH) D\n3 at almost constant \nlevel and showed no difference in pain severity (Figure 2,3). Baseline \nVAS scores were (7.95±1.2SD) in the group did not receive vitamin \nD and did not change significantly after one month of treatment \n(7.55±0.99SD); or after two months of treatment (7.55±0.82SD). \nRequirement of NSAIDs was significantly lower in vitamin D group \nthan the group did not receive vitamin D (4 participants vs 19 \nparticipants, p<0.001). We found significant decrease of pain severity \nin the vitamin D group. The median VAS scores after treatment were \nsignificantly lower in vitamin D group compared to the group did not \nreceive vitamin D (p<0.001; Table 4).\nDiscussion\n Dysmenorrhea is one of the most common gynecological problems \nand is a main cause for school and work abstinence. Dysmenorrhea \nhas been studied for long and the relationship between dysmenorrhea \nand vitamin D deficiency have been demonstrated in a number of \nstudies in the few lasts years. The first study was conducted by Lasco \net al., in Italy, high dose vitamin D (300,000 IU) was administered \nto women with primary dysmenorrhea five days before the putative \ndate of their next cycle. In this study, significant pain reduction has \nbeen reported as serum 25-hydroxycholicalciferol levels increased \nafter supplementation [24]. Moini et al., used the dosing schedule \nfor treatment of vitamin D deficiency 50,000 IU weekly for 8 weeks \ninstead of the high single dose (300,000 IU) and reported similar \nresults. This study also showed reduction in the need to NSAIDs upon \nthe use of vitamin D supplements [27]. Alshiagi et al., compared the \neffect of NSAIDs alone and the effect of combined use of vitamin \nD with NSAIDs for treatment of dysmenorrhea. Here, again higher \n \nVitamin D Did not receive vitamin D\nn=20 n=20\nMedian\nMean ±SD\nMedian\nMean ±SD\n(Min-Max) (Min-Max)\nAge 27 (19-37) 27.2±5.8 27.5 (18-37) 27.05±6.01\nBMI 21.95 (19.3-30.2) 23.24±3.3 22.4(19.7-33.5) 23.38±3.7\nVAS-1 8(6-10) 7.8±1.2 8 (6-10) 7.95±1.2\nTable 3: Baseline characteristics of the women with dysmenorrhea.\nMin: Minimum, Max: Maximum; SD: Standard Deviation; BMI: Body Mass Index; \nVAS-1: Baseline Visual Analogue Scale.\n \nVitamin D Did not receive vitamin D\nn= 20 n= 20\nMedian\nMean ±SD\nMedian\nMean ±SD\n(Min-Max) (Min-Max)\nVAS-1 8(6-10) 7.8±1.2 8 (6-10) 7.95±1.2\nVAS-2 5 (4-7) 5.2±0.95 7.5(6-9) 7.55±0.99\nVAS-3 2(1-4) 2.3±1.08 7(6-9) 7.55±0.82\nP <0.001 >0.05\nTable 4: VAS scores after drug regimen for each group.\nMin: Minimum; Max: Maximum; SD: Standard Deviation; VAS-1: Baseline Visual \nAnalogue Scale before treatment; VAS-2: Visual Analogue Scale after 1-month \ntreatment; VAS-3: Visual Analogue Scale after 2 months treatment.\ndegree of pain reduction have been demonstrated upon the addition \nof vitamin D to NSAIDs [28]. Ozel et al., compared supplementation \nwith vitamin D, E and Ibuprofen as for their effect in the treatment of \ndysmenorrhea; vitamin D showed comparable efficacy to ibuprofen \nand superior efficacy to vitamin E supplementation [29]. Another \nstudy conducted by Karacin et al., in Turkey showed that women \nwith low serum level of 25-hydroxy-D3 had more severe menstrual \nsymptoms [30].\nBecause the vitamin D receptor is widespread and the \nmitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D \nhydroxylase, is expressed in the human uterus and in immune system \ncells, and because vitamin D reduces the synthesis of PGs, a beneficial \neffect of vitamin D in the uterus pathophysiology is possible [24].\nIn the endometrium, the active form of vitamin D reduces the \nsynthesis of IL-6, TNF 20 and prostaglandins by suppressing COX-\n2 expression. Besides increasing prostaglandin inactivation of \n15-hydroxy prostaglandin dehydrogenase, high concentrations of 1, \n25(OH)-D inhibit PG21 receptor expression [31]. From all this the \nrole of vitamin D in dysmenorrhea had become evidenced. Our study \nsuggests the use of 5000IU of vitamin D in women with vitamin D \ndeficiency and dysmenorrhea for two months. The results from this \nstudy were comparable to those from previous studies with women \nreceiving vitamin D having much less menstrual pain. A daily dose of \n5000IU vitamin D boosts serum levels of 25-hydroxycholecalciferol. \nBased on this observation more attention should be paid to \nthe possibility of having vitamin D deficiency as the cause of \ndysmenorrhea. We used a different dosing schedule and obtained \ncomparable results to those of previous work conducted about the \nsame topic. Treatment of vitamin D deficiency markedly reduced the \nneed for NSAIDs.\nConclusion\nTo our knowledge, this is the first study that used 5000IU vitamin \nD as treatment for dysmenorrhea. A daily dose that is lower than \ntotal doses used at different intervals in previously conducted studies. \nIt was effective in reducing menstrual pain, reduced the need for \nNSAIDs. Future work should be directed towards finding if there is a \ndifference in the degree of pain reduction upon using higher or lower \ndoses of vitamin D and on finding what could be a better effective \ndosing schedule in women without vitamin D deficiency.\nReferences\n1. Gerzon LR, Padilha JF, Braz MM, Gasparetto A. Physiotherapy in primary \ndysmenorrhea: literature review*. Rev Dor. Sao Paulo. 2014; 15:290-295.\n2. Stella I, Avidon I, Baker FC. What we know about primary dysmenorrhea \ntoday: a critical review. Human Reproduction Update. 2015; 21: 762-778.\n3. Proctor M, Farquhar C. Diagnosis and management of dysmenorrhea. BMJ. \n2006; 332: 1134-1138.\n4. Osyande AS, Mehulic S. Diagnosis and Initial Management of Dysmenorrhea. \nAmerican Family Physician. 2014; 89: 341-346.\n5. Burnett M, Winnipeg, Lemyre M. No. 345-Primary Dysmenorrhea Consensus \nGuideline. Jogc Juillet. 2017; 39: 585-595. \n6. Hong J, Mark J, Gita M. The Prevalence and Risk Factors of Dysmenorrhea. \nEpidemiol Rev. 2014; 36: 104-113.\n7. Bernardi M, Lazzeri L, Perelli F, Reis FM, Petraglia F. Dysmenorrhea and \nrelated disorders. F1000Research. 2017; 6: 1645.\n\nAustin J Obstet Gynecol 7(2): id1159 (2020)  - Page - 05\nDawod LH Austin Publishing Group\nSubmit your Manuscript | www.austinpublishinggroup.com\n8. Sahin N, Kasap B, Kirli U, Yeniceri N, Topal Y. Assessment of anxiety-\ndepression levels and perceptions of quality of life in adolescents with \ndysmenorrhea. Reproductive Health. 2018 ;15.\n9. Armour M, Smith CA, Steel KA, Macmillan F.  The effectiveness of self-care \nand lifestyle interventions in primary dysmenorrhea: a systematic review and \nmeta-analysis. BMC Complementary and Alternative Medicine. 2019; 19: 22.\n10. Armour M, Parry K, Al-Dabbas MA, Curry C, Holmes K, MacMillan F, et al. \nSelf-care strategies and sources of knowledge on menstruation in 12,526 \nyoung women with dysmenorrhea: A systematic review and meta-analysis. \nPLoS One. 2019; 14: e0220103. \n11. Sharghi M, Mansourkhani SM, Ashtary-Larky D, Kooti W, Niksefat M, \nFiroozbakht M, et al. An update and systematic review on the treatment of \nprimary Dysmenorrhea. JBRA Assisted Reproduction. 2019; 23: 51-57.\n12. Ricciotti E, FitzGerald GA. Prostaglandins and Inflammation. Arterioscler \nThromb Vasc Biol. 2011; 31: 986-1000.\n13. Sugimoto Y, Inazumi T, Tsuchiya S. Roles of prostaglandin receptors in \nfemale reproduction. J Biochem. 2015; 157: 73-80.\n14. Dehnavi ZM, Jafarnejad F, Kamali Z. The Effect of aerobic exercise on \nprimary dysmenorrhea: A clinical trial study. Journal of Education and Health \nPromotion. 2018; 7: 1-2.\n15. Oladosu FA, Frank F Tu, Hellman KM.  NSAID resistance in dysmenorrhea: \nepidemiology, causes, and treatment. Am J Obstet Gynecol. 2018; 218: 390-\n400. \n16.  Sharghi M, Mansourkhani SM, Ashtary-Larky D, Kooti W, Niksefat M, \nFiroozbakht M, et al. An update and systematic review on the treatment of \nprimary Dysmenorrhea. JBRA Assisted Reproduction. 2019; 23: 51-57.\n17. Feng X, Wang X. Comparison of the efficacy and safety of non-steroidal anti-\ninflammatory drugs for patients with primary dysmenorrhea: A network meta-\nanalysis. Molecular Pain. 2018; 14: 1744806918770320.\n18. Zhang R, Naughton DP.  Vitamin D in health and disease: Current \nperspectives. Nutrition Journal. 2010; 9: 65.\n19. Pludowski P, Holick, Michael FH, Grant WB, Konstantynowicz J, Mascarenhas \nMR, Haq A, et al. Vitamin D supplementation guidelines. Journal of Steroid \nBiochemistry & Molecular Biology. 2018; 175: 125-135.\n20.  Pilz S, Zittermann A, Trummer C, Theiler-Schwetz V, Lerchbaum E, Keppel \nMH, et al. Vitamin D testing and treatment: a narrative review of current \nevidence. Endocrine Connections. 2019; 8: R27-R43.\n21.  Chang S-W, Lee H-C. Vitamin D and health - The missing vitamin in humans. \nPediatrics and Neonatology. 2019; 60: 237-244.\n22. Aatsinki S-M, Elkhwanky M-S, Kummu O, Karpale M, Buler M, Viitala P, et \nal. Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, \na Mechanism for Vitamin D Deficiency in Diabetes. Diabetes. 2019; 68: 918-\n931.\n23.  Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-\nPietsch B, Bianchi ML, et al. Current vitamin D status in European and Middle \nEast countries and strategies to prevent vitamin D deficiency: a position \nstatement of the European Calcified Tissue Society. European Journal of \nEndocrinology. 2019; 180: P23-P54.\n24. Lasco A, Catalano A, Benvenga S. Improvement of Primary Dysmenorrhea \nCaused by a Single Oral Dose of Vitamin D: Results of a Randomized, \nDouble-blind, Placebo-Controlled Study. Arch Intern Med. 2012; 172: 366-\n367.\n25.  LeFerve ML, LeFerve NM. Vitamin D Screening and Supplementation in \nCommunity-Dwelling Adults: Common Questions and Answers. American \nFamily Physician. 2018; 97: 254-260.\n26. Bashmakova NV, Lisovskaya TV, Vlasova VY. Pathogenetic role of vitamin \nD deficiency in the development of menstrual dysfunction in pubertal girls: a \nliterature review. Gynecological Endocrinology. 2017; 33: 52-55.\n27. Moini A, Ebrahimi T, Shirzad N, Hosseini R, Radfar M, Bandarian F, et al. \nThe effect of vitamin D on primary dysmenorrhea with vitamin D deficiency: \na randomized double blind controlled clinical trial. Gynecol Endocrinol. 2016; \n32: 502-504.\n28.  Lama A, Najla A, Azzah A, Areej A, Alaa E, Alsuwaidan S. Vitamin \nD Supplements as Adjunctive Therapy with Analgesics for Primary \nDysmenorrhea: A Randomized Clinical Trial. International Journal of \nReproductive Medicine & Gynecology. 2019.\n29. Ozel A, Ates S, Sevket O, Demir M, Ilhan G, Davutoglu E. A Randomized \nControlled Study of Vitamin D in the Treatment of Primary Dysmenorrhea. \nDuzce Medical Journal. 2019; 21: 33-36.\n30. Karacin O, Mutlu I, Kose M, Celik F, Kanat-Pektas M, Yilmazer M. \nSerum vitamin D concentrations in young Turkish women with primary \ndysmenorrhea: A randomized controlled study. Taiwanese Journal of \nObstetrics & Gynecology. 2018; 57: 58-63.\n31. Halpern G, Schor E, Kopelman A. Nutritional aspects related to endometriosis.  \nRev Assoc Med Bras. 2015; 61: 519-523.","source_license":"CC0","license_restricted":false}