A comparison of the effect of Vitamin D and Vitamin E supplementations, alone, and in combination, on reducing the intensity and duration of dysmenorrhea in women: A randomized controlled trial

Tahereh Behrouzi Lak; Nader Aghakhani; Davoud Vahabzadeh; Samereh Eghtedar; Rozita Cheraghi; Nazafarin Ghasemzadeh; Vahid Alinejad; Maryam Mesgarzadeh

doi:10.4103/jin.jin_49_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 5 | Issue : 1 | Page : 21-26

A comparison of the effect of Vitamin D and Vitamin E supplementations, alone, and in combination, on reducing the intensity and duration of dysmenorrhea in women: A randomized controlled trial

Tahereh Behrouzi Lak¹, Nader Aghakhani², Davoud Vahabzadeh³, Samereh Eghtedar⁴, Rozita Cheraghi⁴, Nazafarin Ghasemzadeh⁵, Vahid Alinejad⁶, Maryam Mesgarzadeh⁷
¹ Reproductive Health Research Center, Urmia University of Medical Sciences, Urmia, Iran
² Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran
³ Department of Nutrition and Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
⁴ Department of Medical Surgical Nursing, School of Nursing and Midwifery, Urmia University of Medical Sciences, Urmia, Iran
⁵ Department of Medical Ethics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
⁶ Department of Biostatics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
⁷ Department of Midwifery, School of Nursing and Midwifery, Urmia University of Medical Sciences, Urmia, Iran

Date of Submission	25-May-2022
Date of Decision	25-Jul-2022
Date of Acceptance	18-Jan-2023
Date of Web Publication	23-Mar-2023

Correspondence Address:
Dr. Nader Aghakhani
Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia
Iran

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jin.jin_49_22

Abstract

Objective: The aim of this study is to compare the effect of Vitamin D and Vitamin E supplementations, alone, and in combination, on reducing the intensity and duration of dysmenorrhea in women who were referred to the Kowsar gynecological clinics of Shahid Motahari Hospital of Urmia University of Medical Sciences.
Materials and Methods: A double-blinded clinical trial was conducted on 112 women with dysmenorrhea who were randomly allocated into the four study groups. Finally, 100 women complete the study and received capsules containing a placebo (n = 25), 1000 IU of Vitamin D (n = 25), 400 mg of Vitamin E (n = 25), and 1000 IU of Vitamin D + 400 mg of Vitamin E (n = 25) every 24 h for 2 consecutive months at the beginning of the menstrual period. The pain intensity and duration among groups were compared before and after the intervention.
Results: The mean menstrual pain duration in all three experimental groups (Vitamin E, Vitamin D, and the combination of them) was lower than the placebo group (all P < 0.05), and the mean pain intensity scores in all three experimental groups were significantly lower than the placebo group (all P < 0.05). The results (means) for all of the drugs administered at the end of the 2^nd month were better than the 1^st month (all P < 0.01).
Conclusions: Vitamin E and Vitamin D, as well as their combination, are recommended as an effective and safe treatment for the management of the complications of dysmenorrhea.

Keywords: Duration, dysmenorrhea, intensity, randomized controlled trial, Vitamin D, Vitamin E, women

How to cite this article:
Behrouzi Lak T, Aghakhani N, Vahabzadeh D, Eghtedar S, Cheraghi R, Ghasemzadeh N, Alinejad V, Mesgarzadeh M. A comparison of the effect of Vitamin D and Vitamin E supplementations, alone, and in combination, on reducing the intensity and duration of dysmenorrhea in women: A randomized controlled trial. J Integr Nurs 2023;5:21-6

How to cite this URL:
Behrouzi Lak T, Aghakhani N, Vahabzadeh D, Eghtedar S, Cheraghi R, Ghasemzadeh N, Alinejad V, Mesgarzadeh M. A comparison of the effect of Vitamin D and Vitamin E supplementations, alone, and in combination, on reducing the intensity and duration of dysmenorrhea in women: A randomized controlled trial. J Integr Nurs [serial online] 2023 [cited 2023 May 27];5:21-6. Available from: https://www.journalin.org/text.asp?2023/5/1/21/372414

Introduction

Menstruation is a physiological occurrence that serves as a key predictor of a woman's endocrine, reproductive, and overall health. Dysmenorrhea is defined as pelvic pain and is associated with excessive bleeding or irregular bleeding. Dysmenorrhea, also known as painful menstruation, is a gynecologic condition that causes a lot of discomforts such as backache, bloating, nausea and vomiting, diarrhea, dizziness, and headaches, accompanied by cramping and painful sensations in the lower abdomen.^[1] It can interfere with daily activities and lead to infertility and a reduction in the patients' quality of life.

Some pharmacological treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or contraceptives, have been used for decreasing the problems with many side effects, making them contraindicated for a large number of patients.^[2],[3] Complementary, nonpharmacologic, and alternative medicine, such as supplement or vitamin administration, have been used as a new approach with fewer side effects that can reduce the inflammatory stimulus without the unpleasant effects of chemical drug administration.^[4],[5] Vitamin E has been discovered to be an arachidonic acid inhibitor, allowing it to release and convert arachidonic acid to prostaglandin, increasing internal endorphin and reducing pain.^[6] It is a fat-soluble antioxidant whose deficiency can result in poor conduction of impulses along nerves that cause peripheral myopathies and neuropathies.^[7] Possible proposed mechanism for Vitamin D in the alleviation of dysmenorrhea complications is its anti-inflammatory effects on tumor necrosis factor and cytokines, which reduce the release of prostaglandins.^[8]

The role of these vitamins in reducing dysmenorrhea and having beneficial effects on women's daily and social activities has been implicated. Therefore, our study was carried out to compare the effect of Vitamin D and Vitamin E supplementations, alone, and in combination, on reducing the intensity and duration of dysmenorrhea in women who were referred to the Kowsar gynecological clinics of Shahid Motahari Hospital of Urmia University of Medical Sciences.

Materials and Methods

Ethical considerations

The study protocol was approved by the Ethical Committee of Urmia University of Medical Sciences with an allocated ethical code number (IR.UMSU.Rec. 1394.63) in 2019. Furthermore, this study was registered in the Iranian Clinical Trial System (Identifier code: (IRCT20160308026962N4). The participants signed a written informed consent form in accordance with the Helsinki Declaration.^[9]

Study design

This is a double-blind, randomized, placebo-controlled clinical trial. The study was carried out for 2 consecutive months at the beginning of the menstrual period.

Participants

The following were the inclusion criteria: Being between the ages of 18 and 50, having no current history of gynecologic or psychological diseases, having no stressful events, having no urogenital disorders, having no abnormal vaginal and cervical secretions, no use of herbal remedies, being a nonsmoker or nonalcoholic, no coagulation disorders, irregular menstrual cycles, no history of pelvic or abdominal surgery, and no history of uterine and ovarian disorders. Furthermore, patients who had a history of primary dysmenorrhea over three menstrual cycles for at least 1 day per month.

Exclusion criteria included gastrointestinal disorders, mental illness and sedate use, hormonal contraceptive use, pregnancy, heart and kidney disease, an allergy to Vitamin D and E supplements, and an unwillingness to participate in the study.

Sample size and randomization

The sample size in this study was calculated using a parallel clinical trial formula: N = 2 ([z1/2 + z1] 2. s2)/d2.^[10] In this formula, n is the number of subjects in each bunch. For estimating sample size, we considered type one and type two errors of 0.05 and 0.20 (power = 80%), respectively. Therefore, 112 eligible women were allocated into four groups, each with 28 members. The flow diagram of subjects in each group at each stage is depicted in [Figure 1]. The sampling process is shown in [Figure 1].

Figure 1: CONSORT 2010 flow diagram

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Using computer-based randomization, participants were randomly allocated to the Vitamin E group, Vitamin D group, Vitamin E + Vitamin D group, and placebo group at the allocation ratio of 1:1. With regard to the number of subjects within each group, the codes have been created for each subject in one group. At the time of delivering drugs, one capsule inside one concealed box with one of the below codes was given.

Intervention

Participants received drug boxes monthly, and possible adverse drug reactions were explained for all of them. The Vitamin E group received a package of capsules containing 400 mg of Vitamin E; the Vitamin D group used a package of capsules containing 1000 IU of Vitamin D (D-Vigel, Dana Pharmaceutical Co, Iran); the Vitamin E + Vitamin D group used a package of capsules containing 1000 IU of Vitamin D and capsules containing 400 mg of Vitamin E; and placebo group used a package of received placebo capsules containing starch in the 1^st and 2^nd month (three menstrual cycles). All subjects were recommended to take medicines and continue consumption after the onset of menstrual flow. The severity of dysmenorrhea was evaluated after the end of menstruation.

Outcome measures

Participants were given a form to fill out about demographic characteristics, the first onset of pain, history of sedative usage, intensity, menstrual cycle, and duration of menstrual pain. The intensity and duration of pain before and after the intervention were compared. The samples were delivered supplements in the 1^st and 2^nd months (three menstrual cycles) for 2 consecutive months at the beginning of the menstrual period.

The participants were given a form of Visual Analog Scale (VAS) to rate the severity of their menstrual pain, and they were asked to determine the intensity of pain at the first onset of bleeding, and 1 and 2 months later (two occurrences of dysmenorrhea). Absolute analgesia and intolerable pain are indicated by a horizontal line rated from 0 to 10 on the VAS. The patients were taught to mark the severity of their pain on a ruler.

The duration of pain from the onset of dysmenorrhea was measured using Cox Menstrual Symptom Scale (CMSS). The CMSS includes 17 items measuring pain duration on a five-point scale.^[11]

Statistical methods

Statistical Package for the Social Sciences SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc. (IBM Company, USA) was used to analyze the data. The data were presented using descriptive tests such as frequency, percentage, mean, and standard deviation (SD), and analyzed using t-tests, Mann–Whitney, and Kruskal–Wallis tests. Variable changes were expressed as mean ± SD. P < 0.05 was regarded as statistically significant.

We used the Cochrane risk of bias tool, including selection bias (random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome data), reporting bias (selective reporting), and other biases.

Results

At the end, a total of 100 participants completed the study. The mean age, the mean age of menstrual cycle initiation, the mean age for the first time of pain triggering, and the history of sedative usage are presented in [Table 1]. There was not any statistically significant difference in the mean age of the groups (P = 0.69). Seventy-six percentage of the subjects had missed daily activities due to dysmenorrhea, and 38% had a family history of dysmenorrhea.

Table 1: Baseline characteristics of the participants

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Before supplement administration, the mean scores of maximum pain intensity in all groups (except the placebo group) were greater than those 1 and 2 months later (P < 0.001) [Table 2].

Table 2: Comparison of pain intensity visual analog scale scores within and between groups (mean±standard deviation)

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The duration of symptoms associated with menstruation was significantly lower after the treatment in comparison with the before the administration of Vitamin E (P < 0.001), Vitamin D (P = 0.01), and both of them (P < 0.001), respectively [Table 3].

Table 3: Comparison of duration of pain within and between groups based on the Cox Menstrual Symptom Scale (mean±standard deviation, days)

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Discussion

Dysmenorrhea is one of the most widespread forms of illness that many women face. Moreover, it can create a sense of fear from the beginning to the next cycle, compromising psychological health. In addition to financial burdens, it may also affect their social and familial relations. It is one of the most reasons for their referring to female obstetrics and gynecology clinicians.^[9],[12] It has been proposed that some vitamin supplements may reduce pain severity and duration through anti-inflammatory effects mediated by reducing cytokines and tumor necrosis factor, as well as decreasing the release of prostaglandins in other ways.^[12] As a result, they may be suitable substitutes for nonsteroidal anti-inflammatory drugs (NSAIDs) in contraindicated patients. Researchers have recently considered complementary and alternative medicine approaches for the treatment of dysmenorrhea, such as Vitamin D and Vitamin E supplementation prescriptions. Vitamin D suppresses T-cell responses and decreases pro-inflammatory cytokines levels, which have anti-inflammatory properties. Vitamin E has antioxidant properties in the nervous and musculoskeletal systems, which may help to reduce pain.^[13],[14]

This study was carried out to compare the effects of Vitamin D and Vitamin E supplementations, as well as their combination, on the duration and intensity of dysmenorrhea in a sample population of Iranian women in Urmia. The mean period and maximum pain intensity in all groups (except the placebo group) were more than those at 1 and 2 months later. Before supplement administration, the mean period and maximum pain intensity in all groups (except the placebo group) were greater than the mean of maximum pain at 1 and 2 months later. Most previous studies have assessed the effects of Vitamin D or Vitamin E separately but not in combination on relieving dysmenorrhea pain.^{[6],[7],[10],[15]} However, in the current study, not only the effect of each supplement has been assessed alone, but also their combination has been studied. Another difference is that the effect of applied supplements has been measured not only immediately at the end of the study, but also in 1 and 2 months later.

In a study by Nayeban et al.,^[16] Vitamin E was discovered to be helpful for treating dysmenorrhea complications. They found a significant difference in pain severity and duration between the pre-and posttreatment periods in the Vitamin E-treated group, so their findings are similar to ours in this regard. In our study, we used Vitamin E alone and in combination with Vitamin D, and we evaluated their benefits in three phases after the intervention, which is one of the major differences between the two studies. In comparison with the control group, the duration of the menstrual cycle and the intensity of dysmenorrhea pain were significantly reduced in all of the experimental groups. A study by Pakniat et al.^[17] was found that Vitamin D and Vitamin E supplementation significantly lessened the severity of dysmenorrhea. Moreover, they have emphasized that treating with ginger, followed by Vitamin D and Vitamin E supplementation, has the most significant pain-relieving effect. Although these two studies presented the same results in terms of the effect of Vitamin E supplements on primary dysmenorrhea,^[17],[18] they were conducted in different ways than ours. In another study, the effect of Vitamin E supplementation was surveyed, but not alone or in combination with other nutrients such as omega-3 fatty acid supplements. Similar results were reported that Vitamin D supplementation reduced the intensity of pain and duration of menstrual bleeding as well as the effectiveness of NSAID medicines in women with dysmenorrhea.^[19],[20] Furthermore, it has been observed that a high dose of Vitamin D supplementation may alleviate premenstrual syndrome or menstrual complications, in spite of its sedative effects on the physical and psychological symptoms.^[21] Lasco et al.^[8] used Vitamin D before menstruation in women with painful menstruation who also had a low Vitamin D level in their serum and showed a reduction in dysmenorrhea disorders. Findings of this study showed that simultaneous prescriptions of Vitamin D and Vitamin E can be used for dysmenorrhea instead of NSAIDS, with fewer complications.

However, the effects of Vitamin D supplementation alone, not in combination with the other nutrients, were studied, and were found that Vitamin D supplementation can relieve the severity of dysmenorrhea symptoms, and that low Vitamin D intake is linked to the aggravation of menstrual complications.^{[22],[23],[24]}

This study's weaknesses and strengths are related to some participants' unwillingness to cooperate and the exclusion that resulted from it. Due to cost constraints, we were unable to measure the participants' Vitamin D and Vitamin E levels before and after the intervention, as well as the impact of the intervention on other biochemical parameters. Because the intervention effects may be influenced by baseline vitamin levels, this can be seen as a drawback for this study, particularly in terms of its generalizability. The type of clothing of Iranian Muslim women affects the amount of sunlight and Vitamin D intake and the generalizability of the results. Further research is needed to determine the cutoff value of Vitamin D in the Iranian context contributing to dysmenorrhea.

The results of this investigation were statistically presented, but more studies with larger sample sizes, diverse dosages, controlling contextual limitations, and longer durations are required to understand the therapeutic implications of these results. This study has shown that Vitamin D and E administration can lessen pain intensity and improve systemic symptoms in women with primary dysmenorrhea. Supplementing with Vitamin D and E may be an efficient and secure method for the supplemental treatment of primary dysmenorrhea.

Conclusions

As a result of our research, we can conclude that the use of Vitamin E and D supplementation is effective and safe for the complementary treatment of dysmenorrhea and can be used to replace chemical drugs with safe and cost-effective alternatives. Large-scale controlled trials, as well as meta-analyses and systematic reviews, are recommended for validating and applying these findings in clinical practice.

Acknowledgments

The authors gratefully acknowledge the research vice chancellor of the Urmia University of Medical Sciences for assistance with regard to the funds and support for conducting this study. The authors are also grateful to the managers and staff of Kowsar gynecological clinic of Shahid Motahari Hospital in Urmia University of Medical Sciences.

Financial support and sponsorship

This study was supported financially by the vice chancellery at the research of the Urmia University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.

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