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Introduction

Dysmenorrhea is a common gynecologic complaint in adolescent and young females. Different types of studies have found a consistently high prevalence of dysmenorrhea in women of different ages and nationalities with an estimated prevalence ranging from 45% to 97%.1, 2 and 3 As a disorder, dysmenorrhea is characterized by lower abdominal pain that occurs during menstruation.4 The severity of dysmenorrheal pain varies among different females. Approximately 10%-15% of women have severe dysmenorrhea.5 Severe dysmenorrhea can cause a substantial negative impact on women's daily activities during their reproductive age6, 7 and 8 in addition to significant costs to the health care system.9

 

There are 2 types of dysmenorrhea: primary, which occurs in the absence of organic pelvic diseases, and secondary, which is associated with certain specific diseases or disorders.10 The pathogenesis of primary dysmenorrhea is not fully understood. Prostaglandins seem to be well involved, causing uterine contractions and pain.11, 12, 13 and 14 Previously, we observed a strong correlation between dairy products intake and dysmenorrhea and its associated symptoms among university female students.13 The results of the study revealed that, out of 127 students included in the study, 111 students (87%) were dysmenorrheic. Approximately half of the sample studied decribed their dysmenorrheal pain as severe. A significantly higher percentage of participants expressing severe dysmenorrhea were found when their intakes of dairy products were none as compared to participants who took 3 or 4 servings per day (97% vs 36%). In addition, the severity of menstrual pain decreased with increasing the number of daily dairy products intake. No participants claimed to have very severe pain as their dairy intake was increased to 4 servings per day. The relationship between dietary calcium and the risk of dysmenorrhea was related to the physiological function of calcium which controls the contractility, tone, and relaxation of smooth muscles including uterus muscle. Low calcium level increases spasms and contractions of uterus muscle15 and 16 causing pain as a result of reduced blood supply to the uterus.17

 

Calcium is mostly found in 1 class of food, namely milk.18 and 19 While vitamin D sources are limited to a few foods, including fatty fish and their oils, or it may be fortified in certain foods such as milk and milk products, and can also be made in skin after exposure to sunlight, low dietary calcium intake have been shown.18, 20 and 21

 

Calcium homeostasis is managed through the concerted action of 3 hormones, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D) (the active form of vitamin D) and calcitonin. PTH is the major regulator of calcium in the extracellular fluid (ECF). As ECF calcium decreases, PTH is released to restore ECF calcium to normal by promoting renal tubular reabsorption of calcium, and enhances calcium and phosphate absorption by the intestine through stimulating the kidneys to produce 1,25(OH)2D and bone resorption.22 and 23 Increased 1,25(OH)2D inhibits the production of PTH.24 and 25

 

Parathyroid hormone (PTH) was inversely correlated with total calcium intake.26 Calcium supplementation is reported to inhibit PTH production and secretion even during vitamin D insufficiency in adults.27 and 28 While low dietary calcium intake have been shown to increase PTH and 1,25(OH)2D levels in animals.

 

As a result of available information and our previous research findings,13 we conclude that otherwise healthy adolescent and young females with severe and very severe dysmenorrhea may be at risk of developing secondary hyperparathyroidism.

 

This research was undertaken to evaluate vitamin D and parathyroid hormone status in a cohort of healthy adolescent and young females with severe and very severe dysmenorrhea.

 

Materials and Methods

Sample

Fifty-six young females with severe and very severe dysmenorrheal pain were recruited from the emergency department in King Abdullah University Hospital (KAUH), emergency department of University Teaching Primary Health Care Center, Jordan University of Science and Technology and by advertising the projects in schools of pharmacy, agriculture, and nursing for the period from January to April 2010. Institutional Review Board (IRB) Committee at Jordan University of Science and Technology approved this study. Written informed consent was obtained from all participants. Participants were excluded for use of calcium or vitamin D supplements on regular basis. Participants were instructed to complete a guided self-assessment questionnaire including their demographics and, information regarding menstruation. A detailed description of field data collection can be found elsewhere.13 Participants also answered questions regarding their daily exposure to sun light and the frequent use of sun screen.

 

Frequency and type of dairy product intake (milk, yogurt, cheese, and labanah which is a soft cream cheese made by removal of whey from yogurt through cheese cloths) were recorded. Intake of dairy products was determined on daily basis as none, single, 2, 3 or more dairy servings per day. A dairy serving is defined as: 1 cup of milk or yogurt, 2 tablespoons (2 oz) of labanah, or a piece of cheese, 1 ounce (about the size of domino or 2 fingers).

 

Pain severity was graded as the following13: Mild: pain that resolved without the need for medication; Severe: pain that is resolved with simple analgesics (NSAIDs, paracetamol); Very severe: pain that is not relieved with simple analgesics and may interfere with usual daily activities. Also Pain severity was assessed by using a 0-10 numerical rating scale (NRS).

 

Blood Samples

About 10 ml of venous blood samples was collected in heparinized tubes. Plasma was assayed for plasma 1,25(OH)2D level and intact parathyroid hormone (PTH) level using a chemiluminescent assay [modular E analyzer (Roche). Plasma Calcium (Ca), Magnesium (Mg), Phosphate (P) and] Alkaline Phosphatase (ALP) activity level were measured in modular P analyzer (Roche). Blood tests were performed in KAUH laboratory.

 

Definitions

Vitamin D status was divided into 3 diagnostic categories according to plasma 1,25(OH)2D levels. Vitamin D deficiency (<10 ng/ml), Vitamin D insufficiency (VDI), 10-19 ng/ml, and Vitamin D sufficiency (20-43 ng/ml). Normal reference values of other plasma measured parameters were defined as follows: PTH (13-54 pg/ml), Ca (2.1-2.6mmol/l), Mg (0.7-1.05mmol/l), P (0.8-1.6 mmol/l), and ALP (up to 240 IU/L). These reference ranges were provided by the manufacturer of the assay.

 

Statistical Analysis

Data were analyzed using the Statistical Package for Social Science (SPSS, version 16.0). Chi-square test was performed to test for differences between the variables of interest. P < .05 was considered statistically significant.

 

Results

The age of the participating female ranged between 17 and 24 years, with mean of 21.9 ± 2.76 years. The mean age at menarche was 13.6 ± 1.4 years and dysmenorrhea started at age of 15.7 ± 3.8.

 

Among participants; 25% have their dysmenorrheal pain started before the onset of menstruation; 12.5% have their dysmenorrheal pain onset during menstruation and the majority of participants (62.5%) had their dysmenorrheal pain started before the onset of menstruation and continued through the first two days of menses. Most of the participants (60.7%) described their menstrual pain as very severe (NRS average 8.73 ± 1), while 39.3% of participants reported severe dysmenorrhea (NRS average 7.53 ± 1.23). It was noticed that the majority of participants (94.6%) reported dysmenorrheal pain more frequently in the abdominal area radiating to the lower back and/or thighs. Among participants, 92.9% indicated that their daily activities were affected by dysmenorrhea for several days each month. In addition to pain, female students reported different symptoms associated with dysmenorrhea. Abdominal bloating was the most frequently reported symptom in the sample studied followed by dizziness, sweating, passage of loose stools, nausea and vomiting and (Figure 1).

 

 

With respect to treatment options for dysmenorrheal pain, 98.2% of participants used multiple treatments to relieve pain. NSAIDs were the most common followed by paracetamol while antispasmodics and herbal remedies came last (Figure 2). Regarding routes of drug administration (orally or injection), 16.1% of participants usually took the drug by injection, 39.3% both orally and by injection, and 41.1% took the drug orally.

 

 

Regarding dairy products intake, half of participants (n = 28) had dairy intake <1 serving per day, and 39.3% (n = 22) had dairy intake 1-2 servings per day, and only 10.7% (n = 6) of the participants had dairy intake of 3 or more servings per day.

 

In regard to the association between the daily intake of dairy products and severity of dysmenorrhea, our results revealed that the majority of participants who experienced very severe dysmenorrhea had dairy products intake <1 serving per day and a significantly lower number of participants reported very severe dysmenorrheal pain when dairy products intake increased up to 3 or more servings per day. The majority of participants who experienced severe dysmenorrhea had dairy product intake of 1-2 servings per day (Table 1).

 

 

The results of this study revealed that 78.6% (n = 44) of the participants exposed to the sun light. Daily sun exposure for 64.4% (n = 28) of the participants was <30 minutes and 35.6% (n = 16) of them their daily sun exposure were >30 minutes. More than half of the participants (53.6%, n = 30) used sun screen, with 39.3% of having used sun screen daily, while 7.1% and 12.5% used sun screen 4-5 and 2-3 times per week, respectively.

 

Prevalence of Vitamin D and PTH Status among the Study Population

The majority of the study participants (80.4%) had VDI. No significant difference in vitamin D status among the study population was found (Table 2). 48.2% of the study population had hyperparathyroidism (Table 3). No correlation of menstrual pain severity and vitamin D status, plasma calcium, and ALP activity was found.

 

 

Biochemical Characteristics of the Study Population

Plasma Calcium level and ALP activity were measured for 82.1% (n = 46) and 80.4% (n=45) of participants respectively due logistic difficulties.

 

The majority of participants had normal plasma calcium and ALP activity (82.1% and 80.4% respectively). All participants had normal plasma magnesium and phosphate levels. Plasma calcium and phosphate levels tend to increase while plasma PTH and ALP levels tend to decrease with better vitamin D status, but the association was not statistically significant.

 

Discussion

The most notable finding was a high prevalence of vitamin D insufficiency and hyperparathyroidism among otherwise healthy young adult females who experience severe and very severe dysmenorrhea.

 

In this study, the prevalence of vitamin D insufficiency and hyperparathyroidism among healthy adolescent and young females with severe and very severe dysmenorrhea is much higher than that reported by a recent national population-based household study29 and in a recent published study which involved 177 single and healthy college students who experienced primary dysmenorrhea.30 The prevalence of vitamin D status (1,25(OH)2D <30 ng/ml) among 5,640 subjects was 5.1% in males and 37.3% in females. Considering age groups, the prevalence of vitamin D insufficiency among 2099 females aged 19-39 years was 24.7% and vitamin D deficiency was16.1%. Plasma PTH level for the same age group was 28.7±18 pg/ml. While the prevalence of vitamin D insufficiency and hyperparathyroidism among healthy adolescent and young university female students with dysmenorrhea was 56.5% and 27.6% respectively.30

 

Vitamin D plays a central role in calcium hemostasis throughout life cycle.31 Vitamin D is biologically inert and must be metabolized by 2 steps of hydroxylation, first to 25-hydroxyvitamin replace D3 by D (1,25(OH)2D) in the liver and then to 1,25-dihydroxyvitamin D (1,25(OH)2D) in the kidney which enhances intestinal calcium and phosphate absorption, thereby promoting bone mineralization and maintaining bone health.32 and 33

 

When plasma vitamin D level is reduced to 30ng/ml or less, a significant decrease in intestinal calcium absorption will occur,23 associated with increased PTH to maintain plasma calcium level. Low dietary calcium intake has similar rseults.26, 27 and 28

 

The majority of the cases of primary dysmenorrhea usually begin during early adolescence10 and 13 when most of the increase in bone mass is achieved.34 Accordingly, females should achieve the highest bone density during early adolescence to avoid the development of osteomalacia and osteoporosis in older age.35 Therefore diet should deliver an adequate supply of dietary calcium, and vitamin D.

 

In this study, the majority of participants who experienced severe dysmenorrhea had insufficient circulating 1,25(OH)2D and about half of them had hyperparathyroidism. In addition, half of the participants have low dietary calcium intake 1< serving/day which is less than 1/3 of the recommended daily servings (3-4 servings of dairy products for 9 years and older19). Insufficient circulating 1,25(OH)2D and calcium intake <60% of total recommended daily was found to have negative influence on bone mineral density and increases the risk of osteopenia in children.23, 36 and 37

 

The findings of this research suggest that chronic severe and very severe dysmenorrhea in adolescent and young females results from inadequate intakes of calcium, consequently may negatively affect bone metabolism during achievement of peak bone mass at a young age and adverse bone health at older age.37 and 38 In addition to that, insufficient circulatory serum 1,25(OH)2D levels may predispose those adolescent and young females to the development of various nonskeletal chronic diseases such as hypertension, cardiovascular diseases, diabetes mellitus, as well as some inflammatory and autoimmune diseases, and some forms of cancers.39

 

Therefore, measuring circulatory 1,25(OH)2D level among young adult women who experience dysmenorrhea will have a positive impact on women's health, especially a beneficial effect of large dose of vitamin D supplementation on menstrual pain was observed.40

 

In this study, the majority of participants who experienced severe dysmenorrhea had dairy products intake of <1 serving per day. Therefore, low intake of dietary calcium may predispose to increase uterine cramping and pain among women with primary dysmenorrhea. This finding and explanation is supported by our previous report.13

 

The major determinant of vitamin D status is exposure to sunlight.41 Therefore factors that can influence the amount of UV light reaching the skin or lack of exposure to sun rays will affect vitamin D status. In this study, although the majority of participants are exposed to sun light, but only 35.6% of them had sun exposure >30 min/day and about half of them use sun screen. These lifestyle behaviors are also considered as an etiologic factors of vitamin D deficiency and insufficiency among the study population.

 

 

 

Acknowledgment

According to IRB recommendation, the biochemical results for each participant were handed in for medical record. Besides all participants were informed about the importance of adequate intakes of calcium and vitamin D through life. Participants were advised to consume 3 servings of dairy products daily and increase the exposure to direct sunlight. Participants with severe vitamin D deficiency were advised to visit family physician at KAUH or University Teaching Primary Health Care Center for appropriate treatment.