Dysmenorrhea, PTH, Dietary Calcium and Vitamin D
Khalid K. Abdul-Razzak, PhD
Department of Clinical Pharmacy
Faculty of Pharmacy, Jordan University of Science and Technology
PO Box 3030, Irbid-22110, Jordan
00962 2 7201000 Ext. 23526 / 00962 2 7201075 (FAX)
kkalani@just.edu.jo

“Vitamin D and PTH Status Among Adolescent and Young Females with Severe Dysmenorrhea,”
J Pediatr Adolesc Gyneco, 2014 Jan 6; [Epub ahead of print]. 49819 (3/2014)

KH: Can you please share with us your educational background and current position?

Khalid K. Abdul-Razzak: I have a BSc in Biochemistry from University of Baghdad, Iraq and PhD in Biochemistry from Kansas State University (KSU), USA. I completed my postdoctoral fellowship in the Department of Biochemistry at KSU also. I worked in the Clinical Biochemistry Laboratory, AL-Rasheed Military Hospital in Iraq, before starting an academic position at Al-Anbar University, School of Medicine, Iraq. Currently I am a professor in the Department of Clinical Pharmacy, School of Pharmacy, Jordan University of Science and Technology in Jordan, lecturing in biochemistry, clinical biochemistry and clinical nutrition.

KH: What got you interested in studying the role of vitamin D and parathyroid metabolism and dysmenorrhea?

KKAR: It is known that, calcium homeostasis is managed through the concerted action of three hormones, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D) (the active form of vitamin D) and calcitonin. Vitamin D controls calcium absorption in the small intestine, while PTH is the major regulator of calcium in the extracellular fluid (ECF).

We are the first to observe a strong correlation between dairy products intake and dysmenorrhea and its associated symptoms among university female students (1). 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 three or four 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 four servings per day.

So it is logically to link vitamin D to the etiology of dysmenorrhea. While measuring PTH, calcium, phosphorus and alkaline phosphatase activity along with vitamin D level helps in excluding primary hyperparathyroidism

KH: What is the biochemistry of vitamin D that might alter the pathophysiology of dysmenorrhea?

KKAR: Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism throughout life cycle. Vitamin D works with parathyroid hormone to maintain calcium homeostasis in the blood stream through enhancing intestinal calcium absorption, reduces calcium excretion in urine and mobilize calcium from the bones (bone resorption). The relationship between dietary calcium and the risk of dysmenorrhea was related to physiological function of calcium which is controlling the contractility, tone, and relaxation of smooth muscles including the uterus muscles. Therefore low calcium levels resulted from vitamin D deficiency or low dietary intake increases spasms and contractions of uterus muscle causing pain.

KH: What is the biochemistry of hyperparathyroidism that might alter the pathophysiology of dysmenorrhea?

KKAR: I don’t think PTH is involved in the pathophysiology of dysmenorrhea. Reduced intestinal calcium absorption as a result of an inadequate supply of vitamin D or low dietary calcium intake results in a compensatory rise in parathyroid hormone (PTH). Therefore we routinely measure vitamin D, PTH, calcium, phosphate and alkaline phosphatase activity levels to exclude any case of primary hyperparathyroidism if any. Besides secondary hyperparathyroidism may negatively affect bone metabolism during achievement of peak bone mass at a young age and adversely affect bone health at an older age of adolescent and young adult females with severe dysmenorrhea.

KH: What do you define as deficient, insufficient and adequate levels of vitamin D in ng/ml?

KKAR: Vitamin D status was divided into three diagnostic categories according to plasma 25(OH)D levels. Vitamin D deficiency (VDD) <10 ng/ml, vitamin D insufficiency (VDI) 10-19 ng/ml and vitamin D sufficiency (VDS) 20-43ng/ml. These reference ranges were provided by the manufacturer of the assay.

KH: Can you tell us about your study and the basic results?

KKAR: The aim of this study was to investigate vitamin D and PTH status among adolescents and young females with severe and very severe dysmenorrhea. Participants were recruited from the emergency departments at University Hospital and University Health Care Center; Jordan University of Science and Technology; and by advertising the projects at the university campus. Plasma vitamin D, PTH, calcium, phosphate and alkaline phosphatase activity levels were measured. Besides demographics, participants also answered questions regarding their frequency of dairy product intake. Pain severity was measured using numerical rating scale (NRS). Pain severity was also graded as mild, severe and very severe.

About 61% of the participants 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). Half of participants had dairy intake less than one serving per day. About 80.4% of participants had insufficient plasma vitamin D and 48.2 % of them had hyperparathyroidism. The majority of participant who experienced very severe dysmenorrhea had their dairy products intake <1 serving per day. In this study, the prevalence of vitamin D insufficiently and hyperparathyroidism among healthy adolescence and young females with severe and very severe dysmenorrhea is much higher than that reported by a recent national population-based household  study

KH: Is there any evidence for vitamin D supplementation improving calcium balance and reducing hyperparathyroidism and thereby dysmenorrhea?

KKAR: The functional role of vitamin D and dietary calcium in the etiology of dysmenorrhea and associated symptoms was observed previously (2, 3). Females who experienced dysmenorrhea were advised to consume three servings of dairy products daily and increase the exposure to direct sunlight. Participants with vitamin D deficiency were advised to visit their family physician for appropriate treatment. The effectiveness of dietary calcium and/or vitamin D supplementation as a therapy to relieve pain and symptoms associated with menstruation was reevaluated after at least three consecutive menstruations. In those participants, there was a significant reduction in pain severity as compared to baseline and a significant reduction in number of tablets used for menstrual pain relief. Some females with vitamin D deficiency who experienced dysmenorrhea, re-measured their vitamin D and PTH levels after the intake of 8 tablet of 50,000 IU, once a week for eight weeks of vitamin D and 2 servings per day of dairy products which resulted in PTH levels returning to within normal range.

KH: Are there triggers of a secondary hyperparathyroidism that might increase dysmenorrheal risk? (i.e. high soft drink intake, excess dietary protein, more acid forming diets, etc.)?

KKAR: Adolescence and early adulthood populations are more susceptible to developing unhealthy dietary behaviors such as reduction in milk which is the main sources of dietary calcium and an increase in soft drink intake, which can increase the risk of severe dysmenorrhea and predispose them for chronic diseases later in life (4). Secondary hyperparathyroidism is a consequence and not a cause of dysmenorrhea. Low dietary calcium and /or vitamin D deficiency are the risk factors for severe dysmenorrhea.

KH: How do you suggest reducing the incidence of dysmenorrhea from either lifestyle, diet or nutritional supplement means if possible?

KKAR: Public media and a class-based nutrition course may represent simple and cost effective strategy to reduce the incidence of dysmenorrhea. We found that adolescent and young female’s students responded very well to educational interventions related to decreasing the incidence of dysmenorrhea through motivating participants toward healthier dietary behaviors, increasing daily dairy products intake, exposure to direct sunlight without using sunblock and reduce the intake of soft drinks.

KH: How can the public or health professionals use this information?

KKAR: I think health professionals should be aware that chronic severe dysmenorrhea that results from low dietary calcium intake and/or vitamin D deficiency may negatively affect bone mineralization during achievement of peak bone mass at a young age and adverse bone health at older age. In addition to dysmenorrhea, deficient circulatory serum 25(OH)D levels may predispose those adolescent females to the development of various none-skeletal chronic diseases such as hypertension, cardiovascular diseases, diabetes mellitus, as well as some inflammatory and autoimmune diseases, and some forms of cancers.

KH: Do you have any further comments on this very interesting subject?

KKAR: Dysmenorrhea is a common gynecological complaint in adolescent females. The severity of dysmenorrheal pain varies among different females; however it could be severe enough to cause a substantial negative impact on women’s daily activities. Therefore finding an effective management would have an important social and medical influence. Our published research, as well as the ongoing research, elucidates the correlation between dietary calcium intake and dysmenorrheal risk and/or severity, and suggests that vitamin D and dietary calcium may be  onsidered as a promising nutritional therapy for the relief of  dysmenorrheal pain and associated symptoms.

The findings of this research suggests that, chronically severe and very severe dysmenorrhea in adolescence and young females, that results from vitamin D insufficiency and inadequate intake of calcium, may negatively affect bone metabolism during achievement of peak bone mass at a young age and result in adverse bone health at older age. In addition to dysmenorrhea, deficient circulatory serum 25(OH)D levels may predispose those adolescent females to the development of various none-skeletal chronic diseases such as hypertension, cardiovascular diseases, diabetes mellitus, as well as some inflammatory and autoimmune diseases, and some forms of cancers.

References:
1. Abdul-Razzak KK, Ayoub NM, Abu-Taleb AA, Obeidat BA. Influence of dietary intake of dairy products on dysmenorrhea. J Obstet Gynaecol Res. 2010;36:377-83.
2. Abdul-Razzak KK, Obeidat BA, Ayoub NM, Al-Farras, MI, Abu-Taleb AA. Reproduction, Pregnancy and Women: Diet quality and dysmenorrhea. In: Diet Quality: An Evidence-Based Approach, Volume 1. Edited by VR Preedy et al. Humana Press. 2013. pp 58-63.
3. Vitamin D and Primary Dysmenorrhea among Young Adult Females (submitted for publication)
4. Abdul-Razzak KK, Abu-Taleb AA, Al-Husban A. Kufoof LK. Nutrition Education and Osteoporosis Risk Factors in Early Decades of Life. American Journal of Educational Research. 2013 1 (3). doi: 10.12691/education-1-3-1

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