Zuhra Pavlova, an endocrinologist and scientific MSU University Hospital. hands. "Hospitals system of medicine."
VITAMIN D DIFICIENCY AND MALE INFERTILITY
ACTUAL PROBLEMS OF THE 21st CENTURY: MALE INFERTILITY, OBESITY AND VITAMIN D - IS THERE A RELATIONSHIP?
SUMMARY
In the last half century humanity is rapidly gaining weight and loosing reproductive abilities. The quality and of sperm parameters a constantly getting worse.
Somatic diseases (diabetes, obesity, metabolic syndrome, hypertension etc.) get significantly younger. In addition to the medical aspects the environmental factors and food quality may be harmful for reproductive function. The lack of some substances can not only cause discomfort or functional impairment and lead to serious metabolic disturbances including the loss of some functions or the development of pathological conditions that threaten the life of the organism or its reproduction.
The role of vitamin D in the human body can hardly be overestimated. Vitamin D receptors are found in all body tissues including testicular tissue. Since the end of last century a great number of medical researches was aimed at indentifying the pathogenic mechanism of some diseases, including endocrine disorder and vitamin D deficiency. This article shows the pathogenetic relationships of such conditions as obesity, vitamin D deficiency and male infertility.
Key words: vitamin D, male infertility, obesity, androgen deficiency.
SUMMARY
The last half-century humanity is rapidly gaining weight and losing reproductive abilities. Qualitative and quantitative indicators of semen deteriorates. Significantly younger somatic diseases. Dangerously spread diseases such as diabetes, obesity, metabolic syndrome, hypertension, and many others. In addition to the medical aspects of reproductive ability of a person have a huge impact, and environmental factors environment, adverse and often aggressive influence of the outside world, the food and the lack of vitamins and minerals. The lack of certain substances can not only cause discomfort or functional impairment, and lead to serious metabolic disorders, up to the loss of any function or development of pathological conditions that threaten the life of the organism or its reproduction. One such substance is vitamin D, whose role in the functioning of the human body and necessity of which is versatile, can hardly be overestimated. Vitamin D receptors are found in all body tissues, including the testes tissue. A lot of work at the end of the last century is aimed at identifying the pathogenic mechanisms of development of a number of diseases, including endocrine disorders and deficiency of vitamin D.
This article shows pathogenetic relationship of conditions such as obesity, vitamin D deficiency and infertility in men.
Keywords: vitamin D, male infertility, androgen deficiency, obesity.
State of the question.
Infertility is the inability of a sexually active, do not apply contraceptives couples achieve pregnancy within one year [1]
Infertility and all, including men, today is a national disaster in many countries, including Russia. And the situation is not static - it is changing, and not for the better: the share of the male factor in 2001. It accounted for about 40% of the causes of infertility in marriage [4], while as 10 years later are other tsifry- 48-50% [2].
infertility problem - it is the most urgent problem of the twenty-first century, in which the female infertility is no longer prevalent in frequency causes of infertile marriages, as it was in the twentieth century. According to recent data, the ratio of female and male infertility by 50 -50. Each tenth of a barren couple unable to conceive how the husband and wife.
Several times over the past decade the WHO revised semen parameters in connection with the progressive reduction in the number of spermatozoa in ejaculate: the lower limit of normal sperm count to 60 million / ml (Davis, 1943) was reduced to 20 million / ml in 1999, and in 2010 to 15 mln / ml [4]. In addition, and other parameters are in the negative dynamics, namely the reduction in the number of active-motile sperm, reducing the number of morphologically normal forms [4].
Despite the fact that the value for the life of the body, vitamin D was more than 100 years ago, you know, for a long time, his role was to participate in calcium and phosphorus metabolism. And only in the last decade, a large variety of its points of application was understandable and relevant.
Until the last decade, such factors as vitamin D deficiency was not considered as a state, increases the likelihood of infertility or are its consequence. However, today, more and more data appears on the importance of vitamin D in the maturation of sperm cells (8,9). Expression of vitamin D receptor was detected in Sertoli cells, seminiferous tubule, epididymis, prostate and seminal vesicles (5.6). The largest is currently working on the impact of vitamin D on spermatogenesis was identified relationship between low vitamin D levels and a decrease in both the mobility and the number of morphologically normal spermatozoa (8,9). Several studies have established that vitamin D deficiency can be a cause of hypogonadism in men (8, 9, 10, 11,18). Thus, vitamin D can potentially affect spermatogenesis, both directly and indirectly by influencing the level of testosterone. Vitamin D deficiency should be considered in the treatment of infertility in men.
The modern citizen is experiencing aggressive impact of the environment, which dramatically increases the need for trace minerals, antioxidants and vitamins.
According to some researchers prevalence of vitamin D deficiency is not less than 50% of the world [13,26,31]. In Russia, this situation is exacerbated by the fact that most of it is above the 42 parallel, which means the absence of a sufficient level of insolation in techenie3 / 4 years and even in Sochi (Figure 1).
Another urgent problem today, associated with infertility, is obesity, which according to the WHO called the "epidemic of the XXI century." WHO estimates that in 2005, overweight affects approximately 1.6 billion adults in the world (over 15 years), and 400 million are obese. WHO predicts that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million - obesity, ie, every second person on Earth.
It is important to consider the fact that obesity is often accompanied by a number of serious conditions such as insulin resistance, hypertension, metabolic syndrome and more [14, 16]. All of these conditions have a negative impact on the reproductive function of men and are often accompanied by a marked shortage of D hormone. Pathogenetic mechanism of causation of these conditions is still not fully understood and debated.
Men with increased body mass index (BMI) are more likely to suffer from infertility than men of normal weight. According to the study of the National Institute of Environmental Health Sciences Environment (NationalInstituteofEnvironmentalHealthSciences) United States, exceeding the weight of 20 lbs (approximately 9 kg) increases infertility rate is 10%. The researchers found that goes beyond the norm BMI is completely independent risk factor (in this case have been excluded other contributing causes of infertility - smoking, alcohol consumption, age, higher BMI in women, exposure to pesticides and solvents). In general, increased BMI men doubles the risk of infertility, regardless of age.
It is particularly aggravated this state when it is accompanied by a deficiency of vitamin D. The results of this relationship have been published by several researchers. [5] In addition, low levels of vitamin D caused inhibition of spermatogenesis and increased the ratio of fragmented sperm DNA and 75% [3, 4, 7, 10].
At the heart of the development of disorders of spermatogenesis in men with obesity, with a variety of factors, it is important and fundamental point, namely the reduction of testosterone. The excess fat depot area increases for the "flavor" of testosterone, and relative or absolute increase estrogen carries a pituitary desensitization, which naturally reduces the amount produced gonadotropins. Accordingly, decreasing testosterone production and thus a vicious circle. Everything listed above leads to the development of androgen deficiency that not only supports existing excess body weight, but also aggravates it, as testosterone It is a major anabolic hormone without sufficient concentration which significantly reduced physical activity, whose role in weight reduction difficult overemphasized. In this connection, it will return to the fact that without adequate serum levels of vitamin D can not be provide quality steroidogenesis and thus achieve normal fertility [17,18,20,21,22].
In a study conducted in Austria in 2011, was attended by 165 men (who are overweight, but no type 2 diabetes). Results showed that daily use of 3332ME or 83mkg daily throughout the year of vitamin D, significantly increased total testosterone concentration. 10.7 + -3.9 nmol /, to 13.4 + - 4.7 nmol / l; biologically active testosterone from 5.21 + -1.87 to 6.25 + -2.01 nmol / l; and the level of free testosterone -0.080nmol + 0.222 / l to 0.267 + -0,087nmol / l. At the same time, there were no significant changes in the placebo group [11]
US scientists conducted in 2012. study whose purpose was to study the relationship between sperm quality, hormonal parameters and serum concentrations of vitamin D (25-hydroxy vitamin D, or 25 (OH) D3). The results of this study clearly demonstrated the existence of such a connection, identified optimum concentration of Vitamin D positive affect the reproductive capabilities of men and negative correlation between the presence of excess body weight and serum concentrations 25 (OH) D3. The study included 170 healthy men, whose average age was 29,0 ± 8,5 years. The subject of the study the following parameters were determined: semen, blood hormones (total and free testosterone, sex hormone binding globulin, estradiol, follicle stimulating and luteinizing hormones); were surveyed defined BMI (made 24.3 ± 3.2 kg · m (-2)), the presence or absence of bad habits and determination of serum concentration of vitamin D. The average concentration of 25 (OH) D3 was 34.1 ± 15.06 ng ml (-1). Sperm concentration, sperm motility (category a), their morphology were lower in Men with a concentration of '25 (OH) D3 ≥ 50 ng ml compared to men with levels of '20 ng ml and less than 50 ng ml. It was also revealed that the total volume of the ejaculate and total progressive motility was lower in men with concentration of 25 (OH) D3 less than 20 ng / ml, compared with men whose vitamin D level was from '20 ng ml to 50 ng / ml. [10].
In other words, American scientists have concluded that the optimal levels of vitamin D, positively influencing the quality of spermatogenesis, a serum concentration of 25 (OH) D3 of 20 to 50 ng / ml. Equally adversely affects the performance of semen as high levels of 25 (OH) D3, and its reduced [10].
Full spermatogenesis is only possible when sufficient quantities of testosterone in the testicles is, ie own hormone produced in your own testicles. Violation until spermatogenesis or severe oligospermia aspermia it may be associated with decreased functions of the Leydig cells and decrease in local testosterone concentration. Administration of exogenous testosterone can change the picture of androgen deficiency, but in any case does not improve the situation in the aspect of spermatogenesis.
Increasing the concentration of estrogen is another point of application - often enough increase in prolactin levels, and he, in turn, leads to a decrease sexual desire, and therefore, patients reduced the intensity of sexual activity, which leads to stagnation, also adversely affecting the reproductive function.
We should not forget that the adipose tissue is also the body where there is a synthesis of the hormone leptin, which also contributes to the fact that testosterone levels will steadily decrease.
From a certain age at which figures arise particularly heated debate, human skin progressively loses its ability to synthesis of 7-dehydrocholesterol vitamin D. It is associated with this decline in cognitive function in older people, which gives us reason to believe that decrease in intellectual performance at any age is somehow related including a deficiency of vitamin D [23, 24, 25,34]
And if the influence of obesity and related androgen deficiency on parameters of spermatogenesis obvious [14,15,16,18], the definition of the role of vitamin D in the development of these processes requires a more detailed attention. For a better understanding of the relationship of obesity, vitamin D deficiency and disorders of spermatogenesis should consider vitamin D metabolism and its role in the human body in more detail.
Metabolism of vitamin D (Pic2).
D hormone or vitamin D is a group of sekosteroidov united on the principle of chemical similarity: Vitamin D1 (ergocalciferol and lyumisterola compound in the ratio 1: 1); Vitamin D2 - ergocalciferol; Vitamin D3 - cholecalciferol, produced in animals and humans under sunlight from 7-dehydrocholesterol; is it considered as "true" vitamin D, while the other members of this group believe modified derivatives of vitamin D; Vitamin D4 - digidrotahisterol 22,23-digidroergokaltsiferol; Vitamin D5 - sitokaltsiferol (formed from 7-degidrositosterola). By itself, it is not the actual vitamin in the classical sense of the term, as has varied biological effects through interaction with specific receptors localized in the nuclei of many tissues and cells organs [13, 19].
Under normal conditions, D-hormone in healthy humans daily formed from 0.3 to 1.0 micrograms / day. [19]. The first hydroxylation reaction is carried out mainly in the liver (90%) and around 10% - with the assistance of extrahepatic microsomal enzyme 25-hydroxylase to form biologically inactive intermediate forms of transport - 25 (OH) D (Kaltsidol) [19]. The other vitamin D metabolites can not be used as a general criterion number, how to deal with food and formed in the skin. This form can be deposited in muscle and adipose tissues, as "emergency reserve." Subsequent reaction of 1a-hydroxylation of 25 (OH) D flows mainly in the proximal tubule cells departments kidney cortex by the enzyme 1a-hydroxylase (25-hydroxyvitamin D-1a-hydroxylase, CYP27V1) [13, 19, Figure 2].
Vitamin D is naturally present in only a very limited number of food products (Figure 3, the material taken from the site hsph.harvard.edu Harvard School of Public Health).
In humans it is produced only in certain circumstances, when the ultraviolet rays of sunlight fall on the skin. Certain conditions are: the height of solstice the horizon 45 °, clear skies or translucent clouds, a sufficient volume of aggregate open skin surface being insolation at least 2-3 times a week is not less than 15 minutes.
Biologically inert vitamin D, formed by exposure to the sun, derived from foods and as food additives, for activation in the body must undergo two hydroxylation process. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25 (OH) D], also known as calcidiol - inactive (depot) form of vitamin D. The second hydroxylation takes place predominantly in the kidney and the result is the synthesis of physiologically active 1,25-dihydroxyvitamin D [1,25 (OH) 2 D] or calcitriol [19, 28, Fig. 2].
From all the above formed a disappointing picture of the prospects for improvement of the reproductive function of the male population. Namely, an increasing number of men of reproductive age are overweight or obese; they are, as a rule, most of the time in closed premises of insolation; in addition, their principles of nutrition and physical activity are not conducive to the improvement of their BMI and normalization of the level of androgens that closes fledged vicious circle- ozhirenie- androgen deficient levels of vitamin D in itoge- reproductive disorders have men.
Besides the above pathological conditions of vitamin D deficiency associated with another weight different kinds of diseases and syndromes in both sexes (Fig.4)
Methods of prophylaxis and correction of vitamin D deficiency (Table 1).
methods of prevention and correction of vitamin D deficiency and still not cause less controversy than the effects rendered by them. Table 1 presents general recommendations for all age groups, male and female.
In recommending the use of preparations of vitamin D substances to correct this deficiency must start from its initial level, the presence or absence disorders functions of gastrointestinal tract and the kidneys, the level of metabolism, the selection between the active metabolites of D3 or vitamin D2 native drugs and D3, aqueous or oily solutions. According to many authors about optimal dosages vary considerably [12, 27,28,29,30,32, 33,35,36].
Application for the year in men's vitamin D in an amount of 83 g (about 3332ME) daily significantly increased levels of testosterone, and therefore is beneficial to the reproductive system of men in general, [11, 21]. It is necessary to consider the fact that the presence of obesity significantly increase the need for vitamin D and the dose administered should be higher. As we have said before, it is important not only to eliminate the lack of vitamin D, but also to prevent its excess.
disputes plurality toxicity raises the question of drugs containing various forms of vitamin D and its maximum permissible doses. According to some authors [27] in healthy adults receiving 5 months 10 000 IU / day of vitamin D does not lead to hypercalcemia audio nor an increase in urinary calcium excretion, which is the most sensitive indicator to detect potential toxic effects of vitamin D, which confirms the rationality of the maximum allowable level of consumption for adults 10 000 IU / day.
Based on the foregoing, the detection of reproductive disorders, especially in combination with overweight or obese is necessary to determine the serum concentrations of vitamin D and its correct promptly deficit. In addition, it must be remembered that the compensation of only one vitamin D deficiency, can not solve all one set of problems, which usually takes place in patients with impaired reproductive function. Unfortunately, a change in eating behavior and introduction to day exercise regimes, often also do not solve fully the problems of overweight and not be able to reverse the androgen deficiency, if it occurs to be. At the same time, with no respect for the principles of proper nutrition and lack of muscular "skeleton", drug therapy is not completely effective. Timely compensated deficit Vitamin D - a pledge of effective treatment of obesity and infertility, provided a comprehensive treatment of all existing violations.
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