© Borgis - Postępy Nauk Medycznych 10/2015, s. 688-692
Katarzyna Chmiel-Majewska1, Dorota Daniewska1, Grzegorz Misiorowski2, Wojciech Zgliczyński2, *Ryszard Gellert1
Witamina D, hormony płciowe a niedokrwistość u mężczyzn – czy suplementacja cholekalcyferolu wpływa na stężenia hemoglobiny oraz regulację gospodarki hormonów płciowych u hemodializowanych mężczyzn? Badanie pilotażowe
Vitamin D, sex hormones and anaemia in men – is there an influence of cholecalciferol supplementation on haemoglobin concentrations or regulation of sex hormones in male haemodialysis patients? A pilot study
1Department of Nephrology and Internal Medicine, Center of Postgraduate Medical Education, P. Jerzy Popiełuszko Bielański Hospital, Warszawa
Head of Department: prof. Ryszard Gellert, MD, PhD
2Department of Endocrinology, Center of Postgraduate Medical Education, P. Jerzy Popiełuszko Bielański Hospital, Warszawa
Head of Department: prof. Wojciech Zgliczyński, MD, PhD
Streszczenie
Wstęp. Zarówno witamina D, jak i androgeny mogą mieć wpływ na przebieg niedokrwistości rozwijającej się wtórnie do przewlekłej choroby nerek (PChN).
Cel pracy. Ocena zależności pomiędzy stężeniami metabolitu witaminy D – 25(OH)D, poziomami hormonów płciowych a nasileniem niedokrwistości związanej z przewlekłą chorobą nerek z jednoczesnym sprawdzeniem wpływu suplementacji witaminy D na stężenia hemoglobiny oraz hormonów płciowych u hemodializowanych mężczyzn.
Materiał i metody. Spośród 81 mężczyzn hemodializowanych w Stacji Dializ Diaverum przy ul. Cegłowskiej 80 w Warszawie u 18 pacjentów w wieku od 35 do 65 lat spełniających kryteria włączenia do badania, którzy wyrazili świadomą zgodę na udział w badaniu, oznaczono stężenia metabolitu 25(OH)D. Hipowitaminoza nie była kryterium włączenia do badania, natomiast u wszystkich zakwalifikowanych do badania mężczyzn zaobserwowano niedobór witaminy D. Wobec powyższego u wszystkich pacjentów przez okres trzech miesięcy suplementowano cholekalcyferol w dawce dostosowanej do stopnia niedoboru. W trakcie badania oznaczano parametry składu morfologicznego krwi obwodowej, gospodarki żelazowej, wapniowo-fosforanowej oraz stężenia hormonów płciowych.
Wyniki. Optymalne stężenie metabolitu 25(OH)D po zakończeniu suplementacji osiągnięto u 11 z 16 pacjentów (68,75%), którzy ukończyli badanie. U połowy pacjentów podczas suplementacji zaobserwowano znamienny wzrost stężenia hemoglobiny (P = 0,001). Początkowe stężenia 25(OH)D silnie korelowały ze stężeniami testosteronu całkowitego, słabo zaś ze stężeniami hemoglobiny. Ponadto, wartości indeksu wolnego testosteronu (FTI) wykazały umiarkowaną korelację ze stężeniami hemoglobiny. Podczas suplementacji zaobserwowano wzrost stężeń androstendionu i spadek LH, nie stwierdzono jednak istotnych statystycznie zmian w stężeniach całkowitego testosteronu i FTI.
Wnioski. Suplementacja cholekalcyferolu jest skutecznym sposobem na podwyższenie w ciągu trzech miesięcy stężenia 25(OH)D u 2/3 hemodializowanych mężczyzn. Silna korelacja pomiędzy stężeniami 25(OH)D oraz testosteronu sugeruje związek patofizjologiczny, nie wykazano jednak istotnego klinicznie wpływu trzymiesięcznej suplementacji witaminy D ani na poprawę stężeń hemoglobiny, ani testosteronu, obniżonych w przebiegu PChN.
Summary
Introduction. Active metabolites of vitamin D, as well as androgens, may play a substantial role in the correction of anaemia caused by chronic kidney disease.
Aim. Aim of the study was to analyze the association among vitamin D metabolite – 25(OH)D, sex hormones and anaemia and assess the influence of vitamin D supplementation on haemoglobin concentrations, and sex hormones levels in male haemodialysis patients.
Material and methods. The study was performed in male patients on haemodialysis at the Diaverum Dialysis Unit at Cegłowska Street in Warsaw. In 18 eligible patients aged 35-65 who gave informed consent, out of the total of 81, concentrations of 25(OH)D were measured. All patients had vitamin D deficiency. Thus, in all patients included in the study cholecalciferol was supplemented for three months in the dose adjusted to the vitamin D deficiency. During the study the complete blood count, parameters of iron, calcium and phosphate homeostasis, and concentrations of sex hormones were measured.
Results. Normalization of 25(OH)D concentration was achieved in 11out of 16 patients who completed the study (68.75%). In 8 patients (50%) a significant increase in haemoglobin concentration was observed (P = 0.001). Baseline concentrations of 25(OH)D correlated strongly with total testosterone levels and weakly with haemoglobin concentrations. Moreover, free testosterone index (FTI) moderately correlated with haemoglobin concentrations. Substantial increase in androstenedione concentrations and a decrease in LH, but no significant changes in testosterone concentrations or FTI values were observed during cholecalciferol supplementation.
Conclusions. Cholecalciferol supplementation in vitamin D deficient men on haemodialysis effectively normalized its serum concentration. Strong correlation between 25(OH)D and testosterone concentrations may suggest pathophysiologic association, however, the influence of vitamin D supplementation on testosterone and haemoglobin levels seems clinically negligible.
Introduction
Chronic kidney disease, as well as haemodialysis therapy – one of its therapeutic options, has various debilitating consequences. Among them anaemia is one of the most prevalent and cumbersome – it contributes to increased morbidity and mortality. The etiology of anaemia in the course of the disease is multifactorial. It may result from a relative or absolute erythropoietin deficiency, increased eryptosis or circulating uremic toxins. Moreover, dialysis patients have negative iron balance caused by significant loss of this microelement during dialysis procedure, poor absorption from the gastrointestinal tract and sequestration in the mononuclear phagocyte system as a result of elevated hepcidin concentration, and simultaneous increased utilization of iron due to erythropoiesis stimulating agents (ESAs) (1). However, more and more data suggest that vitamin D and sex hormones deficiency may participate in the pathogenesis of anaemia in chronic kidney disease not. The vitamin deficiency in haemodialysis patients is not less present than in general population.
Active metabolites of vitamin D regulate diverse metabolic processes, including calcium and phosphate homeostasis, cell growth and differentiation and immunologic responses. Vitamin D receptor (VDR) and 1α-hydroxylase CYP27B1, an extrarenal enzyme responsible for conversion of 25(OH)D to an active metabolite 1,25(OH)2D, were also discovered in the bone marrow (2). High local 1,25(OH)2D concentration in the erythroid marrow is supposed to directly stimulate the erythroid progenitor cells – by paracrine regulation – to proliferate (3). Thus, low levels of vitamin D frequently observed in CKD patients may negatively influence effective erythropoiesis.
Androgens are another group of endogenous factors that for decades have been suspected of playing a substantial role in erythropoiesis. There is the evidence for direct stimulating effect of androgens on the erythroid line progenitor cells, and for indirect androgen regulation of erythropoiesis via hepcidin and erythropoietin (4, 5). The frequency of male hypogonadism, described as low levels of total and free testosterone, raises along with the stage of CKD – from 17% in patients with CKD G1 to 57% in patients with end- stage renal failure (6). Moreover, apart from association with anaemia, low testosterone levels are related to increased mortality due to cardiovascular diseases (7). The past trials gave conflicting results of anaemia treatment with androgens. Thus current KDIGO 2012 recommendations discourage the androgen administration as an adjuvant therapy to erythropoiesis stimulating agents (8).
To emphasize the complex interplay among various endogenous factors regulating erythropoiesis it is worth noticing that vitamin D may play a role in maintaining hormonal homeostasis in men. Vitamin D receptor and enzymes activating native form of vitamin D were found in numerous cells of the male genitourinary tract and pituitary gland, where their influence on androgenesis through paracrine activity is currently under investigation (9, 10). In several studies an association between vitamin D and male hormone levels was found (11, 12).
Aim
The aim of this study was to assess the existence of an association between concentrations of the circulating metabolite of vitamin D – 25(OH)D, sex hormones and anaemia in male haemodialysis patients, and if androgen or haemoglobin concentrations may rise during supplementation of native vitamin D.
Material and methods
The authors declare that the study has been conducted according to the principles of the Declaration of Helsinki, and it was approved by the Bioethics Committee at the Center of Postgraduate Medical Education in Warsaw.
The study involved 18 patients with end-stage renal failure. The inclusion criteria were: male sex, age 35-65, and duration of haemodialysis therapy for at least two months. Patients with malignant tumours, liver failure, hypo- or hyperadrenocorticism, primary or secondary hypopituitarism, advanced aortic, or common iliac arteries atherosclerosis, and Leriche’s syndrome, were excluded from the study. Baseline values of the markers of calcium-phosphate homeostasis, complete blood count, markers of iron homeostasis and sex hormones concentrations were measured in each patient. Three stages of vitamin D deficiency were set according to the concentrations of 25(OH)D: < 10 ng/ml – severe deficiency, 10-20 ng/ml – moderate deficiency, 20-30 ng/ml – mild deficiency (tab. 1).
Table 1. Levels of vitamin D deficiency and adjusted dose of vitamin D.
| 25(OH)D level [ng/ml] | Number of patients | Weekly dose of vitamin D [IU] |
| < 10 | 9 | 40 000 |
| 10-20 | 8 | 20 000 |
| 20-30 | 1 | 15 000 |
In patients with vitamin D deficiency, cholecalciferol – a form of native vitamin D – was supplemented orally in doses adjusted to the stage of the deficiency – in severe deficiency 40 000 IU per week, in moderate deficiency 20 000 IU per week, and in mild deficiency 15 000 IU per week. For three consecutive months, weekly doses of cholecalciferol were administered after the first weekly dialysis sessions, supervised by qualified nurses. During the supplementation period, complete blood count, calcium-phosphate and iron balance were monitored and sex hormones measured. Haemoglobin increase by not less than 0.5 g/dl at the end of the third month of cholecalciferol supplementation was set as the endpoint of the study. The results were analyzed with the use of Student t-test, ANOVA and Pearson’s analysis of correlation. The significance level was set to 0.05.
Results
Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
- Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
- Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
- Aby kupić kod proszę skorzystać z jednej z poniższych opcji.
Opcja #1
29 zł
Wybieram
- dostęp do tego artykułu
- dostęp na 7 dni
uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony
Opcja #2
69 zł
Wybieram
- dostęp do tego i pozostałych ponad 7000 artykułów
- dostęp na 30 dni
- najpopularniejsza opcja
Opcja #3
129 zł
Wybieram
- dostęp do tego i pozostałych ponad 7000 artykułów
- dostęp na 90 dni
- oszczędzasz 78 zł
Piśmiennictwo
1. Babitt JL, Lin HY: Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD. Am J Kidney Dis 2010; 55(4): 726-741.
2. Zhou S, LeBoff MS, Glowacki J: Vitamin D Metabolism and Action in Human Bone Marrow Stromal Cells. Endocrinology 2010; 151(1): 14-22.
3. Meguro S, Tomita M, Katsuki T et al.: Plasma 25-Hydroxyvitamin D Is Independently Associated with Hemoglobin Concentration in Male Subjects with Type 2 Diabetes Mellitus. Int J Endocrinol 2011; 2011: 362981.
4. Shahani S, Braga-Basaria M, Maggio M, Basaria S: Androgens and erythropoiesis: past and present. J Endocrinol Invest 2009; 32: 704-716.
5. Bachman E, Feng R, Travison T et al.: Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. J Clin Endocrinol Metab 2010; 95: 4743-4747.
6. Yilmaz MI, Sonmez A, Qureshi AR et al.: Endogenous Testosterone, Endothelial Dysfunction, and Cardiovascular Events in Men with Nondialysis Chronic Kidney Disease. Clin J Am Soc Nephrol 2011; 6: 1617-1625.
7. Carrero JJ, Qureshi AR, Parini P et al.: Low Serum Testosterone Increases Mortality Risk among Male Dialysis Patients. J Am Soc Nephrol 2009; 20(3): 613-620.
8. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Inter 2012; 2 (suppl.): 279-335.
9. Perez-Fernandez R, Alonso M, Segura C et al.: Vitamin D receptor gene expression in human pituitary gland. Life Sci 1997; 60(1): 35-42.
10. Blomberg Jensen M: Vitamin D metabolism, sex hormones, and male reproductive function. Reproduction 2012; 144(2): 135-152.
11. Nimptsch K, Platz EA, Willett WC, Giovannucci E: Association between plasma 25-OH vitamin D and testosterone levels in men. Clin Endocrinol (Oxf) 2012; 77(1): 106-112.
12. Lee DM, Tajar A, Pye SR et al.: Association of hypogonadism with vitamin D status: the European Male Ageing Study. Eur J Endocrinol 2012; 166(1): 77-85.
13. Manolagas SC, Yu XP, Girasole G, Bellido T: Vitamin D and the hematolymphopoietic tissue: a 1994 update. Semin Nephrol 1994; 14: 129-143.
14. Alon DB, Chaimovitz C, Dvilansky A et al.: Novel role of 1,25(OH)2D3 in induction of erythroid progenitor cell proliferation. Exp Hematol 2002; 30(5): 403-409.
15. Patel NM, Gutièrrez OM, Andress DL et al.: Vitamin D deficiency and anemia in early chronić kidney disease. Kidney Int 2010; 77(8): 715-720.
16. Kiss Z, Ambrus C, Almasi C et al.: Serum 25(OH)-cholecalciferol concentration is associated with hemoglobin level and erythropoietin resistance in patients on maintenance hemodialysis. Nephron Clin Pract 2011; 117: 373-378.
17. Kinuta K, Tanaka H, Moriwake T et al.: Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology 2000; 141: 1317-1324.
18. Lerchbaum E, Obermayer-Pietsch B: Vitamin D and fertility: a systematic review. Eur J Endocrinol 2012; 166(5): 765-778.
19. Blomberg Jensen M, Nielsen JE, Jorgensen A et al.: Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod 2010; 25: 1303-1311.
20. Nangia AK, Hill O, Waterman MD: Testicular maturation arrest to testis cancer: spectrum of expression of the vitamin D receptor and vitamin D treatment in vitro. J Urol 2007; 178: 1092-1096.
21. Kim SW, Hwang JH, Cheon JM et al.: Direct and indirect effects of androgens on survival of hematopoietic progenitor cells in vitro. J Korean Med Sci 2005; 20(3): 409-416.
