Martin Blomberg Jensen1, Jacob Gerner Lawaetz2, Anna-Maria Andersson2, Jørgen Holm Petersen2, Loa Nordkap2, Anne Kirstine Bang2, Pia Ekbom2, Ulla Nordström Joensen2, Lisbeth Prætorius3, Peter Lundstrøm4, Vibeke Hartvig Boujida5, Beate Lanske6, Anders Juul2, Niels Jørgensen2. 1. Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, Copenhagen DK-2100, Denmark Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA, USA blombergjensen@gmail.com. 2. Department of Growth and Reproduction and International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 9, Copenhagen DK-2100, Denmark. 3. Department of Obstetrics and Gynaecology, Hvidovre Hospital, Copenhagen, Denmark. 4. Fertility Clinic IVF, Ballerup, Denmark. 5. Danish Fertility Clinic, Frederiksberg, Denmark. 6. Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA, USA.
Abstract
STUDY QUESTION: Are low vitamin D levels linked with semen quality and sex steroids in infertile men? SUMMARY ANSWER: Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. WHAT IS KNOWN ALREADY: Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men. STUDY DESIGN, SIZE, DURATION: This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total 1427 infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25-OHD), ionized calcium (Ca(2+)) and karyotype. There were 179 men excluded due to serious comorbidities or anabolic steroid usage, leaving 1248 patients for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Men with 25-OHD >75 nmol/l had higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P < 0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower, respectively, while free testosterone and estradiol ratios were 6 and 13% higher, respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio (all P < 0.05). LIMITATIONS, REASONS FOR CAUTION: All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design. It remains to be shown whether the links between vitamin D, calcium, semen quality and sex steroids in infertile men are causal. WIDER IMPLICATIONS OF THE FINDINGS: The associations between vitamin D deficiency and low calcium with semen quality and sex steroids support the existence of a cross-link between regulators of calcium homeostasis and gonadal function in infertile men. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Danish Agency for Science, Technology and Innovation, Hørslev Fonden, Danish Cancer Society and Novo Nordisk Foundation. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT01304927. DATE OF TRIAL REGISTRATION: 25 February 2011. DATE OF ENROLMENT OF FIRST PATIENT: 8 March 2011.
STUDY QUESTION: Are low vitamin D levels linked with semen quality and sex steroids in infertile men? SUMMARY ANSWER: Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. WHAT IS KNOWN ALREADY: Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men. STUDY DESIGN, SIZE, DURATION: This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total 1427 infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25-OHD), ionizedcalcium (Ca(2+)) and karyotype. There were 179 men excluded due to serious comorbidities or anabolic steroid usage, leaving 1248 patients for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Men with 25-OHD >75 nmol/l had higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P < 0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower, respectively, while free testosterone and estradiol ratios were 6 and 13% higher, respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio (all P < 0.05). LIMITATIONS, REASONS FOR CAUTION: All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design. It remains to be shown whether the links between vitamin D, calcium, semen quality and sex steroids in infertile men are causal. WIDER IMPLICATIONS OF THE FINDINGS: The associations between vitamin D deficiency and low calcium with semen quality and sex steroids support the existence of a cross-link between regulators of calcium homeostasis and gonadal function in infertile men. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Danish Agency for Science, Technology and Innovation, Hørslev Fonden, Danish Cancer Society and Novo Nordisk Foundation. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT01304927. DATE OF TRIAL REGISTRATION: 25 February 2011. DATE OF ENROLMENT OF FIRST PATIENT: 8 March 2011.
Authors: S D'Andrea; A Martorella; F Coccia; C Castellini; E Minaldi; M Totaro; A Parisi; F Francavilla; S Francavilla; A Barbonetti Journal: Endocrine Date: 2020-09-03 Impact factor: 3.633