Yahyavi Sam Kafai, Wall-Gremstrup Gustav, Probst-Drejer Benedicte, Toft Frederikke Bay, Jorsal Mads Joon, Holt Rune, Aksglaede Lise, Jørgensen Niels, Juul Anders, Blomberg Jensen Martin
Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital, Herlev, Gentofte, Denmark.
Group of Skeletal, Mineral and Gonadal Endocrinology, Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Hum Reprod. 2025 Feb 1;40(2):226-235. doi: 10.1093/humrep/deae293.
Is serum phosphate linked with semen quality and reproductive hormones in infertile men?
Hypophosphatemia is a frequent finding in infertile men and is associated with lower number of motile sperm.
Phosphate is available in fluid from all segments of the male reproductive tract in concentrations manyfold higher than in serum. However, the role of phosphate in male fertility is largely unknown.
STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 1242 men referred due to infertility between January 2017 and May 2020 at the Department of Growth and Reproduction, Rigshospitalet, Copenhagen.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Each man underwent a physical examination, had semen parameters assessed, and had blood analyzed prospectively for concentrations of phosphate, ionized calcium, alkaline phosphatase, parathyroid hormone, serum 25-hydroxyvitamin D (25OHD), and reproductive hormones. After 246 men were excluded due to serious comorbidities, 1242 were included in the analyses.
Infertile men have a high prevalence of mild (25.5%, 0.66-0.80 mmol/l) and moderate hypophosphatemia (10.9%, 0.32-0.65 mmol/l). The percentages of motile spermatozoa and progressively motile spermatozoa were lower in men with moderate hypophosphatemia than in men with mild hypophosphatemia or normophosphatemia (44%, 49%, 51%, P = 0.040, and 32%, 35%, 41%, P = 0.036, respectively). The total numbers of motile and progressively motile spermatozoa were also lower (13, 12, 18 million, P = 0.009, and 10, 9, 14 million, P = 0.006, respectively). Serum concentrations of total and free estradiol were highest in men with moderate hypophosphatemia (97.5, 96.2, 92.1 pmol/l, P = 0.004, and 2.4, 2.3, 2.2 pmol/l, P = 0.034, respectively).
LIMITATIONS, REASONS FOR CAUTION: The study question is compromised by the descriptive study design. It remains to be shown whether there exist a causal link between serum phosphate and semen quality in infertile men.
As fertility stands as a critical concern in the world, there is a need to find regulators of fertility during adulthood to identify possible treatments. Therefore, the precise mechanisms through which hypophosphatemia may impact sperm motility remain needs to be further clarified.
STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Novo Nordisk Foundation, Beckett Foundation, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Candys Foundation, and The Innovation Foundation. There was no influence from any sponsor on the study design, and the authors have nothing to declare.
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血清磷酸盐与不育男性的精液质量和生殖激素有关吗？
低磷血症在不育男性中很常见，且与活动精子数量减少有关。
男性生殖道各段液体中的磷酸盐浓度比血清中的高许多倍。然而，磷酸盐在男性生育中的作用很大程度上尚不清楚。
研究设计、规模、持续时间：这项横断面研究纳入了2017年1月至2020年5月间因不育转诊至哥本哈根里格霍斯医院生长与生殖科的1242名男性。
研究对象/材料、地点、方法：每位男性均接受了体格检查，评估了精液参数，并前瞻性地分析了血液中磷酸盐、离子钙、碱性磷酸酶、甲状旁腺激素、血清25-羟维生素D（25OHD）和生殖激素的浓度。在排除246名患有严重合并症的男性后，1242名男性纳入分析。
不育男性中轻度（25.5%，0.66 - 0.80 mmol/L）和中度低磷血症（10.9%，0.32 - 0.65 mmol/L）的患病率较高。中度低磷血症男性的活动精子百分比和进行性活动精子百分比低于轻度低磷血症男性或血磷正常男性（分别为44%、49%、51%，P = 0.040；以及32%、35%、41%，P = 0.036）。活动精子总数和进行性活动精子总数也较低（分别为1300万、1200万、1800万，P = 0.009；以及1000万、900万、1400万，P = 0.006）。中度低磷血症男性的血清总雌二醇和游离雌二醇浓度最高（分别为97.5、96.2及92.1 pmol/L，P = 0.004；以及2.4、2.3及2.2 pmol/L，P = 0.034）。
局限性、谨慎理由：该研究问题受描述性研究设计影响。不育男性血清磷酸盐与精液质量之间是否存在因果关系仍有待证实。
鉴于生育是全球关注的关键问题，需要找到成年期生育的调节因子以确定可能的治疗方法。因此，低磷血症影响精子活力的确切机制仍需进一步阐明。
研究资金/利益冲突：本研究由诺和诺德基金会、贝克特基金会、医学博士索弗斯·卡尔·埃米尔·弗里斯及其配偶奥尔加·多丽丝·弗里斯的赠款、坎迪斯基金会和创新基金会资助。任何赞助商均未对研究设计产生影响，作者无利益冲突声明。
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