High Seminal Fluid Calcium Is Associated With Higher Sperm Concentration in Infertile Men and Men From the General Population

BACKGROUND: The extracellular calcium concentration is important for sperm function, maturation, and survival, however, studies exploring the link between seminal calcium and reproductive function have reported inconsistent findings. OBJECTIVES: To investigate the association between seminal calcium levels and semen quality in both healthy and infertile men. MATERIALS AND METHODS: A total of 301 young men from the general Danish population who participated in a study of semen quality, and 228 infertile men who were supplemented with calcium (500 mg) + cholecalciferol (300,000 IU bolus followed by 1400 IU daily), or placebo in a randomized controlled trial were included. Each man underwent a physical examination, routine semen analysis, analysis of calcium concentrations in the seminal fluid, and blood sampling for assessment of PTH, testosterone, estradiol, inhibin B, and AMH. RESULTS: In young men from the general population, sperm concentration was higher in those within the highest seminal calcium quartile (Q4: 9.0-19.2 mmol/L) compared with the lowest (Q1: 1.3-4.7 mmol/L; 53.0 million/mL vs. 31.0 million/mL, p = 0.010). Accordingly, infertile men in Q1 had the lowest sperm concentration (e.g., 6.6 vs. 22.5 million/mL in Q3), but also fewer progressively motile spermatozoa (p = 0.030). Supplementation with calcium and cholecalciferol did not affect seminal calcium concentration (p = 0.33), however, infertile men who experienced an increase in their seminal calcium concentrations > 30% at the end of intervention had a higher sperm concentration (p = 0.048) and total sperm count (p < 0.001) compared with baseline. There was a weak positive correlation between longitudinal changes of seminal calcium and serum estradiol (r = 0.17, p = 0.016). CONCLUSIONS: Lower seminal calcium concentration is associated with poorer semen quality but was not influenced by calcium supplementation. Future research should focus on uncovering possible regulators, for instance, estrogens. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT01304927 (registered February 28, 2011).