Calcium deficiency is associated with impaired semen quality in 1230 infertile men

What associations exist between serum calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), semen quality and reproductive hormones?

Cross-sectional study of men (n = 1230) referred for infertility evaluation between January 2017 and August 2020. Participants underwent physical examination, semen analysis, blood testing for ionized and corrected calcium, PTH, 25OHD and reproductive hormones. Men were stratified by hypocalcaemia (ionized calcium <1.18 mmol/l), high-normal PTH (≥4.9 pmol/l) and vitamin D deficiency (25OHD <25 nmol/l).

Serum ionized calcium showed a stronger inverse correlation with PTH (r = -0.28, P < 0.0001) than corrected calcium. Total testosterone, sex hormone-binding globulin and testosterone-LH ratio were significantly higher in the high tertile (top 5%) than in the low tertile (bottom 5%) of ionized calcium levels, whereas oestradiol was significantly lower (P = 0.004, P = 0.002, P = 0.046 and P = 0.004, respectively, all adjusted for age and body mass index [BMI]). FSH and inhibin B were significantly higher and lower, respectively, in the highest than in the lowest tertile of PTH levels (P = 0.002 and P = 0.004, respectively, adjusted for age and BMI). Percentages of motile and progressively motile spermatozoa were significantly lower in the less than 25 nmol/l 25OHD tertile than in the greater than 50 nmol/l 25OHD tertile (P = 0.012 and P = 0.005, respectively, adjusted for age and BMI). Men with combined low ionized calcium, elevated PTH and low 25OHD had poorer semen quality, including reduced motility, sperm count and percentage of morphologically normal spermatozoa, than men with normal biochemical profiles.

Disrupted calcium homeostasis characterized by low ionized calcium, elevated PTH, or vitamin D deficiency is associated with impaired semen quality and altered reproductive hormones. Interventional studies are warranted to determine whether correction improves gonadal function.