Profound hypogonadism has significant negative effects on calcium balance in males: A calcium kinetic study

The impact of estrogen deficiency on bone has been extensively studied in t he female; however, the effects of androgen deficiency on calcium fluxes in males have been less well characterized. We investigated the effect of sho rt-term, severe androgen deficiency on measures of calcium absorption and k inetics as well as on markers of bone turnover in males. To accomplish this , 11 healthy male volunteers were recruited (mean age 23.3 +/- 0.5 years [S EM], body mass index 25.3 +/- 0.8 kg/m(2)). They consumed a weight maintena nce diet for at least 3 days prior to admission to our Research Unit, with a calcium intake of similar to 1200 mg/day. At baseline (D1), subjects rece ived Ca-42 intravenously as well as Ca-44 PO mixed with milli or juice. A 2 9-h urine collection was begun and blood samples collected at frequent inte rvals for the measurement of the isotopic enrichment of Ca-42 and Ca-44 usi ng thermal ionization mass spectrometry. Twice daily urine samples were col lected for 5 days after the administration of the isotopes. A gonadotropin- releasing hormone agonist (Lupron) was given after D1, again 3 weeks later, and studies repeated identically 4 weeks (D2, n = 6) and 10 weeks from bas eline (D3, n = 7) (two subjects completed three studies). Testosterone conc entrations were markedly suppressed on both D2 and D3 (-95%, p < 0.006), wh ereas there were no detectable changes in growth hormone and insulin-like g rowth factor-1 concentrations. Urinary calcium excretion increased signific antly after 4 weeks (43%, p = 0.0007) and 10 weeks (73%, p = 0.003) of sust ained hypogonadism. Using a multicompartmental kinetic model, the contribut ion of oral calcium to the urinary losses was decreased by D3 (-41%, p = 0. 01), get the contribution of bone calcium to urine losses increased by 10 w eeks (+11%,p = 0.01). There was a 21% decrease in bone calcium deposition ( Vo(+)) by D3 (p < 0.05) with no significant change in bone resorption rates (Vo(-)). There was a significant correlation between the decrease in testo sterone concentration and the increase in urinary calcium excretion, especi ally at 10 weeks (R-2 = 0.84, p = 0.004). These kinetic changes were accomp anied by a decrease in osteocalcin concentrations on D2, with improvements by D3. Urinary N telopeptide, a measure of bone resorption, also increased during the studies. In summary, profound hypogonadism in young males is ass ociated,with marked increases in urinary calcium losses, with a greater con tribution of bone calcium to those losses and decreased kinetic markers of bone calcium deposition. We conclude that even short-term, severe deficienc y in gonadal steroids can have profound negative effects on calcium and bon e metabolism in males.