The impact of
estrogen deficiency on bone has been extensively studied in the female; however, the effects of
androgen deficiency on
calcium fluxes in males have been less well characterized. We investigated the effect of short-term, severe
androgen deficiency on measures of
calcium absorption and kinetics 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 [SEM], body mass index 25.3 +/- 0.8 kg/m2). They consumed a weight maintenance diet for at least 3 days prior to admission to our Research Unit, with a
calcium intake of approximately 1200 mg/day. At baseline (D1), subjects received 42Ca intravenously as well as 44Ca PO mixed with milk or juice. A 29-h urine collection was begun and blood samples collected at frequent intervals for the measurement of the isotopic enrichment of 42Ca and 44Ca using thermal ionization mass spectrometry. Twice daily urine samples were collected 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 baseline (D3, n = 7) (two subjects completed three studies).
Testosterone concentrations were markedly suppressed on both D2 and D3 (-95%, p < 0.006), whereas there were no detectable changes in
growth hormone and
insulin-like growth factor-1 concentrations. Urinary
calcium excretion increased significantly after 4 weeks (43%, p = 0.0007) and 10 weeks (73%, p = 0.003) of sustained
hypogonadism. Using a multicompartmental kinetic model, the contribution of oral
calcium to the urinary losses was decreased by D3 (-41%, p = 0.01), yet the contribution of bone
calcium to urine losses increased by 10 weeks (+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
testosterone concentration and the increase in urinary
calcium excretion, especially
at 10 weeks (R2 = 0.84, p = 0.004). These kinetic changes were accompanied 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 associated with marked increases in urinary
calcium losses, with a greater contribution of bone
calcium to those losses and decreased kinetic markers of bone
calcium deposition. We conclude that even short-term, severe deficiency in gonadal
steroids can have profound negative effects on
calcium and bone metabolism in males.