TREATMENT OF ISOLATED HYPOGONADOTROPIC HYPOGONADISM EFFECT ON BONE-MINERAL DENSITY AND BONE TURNOVER

Isolated hypogonadotropic hypogonadism (IHH) presents with delayed pub erty in the late teens or early twenties, with a period of testosteron e deficiency during active growth. The aims of the study were to deter mine 1) whether long term treatment of IHH results in normalization of bone density (BMD) and bone turnover, and 2) whether BMD and bone tur nover respond to increasing doses of hCG. We studied 10 men, aged 26-4 6 yr, with IHH who were treated with hCG or testosterone esters (Susta non) for 2-22 yr, with age at the start of treatment between 17-29 yr, and 10 age- and body weight-matched normal men as a control group. At baseline, lumbar spine, femoral neck, trochanter, and Ward's triangle BMD values were decreased, and serum bone Gla-protein, bone alkaline phosphatase, and urinary pyridinoline, deoxypyridinoline, and N-termin al telopeptide of type I collagen were increased compared with control values (by paired t test, P = 0.02, 0.03, 0.01, 0.05, 0.002, 0.02, 0. 02, 0.007, and 0.006, respectively). The age at initial therapy was si gnificantly correlated with total body BMD (r = -0.73; P = 0.017) and lumbar spine BMD (r = -0.756; P = 0.0097). Serum free testosterone was correlated with total body and trochanter BMD (r = 0.635; P = 0.048 a nd r = 0.629; P = 0.05), and serum free estradiol was correlated with total body and trochanter BMD (r = 0.641; P = 0.045 and r = 0.634; P = 0.048). Six of the 10 patients were recruited for a longitudinal stud y in which the dose of hCG was increased monthly from 2000 IU twice pe r week to 6000 IU twice per week. After increasing doses of hCG, level s of serum testosterone and estradiol and total body BMD increased sig nificantly (by paired t test P = 0.001, 0.003, and 0.01, respectively) . Serum bone Gla-protein levels increased by the first month and then decreased (paired t test, corrected by Bonferroni's method). Serum bon e alkaline phosphatase and urinary N-terminal telopeptide of type I co llagen/creatinine levels decreased significantly after increasing the dose of hCG. We conclude that patients with IHH who have serum testost erone within the laboratory reference range may require a higher dose of hCG to normalize BMD and bone turnover.