Stimulatory therapy with either GnRH or gonadotropins is an effective treatment to induce spermatogenesis and achieve paternity in men with secondary hypogonadism. However, there is still uncertainty about the optimal treatment modality and schedule, the duration of treatment necessary and the influence of interfering factors such as maldescended testes. We have extended our previous series of men treated for secondary hypogonadism and now present our therapeutic experience with 42 cases. Twenty-one patients with hypothalamic disorders (11 with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with hypopituitarism (group II) were treated with hCG/hMG. A total of 5 7 treatment courses were initiated for induction of spermatogenesis, 36 of these for the purpose of induction of pregnancy in the female partner. Bilateral testicular volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by the appearance of sperm in the ejaculate was induced in 54/57 courses. Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not preclude patients with IHH or KalS from gaining fertility under therapy and spermatogenesis could be successfully initiated even in some individuals with bilateral maldescended testes. In general there was a tendency for a longer duration of therapy until induction of spermatogenesis in patients with a history of bilateral cryptorchidism. However, this did not reach statistical significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH there were no statistically significant differences in terms of duration to appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years spermatogenesis could be induced. In repeatedly treated patients stimulation of spermatogenesis tended to be faster while time until induction of pregnancy was significantly shorter in the second treatment course. In conclusion, GnRH or hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It remains to be determined whether highly purified urinary gonadotropin preparations or recombinant LH and FSH will provide therapeutic advantages.
D Buchter, HM Behre, S Kliesch and E Nieschlag
HM Behre, K Abshagen, M Oettel, D Hubler and E Nieschlag
OBJECTIVE: In the search for long-acting testosterone preparations suited for substitution therapy of hypogonadal men, testosterone undecanoate (TU) dissolved in either tea seed oil or castor oil was investigated. DESIGN: In study I, 1000 mg TU in tea seed oil (125 mg/ml) were injected in equal parts into the gluteal muscles of seven hypogonadal men. In study II, 1000 mg TU in castor oil (250 mg/ml) were injected into one gluteal muscle of 14 patients. RESULTS: In comparison with published data on testosterone enanthate, most widely used for i.m. injections, the kinetic profiles of both TU preparations showed extended half-lives and serum levels not exceeding the upper limit of normal. The castor oil preparation had a longer half-life than TU in tea seed oil (33.9+/-4.9 vs 20.9+/-6.0 days (mean pm S.E.M.)). CONCLUSION: The longer half-life and the smaller injection volume make TU in castor oil a strong candidate for further applications in substitution therapy and in trials for male contraception.
E. Nieschlag, G.F. Weinbauer, J. Gromoll and H.M. Behre
E Leifke, HC Korner, TM Link, HM Behre, PE Peters and E Nieschlag
Loss of bone and muscle mass are major findings of male hypogonadism. In order to determine the long-term effect of testosterone replacement therapy on spinal bone and muscles, the trabecular and cortical bone mineral density, vertebral body area and paraspinal muscle area were assessed by quantitative computed tomography in 32 testosterone-substituted patients, aged 18-74 years, with idiopathic hypogonadotropic hypogonadism (n=6), pituitary insufficiency (n=5), Klinefelter syndrome (n=12) or other forms of primary hypogonadism (n=9). They were followed for a mean period of 3.2+/-1.7 years (mean+/-S.D.), ranging from 1 to 7 years. A significant correlation between initial serum testosterone levels and bone mineral density was found in patients with congenital forms (r=0.58; P<0.05) but not in those with acquired forms. A significant increase in trabecular and cortical bone mineral density (P<0.001) was documented in the course of replacement therapy in all patients regardless of the type of hypogonadism and age of patients. A slight but significant increase in paraspinal muscle area was observed if all patients were taken together (P<0.01). The area of paraspinal muscle correlated with body weight (r=0.58; P<0.001) and moderately with trabecular bone mineral density (r=0.4; P<0.01). Its increase did not correspond to the change observed for trabecular and cortical bone mineral density. Vertebral body area did not change over time. It correlated only with height and weight but not with bone mineral density. In conclusion, testosterone therapy of hypogonadal men improves both trabecular and cortical bone mineral density of the spine independently of age and type of hypogonadism while vertebral area remains unchanged. The effects seen on paraspinal muscles emphasize the clinical benefit of adequate replacement therapy for the physical fitness of hypogonadal men.