Anselmo Palacios

Comparison of the kinetics of injectable testosterone in eugonadal and hypogonadal men

Serum reproductive hormone levels were measured serially after eugonadal and hypogonadal men had received either a 200-mg or a 100-mg intramuscular injection of testosterone enanthate. The calculated mean integrated testosterone and estradiol levels indicated that the 200-mg testosterone enanthate injection in the hypogonadal subjects maintained eugonadal levels of these hormones through day 11. The 100-mg dose maintained eugonadal levels of these hormones through day 11. The 100-mg dose maintained eugonadal testosterone levels through day 7. The testosterone:estradiol ratios in both groups following the 200-mg injection remained above or at the eugonadal baseline trough day 21. The authors recommend that replacement therapy for hypogonadal men should be 200 mg of testosterone enanthate every 10 to 14 days. A similar dosage would be recommended if testosterone enanthate were to be used as an experimental inhibitor of spermatogenesis (contraceptive agent).

Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in growth-hormone-treated and untreated patients.

Objective: To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents. Methods: Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal. Results: Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents. Conclusions: GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.

Suppression of human spermatogenesis by depot androgen: potential for male contraception.

Abstract The gonadotropic hormones, LH and FSH, are required for normal sperm production. Inhibition of gonadotropin secretion by exogenously administered sex steroids represents one possible approach for male contraception. In the present study testosterone enanthate (TE) was administered IM to 39 normal adult men (age 21–39) to assess its efficacy as a suppressor of spermatogenesis and to determine possible adverse effects. Seventeen subjects (Group A) received TE (200 mg/wk) for 16–20 weeks. 16 17 lowered sperm counts to less than 5 million/cc; 11 17 to less than 300,000; and 10 17 became azoospermic. Group B received TE (200 mg/2 wk). In 10 22 , sperm counts were less than 5 million/cc at 16 weeks; 9 22 were less than 300,000; and 5 22 were azoospermic. When those with sperm counts greater than 5 million/cc were switched at 16 weeks to weekly treatment (additional 3–16 weeks), 9 12 lowered sperm counts to less than 5 million/cc. Overall, 19 22 of Group B attained this level. Serum LH and FSH were decreased on both regimens. These effects were dose-related. Mean serum testosterone was elevated above baseline (+64%) at 1 week after injection (Group A), but remained at basal levels 2 weeks after TE injection in Group B. Serum oestradiol levels parallel those of serum testosterone. Decreasing the frequency of TE (3 or 4 weeks) resulted in a rebound of FSH and LH above baseline and increased sperm counts. After discontinuing treatment, sperm counts and hormonal measurements returned to normal in all subjects. Modest increase in body weight, red cell mass, oiliness of skin and mild acne were seen in some subjects. Liver function tests, glucose tolerance, blood lipids and renal function were unchanged. Based on these data, testosterone enanthate demonstrates significant suppression of spermatogenesis. Further refinement of dose and/or delivery system, as well as investigation of combination hormonal regimens show promise for the development of a safe, effective male contraceptive agent.

Effect of testosterone enanthate on hematopoiesis in normal men

Testosterone enanthate, a commonly used depot form of androgen, was administered to normal men according to several dose schedules. This resulted in significant increments in serum testosterone levels despite the fact that testosterone concentrations remained within the normal population range in almost all instances. Mild but significant increases in white blood cell, red blood cell, hematocrit, and hemoglobin concentrations were noted. These effects correlated with the dose frequency schedules. Negligible changes in mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were observed. Despite the significant individual increases in blood parameters, all values remained within the normal population range and no clinical manifestations were observed.

Serum lipids, lipoprotein Ip(a), and plasminogen activator inhibitor-1 in patients with Turner's syndrome before and during growth hormone and estrogen therapy

OBJECTIVE To evaluate whether girls with Turners syndrome have an increased risk for cardiovascular disease due to alterations in their lipoprotein metabolism. DESIGN Controlled clinical study. SETTING Private academic hospital. PATIENT(S) Fifteen untreated girls with Turners syndrome were studied initially; 11 of these patients were evaluated further while on therapy. INTERVENTION(S) Serum lipids, lipoprotein lp(a), and plasminogen activator (PA) inhibitor-1 were measured before and during 6 months of either GH or estrogen (E) treatment. MAIN OUTCOME MEASURE(S) Serum lipids, lipoprotein lp(a), and PA inhibitor-1 (PAI-1). RESULT(S) Total and low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein lp(a), and PA inhibitor-1 levels were normal in Turners syndrome patients compared with age-matched controls; HDL cholesterol was increased. During GH treatment, a significant decrease in total and LDL cholesterol was noted, whereas lipids, lipoprotein(a), and PA inhibitor-1 levels did not change with E therapy. CONCLUSION(S) The normal lipoproteins of untreated adolescents with Turners syndrome, as well as the further decrease of total and LDL cholesterol during GH treatment, would seem to indicate that lipoproteins do not increase the cardiovascular risk of these girls.

Effectiveness and limitations of the use of the gonadotropin-releasing hormone agonist leuprolide acetate in the diagnosis of delayed puberty in males.

In order to evaluate the effectiveness of the gonadotropin-releasing hormone agonist leuprolide acetate in distinguishing gonadotropin deficiency from delayed puberty, a single subcutaneous dose of 20 micrograms/kg of leuprolide acetate was administered at 07.00 h to 14 patients with constitutionally delayed puberty and to 8 gonadotropin-deficient subjects, and serum gonadotropin and testosterone levels were determined at baseline and 1,2,3,6,12, and 24 h thereafter. The increase in gonadotropin and testosterone levels was significant in patients with delayed puberty, so that the mean peak luteinizing hormone and to a lesser degree the mean peak testosterone levels clearly differentiated normally delayed from gonadotropin-deficient puberty. However, when the peak gonadotropin and testosterone concentrations were analyzed individually, there was a considerable overlap between the two groups of males, limiting the usefulness of this test.

Circulating levels of high-sensitivity C-reactive protein and soluble markers of vascular endothelial cell activation in growth hormone-deficient adolescents.

Background/Aims: Significant endothelial dysfunction as determined by lower flow-mediated vasodilation of the brachial artery was recently reported by us in growth hormone-deficient (GHD) adolescents. The circulating concentrations of markers of vascular endothelial cell and platelet activation and their relationship to inflammatory markers have not been previously evaluated in this group of patients. Objective: To assess the relationship between circulating levels of high-sensitivity C-reactive protein (CRP) and soluble markers of vascular endothelial cell activation in GHD adolescents. Design/Methods: Twenty-eight GHD children on GH treatment with a chronological age of 15.7 ± 2.6 years and 16 untreated GHD adolescents with a chronological age of 16.6 ± 3.3 years were studied. Concentrations of CRP, as an inflammatory marker, were measured in all patients and the association between CRP and the fasting soluble markers of vascular endothelial cell activation intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin levels was evaluated. Sixteen healthy adolescents with a mean chronological age of 15.1 ± 2.2 years served as controls. Results: CRP and P-selectin levels were significantly higher in untreated GHD adolescents than in treated GHD subjects or in healthy controls (p < 0.02), while VCAM-1 concentrations were increased in both untreated and treated GHD adolescents when compared to controls (p < 0.007). E-selectin and ICAM-1 levels were similar in all three groups. CRP was found to be associated with BMI (r: 0.62; p < 0.001), P-selectin (r: 0.43; p < 0.01), E-selectin (r: 0.27; p < 0.03), ICAM-1 (r: 0.23; p < 0.05) and VCAM-1 (r: 0.40; p < 0.001) concentrations in untreated GHD adolescents and with P-selectin (r: 0.88; p < 0.001) and E-selectin (r: 0.29; p < 0.01) in treated GHD subjects. A weak inverse association was observed in a subgroup of patients between brachial artery endothelium-dependent dilation and P-selectin (r: –0.56; p < 0.07). Conclusions: Low-grade inflammation as manifested by increased circulating levels of CRP seems to be associated with the early activation of vascular endothelial cells in GHD adolescents

The metoclopramide test: a useful tool with the luteinizing hormone-releasing hormone test in distinguishing between constitutional delay of puberty and hypogonadotropic hypogonadism

To evaluate the effectiveness of intravenous metoclopramide, alone or in combination with luteinizing hormone-releasing hormone (LH-RH), in distinguishing between constitutional delay of puberty and hypogonadotropic hypogonadism, 12 patients with constitutional delay of puberty and 10 patients with hypogonadotropic hypogonadism were studied. All patients received 10 mg/m2 of intravenous metoclopramide and 100 micrograms of intravenous LH-RH on separate days. The mean prolactin (PRL) response following metoclopramide was significantly higher in the constitutional delay of puberty group when compared with the hypogonadotropic hypogonadism patients (P less than 0.01 at 15, 30, 45, and 60 minutes); all patients with constitutional delay of puberty increased their PRL level to greater than or equal to 60 ng/ml, except one who had a peak PRL level of 38 ng/ml. While only 2 of the hypogonadotropic hypogonadism subjects reached a peak PRL concentration of greater than or equal to 60 ng/ml, 4 had peak PRL levels greater than 38 ng/ml. The mean LH and follicle-stimulating hormone (FSH) responses after LH-RH were significantly higher in the constitutional delay of puberty group (P less than 0.01 at 30, 45, and 60 minutes for LH and P less than 0.01 at 45 and 60 minutes for FSH). All constitutional delay of puberty subjects responded to both the metoclopramide and LH-RH tests, while patients with hypogonadotropic hypogonadism responded only to one or to neither of these tests. Therefore, while metoclopramide alone did not allow us to clearly distinguish constitutional delay of puberty from hypogonadotropic hypogonadism, the combined use of both of these stimuli permitted us to detect all subjects with constitutional delay of puberty.

Acknowledgements to Reviewers

Badenhoop, K., Frankfurt am Main Bang, P., Stockholm Baron, J., Bethesda, Md. Barreca, A., Genoa Barrios, V., Madrid Bartalena, L., Varese Bartrons, R., L’Hospitalet Baudin, E., Villejuif Bauer, K., Hannover Baumgartner, A., Berlin Baxter, R., St. Leonards Beauvillain, J.C., Lille Beck, M., Mainz Beck-Peccoz, P., Milan Ben-Shlomo, A., Los Angeles, Calif. Bettendorf, M., Heidelberg Bianchi, G., Bologna Bland, M.L., San Francisco, Calif. Blasi Cabus, J.M., Barcelona Böhm, B., Ulm Brabant, G., Hannover Brain, C.F., London Brämswig, J.H., Münster Breckwoldt, M., Freiburg i. Br. Brucker, C., Ulm Buchanan, C., London Burbach, J.P., Utrecht Buyse, M., Paris Buyukgebiz, A.B., Izmir Carel, J.-C., Paris Chaussain, J.-L., Paris Chiarelli, F., Chieti Chrousos, G.P., Bethesda, Md. Clark, A.J.L., London Coerper, S., Tübingen Cohen, L.E., Boston, Mass. Cohen, M.M., Halifax Cole, T.J., London Corry, D.B., Sylmar, Calif. Cowell, C.T., Westmead Crofton, P.M., Edinburgh Cutfield, W., Auckland Czernichow, P., Paris

Contents Vol. 60, 2003

Anne Marcovich: Quelles missions pour les médecins de campagne du XIX siècle français? Soigner, éduquer, civiliser. Le rapport d’un médecin cantonal du Haut-Rhin (Alsace) en 1849 [Which Tasks for Countryside Physicians in 19th Century France? To Heal, to Educate, to Civilise the People.A Country Physician’s Report from the French Department of the Haut-Rhin in 1849] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170