Serum luteinizing hormone pulsatility and intratesticular testosterone and oestradiol concentrations in idiopathic infertile men with high and normal follicle stimulating hormone serum concentrations.

The purpose of the study was to evaluate pulsatile luteinizing hormone (LH) release and intratesticular concentrations of testosterone and oestradiol in infertile men, to determine if alterations in gonadotrophin secretion are associated with changes in the testicular concentrations of steroids. Patients with idiopathic oligo/azoospermia were divided into a high follicle stimulating hormone (FSH) group (n = 5) and a normal FSH group (n = 6). Blood samples were taken every 15 min for 6 h to determine LH, FSH, testosterone, oestradiol, sex hormone binding globulin, bioactive LH and bioavailable testosterone. The patients underwent a bilateral testicular biopsy for histological assessment and to determine testosterone and oestradiol concentrations. Serum measurements were compared with those of seven fertile men. The high FSH group had a higher concentration of serum LH and oestradiol than normal men (P < 0.01) and showed a lower frequency of LH pulses than the normal FSH group and control men (P < 0.01). Intratesticular oestradiol was higher in the high FSH group (P < 0.001), with a lower testosterone/oestradiol ratio (P < 0.01). Patients showed a negative correlation between the serum testosterone/LH ratio and FSH (r = -0.75; P < 0.01) and a positive correlation between the testicular oestradiol concentration and serum FSH (r = 0.86; P < 0.01). The histopathological examination only showed a smaller tube diameter in the high FSH group (P < 0.05). These data seem to indicate that a higher intratesticular concentration of oestradiol with a lower testosterone/oestradiol ratio in the high FSH group could have a deleterious effect on spermatogenesis.

Cholinergic modulation of GH secretion in acromegalic patients before and after pituitary surgery.

Cholinergic neurotransmission exerts a physiological control on GH secretion. Pirenzepine (Pz), an antagonist of muscarinic receptors, by enhancing hypothalamic somatostatin release, inhibits stimulated GH secretion in normal subjects but not in acromegalic patients. To address the hypothesis that a feedback effect of GH hypersecretion can be involved in this condition, GH responses to GHRH 1-29, 1 microgram/kg iv, with and without administration of Pz, 40 mg iv before tests, were investigated in eight acromegalic patients, before and 20-30 days after transsphenoidal adenomectomy. Pz diminished (p < 0.001) the incremental area under the curve (AUC) of GH responses to GHRH in seven normal controls. In contrast, GHRH responsiveness in untreated acromegalic patients was not affected by Pz. Postoperative basal GH levels decreased by 62.4 +/- 14.9% (p < 0.01). Pz inhibited GH responses to GHRH (p < 0.01). Furthermore, a direct relationship (r = 0.73, p < 0.01) between basal concentrations and the AUC of GH responses following Pz plus GHRH-test was found. The finding that muscarinic receptor activity recovered after the reduction of serum GH basal levels by pituitary surgery lends support to the proposed pathophysiological role of GH excess as a possible determinant factor in cholinergic-somatostatinergic dysfunction in acromegaly.

Effect of an antiestrogen on the testicular response to acute and chronic administration of hCG in normal and hypogonadotropic hypogonadic men: tamoxifen and testicular response to hCG.

The effect of the antiestrogen tamoxifen (Tx) on the acute and chronic hCG administration was evaluated in patients with hypogonadotropic hypogonadism (HH) and in normal men. An hCG test (5000 IU hCG) was performed before, after two months of hCG administration (2000 IU hCG three times weekly) and after two months of hCG + Tx (2000 IU hCG three times weekly plus 20 mg/day of tamoxifen). Blood samples were obtained before and following 24 and 72 h of every test to determine T, E, 17OHP and SHBG. T increased only in HH with both treatments (X +/- SEM: Basal: 97.9 +/- 19.7; hCG: 237.7 +/- 43.2; hCG +/- Tx: 204.7 +/- 10.7 ng/100 ml). 17OHP rose with hCG alone, but not with hCG + Tx in both groups. E, SHBG and 17OHP/T ratio did not change after treatments. hCG tests: E increased 24 h following hCG administration in every test. The ratio 17OHP/T rose at 24 h in the first and second test but in the third test it did not change. These results support the role of E in the acute hCG-induced Leydig cell desensitization. However, the association of Tx does not improve T serum levels, suggesting that E might not be the unique factor involved in the mechanisms for testicular desensitization.

Effects of pirenzepine, bromocriptine and their association on basal and GHRH- and TRH-induced GH secretion in acromegaly.

In order to ascertain if pirenzepine (Pz), an antimuscarinic drug, could inhibit GH secretion in acromegaly, 8 patients were submitted to 3 successive treatment courses of 9 days each: Pz, bromocriptine (BRC) and Pz plus BRC. No change in basal levels of GH after Pz administration was seen, but its reduction (p less than 0.05) by BRC was observed. Pz plus BRC did not improve this response. None of these drugs abolished the paradoxical GH response to TRH. In 7 normal controls, Pz suppressed the GH responsiveness to GHRH (p less than 0.001), but not in acromegalic patients. BRC, instead, blunted this response. In conclusion, cholinergic control of GH secretion is altered in acromegaly. Pz, either when administered alone or associated with BRC, is not useful for the treatment of this disease.

[Effectiveness of somatostatin in the treatment of acute upper digestive hemorrhage]. / Eficacia de la somatostatina en el tratamiento de la hemorragia digestiva alta aguda.

Our study has been made on a retrospective basis in order to evaluate the efficacy of somatostatin (SST) in the treatment of acute haemorrhage caused by gastroduodenal ulcer. Sixty patients were allocated in 2 groups: those who received SST (n = 30), and those who did not received it (n = 30), and were treated only with conventional measures (nasogastric catheter, H2 blockers, blood or derivatives, etc.). Both groups were monitored and controlled at the Anesthesia-Intensive Care Unit. The patients in the SST group received a continuous intravenous infusion of 250 micrograms/h. These patients showed better hemodynamic parameters, and only seven needed surgery. The patients in the conventional treatment group showed worse hemodynamics, needed higher volumes of hemoderivatives, and 25 of them needed surgery. The statistical analysis of our data supports the efficacy of SST in the treatment of uncontrollable upper gastrointestinal bleeding due to gastroduodenal ulcer.

Altered pulsatile pattern of luteinizing hormone in men with idiopathic normogonadotropic oligospermia.

Gonadotropin serum levels and pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) are regulated by sexual steroids and perhaps inhibin, but the relative rates of LH and follicle-stimulating hormone (FSH) secretion are modulated by the frequency of GnRH pulses. This study evaluated LH pulsatility in patients with idiopathic normogonadotropic oligospermia (INO) and normal men before and after clomiphene citrate (CC) administration. INO patients evidenced a lower mean LH levels (P less than 0.001), a higher mean pulse frequency (P less than 0.05) and similar pulse amplitude than normal men. CC induced in normal men a higher LH and testosterone (T) increments and increased pulse amplitude only in normal men. Estradiol (E2) showed no difference in either group. Patients with INO might evidence a hypothalamic disorder that may alter pulsatile GnRH secretion. A different response to CC in patients with INO seems to lend support to a primary hypothalamic lesion. A probable gonadotropin imbalance might alter intratesticular concentrations of T and E2 and be the cause of spermatogenic failure.

Restoration and maintenance of spermatogenesis by HCG therapy in patients with hypothalamo-hypophyseal damage.

Both gonadotropins are necessary to induce spermatogenesis in man and to recover hypophysectomized males. The patients who suffer from tumoral or traumatic hypothalamo-hypophyseal lesion use to have low endogenous gonadotropins (opposite to hypophysectomized patients), which can produce a minor involution of spermatogenesis. Three patients with postpubertal hypogonadotropic hypogonadism and oligozoospermia were studied. Two of them were operated on for chromophobous adenoma of pituitary, and the other patient had traumatic hypothalamo-hypophyseal lesion. The three patients were treated with 5000 IU HCG/week, associated with testosterone enanthate, in two cases and with bromocryptine in the remaining one. All the patients had normalized spermiogram, but when HCG was interrupted, the sperm count regressed to pretreatment levels in spite of the maintenance of treatment with testosterone or bromocryptine. Minimal amounts of FSH together the testosterone supplied by Leydig cell under the HCG stimulus, are able to recover and maintain the spermatogenesis in these patients.

Bromocriptine in the management of infertile men after surgery of prolactin secreting adenomas.

This study evaluated bromocriptine treatment in nine patients with prolactin secreting adenomas who continued to have elevated circulating levels of prolactin after surgery, and who were interested in improving their sperm counts. These patients were brought into the study 3.2 +/- 1.8 years (mean +/- SD) after surgery. All of them presented with high circulating levels of prolactin, and eight of the patients had oligozoospermia (range 0-10 X 10(6) spermatozoa/ml). LH and testosterone levels were low in seven patients, and eight patients had low FSH values. All patients were treated for 90 days with 7.5 mg/day of bromocriptine. After treatment, prolactin levels decreased significantly in all patients, while sperm counts increased significantly in five of them. Testosterone levels increased in four subjects. Bromocriptine therefore seems useful in the management of this type of patient because of the observed decline in prolactin levels and the increase in sperm counts. Possible mechanisms involved in this action are discussed.

Prolactina: regulación y secreción en algunos estados fisiológicos / Prolactin: its regulation and secretion in some physiologic states

La prolactina es una hormona cuya acción fisiológica más importante es su participación en el desarrollo mamario y en la inducción de la lactancia. Es a partir de 1970 que se obtuvo una clara demostración de su existencia en el plasma humano como hormona diferente de la somatotrofina, es secretada por la glándula hipófisis y se halla bajo un control tónico predominantemente inhibidor del hipotálamo, a través de un péptido aún no caracterizado químicamente llamado Prolactin Inhibiting Factor (PIF), aunque se postula que la dopamina sería la mayor responsable de la inhibición de esta hormona. Los niveles de prolactina sérica varían con la edad hasta llegar a las concentraciones de 5-10 ng/ml en la mujer adulta normal, para disminuir a partir de la menopausia. Nuestro grupo investigó esta hormona en diversas condiciones fisiológicas y en diferentes etapas de la vida : en el nacimiento, pubertad; hombre y mujer adulta, durante el embarazo, en donde se observa un aumento progresivo a partir de la séptima semana hasta el término; y durante la lactancia. Estos estudios se realizaron en condiciones basales y mediante pruebas de estimulación de prolactina: sulpirida y TRH (hormona liberada de tirotrofina), y de inhibición con la administración de bromocriptina, L-dopa. Nuestros mayores esfuerzos fueron efectuados en el estudio de las condiciones patológicas de hiperprolactinemia. Pudimos comprobar que esta podía ser la causa farmacológica, por la administración de drogas tales como sulpirida, metoclopramida, alfa metil dopa, antidepresivos tricíclicos, cimetidina; hiperprolactinemia funcional cuando no pudimos demostrar la presencia de un adenoma hipofisiario; y orgánica cuando el adenoma era radiológicamente y quirúrgicamente demostrable. El control de la hiperprolactinemia mediante la estirpación selectiva del adenoma por la vía transeptoesfenoidal o por medio de la bromocriptina nos permitió además grandes avances en el terreno de la fertilidad tanto en el hombre como en la mujer.

D-tryptophan-6-LH-RH-at los doses in the treatment of male subfertility.

The aim of this trial was to evaluate the effect of D-TRP-6-LH-RH in patients with idiopathic normogonadotropic oligoasthenozoospermia (I.N.O.). The LH and FSH response to LH-RH before and during treatment was also studied. Seven patients (age 27 to 32 years) with long standing infertility were incorporated. All of them were considered to have I.N.O. on the basis of at least three spermatograms and absence of evidence of other diseases. All patients were treated wtih D-TRP-6-LH-RH (2 microgram i.m. every two days) during 90 days. Control spermatograms were performed at monthly intervals during and after treatment. The responses of LH and FSH to 50 microgram i.v. LH-RH were studied before and after 90 days of treatment. Five of the patients achieved a normalization of the concentration of spermatozoa per ml and of the percentage of forwardly progressive spermatozoa. None of the patients showed inhibition of the response to LH and FSH to LH-RH during treatment. These results differ from others in which larger doses of D-TRP-6-LH-RH determined an inhibition of the pituitary response to LH-RH and an impairment of the spermogram.

[Surgical treatment in Cushing's disease (authors' translation)]. / Traitement chirurgical de la maladie de cushing.

We are presenting a series of 23 patients with Cushing disease selected from a larger study in which the ectopic production of ACTH (paraneoplastic or tumoral), adrenal adenoma or carcinoma were discarded. Sixteen were female and seven male. Diagnosis was fundamentally realized by clinical manifestations derived from hypercortisolism (obesity, muscular atrophy, diabetes, osteoporosis or polyglubulia). The polytomography demonstrated a deformed sella in 19 patients. Endocrine exams showed an alteration in rhythm of Cortisol and elevated levels of urinary metabolites. Others exams, Liddle Test, Metopirona Test, or stimulation of exogenic ACTH did not always permit diagnosis of pituitary adenoma. Plasmatic dosage of ACTH is the best test although results did not always agree with clinical manifestations. In each case we performed clinical treatment in preparation for surgery and later selective removal of adenoma or total pituitary ablation by transphenoidal approach. Of 21 patients, we found an adenoma during surgery in 15; the other 6 on whom we performed a total hypophysectomy, the pathological study showed an adenoma in 5 and a hyperemic gland with thick capillaries in 1. Another type of treatment was used on 2 due to their age. Nine patients were given post-operative radiotherapy. We conclude that microsurgery by transphenoidal approach offers the best possibilities for patients with Cushing disease.

The effect of a treatment with doxycycline on semen of asthenozoospermic patients with T-mycoplasma genital infection.

The pathogenic role of T-Mycoplasma seminal infection in male sterility is a matter of controversy. The aim of this study was to observe the effect of a specific treatment in asthenozoospermic patients in which the only finding was the presence of T-Mycoplasma in semen. Twenty five patients (age 24 to 49 years) were incorporated. Average time of known infertility was 4.0 +/- 0.5 years. Asthenozoospermia was diagnosed by at least three previous spermatograms. All other studies were negative with the only exception of the tests to study the presence of T-Mycoplasma in semen. Each patient was treated with doxycycline (200 mg/day) during 20 days. Control spermatograms were performed at 30 and 90 days from the initiation of treatment. After treatment the tests to detect the presence of T-Mycoplasma in semen were negative in all patients. A significant increase of the percentages of forwardly progressive spermatozoa and of live and motile spermatozoa was observed together with a significant decrease of the percentage of non motile spermatozoa. Qualitatively eleven patients (44%) achieved a normalization of the spermogram; five patients (20%) obtained significant improvements while nine patients (36%) did not experience any significant change. Although the real significance of T-Mycoplasma in the determination of male sterility is still a matter of controversy, its presence in semen in asthenozoospermic patients should be considered and, consequently, treated.