Treatment of hypogonadotropic hypogonadal male patients with the luteinizing hormone-relasing hormone (LH-RH) anolog D-Ser(TBU)6 EA10 LH-RH: transient disappearance of gonadotropin stimulation.

We have studied the effect of prolonged treatment with a long-acting luteinizing hormone-releasing hormone (LH-RH) analog (D-Ser-(TBU)6 EA10 LH-RH in six patients with isolated gonadotropin deficiency. Before treatment, all subjects responded to LH-RH (100 microgram intravenously [IV]); one responded immediately, and five after 5 daily infusions of LH-RH (200 microgram). Treatment by LH-RH analog (348 microgram every 2 days with a nasal spray for 90 or 120 days) is only efficient for 1 month; a consistent increase in serum LH and a slight increase in testosterone (T) were observed in all patients, but no increase of serum follicle-stimulating hormone (FSH) was detectable. Then a paradoxical effect appeared: LH and T levels returned to the basal values. Moreover, this treatment induced refractoriness of the pituitary to LH-RH for several months after the end of treatment. The appearance of antibodies to LH-RH and LH-RH analog was eliminated. A pituitary response was obtained in three patients when a new LH-RH stimulation was repeated 7 and 11 months after the end of treatment. The mechanism of this pituitary desensitization is discussed.

[Idiopathic hemochromatosis and gonadotropin secretion (author's transl)]. / Hemochromatose idiopathique et fonction gonadotrope.

18 patients suffering from idiopathic hemochromatosis were studied. Plasma testosterone was stimulated by HCG. Basal plasma LH and FSH were significantly lower for the male group compared to healthy men. Lack of reponse of plasma LH and FSH after IV LHRH (100 microgram) was observed in 10 cases; among the patients with a normal response there were a postmenopausal woman, a 47 XXY syndrome, and the two youngest patients. Repeated infusions of LHRH (200 microgram/day x 5 d) did not increase LH in 8 out of 9 cases. Repeated plasma LH determination for 4 hours showed no pulsatile pattern in 6/7 patients. Plasma LH-RH measured in 7 cases was not elevated. The conclusion is that hypogonadism in hemochromatosis, when present, is related to a gonadotropin secretion defect, presumably of pituitary origin.

[Changes in plasma binding protein of sex steroids and transcortin during the treatment of menopause with oral estrogens]. / Etude des variations de la protéine de liaison plasmatique des stéroïdes sexuels et de la transcortine au cours du traitement de la ménopause par les estrogènes par voie orale.

Sex steroid binding protein (SBP) and transcortin (CBG) plasma concentrations were measured in 15 postmenopausal women before and during oral administration of estradiol 2 mg plus estriol 1 mg given alone for one month and in sequential combination with noresthisterone 1 mg for the following months. The results were compared with those obtained in a group of 13 premenopausal women who were studied during the early follicular phase or during administration of estroprogestagens. The oral administration of estrogens slightly increased CBG levels (56.1 +/- 11.4 vs 46.0 +/- 5.2 mg/l, P less than 0.05) which in 4 patient were higher than in premenopausal women. The mean SBP level was lower in postmenopausal women than in premenopausal women (1.02 +/- 0.40 vs 1.35 +/- 0.38 micrograms/dl, P less than 0.02), and SBP correlated negatively and significantly with the body mass index (r = 0.794, P less than 0.02). On average, SBP increased twofold during the estrogen treatment. In 6 patients the concentrations of estrogen-stimulated SBP were higher than the upper limit for premenopausal women. Lowered SBP levels were normalized during estrogen therapy. During estrogen substitution in the postmenopausal women, the mean E2 to SBP ratio (an index of free estradiol) was within the normal limits for premenopausal women. These results demonstrate that SBP is highly sensitive to oral estrogens. The increase in SBP is associated with a free E2 index which is within the physiological range of premenopausal women. The risk(s) or benefit(s) associated with the increase in SBP during estrogen therapy in postmenopausal women deserve to be evaluated by further investigations.

[The hypothalamic hormone regulating the release of pituitary luteinizing hormone -- LH-RH]. / L'hormone hypothalamique commandant la liberation de l'hormone luteinisante hypophysaire -- L.H.R.H.

PIP: The present state of knowledge of luteinizing hormone releasing horm one (LH-RH) is reviewed. After a brief description of the isolation and activity of LH-RH, the physiology and therapeutic uses of the substance are discussed. In normal subjects, intravenous or subcutaneous injection of LH-RH is followed by a rapid rise in blood LH levels, which decline slowly; individual variations may be important. Clincally, LH-RH is used in the differential diagnosis of pituitary and gonadal hypofunction. Clinical experimentation suggests that LH-RH may be useful in inducing ovulation.^ieng

[Prolactin adenoma. Study of gonadotrophic function by the sassoles G LHRH test]. / Adénome à prolactine. Etude de la fonction gonadotrope par l'épreuve à la LHRH. Dix cas

An intravenous injection of synthetic LHRH (50mug) was given in 10 patients with prolactin secreting pituitary adenomas. Variations in circulating levels of gonadotrophic hormones were measured by radioimmunological estimation. The increase in blood level of luteinizing hormone was constant, low in three cases, normal in 3 and high in 4. An increase in follicle stimulating hormone (FSH) was absent in only two cases. The data obtained indicates the absence of any characteristic value of the LHRH test in the aetiological diagnosis of amenorrhoea/galactorrhoea syndromes. They represent an argument in favour of the relative character and of the functional nature of the gonadotrophic insufficiency of prolactin adenomas.

[Mental anorexia: gonadotrophic response to clomifene citrate. Sixteen cases]. / Anorexie mentale: réponse gonadotrope au citrate de clomifène. Seize observations

Sixteen patients with anorexia nervosa and secondary amenorrhoea received clomiphene citrate, eight before any other treatment (200 mg of clomiphene citrate per day for four days) and eight others after partial or total correction of weight loss (50 mg of clomiphene citrate per day for five days). Menstruation occurred in four patients of the second group. An elevation of plasma LH was demonstrated in 4 cases in the first group and 7 of the second group. Variation in FSH was not always parallel with LH. The authors discuss the physiopathological mechanism of gonadotrophic insufficiency in anorexia nervosa and define the role of clomiphene citrate in the treatment of this disorder.

The 24-h cortisol secretory pattern in Cushing's syndrome.

The 24-h plasma cortisol profile was obtained at 20-min intervals in 18 patients with Cushing's syndrome (10 with Cushing's disease, 5 with adrenal adenoma, 2 with ectopic ACTH secretion and 1 of questionable aetiology). The mean cortisol level was maximum in the case of ectopic ACTH secretion. The coefficient of variation of cortisol levels was subnormal in all except 2 subjects. Periodogram calculations, providing a best-fit curve (B F C) for each profile, showed that the existence of a significant baseline variation is a frequent feature. In certain cases, it is compatible with the persistence of a true circadian rhythm (2 patients with Cushing's disease; 1 patient with adrenal adenoma). The alteration of plasma cortisol pulsatility is much more pronounced in patients with adrenal adenoma than in patients with Cushing's disease. This is consistent with the hypothesis of a predominantly tonic secretion blunting the episodic hormone release. In 9 patients with Cushing's disease, the plasma cortisol pattern was suggestive of a combination of episodic cortisol release under CRF control and of continuous cortisol secretion due to constant stimulation from an autonomous ACTH source. Two cases were possibly of hypothalamic origin, as suggested by the presence of enhanced cortisol pulsatility and of a normal circadian amplitude. The analysis of the 24-h profile of plasma cortisol in Cushing's syndrome contributes to our understanding of the physiopathological mechanisms underlying this disorder and may help the diagnosis of its aetiology.