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Biomedical subjects

P Bouchard

Publications and source records attributed to P Bouchard.

At least 109 records · Page 6Linked to original sources
PubMed1995

[Perspectives of contraception].

According to demographic provision, the world population will soon reach 6 billions. It is therefore urgent to increase women's access to well tolerated, efficient, low cost contraceptives. The primary goal is to inform women on their reproductive health and on the use of contraceptives. Secondly, new molecules should be shortly available: low dose estroprogestins containing new non androgenic progestins and 17 beta-estradiol, RU 486 as a post-coïtal pill, levonorgestrel or desogestrel containing IUDs. The daily intake of low dose antiprogestins to interfere with endometrial maturation is also currently studied. In the future, anti-FSH molecules or tissue-specific steroids could be designed.

Contraception↗
PubMed1995

In vivo modulation of sigma receptor sites by calcitonin gene-related peptide in the mouse and rat hippocampal formation: radioligand binding and electrophysiological studies.

Possible interactions between sigma (sigma) receptor sites and calcitonin gene-related peptides (CGRP) were investigated using receptor subtype-related analogues and fragment in in vivo [3H](+)SKF 10 047/sigma binding in the hippocampus, and electrophysiological recording of the N-methyl-D-aspartate (NMDA)-induced activation of CA3 pyramidal neurons, two well-established sigma assays. In both paradigms, CGRP and the agonist [Cys(ACM)2,7]hCGRPalpha modulated sigma systems. In vivo binding experiments demonstrated that CGRP and [Cys(ACM)2,7]hCGRPalpha inhibited 25-40% of specific [3H](+)SKF 10 047 labelling in the mouse hippocampal formation while the purported antagonist hCGRP8-37 was inactive. The specificity of this modulation was demonstrated further by the lack of effect of other vasoactive peptides, including the atrial natriuretic peptide, substance P, and its N-terminal fragment, substance P1-7. In the CA3 subfield of the rat dorsal hippocampus, hCGRP alpha decreased (up to 61%) the NMDA-induced activation of the pyramidal neurons. Conversely, the linear analogue [Cys(ACM)2,7]hCGRP alpha enhanced (by 85%) the NMDA-induced activation of CA3 pyramidal neurons, while the antagonistic fragment hCGRP8-37 had no effect. Haloperidol, a high-affinity sigma receptor ligand, inhibited by 90% the in vivo [3H](+)SKF 10 047 labelling, and prevented the modulation of the NMDA-induced activation by hCGRP alpha and [Cys(ACM)2,7]hCGRP alpha. It thus appears that CGRP can modulate sigma-related systems in the hippocampal formation.

Animals↗
PubMed1995

[Non-oral administration of progesterone: experiences and possibilities of the transvaginal route].

Recent development of transdermal therapy permits application of estrogen, usually produced in the ovaries, in physiological dosage by means of continuous release from either an epidermal patch or dermal application of a gel. Transdermal therapy with progesterone, however is impossible due to poor dermal absorption and high dose requirements (release from corpora lutea: 25 mg/24 hours). Two other possibilities have been proposed. On one hand it is possible to apply norethisterone-acetate (NETA), another gestagen, epicutaneously. This mode of administration carries the same problems as oral application thus allowing for a dose reduction. On the other hand progesterone can be applied vaginally. This mode leads to significantly higher plasmatic concentrations of progesterone and has effects on the uterine mucosa similar to those in a normal cycle. This modality thus permits application of estradiol and progesterone in a physiological manner by a non oral route. It appears particularly interesting in patients at cardiovascular risk.

Administration, Intravaginal↗
PubMed1995

Binocular interactions and visual acuity loss in esotropic cats.

Visual acuity was measured behaviorally in various groups of cats by using a two-choice discrimination procedure. Cats in group 1 were rendered strabismic soon after birth by sectioning the tendon of the lateral rectus muscle (unilateral esotropia); at adulthood, their visual acuity (VA) was evaluated, after which the optic chiasm was sectioned and VA reassessed. Cats in group 2 were not only tenotomized but also chiasmatomized neonatally, while cats in group 3 underwent a neonatal section of the optic chiasm only. VA was measured at adulthood in the two latter groups. Group 4 consisted of adult cats whose VA was evaluated before and after an optic chiasm section. Stimuli consisted of square-wave gratings of various spatial frequencies. Results showed that in normal cats, the average threshold values under monocular viewing were identical for each eye (4.76 cycles/degree); however, following optic chiasm section, monocular VA was reduced to 1.23 cycles/degree. VA in early optic chiasm section cats was lower than that of the normal cats but higher than that of late-lesioned animals (2.33 cycles/degree). In strabismic cats, mean VA was 1.25 cycles/degree for the deviated eye and 2.8 cycles/degree for the normal eye. Following the optic chiasm section at adulthood, VA was lower not only for the deviated eye (< 0.17 cycles/degree) but also for the normal eye (1.14 cycles/degree). Similar results were found when both the deviation and chiasmatomy were performed neonatally. The elimination of interocular interactions through chiasm transection failed to improve VA in the strabismic eye.

Animals↗
PubMed1995

Nature and bioactivity of gonadotropin-releasing hormone (GnRH) secreted during the GnRH surge.

Previous studies have demonstrated a neural action of estradiol in inducing a surge of GnRH in the ewe. However, although the GnRH and LH surges began concurrently, the GnRH surge consistently continued well beyond the surge of LH. Three experiments were conducted to test the hypothesis that the termination of the LH surge results from the secretion of a relatively inactive variant of GnRH during the later phases of the GnRH surge. In the first experiment, hypophyseal portal blood collected during an estrogen-induced LH surge was analyzed for GnRH immunoreactivity using two antibodies having specificity for the N- or C-terminal portion of the GnRH molecule. The duration, amplitude, and time course of the GnRH surge were found to be similar irrespective of the antisera used. In a second experiment, a competitive GnRH antagonist was administered at the beginning of the estrogen-induced GnRH/LH surge at a dose capable of blocking pituitary responsiveness for approximately half the duration of the GnRH surge. Antagonist treatment did not result in any change in the time of onset of the GnRH surge, but there was no increase in LH that naturally occurs coincident with onset of the GnRH surge. Rather, a persistent increase in LH secretion was observed during the latter stages of the GnRH surge, indicating that the GnRH molecules secreted at this time were biologically active. Finally, a sensitive and specific ovine pituitary cell bioassay was used to test bioactivity of GnRH in hypophyseal portal blood during different phases of the GnRH surge. GnRH bioactivity in samples collected early in the GnRH surge was greater than that before the onset of the GnRH surge but no greater than that collected during the descending limb of the surge. The results of all three experiments fail to support the hypothesis that the LH surge ends because of a change in the nature of the GnRH secreted. Rather they show that GnRH secreted throughout the surge is biologically active. Thus, the termination of the LH surge before that of the GnRH surge occurs for reasons other than lack of a bioactive GnRH signal.

Animals↗
PubMed1995

[Recombinant FSH. Characteristics and therapeutical values].

Pituitary glycoproteins LH and FSH control gonadal physiology. Modern techniques of molecular biology have allowed the synthesis of human recombinant hormones (rec). In particular rec-FSH is now available for clinical use. This pure preparation of FSH, is available in unlimited quantity. The pharmacokinetics of the rec-hormone is identical to its natural counterpart. The use of rec-FSH in hypophysectomized women has allowed the reconfirmation of the "Two-cell--Two gonadotropins" theory. Indeed rec-FSH induces follicular growth without rise in Estradiol secretion. Clinical applications of rec-FSH and LH include ovarian stimulation, as well as, induction of spermatogenesis in men with hypogonadotrophic hypogonadism. Overall, these pure gonadotropins have the critical advantage of purity, reproducibility and in addition they allow easy modulation of the FSH/LH ratio.

Animals↗
PubMed1995

Scheduled administration of a gonadotrophin-releasing hormone antagonist (Cetrorelix) on day 8 of in-vitro fertilization cycles: a pilot study.

To assess in a pilot study the ability of a single injection of a GnRH antagonist (Cetrorelix) to prevent premature luteinizing hormone (LH) surges in an in-vitro fertilization (IVF) embryo transfer programme when administered on a fixed day in the late follicular phase, ovarian stimulation was carried out in 11 women with two ampoules of human menopausal gonadotrophin per day beginning on day 2 of the menstrual cycle. A 3 mg dose of Cetrorelix was administered on day 8 of the stimulation cycle. A second injection was administered 72 h later if ovulation was not triggered in the meantime. We did not observe a premature LH surge in any of the cycles studied. The injection of 3 mg Cetrorelix was capable of preventing LH surge in all the patients studied, introducing a very simple treatment protocol. Among the patients who received two injections (n = 3), the day of the first administration was delayed in two subjects due to slow follicular maturation kinetics. Out of 11 patients, 10 had an embryo transfer. Four clinical pregnancies were obtained (40% per embryo transfer), of which 3 are ongoing (30% per embryo transfer). A simple administration protocol for a new GnRH antagonist (Cetrorelix) was able to prevent LH surges in the 11 patients studied.

Adult↗
PubMed1994

Involvement of microsomal vesicles in part of the sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition in mitochondrial fractions of rat liver.

Liver mitochondrial fractions as normally isolated contain only 10-20% of total mitochondria and may not be representative of the whole mitochondrial population. This study was designed to evaluate the dependence of the sensitivity of carnitine palmitoyl-transferase I (CPT I) to malonyl-CoA inhibition in mitochondrial fractions that are not normally studied. Four fractions prepared from rat liver were found to be contaminated to different extents by microsome vesicles, on the basis of marker-enzyme activities and micrographic data. Purification of mitochondrial fractions on a Percoll gradient decreased to some extent the microsomal contamination, which was due in part to the existence of close bonds between microsomes and the outer membranes of mitochondria. A greater degree of contamination of mitochondrial fractions by microsomes was correlated with a greater sensitivity of CPT I to malonyl-CoA inhibition. Attempts were made to enhance the sensitivity of CPT I to malonyl-CoA with the use of microsomes. Measurements performed by adding mitochondria and microsomes in the same CPT I assay failed to demonstrate any significant enhancement of malonyl-CoA inhibition. However, addition of ATP to a mixture of mitochondria and microsomes was shown to trigger the binding of both particles, as assessed by enzymic and micrographic data, and to increase the sensitivity of CPT I to malonyl-CoA inhibition. These results demonstrated that the binding of microsomes to mitochondria, unlike the simple mixing of both particles, was capable of altering the sensitivity of CPT I to malonyl-CoA. The data also suggest that this process could be of physiological importance, owing to the frequency of contiguous zones between mitochondria and endoplasmic reticulum observed in sections of intact liver cells.

Adenosine Triphosphate↗
PubMed1994

Cohort study of silicon carbide production workers.

Silicon carbide is produced by a chemical reaction at high temperature between free crystalline silica and petroleum coke. The process generates airborne fibers and fibrogenic dusts such as alpha-quartz and cristobalite, which are also potentially carcinogenic. The authors report that this is the first cohort study in this industry. The study was carried out among 585 Québec silicon carbide production workers who had worked at any time from 1950 to 1980. Follow-up was to December 31, 1989, and 167 deaths were observed. The standardized mortality ratio (SMR) for all causes of death was 1.05 (95% confidence interval (CI) 0.90-1.23); for nonmalignant respiratory diseases it was 2.03 (95% CI 1.21-3.22); and for lung cancer it was 1.69 (95% CI 1.09-2.52). Controlling for smoking status using a Cox regression analysis, the risk for nonmalignant respiratory diseases and for lung cancer increased with exposure to total dust; in the highest exposure category, rate ratios (RR) were 4.08 (95% CI 1.11-14.96) for nonmalignant respiratory diseases and 1.67 (95% CI 0.57-4.83) for lung cancer. Results were in the expected direction, but the power of the study was low, because of small sample size and use of cumulative total dust as the exposure variable, which may be a poor indicator of lung irritants and other potential carcinogens in this industry, notably silicon carbide ceramic fibers.

Adult↗
PubMed1994

Phosphorylation and identification of a major tyrosine phosphorylation site in protein tyrosine phosphatase 1C.

Protein tyrosine phosphatase 1C (PTP1C) was the first member of the protein tyrosine phosphatase family demonstrated to contain the src homology 2 (SH2) domain. This enzyme is believed to play a role in regulating downstream signaling in hematopoietic cells since it was predominantly expressed in these cells. However, recent studies have revealed that the protein is expressed in other tissues as well. This report describes both the phosphorylation of PTP1C in non-hematopoietic cells treated with growth factors (in vivo) and incubation of purified PTP1C with a variety of protein kinases (in vitro). PTP1C was transiently phosphorylated in A431 and 293 cells and also when the purified enzyme was incubated with receptor protein tyrosine kinases. In vitro, the tyrosine-phosphorylated PTP1C underwent rapid auto-dephosphorylation, an effect which could be blocked by the addition of sodium vanadate. On the other hand, cells containing a PTP1C in which the catalytic site had been inactivated through mutagenesis, stably phosphorylated the phosphatase. These results suggested that PTP1C was responsible for its own auto-dephosphorylation. The sites of tyrosine phosphorylation were characterized from purified enzyme following treatment with insulin receptor kinase and from PTP1C expressed in 293 cells which had been stimulated with platelet-derived growth factor. Through the techniques of peptide mapping and microsequencing, Tyr538 was determined to be the major phosphorylation site. This result was confirmed in vivo through site-specific mutagenesis of PTP1C expressed in 293 cells; changing Tyr538 to Phe538 completely abolished tyrosine phosphorylation of the molecule. In addition, Tyr538 lies within the sequence ESEYGNI which can be correlated with the consensus sequence pYXNX associated with GRB2 binding. These results suggest that PTP1C plays a prominent role in growth factor receptor-mediated signal transduction within both hematopoietic cells and tissues of non-lymphoid origin.

Amino Acid Sequence↗
PubMed1994

Responses to gonadotropin releasing hormone agonist and antagonist administration in patients with gonadotroph cell adenomas.

As they are clinically silent, gonadotroph cell pituitary adenomas are usually diagnosed only when pituitary enlargement causes visual impairment or hypopituitarism. In postmenopausal women presenting with pituitary tumors it can be difficult to determine whether gonadotropin hypersecretion is due to adenomatous or normal gonadotrophs prior to surgery. The usual GnRH dependency of gonadotropin secretion may be of diagnostic and therapeutic value. We therefore evaluated responses to the GnRH antagonist Nal-Glu-GnRH and to the long-acting GnRH agonist D-Trp6 (3.75 mg IM) in 9 and 4 patients with FSH- and/or alpha-subunit-secreting adenomas, respectively. Six of the 7 patients with FSH-secreting adenomas and one of the 2 patients with pure alpha subunit-secreting adenomas were studied postoperatively. In these patients postoperative FSH and/or alpha-subunit levels remained elevated and pituitary imaging by CT-scan and/or MRI disclosed tumoral residues. In the 2 remaining patients testing was performed preoperatively. A single administration of 5 mg Nal-Glu to the 7 patients with FSH-secreting adenomas produced a slight but significant fall in above-normal FSH levels from 24.4 +/- 15.4 IU/l to a nadir of 20.3 +/- 11.9 IU/l (-17%, p < 0.05) 20 h following the injection. LH levels fell markedly in the 6 patients with normal basal serum LH concentrations to those observed in hypophysectomized patients, while mean alpha-subunit levels were not modified. Alpha-subunit levels were not modified by Nal-Glu administration in the 2 patients with alpha-subunit-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

A single injection of a gonadotropin-releasing hormone (GnRH) antagonist (Cetrorelix) postpones the luteinizing hormone (LH) surge: further evidence for the role of GnRH during the LH surge.

OBJECTIVES: To assess the ability of a new third-generation GnRH antagonist, Cetrorelix (Asta Medica AG, Frankfurt am Main, Germany), to postpone the LH surge after a single injection during the late follicular phase. DESIGN: A single 5-mg (group 1, n = 7) or 3-mg (group 2, n = 3) dose SC of Cetrorelix was administered during the late follicular phase, on the day of the cycle when plasma E2 exceeded 150 pg/mL (550 pmol/L). Estradiol, LH, FSH, and P levels were measured daily from day 5 of the cycle until day 10 after antagonist administration. Transvaginal ultrasonographies were performed on the day of injection and after antagonist treatment. SUBJECTS: Ten normal women with regular ovulatory menstrual cycles. RESULTS: In group 1, Cetrorelix was administered on day 14.6 +/- 5 (mean +/- SD) of the cycle, when the mean plasma E2 level was 181 +/- 32 pg/mL (664 +/- 117 pmol/L) (mean +/- SD). Plasma LH and FSH decreased by 56% +/- 19% and 29.5% +/- 16% (mean +/- SD), respectively, reaching the nadir 24 hours after Cetrorelix administration. Estradiol decreased by 85% +/- 17%, reaching the nadir 48 hours after antagonist injection. In group 2, Cetrorelix was administered on day 14.3 +/- 1.2 of the cycle when the mean plasma E2 level was 169 +/- 21 pg/mL (618 +/- 77 pmol/L). Plasma LH and FSH decreased by 66% +/- 18% and 32% +/- 6%, respectively, reaching a nadir 24 hours after Cetrorelix administration. Estradiol decreased by 81% +/- 9%, reaching the nadir 24 to 48 hours after antagonist administration. The LH surge was interrupted in every case. In six of seven subjects from group 1, the LH surge was delayed, occurring 6 to 17 days after the antagonist injection. In the remaining woman, Cetrorelix was administered at the beginning of the LH surge (LH = 13 IU/L): the LH level fell immediately by 54%, and the surge was postponed by 3 days. In group 2, in three of three subjects, the LH surge was delayed, occurring 6 to 9 days after the antagonist injection. No adverse effects were observed, except for very slight and transient erythema and pruritus at the injection site. CONCLUSION: Cetrorelix is a very potent new GnRH antagonist. A single injection during the late follicular phase delays the LH surge, even if the latter has already begun. In addition, this new-generation GnRH antagonist is very well tolerated and simple to use. Our data reinforce the role of GnRH during the LH surge and point to a role for new GnRH antagonists in controlled ovarian hyperstimulation to avoid premature LH surges and subsequent luteinization.

Adult↗
PubMed1994

The single or dual administration of the gonadotropin-releasing hormone antagonist Cetrorelix in an in vitro fertilization-embryo transfer program.

OBJECTIVE: To assess the ability of a GnRH antagonist (Cetrorelix, Asta Medica AG, Frankfurt, Germany) to prevent premature LH surges in an IVF-ET program using a simple protocol with one or two administrations. DESIGN: Controlled ovarian hyperstimulation was carried out in 17 women with three ampules a day of hMG, starting on day 2 of the menstrual cycle. A dose of 5 mg of Cetrorelix was administered when plasma E2 levels were between 150 and 200 pg/mL (conversion factor to Sl unit, 3.671) per follicle of > or = 14 mm. A second injection was performed 48 hours later if the triggering of ovulation was not decided in the meantime. RESULTS: Six patients received one injection and 11 patients received two administrations. Plasma LH levels showed a marked decrease and remained low after the administration of the GnRH antagonist. In six patients, the first administration of Cetrorelix was performed when a significant rise in LH plasma level was present. Even in these patients the GnRH antagonist was able to prevent an LH surge. The tolerance of the product was good. Six clinical pregnancies were obtained, of which four are ongoing (25% per ET). Two ongoing pregnancies were obtained after the transfer of a frozen-thawed embryo (35.3% per retrieval). CONCLUSIONS: The GnRH antagonist Cetrorelix in a simple, unique or dual administration, protocol was able to prevent premature LH surge in all of the 17 patients studied. If these results are confirmed by larger, randomized studies, the good tolerance and efficacy that we observed suggest a bright future for this product is assisted reproductive technologies.

Adult↗
PubMed1994

Recombinant human follicle-stimulating hormone and ovarian response in gonadotrophin-deficient women.

Seven women suffering from hypogonadism due to previous hypophysectomy, isolated gonadotrophin deficiency, or Kallman's syndrome [median age 39 years (range 24-45)] volunteered to participate in a study to assess ovarian response following multiple-dose administration of recombinant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone (LH) concentrations were 0.25 (< 0.05-1.15) IU/l and 0.06 (< 0.05-0.37) IU/l, respectively. Subjects received daily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day, week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling and sonographic investigations were performed on alternate days. Steady-state FSH concentrations were reached approximately 3-5 days after alterations of the doses administered. Maximum FSH concentrations were between 7.1 and 11.8 IU/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (INH) (response failure possibly due to early ovarian failure or resistant ovary syndrome) in two subjects, analysis of ovarian response was restricted to five volunteers. Serum androstenedione levels showed no significant changes during rhFSH administration. Although serum immunoreactive INH concentrations reached normal late follicular values [659 (388-993) IU/l], serum oestradiol revealed only a minor increase [77 (18-210) pmol/l]. Moreover, growth of (multiple) ovarian follicles was observed up to pre-ovulatory sizes (> 15 mm) in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels.

Although progesterone and estrogens are essential to maintain human pregnancy after implantation, the localization of their specific receptors in different uterine cell types during pregnancy has not been investigated. We studied uteri (n = 40) obtained during the first 3 months of pregnancy (n = 21) and in late pregnancy (n = 9) as well as from women 5-14 weeks pregnant (n = 10) who had received the antiprogestagen RU 38486 (Roussel-UCLAF) to induce cervical dilation. Frozen tissues were processed for indirect immunocytochemical staining with specific monoclonal antibodies against estrogen receptors (ER; Abbott Laboratories) and progesterone receptors (PR; Li 417). Specific staining for steroid receptors was only detected in the nucleus. In the endometrium, PR staining remained fairly constant throughout pregnancy, whereas ER staining was initially weak and then undetectable. PR was widely expressed in stromal cells and in spiral arterial wall cells, whereas ER was expressed in scattered stromal cells and arterial cells. Both PR and ER were absent from glandular epithelium, contrasting with the secretory activity during the first trimester. Spiral arteries of the endometrium and myometrial smooth muscle cells showed intense PR and moderate ER staining in early pregnancy. The progesterone antagonist RU 38486 (mifepristone), given in early pregnancy at a dose of 200 mg, caused a marked increase in ER staining and a smaller increase in PR staining in stromal cells, whereas the glandular epithelium remained negative for both ER and PR (except for one and two specimens, respectively). We conclude the following. 1) Stromal cells retain PR despite the high progesterone levels during pregnancy, in keeping with the role of progesterone in stromal decidualization. The absence of PR from the secretory glandular epithelium suggests a paracrine link between decidualized stromal cells and epithelial cells. 2) Significant PR down-regulation by progesterone during pregnancy occurs only in epithelial cells of the endometrium. 3) In contrast, the absence or low level of ER staining in the various cell types of the endometrium during gestation concurs with the known effect (down-regulation) of steroid hormones on ER mRNA or protein levels. The increase in ER in human decidua after RU 38486 treatment indicates that the main cause of the low ER levels is progesterone secretion. 4) The intense PR staining in smooth muscle cells of spiral arteries during early pregnancy suggests that progesterone is essential for modulating blood flow during pregnancy.

Adult↗
PubMed1994

Effect of administration of a gonadotropin-releasing hormone (GnRH) antagonist (Nal-Glu) during the periovulatory period: the luteinizing hormone surge requires secretion of GnRH.

In primates, the LH surge that triggers ovulation is induced by an increase in circulating estradiol (E2) levels. Although several studies suggest that E2 acts on the pituitary, it is still not clear whether GnRH is involved. We investigated the role of GnRH during the periovulatory period in normal women by treating them with the GnRH antagonist Nal-Glu ([Ac-D2Nal1,D4-ClPhe2,D3Pal3,Arg5,DGlu6 (AA),DAla10] when E2 levels exceeded 550 pmol/L. In the first study (A), Nal-Glu was administered in five regimens (n = 4 in each group): a single sc injection of 10 mg (group 1), a single injection of 20 mg (group 2), and an injection of 10 mg, sc, on 2 (group 3), 3 (group 4), and 5 consecutive days (group 5). In the second study (B; n = 4), Nal-Glu (10 mg, sc, on 3 consecutive days) was coadministered with E2 benzoate (EB; 0.5 mg, im, every 12 h on 3 consecutive days). Controls (n = 4) were treated with EB alone at the same stage of the cycle. In the third study (C), three women received 10 mg/day Nal-Glu, sc, on 3 consecutive days together with pulsatile GnRH therapy (25 micrograms/pulse, one pulse every 90 min, sc, for 3 days); the first pulse was given 12 h after the first Nal-Glu injection. In study A, gonadotropin suppression resulted in a transient decline in E2 in groups 1 and 2. Relative to control cycles, the LH surge occurred with a delay of 24-48 h in group 1 and 24-120 h in group 2. In groups 3, 4, and 5, Nal-Glu administration resulted in the demise of the dominant follicle in half of the women in each group. The remaining women showed a profile similar to that of groups 1 and 2, i.e. a transient decline in E2 levels followed by a recovery, and a LH surge occurring 4 +/- 0.3 days after the last Nal-Glu injection. In study B, simultaneous administration of Nal-Glu and EB induced a rise in E2 levels from 951.3 +/- 79.6 to 4000.1 +/- 772.5 pmol/L 24 h after the beginning of treatment. Serum LH and FSH levels both decreased and remained low throughout Nal-Glu treatment. None of the women showed a LH rise in response to the EB injection. In controls, however, EB administration was followed by a significant gonadotropin discharge 48 h after the first EB injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗