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PubMed2006

Evaluation of the buserelin stimulation test in diagnosing gonadotropin deficiency in males with delayed puberty.

OBJECTIVE: To assess the efficacy of the gonadotropin-releasing hormone (GnRH) agonist buserelin in a stimulated gonadotropin test for the investigation of delayed puberty in males. STUDY DESIGN: Prepubertal males (n = 31; age range, 10.3 to 17.2 years) were studied; buserelin (100 microg) was administered subcutaneously, with blood sampling at 0 and 4 hours for serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH). At follow-up (mean, 4.2 years), 8/31 (26%) failed to progress into puberty, constituting hypogonadotropic hypogonadism (HH), but 23/31 (74%) had testicular enlargement (> or =8 mL) consistent with a normal hypothalamic-pituitary-gonadal (HPG) axis. RESULTS: Stimulated serum LH response to buserelin was lower in males with HH (mean +/- standard error under the mean for HH, 1.4 +/- 0.5 U/L, compared with a normal HPG axis of 17.4 +/- 2.0 U/L; P < .0001). Stimulated serum FSH response was nondiscriminatory (HH, 7.7 +/- 2.2 U/L; normal HPG axis, 11.5 +/- 1.6 U/L; P = .27). All males with HH had a stimulated serum LH level <5 U/L, whereas only 1/23 with a normal HPG axis had a stimulated serum LH below this level. Using this value as the criterion for diagnosing HH, the buserelin stimulation test yielded a sensitivity of 100%, specificity of 96%, and positive predictive value of 89%. CONCLUSIONS: The buserelin stimulation test is a highly specific and sensitive GnRH agonist test for the investigation of males with delayed puberty.

Adolescent↗
PubMed1990

Use of buserelin acetate in an in vitro fertilization program: a comparison with classical clomiphene citrate-human menopausal gonadotropin treatment.

A comparison has been established retrospectively between clomiphene citrate-human menopausal gonadotropin (CC-hMG) and buserelin acetate-hMG treatments in in vitro fertilization trials performed over a 3-year period. The analysis of 466 CC-hMG and 319 buserelin acetate-hMG trials shows that buserelin acetate-hMG stimulation generates a greater ovarian response resulting in higher numbers of oocytes being retrieved (6.2 + 3.8 versus 9.3 + 5.2) and fertilized (2.8 + 2.7 versus 4.3 + 3.8). More embryos are thus obtained, allowing a wider choice for intrauterine replacement and cryopreservation. Mean embryonic vitality scores do not differ (4.33 + 1.51 versus 4.44 + 1.54), implying that the embryonic quality remains similar in both treatments. A premature demise of the corpus luteum occurs in a large proportion of buserelin acetate-hMG cycles. However, when suppletive progesterone treatment is given, there is a trend toward a better implantation rate per embryo, and a significantly higher ongoing pregnancy rate is observed in relation to buserelin acetate-hMG treatment (20%) as compared with CC-hMG cycles (14%).

Adult↗
PubMed1993

Vaginal patterns during danazol and buserelin acetate therapy for endometriosis: structural and ultrastructural study.

OBJECTIVE: To evaluate histologic and ultrastructural changes of the vaginal mucosa in patients given buserelin acetate or danazol treatment for endometriosis. DESIGN: Controlled clinical study. SETTING: Infertility clinic of an academic unit. PATIENTS: Infertile women with endometriosis randomized to receive buserelin acetate or danazol and undergoing vaginal biopsies during treatment were selected. INTERVENTIONS: Buserelin acetate was administered IN 400 micrograms three times per day and danazol orally 600 mg/d. Vaginal biopsies were performed baseline and at 3 and 6 months of treatment, and specimens were examined by light microscopy and scanning electron microscopy. 17 beta-Estradiol and P levels were determined in each patient at the time of each biopsy. MAIN OUTCOME MEASURE: Structural and ultrastructural patterns of vaginal mucosa after 3 and 6 months of treatment. RESULTS: Buserelin acetate treatment induced early, marked hypotrophy of the vaginal mucosa with aspects typical of the menopause. The modifications caused by danazol occurred mainly in the intermediate layer, which was weakly hypotrophic only at the end of the treatment. CONCLUSION: Vaginal mucosa undergoes constant and well-defined modifications during both buserelin acetate and danazol treatment for endometriosis. The modifications are compatible with the biological effects of the drugs.

Biopsy↗
PubMed2000

Effect of continuous infusion of a GnRH agonist (Buserelin) on ovarian hormone secretion and estrous cycle length in cows.

The importance of the ovarian steroid hormones estradiol and progesterone in the control of luteolysis in domestic ruminants is well established. However, there is a lack of studies specifically investigating the effect of stimulating "physiological" changes in endogenous estradiol or progesterone secretion on subsequent luteolysis. In this study we have stimulated endogenous ovarian hormone secretion by infusion of the GnRH analogue, Buserelin, and have assessed the effect of these changes on the timing of luteolysis. Concentrations of estradiol and progesterone were monitored in plasma samples collected from 6 mature, cyclic, lactating, Friesian cows during a control cycle and during a cycle in which Buserelin was infused via osmotic minipump (8.6 microg/h) for 28 days starting on Day 2 of the cycle. Buserelin infusion had little effect on progesterone secretion but did result in a marked stimulation of estradiol secretion from Days 6 to 10 of the cycle (treated cycle 4.3+/-0.2 pg/mL; control cycle 1.8+/-0.3 pg/mL; P<0.001). In addition, there was a significant advancement in the timing of luteolysis during the Buserelin -infused cycle (Day 19.3+/-0.3 compared with Day 21.3+/-0.4; P<0.01). In this study, we have found that infusion of buserelin caused both a significant stimulation of estradiol secretion from the first follicle and a significant advancement in the timing of luteolysis. We hypothesise that the increased secretion of estradiol may have been involved in causing this advancement of luteolysis.

Animals↗
PubMed1996

Mucoadhesive polymers in peroral peptide drug delivery. VI. Carbomer and chitosan improve the intestinal absorption of the peptide drug buserelin in vivo.

PURPOSE: To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. METHODS: Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats. RESULTS: All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as alpha-chymotrypsin. CONCLUSIONS: The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.

Acrylic Resins↗
PubMed2003

Evaluation of cabergoline and buserelin efficacy for oestrous induction in the bitch.

The purpose of this work was to compare two different protocols of oestrous induction, using either a dopamine agonist (cabergoline) or a GnRH agonist (buserelin) in anoestrus bitches. The clinical trial involved 22 Beagle bitches, randomly allotted to two treatment groups: group A (n = 12) was orally administered cabergoline (Galastop(R); Centralvet-Vetem, Milan, Italy; 5 microg/kg SID), until the onset of cytological oestrus or for a maximum of 30 days and group B (n = 10) was treated with buserelin acetate, (Suprefact(R); Aventis Pharma, Milan, Italy), administered subcutaneously t.i.d., at 1.5 microg/kg for 11 days and 0.75 microg/kg for the following 3 days. Blood samples were collected twice a week to measure progesterone and prolactin concentration. Both cabergoline and buserelin produced a significant early decline in prolactin concentration (p < 0.01), but the effect of cabergoline lasted longer. Progesterone concentration was significantly affected by buserelin administration, showing a significant increase (p < 0.01) from day 3 to day 6 of treatment. Cabergoline confirmed its effectiveness in inducing oestrus as 10 of 12 bitches responded to the treatment, were mated and whelped. On the contrary, oestrus was observed in only three of 10 buserelin-treated bitches and in two of them 7 and 13 days after the end of treatment. These same two bitches accepted mating and conceived. The results suggest that in a clinical setting, dopaminergic treatment is the treatment of choice as it yields more consistent results and involves a much easier administration protocol.

Administration, Oral↗
PubMed2006

Comparison of outcome of clomiphene citrate/human menopausal gonadotropin/cetrorelix protocol and buserelin long protocol--a randomized study.

This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium. One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were randomized into two groups. Sixty women were stimulated with the CC/hMG/cetrorelix protocol (cetrorelix group) and 60 received the buserelin long protocol (buserelin group). Fewer oocytes were recovered in the cetrorelix group than in the buserelin group (mean +/- standard deviation (SD): 11.1 +/- 4.0 vs. 17.3 +/- 5.8, p < 0.001); however, the percentages of metaphase II, metaphase I and germinal vesicle oocytes were similar between the two groups. Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group (mean +/- SD: 2600.58 +/- 1189.11 vs. 3293.46 +/- 1221.49 pg/ml, p = 0.006), but the endometrial thickness was similar. The implantation rates (19.2% vs. 17.7%) and the pregnancy rates (41.7% vs. 40.0%) were similar between groups. The ampoules (mean +/- SD: 18.9 +/- 3.0 vs. 38.9 +/- 12.2, p < 0.001) and injections (mean +/- SD: 6.8 +/- 1.1 vs. 15.7 +/- 3.1, p < 0.001) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group. No patients in either group developed a premature luteinizing hormone surge. The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates.

Adult↗
PubMed2000

Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group.

In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.

Adult↗
PubMed2006

Cetrorelix in an oral contraceptive-pretreated stimulation cycle compared with buserelin in IVF/ICSI patients treated with r-hFSH: a randomized, multicentre, phase IIIb study.

BACKGROUND: The aim of this study was to assess the non-inferiority of an oral contraceptive (OC)-pretreated cetrorelix regimen and a buserelin regimen in IVF/ICSI patients treated with r-hFSH in terms of total number of oocytes retrieved. METHODS: Multicentre, randomized study. One hundred and eighty two patients were randomized to receive cetrorelix with OC pretreatment (n = 91) or to receive buserelin (n = 91). The cetrorelix group started with daily OCs on cycle day 5 and continued for 21-28 days. Cetrorelix (0.25 mg) was given daily from stimulation day 6 up to and including the day of r-hCG administration. The buserelin group started with buserelin (500 microg/day) for at least 10 days until down-regulation was achieved, after which the dose was reduced to daily 200 microg up to and including the day of r-hCG administration. r-hFSH was started in both groups on a Friday, in the cetrorelix group 5 days after the last OC pill intake. Both regimens were followed by a standard IVF or ICSI procedure. The primary efficacy endpoint was the number of oocytes retrieved per patient. RESULTS: Number of oocytes, cancellation rates, r-hFSH requirements, number of oocyte retrievals during the weekend or public holiday and number of pregnancies were similar in both groups. Both treatment regimens were well tolerated. CONCLUSIONS: Cetrorelix pretreated with OCs resulted in similar number of oocytes retrieved compared with a long buserelin protocol. Both regimens were well tolerated and allowed scheduling of the oocyte retrieval, with only small number of retrievals falling on a weekend or public holiday.

Adolescent↗
PubMed1990

Use of buserelin in an IVF programme for pituitary-ovarian suppression prior to ovarian stimulation with exogenous gonadotrophins.

Daily s.c. injections of buserelin were commenced in the mid-luteal phase of the preceding cycle in 118 women undergoing in-vitro fertilization (IVF) and embryo transfer. Ovarian and pituitary suppression was said to have been adequately achieved when serum oestradiol was less than 50 pg/ml, serum LH less than 2.0 IU/l, no ovarian cysts greater than or equal to 10 mm diameter were present and menstruation had occurred. Nine groups of women were retrospectively identified after the administration of buserelin for 12 days according to whether pituitary and ovarian suppression had been achieved or not, and the reason for extended buserelin treatment prior to ovarian stimulation. Upon adequate suppression, patients were grouped in terms of the duration of exposure to buserelin, and ovarian stimulation was then started by daily injections of human menopausal gonadotrophin. There appeared to be no differences in the ovarian response for women down-regulated by day 12, 19 or greater than or equal to 26 days; those women requiring extended buserelin treatment did equally well compared to those women down-regulating quickly, in terms of number of oocytes recovered and fertilization rate. Clinical pregnancy rates per embryo transfer were 27/68(40%), 8/33(26%) and 4/17(24%) for those women down-regulated by days 12, 19 or greater than or equal to 26 respectively, and were not significantly different.

Adult↗
PubMed1989

Sustained release of buserelin acetate, a luteinizing hormone-releasing hormone agonist, from an injectable oily preparation utilizing ethylated beta-cyclodextrin.

The possible use of heptakis (2,6-di-O-ethyl)-beta-cyclodextrin (DE-beta-CyD) as a parenteral sustained-release carrier for buserelin acetate, a luteinizing hormone-releasing hormone superagonist, has been examined. The in-vitro release of buserelin from the oily suspension was significantly retarded by the complexation with DE-beta-CyD, mainly due to the poor water solubility of the complex. A single subcutaneous injection of the suspension containing the buserelin-DE-beta-CyD complex to rats provided an effective continuous plasma level of buserelin lasting for at least one month, indicating a potential therapeutic efficacy for the treatment of the endocrine-dependent diseases. These results suggest that DE-beta-CyD serves as an injectable sustained-release drug carrier suitable for chronic treatment with buserelin acetate.

Animals↗
PubMed1997

Spectroscopic characterization of the inclusion complex of a luteinizing hormone-releasing hormone agonist, buserelin acetate, with dimethyl-beta-cyclodextrin.

Inclusion complexation of buserelin acetate, and agonist of luteinizing hormone-releasing hormone, with dimethyl-beta-cyclodextrin (DM-beta-CyD) in aqueous solution was studied spectroscopically and its mode of interaction was assessed. Ultraviolet absorption and circular dichroism (CD) spectroscopies indicate that the aromatic side chains of buserelin acetate, L-tryptophan and L-tyrosine residues, are incorporated into the hydrophobic environment of the DM-beta-CyD activity. Furthermore, proton and carbon-13 nuclear magnetic resonance spectroscopies suggest that in addition to the two aromatic side chains, a tertiary butyl D-serine residue is inserted into the DM-beta-CyD cavity from the secondary hydroxyl side. On the other hand, the continuous variation plots for the buserelin acetate: DM-beta-CyD system showed a 1:1 stoichiometry of the complex. Therefore, the complexation should be initiated by the inclusion of one of the three binding sites on the buserelin molecule into DM-beta-CyD, which may in turn prevent the further access of the second cyclodextrin to the other binding sites, probably due to steric hindrance and/or conformational changes of the peptide. These structural features of the complex would account for the stabilizing effect of DM-beta-CyD on the enzymatic degradation of buserelin acetate.

Buserelin↗
PubMed1984

Desensitization of the pituitary gland induced in vivo by luteinizing hormone-releasing hormone (LRH) or by the LRH-analogue buserelin does not affect the autonomous secretion of luteinizing hormone and follicle stimulating hormone as observed in vitro.

Three-weeks ovariectomized rats were sc implanted with Alzet osmotic minipumps which released either LRH or the LRH-analogue buserelin at the rate of 250 ng/h. Control rats were implanted with a silastic 'shampump'. After explantation, 6 days later, the pituitary glands of part of these rats were exposed to the maximally active LRH concentration of 1 micrograms/ml for a period of 6 h, using a perifusion system. In a second group of rats explantation and perifusion was done not directly, but 5 days after cessation of the LRH pre-treatment. After 6 days in vivo pre-treatment with LRH or with buserelin the pituitary LH and FSH stores were partially depleted, the depletion after buserelin being stronger than after LRH. The pituitary glands of the first group of rats showed rates of both maximally LRH-stimulated and unstimulated (autonomous) LH- and FSH-secretion which were strongly impaired, the impairment after buserelin being stronger than after LRH. In the group with a 5 days interval between in vivo LRH/buserelin pre-treatment and explantation the pituitary LH and FSH stores were restored to the range of pre-treatment levels. Of these pituitaries the autonomous secretion of LH and FSH as well as the maximally LRH-stimulated secretion of FSH was restored to the normal level; the maximally LRH-stimulated secretion of LH, however, remained depressed, indicating that 5 days after cessation of exposure to LRH or to buserelin, and in spite of restored pituitary LH/FSH contents, the sensitivity of the LH releasing system to LRH was still subnormal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

An implant of a gonadotropin releasing hormone agonist (buserelin) which suppresses ovarian function in the macaque for 3-5 months.

Four adult female stumptailed macaque monkeys with regular menstrual cycles and one with irregular cycles and dysfunctional uterine bleeding were treated with a single implant containing 2.6 mg of the GnRH agonist buserelin in a matrix of polylactide/glycolide copolymer (75:25). The implant was used as a cylindrical rod of 0.8 X 0.12 cm and implanted sc in the abdominal wall. The insertion of the implant was followed by a modest rise in serum concentrations of LH and FSH lasting 3-4 days before falling to basal values. The release profile of buserelin from the implant was measured in urine by a radioimmunoassay detecting the intact molecule and its major metabolites. Immunoreactive buserelin in urine was high between days 1-3 after implant after which there was a rapid decline to form a plateau between days 15-70 followed by a further gradual decline. This prolonged release of buserelin suppressed ovulation for a mean of 148 days (range 105-182 days) as indicated by absence of serum progesterone rises. Serum FSH concentrations were low for at least 75 days and during this time serum oestradiol concentrations were uniformly suppressed in all monkeys. Once the buserelin release from the implant declined serum FSH concentrations began to rise. There was a variable delay of 7-60 days before this rise in FSH was associated with stimulation of ovarian oestradiol secretion followed by rises in serum progesterone concentrations indicative of ovulation. Apart from the first menses after insertion of implant, 4 of the monkeys became amenorrhoeic for the period of anovulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Evaluation and significance of the degree of pituitary-gonadal inhibition during intranasal administration of buserelin.

In 12 patients (11 girls, 1 boy) with central precocious puberty and 4 patients (3 girls, 1 boy) with idiopathic short stature treated for 1 year with a GnRH superagonist, buserelin (0.3 mg intranasally, 4 times a day), a variable degree of inhibition of sex steroid secretion and pubertal development was observed. Regression of breast or genital development required a daily dosage of buserelin greater than or equal to 34 microgram/kg. After 3, 6, 9 and 12 months of treatment, the serum oestradiol level in the girls was positively related (r = 0.69) to basal serum LH measured at the same time and to change in breast development during the previous 3 months. In contrast, LH response to GnRH was very low in all the patients and not related to the degree of oestradiol inhibition. Height velocity and bone age velocity during the year of treatment showed no significant correlation with mean oestradiol level. Bone age velocity during treatment was inversely related to bone age at onset of buserelin. These data show that 1) the pituitary gonadal suppression during intranasal administration of buserelin is variable and dose-dependent; 2) gonadotropin response to GnRH is not a sensitive indicator of incomplete pituitary suppression during buserelin treatment; and 3) bone age velocity during treatment is more reduced the more advanced bone age is at onset of treatment.

Administration, Intranasal↗
PubMed1990

Effect of long-term inhibition of gonadotrophin secretion by the gonadotrophin-releasing hormone agonist, buserelin, on sex steroid secretion and ovarian morphology in polycystic ovary syndrome.

In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment. Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition.

Adult↗
PubMed1995

Buserelin alters the development of the corpora lutea in cyclic and early postpartum cows.

Changes in proportions of luteal cells after buserelin treatment were studied in the corpus luteum (CL) that was present at the time of treatment (CLP) and in the buserelin-induced CL (CLI) of cyclic and acyclic postpartum cows. On d 0 of the experimental period, eight cyclic (Cyc-sal) cows were injected with saline, whereas eight cyclic (Cyc-bus) cows and eight acyclic (Acyc-bus) cows were treated i.m. with 8 micrograms of buserelin. On d 3 or 6, ovaries were collected and stained using histological techniques. As determined with the point-counting method, the number of nuclei in the CLP was similar on d 3 in Cyc-bus and Cyc-sal groups but was lower (treatment x day, P < .001) in the Cyc-bus group than in the Cyc-sal group on d 6. The volume of the CLP was similar on d 3 in the two groups but was greater (treatment x day, P < .04) in the Cyc-bus than in the Cyc-sal group on d 6. The number of nuclei in the CLI was greater (P < .001) in cyclic than in acyclic cows on d 3 and 6 after treatment. The volume of the CLI was lower (P < .001) in cyclic than in acyclic cows on d 3 and 6. Buserelin did not change the profile of progesterone in cyclic cows from d 0 to 6, but concentrations of progesterone increased (P < .01) in acyclic cows 3 to 6 d after buserelin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

LH pulsatility and response to a single s.c. injection of buserelin in polycystic ovary syndrome.

The present study was undertaken in order to determine whether patients with polycystic ovary syndrome (PCOS) have LH pulse frequency and/or amplitude higher than those in normal cycling women during the follicular phase, and, if so, to establish possible factors which might influence LH secretion in PCOS. The study was conducted on 14 PCO patients (aged 19-30 years), who were subdivided according to the data on their cycle abnormality into 2 groups: amenorrheic (Am-PCOS, n = 9) and oligomenorrheic (O-PCOS, n = 5). LH pulsatility was assessed in the early follicular phase in controls (n = 5) and O-PCOS and at any time in Am-PCOS. Blood samples were taken every 10 minutes for 4 hours. Pulse analyses of LH data were performed using the Munro program. The buserelin test was performed on the same day by injection of 40 micrograms of buserelin (blood samples were taken every 60 minutes for the following 10 hours). Eleven PCO patients and 12 control subjects had an oral glucose tolerance test (oGTT) (blood samples were taken every 60 minutes for glucose, insulin and C-peptide measurements). Both mean LH pulse frequency and mean pulse intervals were not distinguishably different in PCO women (Am and O) and controls. In contrast, the mean pulse amplitude was significantly higher in the Am-PCOS group than in O-PCOS women and controls (p less than 0.02 and p less than 0.001, respectively). A significant positive correlation was established between nadir LH concentrations and LH pulse amplitude (r = +0.966, p less than 0.001). The LH response to buserelin stimulation was significantly higher in Am-PCOS than in O-PCOS (p less than 0.004). A highly significant positive correlation was observed between LH pulse amplitude and insulin response during oGTT (p less than 0.001) in PCO subjects. Basal (prebuserelin) LH concentrations correlated significantly with fasting insulin levels (p less than 0.008) and insulin and C-peptide responses to oGTT. These results allow us to conclude the following: 1. An increased LH pulse amplitude and an exaggerated LH response to buserelin observed in amenorrheic PCO subjects compared to those in oligomenorrheic PCO subjects fail to support the hypothesis of an intrinsic hypothalamo-pituitary abnormality. 2. The relationship between fasting and glucose-stimulated insulin levels with LH nadir concentrations, pulse amplitude and response to buserelin suggests an etiological role of insulin in the pathogenesis of PCOS.

Adult↗