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PubMed2006

Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development.

The availability of viable oocytes is the limiting factor in the development of new reproductive techniques. Many attempts have been made to grow immature oocytes in vitro during recent decades. Recently, a modified alginate-based three-dimensional culture system was designed to support the growth and maturation of multilayered secondary follicles. This system was able to produce oocytes that successfully completed meiosis, fertilization, and development to the blastocyst stage. Subsequent attempts to culture two-layered secondary follicles were unsuccessful under the original conditions. Herein, we investigated the effect of alginate consistency on two-layered follicle growth and oocyte developmental competence by encapsulating follicles into alginate scaffolds of various concentrations. Although there were no significant differences in survival rates, 0.25% and 0.5% alginate supported more rapid growth of follicles and antrum formation compared with 1.5% and 1.0% alginate after 8 days of culture. Alginate scaffold concentration also affected the proliferation and differentiation of somatic cells (theca and granulosa cells), measured in terms of morphological changes, steroid profiles (androstenedione, estradiol, and progesterone), and specific molecular markers (Fshr, Lhcgr, and Gja1). Theca cell proliferation and steroid production were hindered in follicles cultured in 1.5% alginate. In vitro fertilization and embryo culture revealed that oocytes obtained from 0.25% alginate retained the highest developmental competence. Overall, the present study showed that the alginate scaffold consistency affects folliculogenesis and oocyte development in vitro and that the alginate culture system can and should be tailored to maximally support follicle growth depending on the size and stage of the follicles selected for culture.

Androstenedione↗

PubMed1993

Effects of some non-steroidal anti-inflammatory drugs (NSAIDS) on steroidogenesis in rat and porcine testis.

Using the rapid gas chromatographic steroid profiling technique, a number of metabolites of pregnenolone have been separated and quantified after incubation of this steroid with adult rat and neonatal porcine testicular homogenates. It was shown that the 5-ene-3 beta-hydroxy- and the 4-en-3-oxosteroid pathways for androgen biosynthesis were operating in both species, although the former pathway appeared to be more important in porcine testis. This tissue was characterised by the formation of several odorous, and pheromonal, 16-androstenes, which were quantitatively more important than the androgens. Three non-steroidal anti-inflammatory drugs (NSAIDS) caused dose-related inhibition of androgen and 16-androstene biosynthesis when co-incubated with pregnenolone. The order of potency was flurbiprofen > indomethacin > > > aspirin. The possibility that the NSAIDS may interfere with cytochrome P-450 is discussed, since several steroid-transforming enzymes, known to be dependent on this cytochrome for their activity, were markedly inhibited.

Animals↗

PubMed1975

High-resolution biomedical gas chromatography. Determination of human urinary steroid metabolites using glass open tubular capillary columns.

Recently developed analytical procedures for the qualitative and quantitative analysis of human urine for major and minor steroid metabolites are described. Steroid profile samples were obtained by enzymic hydrolysis with beta-glucuronidase and sulfatase. Methoxime-trimethylsilyl ether derivatives of steroid metabolites were prepared; the recommended procedure converts all ketone groups (except the 11-one group) into methoxime groups and all hydroxyl groups into trimethylsily ether groups. These derivatives are thermally stable, readily volatilized, not subject to dehydration or adsorption on gas chromatographic columns, and suitable for both quanlitative and quantitative analytical studies. Thermostable glass open tubular capillary columns, coated with the non-polar phase SE-30, and containing dispersed particles of silanized silicic acid, were used for the gas chromatographic separation. Illustrations of profiles for normal female and male subjects, and patients with a testosterone-secreting ovarian tumor, congenital adrenal insufficiency and a dehydroepiandrosterone-secreting adrenal tumor are included.

Adrenal Gland Neoplasms↗

PubMed2004

Prenatal diagnosis of P450 oxidoreductase deficiency (ORD): a disorder causing low pregnancy estriol, maternal and fetal virilization, and the Antley-Bixler syndrome phenotype.

We report studies on the second pregnancy of a woman who had previously given birth to a virilized female infant. The cause of the virilization had not been established, but common forms of congenital adrenal hyperplasia (CAH) were excluded. Longitudinal monitoring of the second pregnancy revealed that estriol excretion failed to increase normally, reaching a maximum 0.7 mg/24 hr at the end of pregnancy (normal mean 30 mg/24 hr). The mother showed signs of virilization by the 23rd week of gestation and aromatase deficiency was suspected. However, predicted urinary metabolites for diagnosis of aromatase deficiency (for example, 16alpha-hydroxyandrosterone) were not increased significantly during the pregnancy. Interestingly, excretion of the androgen metabolite androsterone increased rapidly at the beginning of pregnancy and peaked around the 20th week, suggesting increased production of testosterone and 5alphaDHT, probably the cause of maternal virilization. Urine steroid analysis by GC/MS showed gradually increasing excretion (9 mg/24 hr) of the normally minor metabolite 5alpha-pregnane-3beta,20alpha-diol (epiallopregnanediol), an epimer of the dominant progesterone metabolite pregnanediol (5beta-pregnane-3alpha,20alpha-diol). We believe epiallopregnanediol is largely the maternal urinary excretion product of fetal 5-pregnene-3beta,20alpha-diol, the principal metabolite of pregnenolone, implying a build-up of the latter steroid in the fetal adrenal. These findings suggested that the 'block' in the estriol biosynthetic pathway occurs at an early stage with 17-hydroxylation of pregnenolone being affected. The male baby born of this pregnancy had normal genitalia but showed a urinary steroid profile indicating partial deficiencies of P450c17 and P450c21. However, no mutations in the corresponding CYP17 and CYP21 genes were identified. Urinary steroid analysis carried out on his virilized older sibling showed the same pattern of metabolites. Recently, we determined that this disorder is caused by mutations in P450 oxidoreductase (OR), the essential redox partner for CYP17 and CYP21 hydroxylases. The novel metabolic profile has now been seen in many patients, most diagnosed with the skeletal dysplasia Antley-Bixler syndrome. We propose that excessive excretion of epiallopregnanediol together with low estriol may be prenatally diagnostic for OR deficiency (ORD).

Adult↗

PubMed1996

Characterization of a polarized porcine uterine epithelial model system.

A porcine uterine epithelial cell (pUE) culture system that retains structural and functional properties of the surface epithelium in vivo was developed. Uterine luminal epithelial cells were isolated after pancreatin-dispase enzymatic release of epithelium from hysterectomized gilts. Cells were seeded on Millicell filters precoated with Matrigel in 24-well plates and subsequently allowed to proliferate to confluence. Purity of the isolation was confirmed by the presence of > 99% cytokeratin-positive cells. Epithelial cells became polarized in vitro and compared favorably in morphology to uterine epithelial cells in situ once a transepithelial resistance of > 600 omega cm2 was established. Microscopic analysis confirmed the presence of a simple columnar epithelium with prominent microvilli on the apical cell surface and a well-developed junctional complex containing tight junctions, belt and spot desmosomes, and interdigitating lateral cell processes. Indirect immunofluorescence of the tight junction-associated protein, ZO-1, indicated the formation of tight junctional complexes in the subapical region of the polarized cells. Functional polarity of epithelial cultures was also verified by 1) electrical resistance measurements, 2) basal preference for the secretion of prostaglandins F2 alpha and E2, 3) apical preference for the release of 35S-methionine-incorporated secretory proteins, and 4) apically and basally distinct secretory protein profiles. Steroid treatment (estrogen, progesterone, or estrogen plus progesterone) of the polarized pUE cells affected the release of radiolabeled methionine-incorporated secretory proteins. In addition, the protein profiles as compared to samples treated with fetal bovine serum or charcoal/dextran-stripped fetal bovine serum were altered. Steroid treatments did not alter the electrical resistance or the basal preference for prostaglandin secretion. This culture system may be useful for in vitro analysis of maternal recognition of pregnancy paradigms as well as the study of the direct actions of hormones, prostaglandin secretion, and epithelial-stromal interactions.

Animals↗

PubMed1990

Urinary 5-ene-steroid excretion in non-classical congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency (NC-3BHSD).

The diagnosis of non-classical 3 beta-hydroxysteroid dehydrogenase deficiency (NC-3BHSD) is made either on the basis of significantly elevated serum levels of basal and post-ACTH 5-ene-steroids or by the presence of elevated urinary 5-ene-steroid metabolites. There has been only one report to date describing a single patient where the diagnosis was based on both serum and urinary 5-ene-steroid levels. We, therefore, measured both serum 5-ene-steroid responses to ACTH 1-24 (by RIA) and urinary 5-ene-steroid metabolites (GC-MS) in 42 hirsute premenopausal women. While the serum 5-ene-steroid profile was consistent with NC-3BHSD in 5 women, only 2 of them had increased excretion of 5-ene-steroid metabolites. Elevated 5-ene-steroid excretion was also observed in several patients with normal serum 5-ene-steroids. Detection of NC-3BHSD by either elevated serum 5-ene-steroids or increased urinary excretion of their metabolites in isolation may not therefore be reliable.

17-Ketosteroids↗

PubMed2006

Circadian rhythm of urinary steroid metabolites.

BACKGROUND: Samples submitted for urinary steroid profile analysis are often untimed, but influence of collection time on interpretation is unknown. We report circadian rhythms of the major steroid metabolites and derived ratios in urine collected at 3-h intervals over 24 h, after first establishing that disturbance of sleep associated with collection does not alter rhythms on the succeeding day. METHODS: Assay of steroid metabolites (gas chromatography) and creatinine in urine collections made by 10 men and 10 women every 3 h starting at 2,100 for 24 h. Data were subjected to cosinor analysis. RESULTS: Summed cortisol and androgen metabolites exhibited significant circadian rhythms, as expected, but with a surprisingly long time-lag (maxima at around 1,400). Amplitudes were different, so that the ratio cortisol/androgen metabolites also showed a significant rhythm. The ratios 5alpha/5beta tetrahydrocortisol and 20-hydroxy/20-oxo cortisol metabolites showed significant rhythms which were not in phase with total cortisol metabolites, while 11-hydroxy/11-oxo cortisol metabolites showed no rhythm. There were no gender differences in time of maxima. Previously established gender differences in metabolite levels were confirmed. Creatinine levels showed no circadian rhythm. CONCLUSION: Circadian variation should be considered when interpreting results from urine steroid analysis. Calculation of steroid/steroid or steroid/creatinine ratios is not informative in untimed collections.

Adult↗

PubMed1981

Biohydrogenation of cholesterol as an index of bacterial 7 alpha-dehydroxylase activity.

Fecal steroid compositions of 82 human subjects of various ages and diets and gastrointestinal status were examined by gas liquid chromatography. Progressive increases in bacterial activities on both bile acids and neutral sterols were observed with the advance of age in infants and children. The patterns in the 4-year-olds approached those observed in adults. Bacterial activities on fecal steroids were found to be decreased in adult subjects with acute shigellosis and in those challenged by castor oil. In contrast, no significant changes in fecal steroid profiles were observed in the subjects with traveller's diarrhea associated with toxigenic Escherichia coli. The effects of diarrhea on fecal steroids of infants under 1 1/2 years were less consistent than those of adults. However, a close relationship was observed between the degree of 7 alpha-dehydroxylation of cholic acid (expressed as the ratio of deoxycholic to the sum of deoxycholic and cholic acids) and the percentage of cholesterol in the feces (r = -0.921, p less than 0.001). The correlation between the production of lithocholic acid and the percentage cholesterol was also good (r = -0.739, p less than 0.001). Analysis of neutral steroids may be a good index of intraluminal bile acid metabolism.

Adolescent↗

PubMed1993

New identified 15 beta-hydroxylated 21-deoxy-pregnanes in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

The identification of 3 new 15 beta-hydroxylated 21-deoxy-pregnanes in the urinary steroid profile of a 4-month-old girl with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is reported here. These steroids were identified by gas chromatography and gas chromatography-mass spectrometry as 3 alpha,15 beta,17-trihydroxy-5 alpha-pregnan-20-one (5 alpha II), 3 alpha,15 beta,17,20 alpha-tetrahydroxy-5 alpha-pregnane, and 3 alpha,15 beta,17,20 alpha-tetrahydroxy-5 beta-pregnane (20 alpha DH-II). Two other compounds in the urine, 3 beta,15 beta,17- trihydroxy-5 alpha-pregnan-20-one and 3 beta,15 beta,17-trihydroxy-5 beta-pregnan-20-one were also characterized. The identification of the former 3 steroids was obtained by comparing their methylene unit values and mass spectral data with the corresponding data of the standard steroids synthesized from 15 beta,17-dihydroxy-4-pregnene-3,20-dione. Seven other synthesized and identified 15 beta-hydroxylated steroids were 3 alpha,15 beta,17-trihydroxy-5 beta-pregnan- 20-one (II), 3 alpha,15 beta,17,20 beta-tetrahydroxy-5 beta-pregnane, 15 beta,17-dihydroxy-5 alpha-pregnane-3,20-dione, 15 beta,17-dihydroxy-5 beta-pregnane-3,20-dione, 3 alpha,15 beta-dihydroxy-5 alpha-androstan-17-one (15 beta OH-An), 3 alpha,15 beta-dihydroxy-5 beta-androstan-17-one (15 beta OH-Et) and 3 alpha,15 beta,17,20 beta- tetrahydroxy-5 alpha-pregnane. Of these the latter two have not been reported previously. This study supports the findings that 15 beta-hydroxylated steroids are common in the neonate and could play an important role in the diagnosis of CAH due to 21OHD, where II and the newly identified steroids from this investigation viz., 5 alpha II and 20 alpha DH-II appear the most important 15 beta-hydroxysteroid markers for this disease.

Adrenal Hyperplasia, Congenital↗

PubMed1996

Sex differences in the human metabolism of cortisol.

Sex differences in steroid metabolism have been clearly demonstrated in animal studies, but few studies have addressed this question in the human. Our preliminary studies suggested human sex differences in both cortisol production and metabolism. We therefore looked in more detail at indices of cortisol metabolism derived from 24 hour urinary steroid profiles in a group of 20 men and 20 women who were age-matched, drug-free and had no endocrine disorder. Steroid analysis was by high resolution gas chromatography. Men excreted more total cortisol metabolites (7620 +/- 620 v 4750 +/- 380 micrograms/24 h, p < 0.001), 11-oxo metabolites of cortisol (11-oxo FM, 4320 +/- 400 v 2890 +/- 250 micrograms/24 h, p < 0.001) and 11 beta-hydroxy metabolites of cortisol (11-OH FM, 3290 +/- 240 v 1860 +/- 140 micrograms/24 h, p < 0.001). These differences remained significant when corrected for body surface area. The ratio of 11-oxo FM/11-OH FM, an index of 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity, was higher in women (1.57 +/- 0.07 v 1.31 +/- 0.06, p < 0.01). The ratios of 5 alpha/5 beta and 20-oxo/20-OH metabolites of cortisol were both higher in men (1.07 +/- 0.15 v 0.58 +/- 0.04, p < 0.01, and 2.78 +/- 0.06 v 2.27 +/- 0.11, p < 0.01), while the ratio of 20 alpha/20 beta metabolites of cortisol was higher in women (1.79 +/- 0.13 v 1.32 +/- 0.06, p < 0.01). We conclude that there are considerable sex differences in both the production and metabolism of cortisol in healthy men and women. In particular, the data are consistent with a sex difference in 11-HSD activity, with relatively greater conversion of cortisol to cortisone in women.

Chromatography, Gas↗

PubMed2003

[Steroid hormones in the regulation of migration in fishes (study of the Russian sturgeon)].

Serum steroids profiles were determined at different stages of the migratory cycle of Russian sturgeon. In the sea period, before gonads maturation cortisol and sex steroids levels were comparatively low. Elevation of cortisol and testosterone concentrations occurred at the stage of preparation to migration. Significant increase of cortisol and testosterone levels happened at the beginning of the river period of anadromous migration in spring both in the spring forms near to maturity in this period and in the winter forms which were far from maturity. By exception of the river period of anadromous migration of the winter form and sexual cycle completion in the fish farm in the mouth of river (10-11 months), serum cortisol and testosterone concentrations dropped sharply. The data obtained as well as the data on other diadromous fishes indicate a possible role of steroids, especially cortisol and testosterone, in metabolism and migration regulation in sturgeons.

Animals↗

PubMed1999

Sex steroid and prolactin profiles in male American black bears (Ursus americanus) during denning.

Serum sex steroid and prolactin profiles were examined in the male American black bear, Ursus americanus during denning. Sera collected in December and the following March from 8 denning male black bears in Minnesota, U.S.A. were assayed for testosterone, estradiol-17 beta and prolactin. Eight bears were confirmed to be the denning mode based on a serum urea to creatinine ratio less than 10. Serum testosterone concentrations tended to increase from December to the subsequent March whereas serum estradiol-17 beta concentrations tended to decrease during this period. There were few changes in serum prolactin concentrations between December and March. These findings suggest that spermatogenesis and testicular steroidogenesis initiated during denning may be influenced by changes in serum sex steroid concentrations in the American black bear.

Animals↗

PubMed1988

Inhibition of rat testicular microsomal steroidogenesis by oxytocin and metyrapone.

Capillary gas chromatographic 'steroid profiling' has been utilised to separate and quantify the metabolites (derivatized as methyloximes and/or trimethylsilyl ethers) formed from pregnenolone after incubation with rat testicular microsomes. A wide range of steroid metabolites was found, indicating that both the 5-ene and 4-ene pathways of testosterone biosynthesis were operating, as well as 16 alpha-hydroxylation, 20 beta-reduction and the formation of several C19 steroids (the 16-androstenes). At the concentration used, Metyrapone markedly inhibited 16 alpha- and 17-hydroxylation and side-chain cleavage of 17-hydroxylated C21 steroids. 16-Androstene production was also markedly inhibited and the formation of other metabolites was affected to lesser extents. Oxytocin abolished the formation of all C21 and C19 metabolites of pregnenolone.

Animals↗

PubMed2003

Reference values for urinary steroids in Japanese newborn infants: gas chromatography/mass spectrometry in selected ion monitoring.

Urinary steroid profile analysis using gas chromatography/mass spectrometry (GC/MS) has been reported for the diagnosis of abnormal steroidogenesis in newborn infants with some success. We tried to establish the reference values of 63 urinary steroids in Japanese newborn infant, using GC/MS in selected ion monitoring (SIM) that utilizes two characteristic mass ions for each steroid for definitive identification. We studied 36 healthy full-term newborn infants (1-56 days of age) on spot urine samples to define the reference values (mg/g creatinine, median and 10-90 percentile range) and to investigate the possible difference between daytime and nighttime levels. We also studied 23 healthy adult females (20-24 years of age) on 24-hour-urine for the comparison of the reference values of newborn infants. Fifty metabolites of DHEA, pregnenolone, 17-hydroxypregnenolone, androstenedione, progesterone, 17-hydroxyprogesterone, 21-deoxycortisone, corticosterone, 18-hydroxycorticosterone, aldosterone, 18-hydroxycortisol, 11-deoxycortisol, cortisone, cortisol, and estrogen in each infant were measurable without interference, but 13 metabolites of 11-hydroxyandrostenedione, pregnenolone, 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, 21-deoxycortisol, 11-deoxycortisol and cortisol were unmeasurable in each infant due to the interference of fetal cortex steroids as confirmed by abnormal peak area ratios of two mass ions. All 63 metabolites in each control adult were measurable without interference. 16alpha-, 16beta-, and 15beta-hydroxy metabolites of 3beta-hydroxy-5-en-steroids, and 6beta-, 18-hydroxy and 11-oxo-metabolites of corticosteroids were significantly higher in full-term newborn infants than those in adults as previously reported. Urinary steroids showed little circadian variation in the newborn infants, indicating that spot urine can substitute for 24-hour urine.

Adult↗

PubMed2005

Estradiol-17beta and testosterone concentrations in male and female Mya arenaria (Mollusca bivalvia) during the reproductive cycle.

Perturbation of the reproductive cycle as well as vitellin-like protein synthesis have already been reported in Mya arenaria sampled in contaminated areas of the St. Lawrence maritime estuary (Québec, Canada). To assess the potential role of endocrine disruptors in modulating the reproductive cycle in clams, the role of sex steroids has to be clarified. We determined the levels of estradiol-17beta and testosterone during the reproductive cycle in female and male M. arenaria. Both steroids were measured by ELISA in the gonads and no differences in steroid profiles appeared between sexes. Estrogen levels varied between 150 and 400 pg g(-1) wet weight over gametogenesis and were near 10 times higher than testosterone levels. Results showed transient increases of both steroids at the onset of vitellogenesis in females and during the spawning stage in both sexes. These findings indicate that these hormones could have a role as endogenous modulators of gametogenesis. Further studies are, however, needed to describe the pathway of steroid synthesis in clam gonad and elucidate steroid involvement in controlling gametogenesis and as well as their relationship with neurohormones since these latter are required to promote sexual maturation.

Animals↗

PubMed1988

Group fractionation of free and conjugated steroids by means of disposable silica-based anion-exchange columns.

Adsorption and desorption modes have been elaborated which allow the separation of complex steroid mixtures of biological fluids into an unconjugated, a glucuronic acid conjugated and a sulphuric acid and mixed conjugated fraction. Capillary gas chromatographic analysis of the fractions obtained provides "total steroid profiles" of urine, blood, ovarian follicle fluid and amniotic fluid.

Chromatography, Gas↗

PubMed2005

Effect of glutamate and somatostatin-14 on basal and cAMP-stimulated steroidogenesis by rainbow trout (Oncorhynchus mykiss) ovarian follicles, in vitro.

The effects of glutamate and somatostatin-14 (SRIF) on the in vitro basal and cAMP-stimulated steroid production of mid-vitellogenic rainbow trout (Oncorhynchus mykiss) ovarian follicles were investigated. cAMP-stimulation was achieved by the addition of the adenylyl cyclase activator, forskolin (FS), or a membrane permeate cAMP agonist, 8-bromo-cAMP (BA), to the incubation medium. Testosterone (T) and 17beta-estradiol (E(2)) secretion was measured using radioimmunoassay. Solid phase extraction (SPE) was used to measure the relative formation of unconjugated and conjugated steroids, and high performance liquid chromatography (HPLC) was used to examine the steroid metabolites formed from the metabolism of a tritium labelled precursor, pregnenolone (P(5)). The accumulations of T and E(2) in the medium were suppressed in the presence of the glutamate agonists, N-methyl-d,l-aspartate (NMA) or l-glutamic acid (GA), and by the presence of SRIF. The suppression was evident for both basal and cAMP-stimulated steroidogenesis except for T concentrations of GA treatments following basal steroidogenesis, when there were no treatment effects. No significant effects of treatment on conjugated:unconjugated steroid ratios were found. For all treatments E(2) was the major end product steroid synthesized from P(5), and the steroid profiles were similar except for trace amounts of radiolabelled androgens in the medium following cAMP-stimulated steroidogenesis that were not present following basal steroidogenesis. The findings suggest that glutamate and SRIF reduce end point steroid production, possibly by reducing P(5) production. However, since the inhibitory affect was found for basal and cAMP-stimulated steroidogenesis, the response does not appear to be due to the inhibition of cAMP synthesis.

Animals↗

PubMedDate not supplied

Octreotide effect on ovarian morphology in insulin-resistant PCOS patients following six-month decapeptyl treatment.

PROBLEM: Regulation of ovarian folliculogenesis involves bidirectional communication between the immune and endocrine systems. Somatostatin analogues have been reported to acutely suppress elevated androgens in polycystic ovary syndrome (PCOS). The aim of our study was to analyze the morphologic and hormonal-metabolic response to octreotide therapy for one month in insulin-resistant PCOS patients in whom luteinizing hormone (LH) effect had formerly been separated by a six-month GnRH-agonist (GnRH-a) course. METHOD: Fifteen PCOS patients were studied two months after completing a six-month GnRH-a (decapeptyl 3.75 mg monthly injection) course. Seven of the patients (group A), who were insulin-resistant and gave hyperinsulinemic response to a glucose challenge, received a 50-micrograms subcutaneous injection of octreotide twice a day for one month. The nonhyperinsulinemic patients (group B) received placebo injections. Hormonal measurements, oral glucose tolerance test (OGTT), and transvaginal ovarian ultrasound were performed before and toward the end of the treatment period. RESULTS: After octreotide ovarian volume dropped significantly in group A (x +/- SD) (19.2 +/- 5.1 versus 14.7 +/- 5.5 cc, P = .02). LH levels increased (3.25 +/- 1.22 versus 5.95 +/- 4.34 mu/ml, P = .05) as did E2 levels (38.0 +/- 11.4 versus 55.1 +/- 12.7 pg/ml, P = .005). There was no change in follicle-stimulating hormone, 17-hydroxy-progesterone, free testosterone, or androstenedione levels. Insulin secretion during OGTT dropped significantly (555 +/- 294 versus 68 +/- 29 mu u/ml/hr, P = .002). Glucose tolerance was not affected. In contrast, the placebo-treated group B patients showed an increase in ovarian volume (10.9 +/- 3.5 versus 14.8 +/- 3.3 cc, P = .001) while their gonadotropin and steroid profile relapsed, similarly to our patients receiving octreotide. CONCLUSIONS: Octreotide has an adjunctive beneficial effect to GnRH-a on ovarian morphology although, at the dose used, there was no suppression of gonadotropin or ovarian steroid levels. The changes in ovarian morphology are probably mediated through suppression of insulin levels and/or other ovarian growth factors.

Adolescent↗