naloxone and Polycystic-Ovary-Syndrome

Beta-endorphin were detected in the endocrine pancreas and seem able to influence insulin and glucagon release. Hence, endogenous opioids could have a role in glucoregulation and in the pathogenesis of obesity beyond the previously detected effects on appetite. Metabolic abnormalities, such as hyperinsulinemia, insulin-resistance and obesity, are common features of polycystic ovary syndrome (PCOS), and seem to have a pathogenetic role in this disorder. A link between opioids and PCOS-related hyperinsulinism is suggested by the finding of altered central opioid tone and elevated beta-endorphins levels, directly correlated with body weight, in these patients. Furthermore, naloxone and naltrexone significantly reduce the insulin response to glucose load only in hyperinsulinemic PCOS patients. This effect is obtained chiefly through an improvement of insulin clearance. Naltrexone is also able to ameliorate the abnormal gonadotrophins secretion and to improve the ovarian responsiveness in obese PCOS women undergoing ovulation induction with exogenous GnRH. Such effects are believed to be obtained through an amelioration of hyperinsulinemia. Gonadal steroids modulate the opioid system both centrally and in peripheral districts. Nevertheless, the decline of ovarian function does not abolish the opioidergic control of glucoregulation. Post-menopausal period is characterised by a high prevalence of hyperinsulinemia and insulin-resistance. In particular, an association between hyperinsulinemia and increased opioid activity was found in postmenopausal women showing a central body fat distribution. Both naloxone and naltrexone ameliorate the metabolic imbalance also when it appears in the climacteric period, and mainly by increasing insulin clearance. The benefits of naltrexone may represent in the future a useful tool for the treatment of women with hyperinsulinism in the clinical practice.

Topics: Clinical Trials as Topic; Endorphins; Female; Humans; Hyperinsulinism; Insulin Resistance; Menopause; Naloxone; Naltrexone; Narcotic Antagonists; Obesity; Polycystic Ovary Syndrome

To evaluate the influence of the opioid system on the hypothalamic-pituitary-adrenal axis in women with polycystic ovary syndrome (PCOS).. Controlled clinical study.. Academic research environment.. Eight lean and 12 obese women with PCOS, and seven lean and 5 obese control subjects.. Each patient received an i.v. bolus of naloxone at a dose of 125 microgram per kilogram of body weight; 48 hours later, each patient received 16 mg of loperamide p.o.. Samples were collected for 2 hours for the naloxone test and for 3 hours for the loperamide test. Levels of adrenocorticotropic hormone (ACTH) and cortisol were measured in all plasma samples.. The obese women with PCOS had a greater ACTH and cortisol response to opiate blockade than either the lean women with PCOS or the control subjects, but there was no difference between the lean or obese control subjects and the lean women with PCOS. There was no difference in the responsiveness of the hypothalamic-pituitary-adrenal axis to loperamide between the PCOS and control groups.. The data indicate that the sensitivity of the hypothalamic-pituitary-adrenal axis to opioids cannot be altered in women with PCOS. However, abnormalities of the hypothalamic-pituitary-adrenal axis in women with PCOS could be central in origin, as suggested by the effects of naloxone administration, and probably are related to the anthropometric characteristics of these hyperandrogenic patients.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Adult; Body Weight; Female; Humans; Hydrocortisone; Hypothalamus; Loperamide; Naloxone; Narcotic Antagonists; Narcotics; Obesity; Pituitary Gland; Polycystic Ovary Syndrome

To evaluate the influence of body mass on the hypothalamic-pituitary-adrenal (HPA)-axis response to naloxone in polycystic ovary syndrome (PCOS).. Controlled clinical study.. Academic research environment.. Ten lean and 10 obese women with PCOS compared with 7 lean and 8 obese control subjects matched for body mass index.. Each patient received an IV bolus of naloxone at a dosage of 125 microg/kg.. Samples were collected 30 minutes before and 0, 15, 30, 60, 90, and 120 minutes after injection: ACTH and cortisol levels were measured in all plasma samples.. No significant differences were found in the ACTH and cortisol responses to opioid blockade between lean women with PCOS and lean as well as obese control subjects; conversely, obese patients with PCOS showed a higher ACTH and cortisol responses to naloxone compared with all other groups.. Hypothalamic-pituitary-adrenal-axis abnormalities of PCOS may be central in origin and abdominal obesity seems to play a key role in the HPA-axis hyperactivity of women with PCOS when naloxone is administered.

Topics: Adrenocorticotropic Hormone; Adult; Body Mass Index; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Naloxone; Narcotic Antagonists; Obesity; Pituitary-Adrenal System; Polycystic Ovary Syndrome

We previously reported that circulating beta-endorphin levels are increased in obese hirsute women and that plasma immunoreactive insulin (IRI) levels are increased in proportion to the degree of hyperandrogenism in women with the polycystic ovary (PCO) syndrome. We, therefore, tested the hypothesis that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in this syndrome. In the first study, acute naloxone administration significantly reduced the plasma IRI response and IRI/glucose ratio in three euglycemic obese women with PCO and acanthosis nigricans (AN) and marked insulin resistance, but did not alter the glucose response. Naloxone had no effect on these parameters in the normal weight control subjects. In the second study, nalmefene, a new, orally active opiate antagonist, reduced IRI and the IRI/glucose ratio in four women with PCO-AN and marked hyperinsulinemia in a randomized, double blind, crossover protocol. We conclude that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in PCO-AN.

Topics: Acanthosis Nigricans; Adolescent; Adult; Blood Glucose; Female; Humans; Insulin; Insulin Resistance; Naloxone; Naltrexone; Narcotic Antagonists; Polycystic Ovary Syndrome

The most important alkaloid of opium family, morphine, may show unfavorable effect on the reproductive organs. This research investigated the effect of microinjection of morphine into the rat's ventromedial hypothalamus (VMH) on cystic genesis in the ovary and the health of neurons of VMH.. Female rats (Wistar, weighing 200-250 g) kept under standard conditions were cannulated under anesthesia by Stoelting stereotaxic instrument at the coordinates anterior-posterior: -1.92, ventral: 9, lateral: 0.5. After being recovered, they were microinjected single morphine (0.1-0.4 µg/rat, once intra-VMH) and/or naloxone hydrochloride (0.1-0.4 µg/rat, once intra-VMH) using a 5-µL Hamilton syringe with the polyethylene tubing. The control group solely given physiological saline (1 µL/rat, intra-VMH). Three days after the experiment, both ovary and brain samples were collected from the control and the experimental groups, and they were studied histopathologically. The brain samples were checked out with the aid of the cresyl violet, and the ovaries were stained by the hematoxylin and eosin. The samples were also biometrically examined to compare the ovaries' cystic formations. Also, the number of healthy or injured neurons in the nuclei was compared.. The ovaries of morphine-treated rats showed polycystic characteristics in comparison with the control samples. In addition, the brain slices of the morphine-treated rats illustrated a significant decrease in intact neurons. Both mal effects were resolved in the presence of naloxone.. These results may show that the morphine induces anovulatory infertility probably by hypothalamus-pituitary-ovary axis dysfunction.

Topics: Animals; Female; Menstrual Cycle; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Neurons; Ovary; Polycystic Ovary Syndrome; Rats, Wistar; Ventromedial Hypothalamic Nucleus

To assess the therapeutic effects of naloxone and yohimbine on polycystic ovary syndrome (PCOS) in a rabbit model in terms of body weight and endocrinological parameters (luteinizing hormone, insulin, and estradiol).. A total of 50 adult, reproductively mature female rabbits (Oryctolagus cuniculus) were divided into five groups (n = 10/group). In the control group PCOS was not induced (negative control group), whereas in the remaining four groups (n = 40) PCOS was induced with a single i.m. injection of testosterone daily and were designated as follows: positive control, naloxone-treated (NalT), yohimbine-treated (YohT), and naloxone+yohimbine-treated (NalYT) groups.. A steadily ascending trend was noted in all of the studied parameters in the PCOS-induced group as compared to the negative control group. All the parameters showed a descending trend in the NalT group as compared to the positive control. Regarding the YohT and NalYT groups, all parameters showed a descending trend as compared to the positive control group except for estradiol.. Naloxone therapy either alone or combined with yohimbine improves a wide range of the clinical manifestations of PCOS. Furthermore, we suggest this therapy as an alternative to the conventional therapy with insulin-lowering agents in vogue.

Topics: Animals; Body Mass Index; Female; Follicle Stimulating Hormone; Insulin; Insulin Resistance; Luteinizing Hormone; Naloxone; Polycystic Ovary Syndrome; Rabbits; Testosterone; Yohimbine

To investigate the effect of naloxone, an opioid receptor antagonist, on the release of growth hormone (GH) induced by the growth hormone-releasing hormone (GHRH) in normal-weight and obese women with PCOS in relation to feeding.. Prospective clinical study.. Academic research center.. Seventeen women with PCOS (10 who were normal weight and 7 who were obese) and 14 control women (7 who were normal weight and 7 who were obese).. A GHRH test (50 microg i.v.) and, on a different day, a GHRH test during a naloxone infusion (1.6 mg/h) during fasting. The same tests were repeated after a standard meal.. GH response to GHRH (expressed as the area under the curve [AUC]) in different experimental conditions.. All normal-weight women showed a significantly higher AUC-GH compared with obese women in the fasting state. Normal-weight controls had a decrease in GH response to GHRH after feeding, and naloxone did not reverse the decrease. In obese controls, feeding increased the GH response but naloxone induced a decrease in the AUC. In fasting, normal-weight women with PCOS, naloxone significantly decreased the AUC-GH; in these patients, food intake induced an inhibition of GH response to GHRH, reversed by naloxone infusion. In obese PCOS patients, GH levels did not increase significantly after GHRH stimulation, either in the fasting state or after a meal, and naloxone did not affect these responses.. Factors other than obesity and insulin may be involved in disruption of GH secretion in women with PCOS.

Topics: Adult; Area Under Curve; Body Weight; Eating; Fasting; Female; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Naloxone; Narcotic Antagonists; Obesity; Polycystic Ovary Syndrome; Prospective Studies; Reference Values

There are conflicting data on hypothalamic-pituitary-adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects.. Twenty PCOS patients and 10 control women participated in the study.. On days 5-6 of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2-mg naloxone infusion in 100 ml of 0.9% saline over one hour. Samples were collected at -30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples.. PCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261 vs 172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher in PCOS patients (P < 0.05 and P < 0.04 respectively). The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production.. Polycystic ovary syndrome patients showed a hypothalamic-pituitary-adrenal axis hyper-responsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be central in origin.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Naloxone; Narcotic Antagonists; Pituitary-Adrenal System; Polycystic Ovary Syndrome

Ovarian surgery has been demonstrated as an effective means to establish regular menstrual cycles and resumption of ovulation in patients with polycystic ovarian disease (PCO). We questioned whether such reinstitution of menstrual cyclicity may be associated with changes in the opioidergic and dopaminergic activity known to be aberrant in these women. Opioidergic and dopaminergic tone was therefore assessed in patients with PCO before and after ovarian laser vaporization (n = 4) or classical ovarian wedge resection (n = 4). Blood samples for the determination of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were frequently obtained following opioidergic and/or dopaminergic antagonism affected by naloxone (4 mg i.v.) or metoclopramide (10 mg i.v.). In response to either surgical approach, circulating LH levels decreased (p < 0.01), while FSH concentrations remained unaltered. Further, LH and FSH concentrations did not noticeably change following challenges with naloxone or metoclopramide: this applied to conditions before and after ovarian surgery. Prolactin release in response to metoclopramide was markedly (p < 0.01) higher following ovarian surgery than before. Thus, both ovarian laser surgery and classical wedge resection can effectively restore normal menstrual cyclicity in PCO patients, although they failed to alter opioidergic and dopaminergic activity. Dopaminergic inhibition of prolactin secretion was further enhanced after ovarian surgery. These observations suggest that different modes of ovarian surgery are effective in influencing central gonadal control, but that the central opioidergic and dopaminergic control of gonadotropin and prolactin secretion remains unaffected by ovarian surgery in PCO women, even when menstrual cyclicity is resumed.

Topics: Adult; Dopamine; Endorphins; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Kinetics; Luteinizing Hormone; Metoclopramide; Naloxone; Ovary; Polycystic Ovary Syndrome; Pregnancy; Prolactin

To evaluate the involvement of endogenous opiates in the pathophysiology of the hyperinsulinism in patients affected by polycystic ovary disease by administering naloxone and naltrexone. We also studied the hormonal status following long-term opioid antagonist administration.. Twenty-one women affected by polycystic ovary disease participated in the study. An oral glucose tolerance test (GTT) was performed at baseline and repeated after short-term naloxone infusion and after 6 weeks of naltrexone administration. Plasma glucose and insulin levels were evaluated in all samples. Gonadotropins, sex hormone-binding globulin, and androgen levels were determined initially and after the naltrexone treatment.. None of the patients showed any alteration of glucose tolerance. Based on the insulin response to the GTT, the patients were classified as normo- or hyperinsulinemic. Opioid antagonist administration significantly reduced the insulin response to the GTT in hyperinsulinemic patients, without affecting their glycemic levels. In normoinsulinemic patients, glucose plasma levels were increased whereas insulin levels were not modified by the treatments. Gonadotropin and androgen plasma concentrations were not modified after naltrexone administration.. This work supports a role for the endogenous opiates in the regulation of exaggerated insulin secretion in patients with polycystic ovary disease. The reduction of insulin secretion failed to demonstrate any hormonal modification in such hyperandrogenized patients.

Topics: Adult; Endorphins; Female; Glucose Tolerance Test; Gonadal Steroid Hormones; Humans; Hyperinsulinism; Insulin; Naloxone; Naltrexone; Obesity; Polycystic Ovary Syndrome; Time Factors

In order to test the hypothesis that endogenous opiates are at least partially responsible for hyperinsulinaemia in patients with polycystic ovarian disease (PCOD), the effect of naloxone (an opiate receptor blocker) on the insulin response to oral glucose load (OGTT) was studied in 20 women with PCOD and 17 control subjects at days 5-8 of their follicular phase. After fasting overnight for 10-12 h, each woman received an i.v. bolus injection (2 mg) of naloxone or an equal volume of saline infusion followed by a constant infusion of naloxone or saline solution at a rate of 8 ml/h (1 mg/h of naloxone) for 5 h. OGTT (75 g) was performed 1 h after the bolus injection. The naloxone study was performed 48 h after the saline study. Naloxone did not modify the insulin response to OGTT in either group. When the data were related to the insulin response, in PCOD hyperinsulinaemic patients, naloxone significantly reduced (P less than 0.02) the insulin response to OGTT without any change in glycaemic response curves. In control and PCOD normoinsulinaemic patients, naloxone did not change significantly either the glycaemia or the insulin levels after OGTT. No change of gonadotrophin and steroid secretion was found in any patient receiving naloxone. In conclusion, endogenous opiates may play a significant role in hyperinsulinaemia in PCOD.

Topics: Adolescent; Adult; Blood Glucose; Body Weight; Endorphins; Female; Glucose Tolerance Test; Humans; Insulin; Naloxone; Narcotic Antagonists; Polycystic Ovary Syndrome

The purpose of this study was to re-evaluate the quantitative and qualitative responses of LH to exogenous and endogenous GnRH stimulation in normally cycling women and in polycystic ovarian disease (PCOD). Responses of serum LH to GnRH (100 micrograms i.v.) and the opioid antagonist naloxone (10 mg i.v.) were determined in healthy women in the early (n = 5) and late (n = 4) follicular phase, and in patients with PCOD (n = 20). Serum bioactive (B) LH was determined by a mouse interstitial cell in vitro bioassay, and immunoreactive LH by a conventional RIA (I-LH) and a novel sensitive (0.05 IU/l) and specific immunofluorimetric assay (F-LH). The B/I (2.4 +/- 0.1) and B/F (2.7 +/- 0.6) ratios in basal serum samples of the PCOD patients were significantly higher (p less than 0.05) than the corresponding ratios (1.6-1.8 and 1.8-2.0) of the control women. GnRH stimulated the secretion of I-LH (2-4-fold), F-LH and B-LH (3-5-fold each) in all groups studied. There were no apparent changes of the B/I and B/F ratios in normal women during early follicular phase or in patients with PCOD. However, the normal women during late follicular phase displayed a significant (p less than 0.05) increase in the B/I ratio, albeit no change was found in the B/F ratio. During naloxone-induced endogenous GnRH responses, the control women during late follicular phase showed a 3-6-fold increase in B-LH, I-LH and F-LH, with unchanged B/I and B/F ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Biological Assay; Female; Fluoroimmunoassay; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; In Vitro Techniques; Luteinizing Hormone; Mice; Naloxone; Polycystic Ovary Syndrome; Testosterone

Insulin and insulin-like growth factors (IGFs) stimulate ovarian steroidogenesis, and hyperinsulinemia is often accompanied by hyperandrogenemia in women with polycystic ovarian disease (PCOD). Because opioid peptides are involved in the regulation of insulin secretion, we studied the effect of naloxone-induced opiate receptor blockade on the circulating levels of insulin, IGF-I, and IGF binding protein 1 (IGFBP-1) in 13 nonobese and 7 obese PCOD patients and in 6 healthy subjects. In obese PCOD patients, the mean basal insulin concentration was significantly higher and the IGFBP-1 concentration lower than in nonobese PCOD patients. Plasma IGF-I levels were elevated both in obese and nonobese PCOD patients. After an intravenous bolus of 10 mg naloxone, no significant changes were found in the circulating insulin or IGF-I levels, whereas IGFBP-1 levels decreased in nonobese PCOD patients and remained low in obese PCOD patients. No significant decrease was found in healthy subjects. These results suggest that, in addition to insulin, endogenous opioids are involved in the regulation of serum IGFBP-1 level.

Topics: Adolescent; Adult; Carrier Proteins; Endorphins; Female; Humans; Injections, Intravenous; Insulin; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Naloxone; Ovary; Polycystic Ovary Syndrome; Receptors, Opioid; Somatomedins

The response of TSH, PRL, LH and FSH to combined test with LHRH (Relefact LH-RH, HOECHST; 0.1 mg) and TRH (Relefact TRH, HOECHST; 0.2 mg) was examined before (day I) and after naloxone (Narcanti, DUPONT) bolus of 0.8 mg (day III) in 8 patients with polycystic ovary syndrome (POC) diagnosed by established criteria (hirsutism, oligoamenorrhoea, ultrasound appearance of polycystic ovary and serum LH/FSH greater than 2.0). TSH (RIA-INEP), PRL (MAIA-SERONO), LH (MAIA-SERONO) and FSH (MAIA-SERONO) were determined at -15, 0, 10, 20, 30, 45, 60, 90 and 120 min. The hormone responses were calculated as the areas under hormone curves and tested with Wilcoxon sum rank test. No significant difference was found in the hormone responses before and after naloxone injection. In terms of absolute values lower TSH level was found at 30 min after naloxone administration (14.7 +/- 12.0 vs. 9.73 +/- 7.61; P less than 0.05). In conclusion, our data based on short term naloxone application argue against the significant alteration of the opioid activity in patients with POC.

Topics: Adult; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Naloxone; Pituitary Gland; Polycystic Ovary Syndrome; Prolactin; Thyrotropin; Thyrotropin-Releasing Hormone

Women with polycystic ovary syndrome (PCO) display disordered patterns of LH pulsatility and may have an impairment of opioidergic regulation of GnRH-LH. In order to ascertain if these patterns reflect an inherent hypothalamic abnormality or a functional state consequent to the acyclicity of sex steroids, LH pulsatility and gonadotrophin responses to naloxone were examined in six PCO women before and after treatment with incremental daily doses of a progestogen, medroxyprogesterone acetate (MPA), for 10 days to determine (i) if progestogen treatment would alter the LH pulse pattern to resemble that of the luteal phase; and (ii) if the conversion to a luteal phase LH pulse pattern by MPA would involve the induction of opioidergic regulation. LH pulsatility and FSH levels were determined by blood sampling at 10 min intervals for 8 h before and after MPA treatment during a saline infusion on the control day and during a naloxone infusion (1.6 mg/h) on the following day. Basal levels of oestradiol, oestrone, androstenedione, testosterone, and dehydroepiandrosterone-sulphate were measured before and after MPA. All six PCO women responded to MPA administration with a significant reduction in LH pulse frequency (P less than 0.005), an increase in LH pulse amplitude (P less than 0.0025), and an increase in LH pulse duration (P less than 0.025), without changes in mean LH, mean FSH, androgen, or oestrogen levels. Thus, a luteal phase LH pulse pattern was induced by MPA. Naloxone reversed the MPA-induced changes in LH pulsatility, indicating that these responses involved the induction of central opioidergic activity.(ABSTRACT TRUNCATED AT 250 WORDS). To determine whether the disordered patterns of luteinizing hormone (LH) pulsatility and impaired opioidergic regulation of gonadotropin- releasing hormone (GnRH)-LH observed in women with polycystic ovarian syndrome reflect an inherent hypothalamic abnormality or a functional state related to the acyclycity of sex steroids, medroxyprogesterone acetate was administered to 6 women with this syndrome. It was hypothesized that if the apparent lack in women with polycystic ovarian syndrome of opiodergic regulation of GnRH-LH release was in fact secondary to an inherent hypothalamic defect, then the administration of this progestogen would fail to produce opiodergic regulation of GnRH-LH. Medroxyprogesterone acetate was given orally to the 6 study subjects over a 10-day period in an incremental dosage to mimic the luteal phase. LH pulsatility and follicle-stimulating hormone (FSH) levels were measured at 10 minute intervals during the 8 hours before and after treatment and infusions of saline or naloxone were given. All 6 subjects showed significant changes in LH pulsatile activities after steroid administration, specifically a slowing of LH pulse frequency and an increase in pulse amplitude and duration. Naloxone infusion reversed these progestogen-associated changes. There were no changes in mean LH, mean FSH, androgen, or estrogen levels, however, suggesting that a luteal phase LH pulse pattern was produced. Since naloxone reversed the changes in LH pulsatility induced by medroxyprogesterone acetate, it can be concluded that these responses involved the induction of central opiodergic activity secondary to ovarian acyclycity and progesterone deficiency, not a primary hypothalamic defect.

Topics: Adult; Androgens; Estrogens; Female; Humans; Luteinizing Hormone; Medroxyprogesterone; Medroxyprogesterone Acetate; Naloxone; Periodicity; Polycystic Ovary Syndrome; Progesterone

The luteinizing hormone (LH) response to metoclopramide (MCP), a dopamine receptor antagonist, and naloxone (NAL), an opioid receptor antagonist, was evaluated in 7 patients with polycystic ovarian disease (PCOD) before and during treatment with purified human urinary follicle-stimulating hormone (hFSH), and in 6 control women during spontaneously ovulating cycles. Before treatment, in all patients both MCP and NAL administration did not increase plasma LH levels. In the 6 subjects ovulating following hFSH treatment the LH response to MCP and NAL at preovulatory and midluteal phases was restored, as it occurred in control women. Our results suggest that in PCOD the dopamine and opioid activity in the hypothalamus are decreased. The reversal of peripheral ovarian response induced by treatment for the induction of ovulation may restore these impaired neuroendocrine activities.

Topics: Adult; Dopamine; Endorphins; Female; Humans; Luteinizing Hormone; Metoclopramide; Naloxone; Ovulation Induction; Polycystic Ovary Syndrome

In order to investigate the role of the adrenal gland in the pathogenesis of polycystic ovarian disease (PCOD), we evaluated the adrenal steroid response to an opiate receptor blockade. Six healthy menstruating volunteers and 6 patients with PCOD were given a saline or naloxone (4 mg i.v.) injection in the early follicular phase. Blood samples were taken prior to the injections and every 15-30 minutes in the following 2 hours. Cortisol, androstenedione (A) and dehydroepiandrosterone (DHA) plasma levels were determined by RIA after extraction (cortisol) and celite chromatography (A and DHA). While in controls naloxone increased only cortisol concentrations, in PCOD patients DHA plasma levels also were stimulated by the opiate receptor antagonist. In PCOD patients the increase of cortisol (p less than 0.05) and of DHA (p less than 0.001) levels resulted significantly higher than in controls. In both groups A plasma levels remained unchanged after naloxone administration. These data confirm that endogenous opioids exert an inhibitory control on the pituitary-adrenal axis. In PCOD patients the response to naloxone led to a hypersecretion of adrenal delta 5-androgens, which could account for the development of the syndrome.

Topics: Adrenal Glands; Androstenedione; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Naloxone; Polycystic Ovary Syndrome; Receptors, Opioid

To further evaluate the role exerted by endogenous opioids on LH secretion a naloxone challenge (0.08 mg/Kg b.w. i.v.) was performed in 23 healthy children at different stages of puberty, in 5 adolescents in different period of menstrual cycle, in 3 case of idiopathic precocious puberty (PP), in 7 cases of delayed puberty (DP), in 4 females affected by hypogonadotropic hypogonadism (HH) and in 6 patients affected by polycystic ovary disease (PCOD). Naloxone does not induce any significant change on LH plasma levels in prepubertal healthy children and in all the cases of PP and DP. Similarly there was no LH response in healthy adolescents neither in HH nor in PCOD, the response to naloxone appears only in preovulatory and luteal phases. These data indicate that the central opioid system regulating LH secretion in humans is active only at more advanced stages of puberty and it does not seem to play a role in the beginning of sexual maturation. Moreover gonadal steroids seem to play a fundamental modulatory role on opioid-controlled LH secretion.

Topics: Adolescent; Adult; Child; Female; Humans; Hypogonadism; Luteinizing Hormone; Male; Menstrual Cycle; Naloxone; Polycystic Ovary Syndrome; Puberty; Puberty, Delayed; Puberty, Precocious

Dopamine infusion 4 micrograms/kg/min over 4 h, administered to six subjects with diagnosis of polycystic ovarian disease laparoscopically confirmed, produced a significant decrease in serum LH, FSH and PRL, suggesting a reduced dopamine activity in these subjects. The addition of naloxone 4 mg iv bolus plus 4 mg/h over 2 h, a specific opiate antagonist, does not interfere with the well-established dopaminergic inhibitory influence on LH, FSH and PRL secretion. This suggests that opiatergic pathways are not directly involved in the dopamine-induced suppressive effect on LH secretion in subjects with LH-dependent polycystic ovarian disease.

Topics: Adult; Dopamine; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Luteinizing Hormone; Naloxone; Polycystic Ovary Syndrome; Prolactin

Five women with pseudocyesis were evaluated during a two-year period. A random, nontimed blood sample was obtained from each woman at the time of initial encounter that revealed a hormone pattern most consistent with polycystic ovarian disease; mean (+/- SE) concentration of luteinizing hormone (LH) was 14.2 +/- 2.1 mIU/mL, follicle-stimulating hormone (FSH) was 3.3 +/- 0.7 mIU/mL, prolactin (PRL) was 23.5 +/- 1.3 ng/mL, estrone was 74.7 +/- 15.0 pg/mL, and estradiol was 54.7 +/- 13.0 pg/mL. In four of these patients, serum progesterone concentration was elevated over expected follicular phase values. The opiate antagonist, naloxone, was administered to four women before disclosure of their diagnosis. Naloxone treatment failed to induce LH or PRL release. Because naloxone did not cause a change in hormone concentration, naloxone-sensitive opioid mechanisms are apparently not involved in this disorder. After resolution of pseudocyesis, naloxone-induced LH release was appropriate for the phase of the cycle in which the narcotic blocking agent was administered.

Topics: Adult; Endorphins; Estradiol; Estrone; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Naloxone; Polycystic Ovary Syndrome; Progesterone; Prolactin; Pseudopregnancy

It has been hypothesized that brain opioid activity may be decreased in patients with the polycystic ovary syndrome (PCO) and that this decrease may, in part, explain the elevated levels of LH characteristic of the syndrome. We, therefore, examined the LH and PRL responses to naloxone infusions (2 mg/h for 4 h) in seven women with PCO and five weight- and estrogen-matched normal women. The infusions were given both before and after pretreatment with L-dopa-carbidopa (L-DOPA-C) because dopaminergic activity may be decreased in PCO, and dopamine may interact with the brain opioid system. Both PCO patients and normal women had similar responses of serum LH during naloxone treatment; the mean maximum LH responses were 53 +/- 15% (+/- SE) in normal women and 51 +/- 12% in PCO patients (P greater than 0.05). PRL levels were also unaffected by naloxone infusion. After L-DOPA-C pretreatment, baseline LH and PRL levels were unchanged in normal women and PCO patients, and the naloxone-induced LH rise was completely abolished in the normal women. However, in PCO patients, LH increased from 24.7 +/- 4 to 31 +/- 5 mIU/ml, with a mean maximum increase of 112 +/- 33% during naloxone infusion (P less than 0.05). We conclude that 1) brain or central opioid activity is not decreased in PCO; 2) increased central opioid activity does not appear to be responsible for the increased LH levels characteristic of the syndrome; and 3) decreased central dopamine activity and/or the interaction between the dopaminergic and opioid systems may be altered in PCO.

Topics: Adult; Brain Chemistry; Carbidopa; Dopamine; Endorphins; Estrogens; Female; Follicle Stimulating Hormone; Humans; Levodopa; Luteinizing Hormone; Naloxone; Polycystic Ovary Syndrome; Prolactin

The inhibitory role of the dopaminergic and opioidergic mechanisms in the control of LH secretion in patients with polycystic ovary syndrome (PCO) was evaluated. The administration of an opiate receptor antagonist, naloxone, of a dopamine receptor antagonist, metoclopramide, or of human synthetic beta h-endorphin, were unable to alter LH secretory activity in patients with PCO. Since identical doses of these antagonists and the opiate agonist have elicited respectively a rise and fall of LH levels in normal cycling women, these findings suggest that an underlying hypothalamic component of defect in endogenous dopamine and opioid control may be responsible for the inappropriate gonadotrophin secretion in this syndrome.

Topics: beta-Endorphin; Depression, Chemical; Endorphins; Female; Humans; Hypothalamus; Luteinizing Hormone; Metoclopramide; Naloxone; Polycystic Ovary Syndrome

This study assessed the effect of the opiate antagonist naloxone on anterior pituitary hormone release in normal subjects and patients with disturbances of the gonadotropic axis. Intravenous bolus injections of naloxone resulted in a rise of plasma LH, but had no significant effect on plasma levels of FSH or PRL. It also failed to alter the LH, FSH, or TSH response to LRF and TRH, although it did augment the PRL response to TRH. Slow iv infusion of naloxone resulted in increased plasma LH and FSH concentrations in both normal subjects and patients with hyperprolactinemia. The rise of LH correlated with the mean basal LH concentrations; a low basal level only responded to naloxone with a small increase in circulating LH concentration and vice versa. This relationship of the response of LH to the resting levels also held in several other pathological states in which there were marked differences of androgen and estrogen status as well as up to a 100-fold variation in basal LH concentrations. It is concluded that LH is under inhibitory opioid control both in normal subjects and in widely differing pathological states of the gonadotropic axis.

Topics: Adenoma; Adult; Craniopharyngioma; Female; Follicle Stimulating Hormone; Humans; Hypothyroidism; Luteinizing Hormone; Male; Naloxone; Pituitary Neoplasms; Polycystic Ovary Syndrome; Prolactin