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Somatostatin treatment reduces the exaggerated response of adrenocorticotropin hormone and cortisol to corticotropin-releasing hormone in polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of somatostatin analogue (octreotide) in the function of hypothalamic-pituitary-adrenal (HPA) axis in women with polycystic ovary syndrome (PCOS). SETTING: Women referred to the Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore. PATIENT(S): Twelve PCOS women and 12 normo-ovulatory controls. INTERVENTION(S): In early follicular phase, I microgram/kg human corticotrophin-releasing hormone (CRH) was injected at 9:00 A.M. and blood samples were collected for 90 minutes after stimulus; ACTH and cortisol plasma levels were measured. The following day at 8:00 A.M., PCOS patients received an ACTH test (250 micrograms IV) and samples were collected 60 minutes after injection. After 6 weeks of octreotide treatment (100 mg s.c. twice daily), PCOS patients repeated the same study. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH concentrations. RESULT(S): The ACTH and cortisol baseline levels were similar in PCOS and control patients. The responses to human CRH of ACTH (incremental area = 437.86 +/- 188.7 versus 175.78 +/- 87.6 pmol/L; mean +/- SD) and cortisol (incremental area = 17,293.6 +/- 4,320.3 versus 5,885 (912.1 nmol/L) were significantly greater in PCOS with respect to control subjects. After octreotide treatment, ACTH response significantly decreased and no difference was observed with respect to controls (incremental area = 176.94 +/- 91.4). Cortisol responses were decreased by treatment. However, they remained significantly higher than in controls. Treatment did not modify adrenal response to IV ACTH. CONCLUSION(S): Data suggest that, in the HPA axis, hyperfunction of PCOS somatostatin could be involved partially.

Adolescent↗

Androgen excess contributes to altered growth hormone/insulin-like growth factor-1 axis in nonobese women with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship between ovarian androgen excess and impaired growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: A prospective, controlled clinical study. SETTING: Reproductive Endocrine Unit, Department of Obstetrics and Gynecology, Jinling Hospital, Nanjing University School of Clinical Medicine. PATIENT(S): Six patients with PCOS with both clomiphene resistance and gonadotropin hyperreponsiveness and six controls with regular cycles, matched for age and body mass index (BMI). INTERVENTION(S): Bilateral ovarian wedge resection (OWR) was performed to induce ovulation surgically for these refractory women with PCOS. A GH stimulation test with oral L-dopa was arranged for controls and for patients with PCOS before and again 6 months later after OWR. MAIN OUTCOME MEASURE(S): Plasma GH, IGF-1, FSH, LH, testosterone, androstenedione, estradiol, progesterone, prolactin, insulin, and glucose. RESULT(S): Basal levels and areas under the response curve of GH and GH-IGF-1 ratio to L-dopa were significantly lower in patients with PCOS before surgery than those of controls. The OWR in patients with PCOS obviously reduced their androstenedione and testosterone levels and insulin-glucose ratios, and increased the GH and GH-IGF-1 responses to L-dopa. CONCLUSION(S): Impaired somatotrophic axis caused by a defect in central dopaminergic activity may be responsible for severe anovulation in these women with PCOS, which could be reversed by removing excessive androgens with OWR.

Adult↗

Assessment of glucose tolerance and pregnancy outcome of polycystic ovary patients.

OBJECTIVES: To determine the impact of polycystic ovary syndrome (PCOS) on glucose tolerance during pregnancy and perinatal outcome. METHODS: Pregnancy records of 38 PCOS patients were compared retrospectively with 136 non-PCOS patients randomly. Patients with glucose challenge tests values of >130 mg/dl were referred for the 3-h, 100-g oral glucose tolerance test (OGTT). RESULTS: A family history of diabetes mellitus, pre-pregnancy body mass index (BMI), gestational weight gain was significantly higher in PCOS patients than controls. The prevalence of gestational diabetes mellitus (GDM) was similar in both groups. Impaired glucose tolerance (IGT) was observed in 18.4% of PCOS patients vs. 5.1% of controls. The main predictor of GDM was found pre-pregnancy BMI >25 while main predictor of IGT was found as PCOS. Mean gestational age at delivery, prevalence of preterm labor, modes of delivery, mean birthweight, mean Apgar score at 5 min, proportion of babies admitted to the neonatal intensive care unit (NICU) were similar in both groups. CONCLUSIONS: Higher IGT prevalence in PCOS patients might be related to maternal obesity and excess gestational weight gain and does not affect perinatal outcome.

Adult↗

Impact of long-term naltrexone treatment on growth hormone and insulin secretion in hyperandrogenic and normal obese patients.

The growth hormone (GH) response to stimulation tests is impaired in obesity. Moreover, obese patients exhibit a "paradoxical" increase of GH to GH-releasing hormone (GHRH) stimulation after food ingestion; this paradoxical response is reversed by naloxone infusion. On the other hand, beta-endorphin seems to exert profound effects on insulin release. Recent studies also demonstrated an impairment of GH response to several stimuli in polycystic ovary syndrome (PCOS), a condition associated with obesity, hyperinsulinism, and insulin resistance. Chronic inhibition of opioid tone by the opioid antagonist naltrexone (NTX) is able to reduce the insulin response to an oral glucose tolerance test (OGTT) in hyperinsulinemic PCOS patients. Since insulin and GH may reciprocally influence their secretion and the opioid system may have a role in the pathogenesis of hyperinsulinemia and reduced GH secretion, we have explored the involvement of these neuroendocrine mechanisms in essential obesity and in obesity associated with hyperandrogenism by a long-term treatment with an opiate antagonist. We tested seven obese patients affected by PCOS, seven matched women with essential obesity (EO), and five non-obese control subjects. All patients, in the follicular phase, underwent an OGTT (75 g) and basal hormone assay. Two days later, patients were subjected to a GHRH test. The patients then had 4 weeks of treatment with NTX 50 mg/d. Following continuation of the treatment, OGTT and GHRH tests were repeated. Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) plasma concentrations were also determined in the basal condition before and after NTX treatment. NTX treatment reduced fasting insulin levels in patients with EO (P < .05) and restored a normal GH response to GHRH without affecting IGF-1 and IGFBP-3 levels. In PCOS subjects, NTX reduced the insulin response to a glucose load and failed to modify the blunted GH response to GHRH. Our data suggest a significant difference in opioid system function in PCOS and EO subjects, indicating a particular form of obesity in PCOS. The opiate antagonist treatment in EO may act through the reduction of negative insulin feedback on GH secretion. In PCOS patients, the failure to improve GH secretion in obese hyperandrogenized patients may be related to a high opioidergic tone or to the inhibitory predominance of other neurotransmitters.

Adult↗

Hypothalamic dopaminergic tone and prolactin bioactivity in women with polycystic ovary syndrome.

BACKGROUND: The present study was carried out to investigate the functional significance of the reduced dopaminergic tone in subjects affected with polycystic ovary syndrome (PCOS). METHODS: Our group evaluated the response of pituitary PRL, LH, FSH, and TSH to the administration of a single 10-mg oral dose of the dopamine (DA) receptor antagonist metoclopramide in lean (n = 7) and obese (n = 8) PCOS women and in 11 regularly cycling age- and weight-matched controls (six lean and five obese). In addition, circulating PRL bioactivity was evaluated by its mitogenic activity on a lymphoma cell bioassay. RESULTS: Oral administration of metoclopramide resulted in a significant increase in serum PRL in all subjects; however, the highest increments, regardless of body mass index (BMI), were observed in control women (p <0.005). Measurements of PRL mitogenic activity on the Nb2 lymphoma cell bioassay revealed a significant increase in the bioactive/immunoreactive (B/I) ratio of PRL under basal and stimulated conditions in obese PCOS subjects (p <0.05). Mean fasting glucose/insulin and glucose/insulin-AUC ratios were significantly lower (p <0.001) in obese PCOS when compared with all other groups. CONCLUSIONS: These data support the existence of low DA hypothalamic tone in PCOS women that is likely involved in the inappropriate LH and PRL secretion frequently seen in this syndrome. In addition, our results suggest changes in PRL bioactivity in obese PCOS that may play a role in the development of hyperinsulinemia; however, whether PRL has a functional significance in the development of the metabolic disturbances frequently seen in PCOS remains to be elucidated.

Adolescent↗

Mechanisms of hypothalamic-pituitary-gonadal disruption in polycystic ovarian syndrome.

Although the pathogenesis of polycystic ovarian syndrome (PCOS) is still controversial, a series of investigations has demonstrated an array of neuroendocrine abnormalities as a major component of the syndrome. From a neuroendocrine perspective, patients with PCOS exhibit an accelerated frequency and/or higher amplitude of LH pulses, augmentation of LH secretory burst mass, and a more disorderly LH release. Elevated in vitro LH bioactivity and a preponderance of basic LH isoforms, which correlate positively with elevated serum 17-hydroxyprogesterone, androstenedione, and testosterone concentrations, also characterize adolescents with PCOS. Heightened GnRH drive of gonadotropin secretion and a steroid-permissive milieu appear to jointly promote elevated secretion of basic LH isoforms. Positive feedback is implied, because hypersecretion of highly bioactive LH in PCOS probably contributes to inordinate androgen output. However, the precise nature of feedback disruption remains uncertain. Indeed, recent data suggest that PCOS is marked by anomalies of both feedforward and feedback signaling between GnRH/LH and ovarian androgens. From a single hormone perspective, the individual patterns of LH and androstenedione release are consistently more irregular in patients with PCOS. Bihormonal analysis has disclosed concomitant uncoupling of the pairwise synchrony of LH and testosterone, LH and androstenedione, and testosterone and androstenedione secretion. The foregoing ensemble of findings points to deterioration of both orderly uniglandular and coordinate bihormonal output in PCOS. Additional studies are needed to establish the primary pathophysiologic mechanisms underlying this disorder.

17-alpha-Hydroxyprogesterone↗

Higher risk of preeclampsia in the polycystic ovary syndrome. A case control study.

OBJECTIVE: To determine whether the risk of pregnancy-induced hypertensive disorders (PIHD) is higher in patients with the polycystic ovary syndrome (PCOS) than in non-PCOS controls, matched for age and parity. STUDY DESIGN: Retrospective analysis of eighty-one patients with PCOS, consecutively becoming pregnant during a seven-year period. Each PCOS-patient was matched for age and parity with one control patient. Chi-squared, Mann-Whitney or Fisher's exact-tests were used for statistical analysis. RESULTS: Overall incidence of PIHD was similar in both study groups. However, incidence of preeclampsia was significantly higher in patients with PCOS than in controls (P = 0.02). This higher incidence can not be explained by body mass index, endocrine profile before pregnancy, induction of ovulation or treatment regimens. CONCLUSIONS: PCOS-patients are at a significantly higher risk for preeclampsia than non-PCOS controls.

Adult↗

The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks.

Polycystic ovary syndrome is a common problem affecting approximately 5% of women of reproductive age when defined by clinical features of anovulation and hyperandrogenism. Metabolic derangements associated with this condition may predispose to a range of diseases with attendant morbidity and mortality risks. In general, available data support significantly increased rates of type II diabetes mellitus, dyslipidemia, and endometrial cancer in PCOS that are not completely explained by obesity; data also suggest that rates of hypertension, gestational diabetes, and pregnancy-induced hypertension may likewise be increased, although the extent to which obesity mediates these risks is not clear. The increased prevalence of several cardiovascular risk factors in PCOS and limited cross-sectional data suggest that cardiovascular disease should be more likely in PCOS, but prospective data are lacking to confirm this supposition. Limited data have suggested an association between PCOS and ovarian cancer risk and require further study. The present data do not support an increased risk for breast cancer in this condition. Long-term prospective data are clearly needed to better delineate the nature and magnitude of disease risks associated with PCOS, with appropriate adjustment for associated obesity. Such information is a necessary background for understanding the role of established and emerging PCOS therapies, including oral contraceptives, intermittent progesterone, ovulation induction agents, and insulin sensitizers, in modifying such risks. In the meantime, close follow-up of women with PCOS and encouragement of lifestyle practices likely to reduce disease risks, such as regular exercise and weight control, should be standard practice.

Cardiovascular Diseases↗

Fertility concerns and sexual behavior in adolescent girls with polycystic ovary syndrome: implications for quality of life.

OBJECTIVE: To examine the fertility concerns and sexual behavior of adolescent girls with polycystic ovary syndrome (PCOS) as compared to healthy adolescent girls and the effect of these concerns on health-related quality of life. DESIGN AND SETTING: A cross-sectional study of adolescent girls with PCOS (n = 97) and healthy comparisons (n = 186) was conducted at an urban, hospital-based adolescent medicine practice. Participants completed the Child Health Questionnaire Version CF-87 as a measure of health-related quality of life and a general health history questionnaire that included items regarding sexual activity, contraception, fertility concerns, and severity of illness. Findings were evaluated using multivariate logistic and linear regression models. RESULTS: Healthy subjects were 2.8 times more likely to have had sexual intercourse than PCOS participants, though the mean age at initiation of sexual intercourse among sexually active girls was not significantly different between the two groups. Severity of illness and the worry about fertility were not associated with odds of being sexually active. Girls with PCOS were 3.4 times more likely to be worried about their ability to become pregnant than comparisons and concern about future fertility was associated with significant reductions in quality of life. CONCLUSION: Adolescents with PCOS are more concerned about fertility than their healthy peers and this concern may affect their overall quality of life. The finding that more than a third of the adolescents with PCOS in this study were sexually active underscores the importance of providing ongoing counseling on fertility issues, contraception, and STD prevention in the care of adolescent girls with PCOS.

Adolescent↗

[Oocyte and embryo quality in polycystic ovary syndrome].

OBJECTIVE: To compare oocyte and embryo quality in women with Polycystic Ovary Syndrome (PCOS) and in women with normal ovulation. PATIENTS AND METHODS: Forty women with PCOS underwent a total of 67 In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles. The control group consisted of women, of the same age, who underwent IVF (for tubal infertility) or ICSI (for male factor infertility) in the same period. RESULTS: The average number of oocytes recovered was higher in the PCOS group (12,1) than in the control group (9.6) as was the rate of immature oocytes (13.8% vs 5.8%; respectively). The fertilization rate was lower in PCOS patients (52% vs 61% in the controls). The cleavage rates, embryo morphology and pregnancy rates were similar in both groups. DISCUSSION AND CONCLUSIONS: Although more oocytes were recovered from PCOS patients, the number of good quality embryos, suitable for transfer or freezing was similar in the two groups as less of the oocytes were mature and the fertilization rate was lower in the PCOS group. IVF or ICSI (according to the indication) are therefore efficient in PCOS patients.

Cell Count↗

Should insulin-sensitizing drugs be used in the treatment of polycystic ovary syndrome?

Insulin resistance is a central feature of polycystic ovary syndrome (PCOS). Hyperinsulinaemia contributes to anovulation, hyperandrogenism, infertility and early pregnancy loss in women with PCOS. Chronic hyperinsulinaemia also predisposes women with PCOS to increased risks of diabetes and cardiovascular events. Current data indicate that metformin, either as monotherapy or in combination with clomiphene in clomiphene-resistant patients, is an effective treatment for anovulation in PCOS. Initial evidence also suggests that insulin sensitizers may have a role in preventing early pregnancy loss. Of the available insulin-sensitizing agents, metformin has been the agent most frequently studied in PCOS, and has the least undesirable pregnancy safety profile. Ameliorating the metabolic syndrome associated with insulin resistance in PCOS with metformin may also prevent long-term cardiovascular and diabetes complications, pending further evidence. Based on these data, metformin should be a first-line therapy for women with PCOS.

Abortion, Spontaneous↗

Genetics of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a reproductive system disorder characterized by irregular menses, anovulation, clinical and/or biochemical signs of hyperandrogenism (hirsutism and/or acne), ovarian micropolycystic appearance and metabolic abnormalities, such as hyperinsulinaemia and obesity. The aetiopathogenesis of this syndrome is not well known. Several pathogenetic hypotheses have been proposed to explain the full array of symptoms and signs, but with elusive results. A genetic abnormality causing PCOS is supported by the observation that different members of the same family are often affected, and about half of the sisters of PCOS women have elevated serum testosterone concentrations. Therefore, the presence of gene abnormalities in women with PCOS has been widely explored in the attempt to establish whether their mutations or polymorphisms may cause PCOS. The main genes evaluated are those involved in steroidogenesis, steroid hormone effects, gonadotrophin release regulation and action, insulin secretion and action, and adipose tissue metabolism. Despite the vast body of literature produced, none of the genes evaluated seems to play a key role in PCOS pathogenesis. It is likely that PCOS may represent the final outcome of different, deeply inter-related genetic abnormalities that influence each other and perpetuate the syndrome.

Adipose Tissue↗

Assessment of glucose intolerance and insulin sensitivity in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with increased risk of impaired glucose tolerance and type 2 diabetes. PCOS has been considered as a major risk factor for the development of diabetes, and screening of women with PCOS for glucose intolerance is suggested. Detection of glucose intolerance in PCOS is best performed via 2-h oral glucose tolerance test rather than fasting plasma glucose alone, since it enables diagnosis of both impaired glucose tolerance and diabetes. Insulin resistance is a prominent feature of PCOS, although not all women with PCOS have insulin resistance. Measurement of insulin resistance is not included in the diagnostic criteria of the syndrome, and not required for the selection of treatments in current clinical practice. However, this measurement is undoubtedly of great interest for clinical research studies of PCOS. Several methods are available to the clinical investigator for the measurement of insulin resistance, yet there is no universally accepted and clinically useful definition, and no specific guidelines about how to measure it. While hyperinsulinaemic glucose clamp is considered to be the 'gold standard' for the measurement of insulin resistance, several alternative methods have been validated against the gold standard. Each method has its own merits and disadvantages. The choice of method for a particular study should be based on the specific aims, size, and type of that study. Variability in measurement of insulin resistance due to physiological factors, assay-related problems, and protocol differences in dynamic function tests deserves much more emphasis when interpreting the results of a study, or making comparisons between studies.

Female↗

Polycystic ovary syndrome--a systemic disorder?

Polycystic ovary syndrome (PCOS) is the commonest endocrine disturbance affecting women. There is considerable heterogeneity of symptoms and signs amongst women with PCOS and for an individual these may change over time. PCOS is familial and genetics appear to be associated with disturbances of insulin secretion. Polycystic ovaries can exist without clinical signs of the syndrome, which may then become expressed over time. There are a number of interlinking factors that affect expression of PCOS. A gain in weight is associated with a worsening of symptoms whilst weight loss will ameliorate the endocrine and metabolic profile and symptomatology. Women with PCOS are characterized by the presence of insulin resistance, central obesity and dyslipidaemia, which appears to place them at a higher risk of developing diabetes as well as cardiovascular disease. A number of studies have confirmed the higher incidence of diabetes, although they have not shown a higher risk of mortality from ischaemic heart disease (IHD). Cross-sectional studies have demonstrated a significant association between PCOS and IHD. Prospective, long-term longitudinal studies confirming this risk are still awaited. Weight loss remains the most effective first line therapeutic intervention in women with PCOS and recently the use of insulin sensitizing agents has demonstrated benefit.

Cardiovascular Diseases↗

Uterine perfusion and hormonal pattern in patients with polycystic ovary syndrome.

PURPOSE: To evaluate whether polycystic ovary syndrome (PCOS) patients with different pulsatility index (PI) of uterine artery showed differences in their hormonal pattern. METHODS: Eighty-eight PCOS-affected patients and 15 controls were submitted to Doppler flow measurement of uterine artery; LH, FSH PRL, estradiol, and androgens concentration determination; and BMI evaluation during early follicular phase. RESULTS: The mean PI of uterine artery of PCOS patients was significantly higher than control group (2.97 +/- 0.9 vs. 1.89 +/- 0.2 respectively). The distribution of the PI'values was significantly different in the PCOS-affected patients and in control group. The plasma levels of DHEAS and BMI were significantly higher in PCOS patients with PI > or = 3 than in PCOS patients with PI < 3. CONCLUSION: High resistance in the uterine artery is present in PCOS patients, but a wide range PI values of uterine artery is present. BMI and DHEAS seem to be factors interfering with uterine perfusion.

Adult↗

Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms.

OBJECTIVE: To study the association between body size from birth to adulthood and self-reported symptoms of polycystic ovary syndrome (PCOS), particularly hirsutism and menstrual disturbances. DESIGN: Longitudinal, population-based study of a cohort of women born in 1966 in northern Finland. The study population included 2007 women who were not pregnant and did not use hormonal contraception. Of these 528 (26%) had self-reported symptoms of PCOS. RESULTS: Weight at birth, gestational age, being small for gestational age or growth retardation at birth were not associated with PCOS symptoms at 31 y. An increased risk of PCOS symptoms was observed among women with abdominal obesity (waist/hip ratio >85th percentile) at 31 y who had normal weight in adolescence and were overweight (body mass index (BMI) 25.0-29.9 kg/m(2)) or obese (BMI>30.0 kg/m(2)) at 31 y (relative risk (RR) (95% CI) 1.44(1.10-1.89)), and among women with abdominal obesity who were overweight or obese at both 14 and 31 y (1.71 (1.30-2.24)). A total of 30% and 41% of the women with PCOS symptoms in these groups could be attributed, respectively, to overweight, obesity and abdominal obesity at 31 y. CONCLUSIONS: These results suggest that obesity in adolescence and in adulthood, and also weight gain after adolescence, particularly in the presence of abdominal obesity, are associated with self-reported PCOS symptoms in adulthood. Thus, based on the results from intervention studies treating PCOS and the results of this study, the prevention of obesity and abdominal obesity is important among young women.

Adult↗

Dietary intake, physical activity, and obesity in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether dietary intake and physical activity contribute to obesity in women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SUBJECTS: A total of 84 cases and 79 neighborhood controls of similar age. MEASUREMENTS: Fasting insulin, body mass index (BMI, kg/m2), waist/hip ratio, Block Food Frequency Questionnaire, Paffenbarger Physical Activity Questionnaire. RESULTS: Although women with PCOS had a higher BMI than control women, an overall comparison of women with and without PCOS showed no significant difference in dietary intake. However, stratification by BMI revealed that lean women with PCOS reported significantly lower energy intake than lean women without PCOS. CONCLUSION: Differences in dietary intake and physical activity alone are not sufficient to explain differences in weight between women with and without PCOS. Further research is necessary to determine the relative contributions of lifestyle factors and metabolism to obesity in PCOS.

Adult↗

Growth hormone response to GHRH, GHRP-6 and GHRH + GHRP-6 in patients with polycystic ovary syndrome.

OBJECTIVE: Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the underlying mechanisms remain unknown. In recent years considerable attention has been devoted to non-classic GH secretagogues and, in particular, to the series of hexapeptides of which GH-releasing peptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, known as GHRP-6) is the most representative. GHRP-6 seems to be a promising tool for exploring GH secretory mechanisms and it has been reported that GHRH + GHRP-6 is a powerful stimulus to GH secretion. Our aim was to investigate the GH responses to GHRH, GHRP-6 and the administration of GHRP + GHRP-6 in two groups of patients (normal weight and obese) with PCOS in comparison with matched control groups. DESIGN: All subjects were studied three times on different days with GHRH (100 micrograms i.v.), GHRP-6 (90 micrograms i.v.) and GHRH + GHRP-6 (100 micrograms + 90 micrograms). PATIENTS: Sixteen women with PCOS and 22 healthy controls were studied. They were divided into four groups according to BMI: Group A (non-obese PCOS, n = 6, age 21.8 +/- 1.7 years, BMI 22.1 +/- 0.8 kg/m2); Group B: (obese PCOS, n = 10, age 21.7 +/- 1.3 years, BMI 32.9 +/- 2.1 kg/m2); Group C (non-obese healthy women, n = 13, age 26.8 +/- 1.5 years, BMI 21.8 +/- 0.6 kg/m2) and Group D (obese healthy women, n = 9, age 29.4 +/- 4.2 years, BMI 35.7 +/- 1.3 kg/m2). MEASUREMENTS: Serum GH was measured using a time-resolved fluoroimmunoassay (Delphia, Pharmacia). RESULTS: After GHRH administration significant differences were found between GH peaks in Groups A and B (82.4 +/- 16.4 vs 20 +/- 4.9 mU/l, P < 0.05) and in AUC for GH between Groups A and B (4667 +/- 1061 vs 947 +/- 236, P < 0.05) while there were no differences between the same groups in GH peak or AUC after GHRP-6 administration. There were no significant differences in peaks or AUC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined administration of GHRH + GHRP-6 between Groups A and B (211 +/- 26.4 vs 108 +/- 17.6, P < 0.05) as well as between GH AUC in Groups A and B (12068 +/- 2323 vs 5997 +/- 1342, P < 0.05). There were no differences in GH peaks or AUC for GH after GHRH + GHRP-6 administration between Groups A and C or Groups B and D. CONCLUSIONS: The impaired GH response to GHRH found in obese PCOS patients is a consequence of obesity and could be a functional defect, since it can be overridden with GHRP-6 administration.

Adult↗