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Reproductive Medicine Unit (L.J.M., L.T., R.J.N.), Department of Obstetrics and Gynaecology and Departments of Medicine (G.A.W., N.D.L.) and Psychiatry (C.G.), The University of Adelaide, Adelaide, South Australia, Australia 5000; and Commonwealth Scientific and Industrial Research Organization Health Sciences and Nutrition (L.J.M., M.N., P.M.C.), Adelaide, South Australia, Australia 5000
Address all correspondence and requests for reprints to: CSIRO Health Sciences and Nutrition, P.O. Box 10041 BC, Adelaide, South Australia, Australia 5000. E-mail: lisa.moran{at}csiro.au.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Ghrelin is a 28-amino acid acylated peptide produced primarily by the endocrine cells in the stomach (6). It stimulates GH secretion through its action as an endogenous ligand for the hypothalamic-pituitary GH secretagogue receptor. In addition, it is implicated as an important regulatory peptide in food intake, body weight regulation, endocrine pancreatic function, glucose metabolism, and ovarian function (7, 8). Ghrelin levels increase sharply before feeding onset (9, 10, 11, 12) and stimulate hunger and food intake (13, 14, 15) via action on the hypothalamic arcuate nucleus (16). Once feeding commences, either the presence of nutrients in the gut or the metabolic response to feeding leads to the suppression of ghrelin and a resultant change in appetite (9, 10, 11, 12). Fasting ghrelin levels are lower in obese individuals (17), an appropriate response to chronic positive energy balance, and increase with weight loss (10). There is some suggestion that the decrease in ghrelin after a meal may be impaired partially or fully in obesity (12). This may play a role in the pathophysiology of obesity through compromised meal termination and increased food consumption. Additional factors such as leptin, cholecystokinin, and peptide YY may also play a role in the regulation of energy homeostasis, appetite, and ghrelin (18).
In PCOS, fasting ghrelin is decreased, compared with controls in some (19, 20) but not all studies (21). Furthermore, plasma ghrelin is lower in Pima Indians, a population predisposed to obesity, compared with age- and weight-matched Caucasians (17). Postprandial ghrelin has not previously been examined in either of these populations. It is unclear whether ghrelin homeostasis is impaired in PCOS. The effect of varying dietary composition on ghrelin secretion has not been examined extensively in humans. High-protein diets have been proposed to aid in weight loss (22) through an increased satiating effect of dietary protein, compared with carbohydrate or fat (23). It is unknown whether this satiating effect is mediated through ghrelin. A greater suppression of postprandial ghrelin was observed for a high-carbohydrate diet, compared with an isocaloric high-fat meal (24) and diet (25).
The objectives of this study were to determine the effects of standard or high-protein diets on weight loss, body composition, leptin, glucose and insulin homeostasis, and fasting and postprandial ghrelin in women with or without PCOS and to determine the relationship among satiety, PCOS status, diet composition, leptin, and changes in ghrelin homeostasis.
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Subjects and Methods |
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Previous study cohorts were used to select a subset of premenopausal overweight [body mass index (BMI) > 25 kg/m2] women with PCOS (26) and without PCOS (27). From these studies, 20 overweight women with PCOS and 12 overweight women without PCOS matched for weight and BMI were chosen for further comparison of selected hormonal variables. As a result of this selection, we were unable to completely control for age. Diagnosis of PCOS was by menstrual irregularity (cycle length < 21 or > 35 d or variation between consecutive cycles of > 3 d) and clinical (hirsutism/acne) and/or biochemical hyperandrogenism (28). Hyperandrogenism was defined from a range obtained from a representative population of non-PCOS women (n = 80). Clinical hyperandrogenism was assessed initially by self-reported hirsutism and confirmed by the Ferriman-Gallwey score with a score greater than 8, indicating hirsutism (29). PCOS and non-PCOS status was confirmed for all subjects based on these criteria, and all non-PCOS subject displayed menstrual regularity. All subjects were of European Caucasian descent. All subjects gave informed consent for the studies, which were approved by the Human Ethics Committees of The Commonwealth Scientific and Industrial Research Organization (26, 27), The Royal Adelaide Hospital (27), and The North West Adelaide Health Service (26). Inclusion and exclusion criteria have been described previously (26, 27).
Study design
Subjects were stratified to ensure equal distribution for known confounding factors of weight, age, and desire to conceive (for the PCOS subjects) and fasting serum insulin concentrations at screening, BMI, and age (for the non-PCOS subjects). The two groups were then randomized by an independent observer to one of two diets: 1) standard protein (SP) (15% of daily energy as protein, 55% carbohydrate, and 30% fat) or 2) high protein (HP) (30% of daily energy as protein, 40% carbohydrate, and 30% fat). Energy intake was restricted (
6000 kJ/d) for 12 wk. Thereafter, subjects were placed on a weight-maintenance diet of the same macronutrient composition for 4 wk. Both diets were nutritionally complete and had a similar fatty acid profile. Alcohol was not permitted. Ten PCOS and six non-PCOS women were on the HP diet and 10 PCOS and six non-PCOS women were on the SP diet.
Subjects attended the outpatient clinic on two consecutive days monthly. At wk 0, 12, and 16, venous blood samples assessed for insulin, glucose, and ghrelin were taken after an overnight fast. The homeostasis model assessment (HOMA) was used as a surrogate measure of insulin sensitivity [fasting insulin (mU/liter) x fasting glucose (millimoles per liter)/22.5] (30). At all visits, subjects were weighed in light clothes with no shoes (Mettler scales, model AMZ14, A&D Mercury, Kinomoto, Japan), and BMI was calculated by weight (kilograms) divided by squared height (square meters).
At wk 0 and 16, a 3-h meal tolerance test (MTT) was performed with a 2700 kJ test meal using the allocated diet with equivalent energy densities (11% protein, 15% fat, and 76% carbohydrate for the SP and 31% protein, 14% fat, and 55% carbohydrate for the HP diet). Fasting venous blood was taken for measurement of insulin, glucose, and ghrelin (time 0). Subjects were then required to consume the meal within 20 min, and further blood samples were taken for assessment of insulin and glucose at 60, 120, and 180 min and ghrelin at 60 and 120 min. Subjective hunger, fullness, satiety, and desire to eat were assessed using a validated 10-cm linear scale visual analog scores (VAS) immediately before eating and at 60, 120, and 180 min (31). The change in ratings from baseline was quantified (32, 33). A more positive value for satiety and fullness indicates greater satiety and fullness and a more negative value for hunger and desire to eat indicates lesser hunger and desire to eat. Postprandial ghrelin was measured as the change in ghrelin from 0 to 120 min.
Dual x-ray absorptiometry (Norland Medical Systems Inc., Fort Atkinson, WI) was performed at wk 0 and 16 to assess body fat composition as previously described (fat mass of soft tissue and lean mass of soft tissue) (coefficient of variation of 2.3 ± 0.9% for total fat mass and 2.1 ± 0.4% for lean tissue mass) (26, 27). The PCOS subjects attended a weekly exercise/education class (5, 34, 35) and were advised to increase exercise to a minimum of three times per week. Exercise levels were documented at baseline, monthly, and study completion and categorized according to National Health and Medical Research Council Standards (36). The non-PCOS subjects were asked to continue their usual physical activity levels throughout the study, and physical activity levels were not recorded.
Dietary intervention
The dietary intervention has been described previously (26, 27). At wk 0 and 16, dietary compliance was determined by subject adherence to the macronutrient profiles (protein, carbohydrate, fat) and from assessment of random urine samples (26) and 24-h urine samples (27) for urea excretion relative to urine creatinine.
Biochemical measurements
SHBG, total testosterone (bound and unbound), insulin, glucose, thyroid stimulating hormone, prolactin, and 17
-hydroxyprogesterone were measured as previously described (26). Serum leptin was measured with a commercially available ELISA kit (Diagnostic System Laboratories, Inc, Webster, TX) and serum ghrelin (total including Ser3-octanoyl and Ser3-des-octanoyl) was measured with a commercially available RIA kit (Phoenix Pharmaceuticals, Inc, Belmont, CA) with inter- and intraassay coefficient of variation less than 6.2% and sensitivity or least detectable amount 10 pg/ml (2.96 pmol/liter) for ghrelin and 0.05 ng/ml (0.004 nmol/liter) for leptin.
Statistics
All data are presented as means ± SEM. Two-tailed statistical analysis was performed using SPSS for Windows 10.0 software (SPSS Inc, Chicago, IL) with statistical significance set at an alpha level of P 
0.05. Baseline measurements were assessed using one-way ANOVA. Comparisons between time points were assessed using repeated-measures ANOVA with diet and PCOS status as between-subject factors. However, there was no difference in weight loss or metabolic, leptin, and ghrelin responses to weight loss between subjects with and without PCOS depending on diet. The analysis was therefore confined to the effect of diet or PCOS status on the observed variables.
In the event of an interaction, post hoc pairwise comparisons were performed. Relationships between variables were examined using bivariate and partial correlations, analysis of covariance, and multiple linear regression. VAS was analyzed by a four-way repeated-measures ANOVA with week and blood sampling time as the within-subject factors and PCOS status and diet as the between-subject factor. Differences at each blood sampling time were compared by one-way ANOVA. Total areas under the curves (AUCs) for insulin, glucose, and VAS (satiety and fullness) above baseline during the MTT and for total AUC below the curve (hunger, desire to eat) were calculated geometrically (trapezoidal rule) (37). Dietary variables that differed in energy restriction or weight maintenance (polyunsaturated fatty acid, cholesterol, fiber), weight at wk 0, and weight loss over the 16 wk were additionally used as covariates. Where no significant interaction existed between the diet groups, data were combined to compare the PCOS and non-PCOS subjects. One subject did not comply with the intervention (non-PCOS status, HP diet) and her data were used only for baseline comparisons. Weight maintenance dietary composition data are presented for 31 subjects, dual x-ray absorptiometry data are presented for 26 subjects, and VAS data are presented for 29 subjects due to incomplete data.
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Results |
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The study comprised 32 subjects (mean weight 94.5 ± 2.3 kg, mean BMI 35.4 ± 0.9 kg/m2, mean age 35.7 ± 1.1 yr). Baseline characteristics by diet composition and PCOS status are shown in Table 1
, and apart from age there was no difference between groups. HP PCOS had greater abdominal fat mass than HP non-PCOS subjects (P = 0.024) (Table 1).
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Both diets were well tolerated with no adverse events reported. All subjects complied well with the intervention based on urinary urea/creatinine and reported individual macronutrient profiles (previously reported) (26, 27). For the PCOS subjects, exercise levels were similar between the two dietary groups. As designed, protein intake was higher and carbohydrate intake was lower on the HP than on the SP diet during both energy restriction (26.8 vs. 15.9%) and weight maintenance (27.0 vs. 15.6%) (P < 0.001). Minor differences existed between the PCOS and non-PCOS subjects in diet composition for polyunsaturated fat acid intake in energy restriction and fiber intake in weight maintenance (P 0.05). When comparing the SP and HP diets, energy intake was not significantly different in either energy restriction (6.3 ± 0.09 MJ) or weight maintenance (7.75 ± 0.21 MJ) between the two diets. Total fat and saturated fat intake were not different between the two diets in either energy restriction or weight maintenance; however, significant differences existed between the two diets for polyunsaturated fat acid and cholesterol in energy restriction and weight maintenance and fiber in energy restriction (P 0.05).
Weight and body composition
Over the 16 wk, there was no significant difference in weight loss between the SP and HP diets (7.0 ± 0.7 vs. 7.2 ± 0.9 kg) or the PCOS and non-PCOS subjects (7.0 ± 0.8 vs. 7.2 ± 0.6 kg) with a mean weight loss of 7.1 ± 0.6 kg (7.5%) for combined subjects. Weight was maintained during energy balance with a total mean gain of 0.15 ± 0.19 kg and no differences between the SP and HP diets or the PCOS and non-PCOS subjects, indicating good compliance with the weight maintenance regimen. There was no differential effect of diet composition or PCOS status on changes in body composition over the 16 wk, with an overall reduction in BMI (7.5%), total fat mass (13.4%), total lean mass (2.5%), and abdominal fat mass (13.3%) occurring for all subjects (Table
2).
Fasting and postprandial glucose, insulin, and HOMA
There was no effect of diet composition or PCOS status on changes in fasting glucose, insulin, HOMA, or leptin over the study duration (Table 2). There was no effect of diet composition or PCOS status on the area under the insulin curve after the test meal (MTT insulin AUC) at wk 0 or 16 or on the change in MTT insulin AUC with weight loss. The insulin response to the test meal was reduced by 25% after the 16-wk intervention. There was no effect of PCOS status on the area under the glucose curve after the test meal (MTT glucose AUC) at wk 0 or 16. However, the SP meal resulted in a 2.9 times greater AUC at week 0 (P = 0.019) (69.9 ± 16.5 vs. 25.3 ± 8.8 mg/dl·180 min or 3.9 ± 0.9 vs. 1.4 ± 0.5 mmol/liter·180 min) and a 3.4 times greater AUC at wk 16 (P = 0.024) (57.8 ± 12.1 vs. 18.4 ± 11.2 mg/dl·180 min or 3.2 ± 0.7 vs. 1.0 ± 0.6 mmol/liter·180 min), compared with the HP test meal. There was no change in MTT glucose AUC with weight loss (Table 2).
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There was no difference in baseline fasting ghrelin between the HP and SP diets. After the dietary intervention, there was no significant differential effect of diet composition on changes in fasting ghrelin between the SP and HP diets with respective increases of 67.9 ± 26.7 (20.1 ± 7.9) and 120.6 ± 40.7 pg/ml (37.5 ± 11.8 pmol/liter) observed from wk 0 to wk 16 (P = 0.415 for diet x time effect). However, fasting ghrelin was significantly higher by 70.4% in the non-PCOS subjects, compared with the PCOS subjects (P = 0.011) (355.9 ± 60.6 vs. 205.3 ± 23.1 pg/ml or 103.6 ± 17.2 vs. 60.8 ± 6.8 pmol/liter), and non-PCOS subjects had a significantly greater increase in fasting ghrelin, compared with PCOS subjects from wk 0–16 (57.5 vs. 34.0%) (161.7 ± 56.4 vs. 55.8 ± 17.2 pg/ml or 47.9 ± 16.7 vs. 16.5 ± 5.1 pmol/liter) (P = 0.033 for diet x PCOS status effect) (Fig. 1A). Improvement in fasting ghrelin after weight loss occurred in energy restriction. No further changes in fasting ghrelin occurred during the weight maintenance period.
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). VASs
There was no differential effect of diet composition or PCOS status on fasting VAS measures. There was no differential effect of diet composition on the MTT VAS measures. Data were therefore combined to assess subjects with and without PCOS. Figure 2 shows the average hunger, fullness, desire to eat, and satiety response curves for PCOS and non-PCOS groups at wk 0 and 16. There was no significant difference between the PCOS and non-PCOS subjects with regard to changes in MTT VAS AUC scores over time. However, at both wk 0 and 16, the PCOS subjects were significantly more hungry (Fig. 2A, P = 0.007) and less satiated (Fig. 2C, P = 0.001) than the non-PCOS subjects during the MTT. This effect was apparent by 120 min (for satiety at wk 0 and 16) and 180 min (for hunger at wk 0 and 16) (P < 0.05). The non-PCOS subjects had a 2.9 times higher AUC for satiety at wk 0 and a 1.66 times higher AUC for satiety at wk 16, compared with the PCOS subjects (P = 0.003).
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) with a 1.5 times higher AUC at wk 16 (P < 0.001). There was no differential effect of diet composition or PCOS status on any of the fasting VAS values. However, the baseline desire to eat increased from wk 0 to wk 16 (54.8 ± 5.0 to 72.8 ± 4.7 mm) (P < 0.001). Correlations and multiple regressions
Age, fasting insulin, and HOMA did not correlate with any measure of ghrelin or changes in ghrelin. At wk 0, fasting ghrelin correlated with testosterone (r = –0.455, P = 0.009), free androgen index (r = –0.492, P = 0.004), BMI (r = –0.5, P = 0.004), and abdominal fat (r = –0.604, P = 0.001). After correction for BMI at wk 0, fasting ghrelin did not correlate with any of the above variables. Multiple regression analysis showed the best predictor of fasting ghrelin at wk 0 was abdominal fat at wk 0 (r2 = 0.365, P = 0.001). The best predictor of changes in fasting ghrelin from wk 0 to wk 16 was PCOS status (r2 = 0.118, P = 0.033). Fasting ghrelin or changes in fasting ghrelin with weight loss did not correlate with any of the VAS markers. Week 0 MTT ghrelin (0–120 min) correlated with wk 0 VAS fullness (0–120 min) (r = –0.520, P = 0.002). AUC desire to eat at wk 0 correlated with HOMA at wk 0 (r = 0.490, P = 0.004) and insulin at wk 0 (r = 0.482, P = 0.005). Baseline desire to eat at wk 0 correlated with testosterone at wk 0 (r = –0.577, P = 0.001), and hunger at wk 16 correlated with SHBG at wk 16 (r = 0.631, P = 0.005) and weight at wk 16 (r = 0.497, P = 0.006). Fasting leptin correlated with BMI at wk 0 (r = 0.585, P < 0.001) and 16 (r = 0.610, P < 0.001), abdominal fat at wk 16 (r = 0.630, P < 0.001) and total fat at wk 0 (r = 0.573, P = 0.002) and 16 (r = 0.694, P < 0.001).
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Discussion |
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We have confirmed that a 7.5% weight loss in overweight individuals increases fasting ghrelin (10, 42). Similarly Hansen et al. (42) reported a 12% increase in ghrelin after a 5-kg weight loss, although contrary data exist in which there were no increases in either fasting or 24-h AUC ghrelin after a 3.4-kg weight loss in subjects after an ad libitum low-fat, high-carbohydrate diet (25). The variations in weight loss may account for the discrepant results. Reduced ghrelin in obesity (11, 12, 17) and increased ghrelin in weight loss (10, 42) represent appropriate down-regulation and up-regulation of ghrelin in positive or negative energy balance. Ghrelin increases sharply before feeding onset (9, 10, 11, 12) and decreases to reach a trough 1–2 h postmeal (9) consistent with its proposed role in meal initiation and termination. We and other investigators (12) observed impaired ghrelin responses to a test meal in overweight subjects that we found was normalized by weight loss. It is proposed that the chronic positive energy balance of obesity maximally suppresses ghrelin and thus limits further short-term regulation by feeding (12). This is potentially an important consequence of obesity and could influence body weight through compromising meal termination and influencing the size of individual meals, although in overweight individuals, 24-h ghrelin profiles appear not to be impaired (10, 25). It is likely that the shorter time course of our postprandial observation explains this discrepancy because the postmeal ghrelin trough is generally reached by 2 h (9, 10, 11, 12).
After weight loss, subjects displayed a greater desire to eat before the test meal but a reduced desire to eat during the meal, mirroring the observed changes in fasting and postprandial ghrelin. Although we did not observe a direct relationship between subjective measures of hunger and satiety and postprandial ghrelin, a significant relationship has previously been reported (24). It has been proposed that the metabolic changes associated with weight loss (including decreased insulin and leptin and increased ghrelin) increase hunger and decrease satiety, contributing to the reported poor success of long-term weight maintenance (43, 44). Previous investigators have reported increases (43, 45) or no changes (44, 45) in subjective measures of fasting, 24-h, or postprandial desire to eat, hunger, or satiety after weight loss. It can be speculated that although the desire to eat increases in the fasting state after weight loss, appetite regulation after consumption of a meal improves. The effect of this on food intake in postobese subjects is unclear. Postobese subjects may display improved meal termination that could contribute to reduced food intake and improved weight maintenance. Alternatively, Doucet et al. (45) hypothesized that the quality and quantity of foods prepared are likely to be influenced by fasting hunger levels, potentially contributing to passive overconsumption at meal times.
Isocaloric substitution of protein for carbohydrate had no effect on any measures of ghrelin either before or after weight loss. Literature on the effect of varying dietary composition on ghrelin secretion is scarce. Maximal suppression of postprandial ghrelin was observed after substitution of carbohydrate for fat either acutely (24) or after weight maintenance diets (25). Additionally, Erdmann et al. (46) observed an increase in postprandial ghrelin after a high-protein meal, compared with a high-fat or high-carbohydrate meal. It is difficult to determine which macronutrient modulates ghrelin. The effect of weight loss on ghrelin may also be stronger than any effect of diet composition and therefore mask any subtle changes that occur.
Fasting ghrelin has been reported to be decreased in subjects with PCOS, compared with controls (19, 20) but not all studies (21). The reduced fasting ghrelin levels and the relatively smaller increase in ghrelin after weight loss that we have observed in the subjects with PCOS suggest a greater suppression of appetite in obesity and a reduced increase in appetite in weight loss. Moreover, we have now demonstrated that subjects with PCOS are significantly hungrier and less acutely satiated after a test meal. These observations suggest that subjects with PCOS have impaired defenses against overeating and may not have as strong a drive for meal termination as non-PCOS subjects.
The reason for these observed differences in ghrelin between subjects with and without PCOS is unclear. We have confirmed findings that ghrelin negatively correlates with abdominal fat mass (47) and additionally report that abdominal fat was the best predictor of baseline fasting ghrelin. This could indicate a relationship between insulin sensitivity and ghrelin; indeed insulin has been postulated to play an important role in the regulation of ghrelin secretion and feedback (7). However, fasting insulin and HOMA were similar between PCOS and non-PCOS subjects and were not related to any measures of ghrelin. It is thus unclear whether insulin resistance plays a role in ghrelin regulation. Although PCOS status was the strongest predictor for changes in fasting ghrelin with weight loss, no other metabolic variables associated with PCOS (testosterone, SHBG, free androgen index) were related to measures of ghrelin after adjustment for body weight. This has been previously reported (19, 21) although Pagotto et al. (20) reported a negative correlation between androstenedione and ghrelin. Leptin is proposed to be involved in ghrelin regulation (25) and reproductive physiology (48), and some (49) but not all (50) investigators have reported differing fasting levels between women with PCOS and weight-matched controls. Fasting leptin decreased with weight loss as previously reported (43); there was no differential effect of diet composition or PCOS status. Baseline fasting leptin levels were similar between PCOS and non-PCOS weight- and BMI-matched subjects.
In contrast to our findings, however, Pagotto et al. (20) reported that fasting ghrelin was not altered in subjects with or without PCOS after a weight loss of 3.9–10.2 kg after moderate caloric restriction (1200–1400 kcal/d) for 7 months. The reason for these discrepant results is unclear. We did not perform our measurements at a defined stage of the menstrual cycle, and in addition the subjects in the two intervention groups were not perfectly matched.
Nevertheless, this study confirmed that the postprandial ghrelin response is impaired in obesity and that weight loss increases fasting ghrelin levels. Moreover, weight loss restores the impaired postprandial ghrelin response, and subjective measures of desire to eat appear to reflect the changes in fasting and postprandial ghrelin. This study additionally supports previous reports of differences in fasting ghrelin between subjects with and without PCOS, and we have found that ghrelin homeostasis and acute measures of satiety and hunger are significantly impaired in women with PCOS both before and after weight loss. The potential impact of these findings on appetite regulation and the pathogenesis of achieving and maintaining a reduced weight remain to be elucidated.
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Acknowledgments |
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Footnotes |
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Received September 15, 2003.
Accepted March 28, 2004.
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References |
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-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome offer dietary weight loss. J Clin Endocrinol Metab 82:556–560This article has been cited by other articles:
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  T. M Barber, F. F Casanueva, F. Karpe, M. Lage, S. Franks, M. I McCarthy, and J. A H Wass Ghrelin levels are suppressed and show a blunted response to oral glucose in women with polycystic ovary syndrome. Eur. J. Endocrinol., April 1, 2008; 158(4): 511 - 516. [Abstract] [Full Text] [PDF]
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 The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consens Consensus on infertility treatment related to polycystic ovary syndrome Hum. Reprod., March 1, 2008; 23(3): 462 - 477. [Abstract] [Full Text] [PDF]
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 L. J. Moran, M. Noakes, P. M. Clifton, G. A. Wittert, D. P. Belobrajdic, and R. J. Norman C-Reactive Protein before and after Weight Loss in Overweight Women with and without Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2944 - 2951. [Abstract] [Full Text] [PDF]
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D. Glintborg, M. Andersen, C. Hagen, J. Frystyk, V. Hulstrom, A. Flyvbjerg, and A. P. Hermann Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls. Eur. J. Endocrinol., August 1, 2006; 155(2): 337 - 345. [Abstract] [Full Text] [PDF]
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L. J Moran, M. Noakes, P. M Clifton, G. A Wittert, G. Williams, and R. J Norman Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome Am. J. Clinical Nutrition, July 1, 2006; 84(1): 77 - 87. [Abstract] [Full Text] [PDF]
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M. Romon, S. Gomila, P. Hincker, B. Soudan, and J. Dallongeville Influence of Weight Loss on Plasma Ghrelin Responses to High-Fat and High-Carbohydrate Test Meals in Obese Women J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1034 - 1041. [Abstract] [Full Text] [PDF]
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L. J. Moran, N. D. Luscombe-Marsh, M. Noakes, G. A. Wittert, J. B. Keogh, and P. M. Clifton The Satiating Effect of Dietary Protein Is Unrelated to Postprandial Ghrelin Secretion J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5205 - 5211. [Abstract] [Full Text] [PDF]
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D. Panidis, D. Farmakiotis, G. Koliakos, D. Rousso, A. Kourtis, I. Katsikis, C. Asteriadis, V. Karayannis, and E. Diamanti-Kandarakis Comparative study of plasma ghrelin levels in women with polycystic ovary syndrome, in hyperandrogenic women and in normal controls Hum. Reprod., August 1, 2005; 20(8): 2127 - 2132. [Abstract] [Full Text] [PDF]
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) and without PCOS (n = 11; 
) following SP or HP diet for 12 wk of energy restriction and 4 wk of weight maintenance. B, Ghrelin response to a HP or SP MTT (expressed as 
ghrelin from 0 to 120 min) before (wk 0) and after (wk 16) weight loss for subjects with (n = 20, 
). Data are expressed as mean ± SEM and were assessed using a repeated-measures ANOVA with diet or PCOS status as the between-subject factors. Differences at each week were compared by one-way ANOVA. For conversion from picograms per milliliter to picomoles per liter for ghrelin, multiply by 0.296. *, Effect of time, compared with wk 0 (P 
, Significantly greater than PCOS (P 
, Significantly greater change in 
) and after (wk 16;