| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Women’s Exercise and Bone Health Laboratory (M.J.D.S., E.O.), Faculty of Physical Education and Health, University of Toronto, Toronto, Ontario, Canada M5S 2W6; Exercise Endocrinology and Metabolism Laboratory (H.J.L., N.I.W.), Noll Physiological Research Center, Penn State University, University Park, Pennsylvania 16802; and Institute of Toxicology and Environmental Health (B.L.), University of California, Davis, California 95616
Address all correspondence and requests for reprints to: Mary Jane De Souza, Ph.D., FACSM, Women’s Exercise and Bone Health Laboratory, Faculty of Physical Education and Health, 55 Harbord Street, University of Toronto, Toronto, Ontario, Canada M5S 2W6. E-mail: maryjane.desouza{at}utoronto.ca.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Recently, it has been suggested that, in addition to its role in regulating food intake and energy balance, ghrelin may also play a physiological role in reproductive function via actions on LH pulsatility. Furuta et al. (16) recently demonstrated that the intracerebroventricular administration of 0.1 nmol ghrelin rapidly suppressed LH pulse frequency in ovariectomized rats treated with a small dose of 17-ß estradiol. LH pulsatility is controlled by the hypothalamic release of GnRH, primarily from the arcuate nucleus and the ventromedial hypothalamus (17), a region that also expresses GHS-R (2). Ghrelin levels have been shown to be elevated in patients with amenorrhea associated with anorexia nervosa (10, 11) and decreased in women with anorexia nervosa during weight gain (12). The known metabolic actions of ghrelin, combined with a potential role in the modulation of reproductive hormone secretion, make it reasonable to suspect that ghrelin may play a physiological role in the suppression of reproductive function via hypothalamic suppression of GnRH release in women with exercise-associated menstrual disturbances. In support of the latter idea, existing evidence clearly shows a strong association between energy deficiency and menstrual disturbances in physically active women (18, 19, 20, 21, 22), and evidence exists that low energy availability plays a causal role in the induction of exercise-associated amenorrhea (23, 24). However, the relationship of ghrelin levels to menstrual disturbances, including amenorrhea, in exercising women has not been evaluated to date. The primary purpose of this study was to examine ghrelin levels in physically active women who differ in menstrual status and metabolic status.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This study used a prospective observational design to explore the relationship between ghrelin and other metabolic hormones in women of differing menstrual status. The metabolic hormones include total T3, leptin, and insulin. Blood samples previously collected from subjects in whom metabolic hormones and menstrual status were carefully documented over three menstrual cycles (18, 19) were analyzed for ghrelin and compared with levels of metabolic hormones and ghrelin in blood samples from amenorrheic subjects from a new cohort of subjects.
Subjects
This study was approved by the New Britain General Hospital Institutional Review Board, the University of Connecticut Health Center Institutional Review Board, and the University of Toronto Human Ethics Committee. Specific admission criteria have been previously published (18, 19). Forty subjects participated in this study on ghrelin; 32 women were from the original cohort study on menstrual and metabolic status previously published (18, 19), and eight amenorrheic subjects were tested in association with a different cohort of subjects from the University of Toronto meeting identical admission criteria, except that they had not menstruated for at least 3 months.
Training status
Daily training activities were recorded throughout the study. Distance, duration, and heart rate at the termination of exercise were also recorded. Exercise training volume was defined as minutes of activity per week, as recorded on the training logs. Other physical activity performed for 3 or more sustained minutes was also recorded. Weight, menstrual patterns, nutritional and training habits, and any unusual stress events (self report) that might affect ovulatory function were monitored throughout this study. Subjects were weighed weekly.
Blood sampling
Overnight fasting blood samples were drawn between d 2–9 of the menstrual cycle in eumenorrheic subjects and weekly for two 30-d periods in the amenorrheic subjects. All serum analyses were made from these samples. Blood samples were processed according to previously described procedures (18, 19). Samples had not been previously thawed and sample pH was determined to be in the physiological range.
Menstrual categorization
Menstrual calendars were used 1 month before the study and for the duration of the study to record the first and last day of menses for each cycle. Women who had menstrual cycles of less than 20 d or greater than 38 d during the 3-month monitoring period were excluded from these data analyses. For this substudy on ghrelin levels, 10 sedentary and 22 exercising subjects from the previously published studies (18, 19) and eight exercising amenorrheic women from a different cohort were included in this study on ghrelin.
Determination of menstrual status
Menstrual status in eumenorrheic subjects was determined using previously published methods (18, 19). Daily urine samples were assayed for creatinine, LH, pregnanediol-3-glucoronide (PdG), and estrone conjugates (E1C). Menstrual status was determined in amenorrheic subjects by analysis of LH, estradiol, and progesterone from weekly fasting blood samples.
Determination of ovulatory status, day of ovulation, and menstrual cycle phases
Ovulatory status was determined for all subjects using criteria previously published in detail (19, 25). Menstrual cycle length, follicular phase length, and luteal phase length were determined as reported previously (18, 19). LPD was defined as short when a luteal phase length was less than 10 d or as inadequate when peak PdG excretion was less than 1.5 µg/µmol creatinine for 3 or more midluteal phase days (26, 27, 28, 29, 30). Luteal phase adequacy was further examined using several methods, as modified from Jordan et al. (26) in serum and from others in urine (28, 29, 30), including the sum of the 3-d midluteal peak PdG (sum of midluteal peak PdG ± 1 d). E1C and PdG were compared among the cycles by the method of mean steroid levels described by Winters et al. (27). An anovulatory cycle was defined as a cycle in which no increase in E1C was observed in concurrence with a failure of LH to rise at midcycle and no subsequent increase in PdG excretion.
Urine hormone measurements
The validity of the urine technique as representative of the 24-h pattern of E1C and PdG excretion has been reported by other investigators (25, 27, 28). Urine samples were normalized to creatinine excretion and analyzed for E1C and PdG by enzyme immunoassay as described by Munro et al. (28), and data are published elsewhere (18, 19).
Serum hormone measurements
Ghrelin was determined by RIA (Linco Research, St. Charles, MI). The intraassay and interassay coefficients of variation for the high control were 2.72 and 16.7%, respectively; the intraassay and interassay coefficients of variation for the low control were 1.19 and 14.7%, respectively. The sensitivity of the ghrelin assay is 2.96 pmol/liter.
Leptin was determined using an ELISA method (Linco Research). The sensitivity of the leptin assay was 0.05 µg/liter. The intraassay and interassay coefficients of variation were 3.8 and 4.4%, respectively.
Total T3, insulin, and serum reproductive hormones were analyzed using a chemiluminescence-based immunoassay analyzer (Immulite; Diagnostic Products Corporation, Los Angeles, CA). The analytical sensitivity of the total T3 assay was 0.54 nmol/liter. The intraassay and interassay coefficients of variation for the total T3 assay were 9.7 and 8.7%, respectively. The analytical sensitivity of the insulin assay was 13.89 pmol/liter. The intraassay and interassay coefficients of variation were 4.8 and 5.8%, respectively. The analytical sensitivity of the estradiol assay was 55 pmol/liter. The intraassay and interassay coefficients of variation were 8.6 and 9.5%, respectively. The analytical sensitivity of the progesterone assay was 0.3 nmol/liter. The intraassay and interassay coefficients of variation were 5.9 and 5.6%, respectively. The analytical sensitivity of the LH assay was 0.1 mIU/liter. The intraassay and interassay coefficients of variation were 10.6 and 8.1%, respectively.
Peak exercise testing
Peak oxygen uptake (VO2) was determined by measurement of expired metabolic gases using previously published methods (18, 19). Expired air samples were measured using an online Medical Graphics Exercise System 2000 (Medical Graphics, St. Paul, MN) for the menstruating subjects and a Moxus Modular VO2 System (Applied Electrochemistry Inc., Pittsburgh, PA) for the amenorrheic subjects.
Body mass and composition testing
Total body mass was measured to the nearest 0.1 kg on a physician’s balance scale (Detecto, Webb City, MO). Body mass index (BMI) was calculated as weight divided by height squared (kg/m2). For the menstruating subjects in Connecticut, body fat was determined using triplicate skinfold measurements by one investigator (test-retest, r = 0.96) at various sites including the tricep, subscapula, iliac crest, abdomen, and thigh with a constant-pressure skinfold caliper (Holtain Ltd, Crymych, UK) (31) because dual-energy x-ray absorptiometry total body software was not available at that site. For the amenorrheic subjects at the University of Toronto, body fat was determined using dual-energy x-ray absorptiometry measurements using a total body scanner (enCORE 2002 software, version 6.50.069; General Electric Lunar Corporation, Madison, WI). This instrument has a precision of less than 1% coefficient of variation for the total body composition measurements. The separation of soft tissue into fat (g) and lean tissue (g) was based on the attenuation ratio of high-energy and low-energy photons. Fat-free mass (g) was calculated as the sum of lean tissue and bone mineral content (g).
Statistical methods
Data for demographics, menstrual cycle characteristics, and reproductive hormones were analyzed using one-way ANOVA, with individuals grouped according to the predominant menstrual cycle status they exhibited and whether or not they were sedentary or exercised, i.e. sedentary ovulatory (SedOvul), exercising ovulatory (ExOvul), exercising luteal phase defect/anovulatory (ExLPD/Anov), or exercising amenorrheic (ExAmen). When comparing whether metabolic hormones differed between menstrual cycles of different status, a mixed-model ANOVA, accounting for the fact that cycles from a given individual may fall into more than one menstrual cycle category, was used. When a significant main (fixed) effect was observed, Student’s t tests were used with a Bonferroni correction for multiple comparisons to determine where the significant differences existed. Analysis of covariance was used to test whether differences in leptin between groups differing in menstrual status depended on percent body fat. Pearson-product moment correlation analysis was used to examine relationships among variables. Data were analyzed using the Statistica (Statsoft, Tulsa, OK) and SPSS (SPSS Inc., Chicago, IL) software packages. A significance level of P < 0.05 was used to detect the differences for all statistical procedures.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The demographic characteristics of the study participants are presented in Table 1
. Subjects in the ExLPD/Anov and ExAmen groups were significantly younger than the subjects in the ExOvul group (P < 0.05). Height, weight, BMI, and percent body fat were not significantly different among the groups, although there was a trend for the ExLPD/Anov and ExAmen groups to have lower fat mass (P < 0.07). As expected, VO2 peak was significantly higher in the exercise groups compared with the SedOvul group. The body weight of the subjects did not differ (P > 0.05) from week to week across the menstrual cycles monitored (data not shown).
|
Within the exercise groups of women, exercise time was spent in weight-bearing physical activities such as bicycling, step machine, walking or running, resistance training, hiking, tennis, biking, and racquetball. The volume of exercise performed by these subjects was typical of moderate or recreational runners (eumenorrheic subjects, 5.0 ± 0.7 h/wk; and amenorrheic subjects, 6.2 ± 1.0 h/wk).
Subject classification
The sample population consisted of a cohort of women who were initially classified as either sedentary eumenorrheic women (performing no more than 1 h of aerobic exercise per week for the past 12 months, with a peak VO2 of less than 35 ml/kg/min) or exercising women (performing at least 2 h of exercise for the past 12 months, with a VO2 peak greater than 35 ml/kg/min). All subjects completed a maximal exercise test to exhaustion to document peak aerobic power (VO2 peak).
All eumenorrheic subjects were subsequently classified after a two- or three-cycle prospective evaluation of training status (determined by analysis of training diaries) and menstrual status (determined by hormonal evaluations) during a 2- or 3-month study period. For training status, the following two general categories were used: sedentary and exercising. For ovulatory status and determination of luteal phase status, previously published criteria were used (26, 27). Based on these criteria, individual menstrual cycles were classified as ovulatory, luteal phase deficient (LPD), or anovulatory. Confirmation of amenorrheic status in those subjects self-reporting the absence of menses was made from the analysis of LH, estradiol, and progesterone in weekly blood samples over the 60-d period of observation. Individuals were assigned to groups of menstrual status based on the predominant classification of the menstrual cycles observed for each individual, as previously described (19). Individuals with either three out of three or two out of three cycles from one category were placed in that category. The four combined categories of exercise and menstrual cycles evaluated were as follows: sedentary women (n = 10 subjects) with ovulatory menstrual cycles (SedOvul, n = 26 cycles), exercising women (n = 11 subjects) with ovulatory menstrual cycles (ExOvul, n = 22 cycles), exercising women (n = 11) with LPD and/or anovulatory menstrual cycles (ExLPD/ANOV, n = 27), and exercising women (n = 8) with amenorrhea (ExAmen, n = 16 cycles) (30-d periods of observation). One sedentary woman with LPD menstrual cycles (n = 3 cycles) was excluded from this study because the LPD cycles observed did not meet the SedOvul group status. Two exercising women with ovulatory and LPD cycles (n = 3) were also excluded from data analyses for this study when inadequate volumes of serum were available for the ghrelin assays.
Menstrual cycle categorization and characteristics
The menstrual cycle parameters are presented in Table 2. Thirty-five women participated in the prospective evaluation of menstrual status, which was previously published (19). For this substudy examining ghrelin, 10 sedentary and 30 exercising subjects, in whom ghrelin measurements were obtained, were included. For menstrual category comparisons, women were classified according to the predominant menstrual cycle type (ovulatory, LPD, or anovulatory) that they displayed in at least two of the three or two of the two menstrual cycles that were evaluated. The sedentary group included 10 women; six had three of three and four had two of two ovulatory menstrual cycles. These 26 menstrual cycles comprised the SedOvul categorization of menstrual cycles. The exercising women included 11 women with 22 menstrual cycles that comprised the ExOvul category of menstrual cycles; three women had three of three, two women had two of two, five women had two of three, and one woman had one of two ovulatory menstrual cycles. The exercising women also included nine women with 20 menstrual cycles that comprised the ExLPD category of menstrual cycles; four women had three of three, one woman had two of two, three women had two of three, and one woman had one of two LPD menstrual cycles. The subject groups were similar with respect to age of menarche (Table 2), but gynecological age was significantly lower in the ExLPD/Anov and Ex/Amen vs. the SedOvul groups (P < 0.05) due to their lower chronological age (P < 0.05). Although menstrual cycle length was similar among eumenorrheic subjects, the ExOvul subjects had a significantly longer follicular phase than both the SedOvul and ExLPD/Anov groups. As expected, luteal phase length was significantly shorter in the ExLPD/Anov group. The self-reported duration of amenorrhea in the amenorrheic subjects was 8.1 ± 0.9 months.
|
Concentrations of E1C excretion are presented in Table 3. E1C was significantly lower in the follicular and luteal phases of the ExLPD/Anov group compared with the SedOvul and ExOvul groups (P < 0.05). Concentrations of PdG excretion are presented in Table 3. The ExLPD/Anov category of cycles had significantly lower luteal phase PdG levels and a lower 3-d sum of PdG when compared with concentrations in the SedOvul and ExOvul groups; similarly, the ExOvul category had significantly lower PdG concentrations in these same two categories of PdG excretion (P < 0.05) than the SedOvul group. These characteristics are consistent with suppressed luteal phase production of progesterone in exercising women (19).
|
In the ExAmen subjects, serum concentrations of estradiol remained constantly low and less than 30 pg/ml (110 pmol/liter), which is consistent with suppression of follicular development. Serum LH levels remained less than 10 mIU/liter (10 mIU/ml), confirming the absence of ovulation. The amenorrheic subjects failed to demonstrate any evidence of luteinization because levels of serum progesterone were less than 1 ng/ml (3.18 nmol/liter) (26). These reproductive hormone concentrations confirm the amenorrheic status of these subjects.
Ghrelin
Ghrelin concentrations were approximately 100% higher in the ExAmen group, whereas no differences in concentrations existed across all other menstruating groups, as shown in Fig. 1. Regression analyses to examine the contribution of menstrual status to the variance in ghrelin concentrations revealed that menstrual status explained 24.8% of the variance in ghrelin concentrations (P < 0.001; ß = 0.42). When all subjects are included and, thus, all menstrual cycle and exercise categories represented, Pearson correlation analyses revealed that a moderate to weak negative correlation existed between ghrelin and total T3 (r = –0.321, P = 0.049). Ghrelin was not significantly correlated with either leptin (r = –0.039, P = 0.818) or insulin (r = –0.150, P = 0.445). Ghrelin was not correlated with body weight (r = –0.131, P = 0.435), BMI (r = –0.105, P = 0.531), fat mass (r = –0.178, P = 0.284), or fat-free mass (r = –0.249, P = 0.176).
|
Total T3 was significantly lower in both the ExOvul and ExLPD/Anov groups when compared with concentrations in the SedOvul group (Table 4). However, concentrations in ExAmen were significantly lower than all other groups. Leptin was significantly lower in all exercising groups when compared with the SedOvul group. An analysis of covariance, with percent body fat selected as a covariate, revealed that leptin concentrations remained significantly different between the SedOvul group and all other groups (P < 0.05). Insulin was significantly lower in ExLPD/Anov and ExAmen groups when compared with the ExOvul and SedOvul groups.
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The observed elevation of fasting ghrelin in our amenorrheic athletes is similar to numerous observations of elevated ghrelin with amenorrhea that accompanies anorexia nervosa (11, 12, 32) and, thus, may be explained by the mutual association of the two conditions with chronic energy deficiency. In contrast to healthy women, anorexic patients do not exhibit the typical fall in plasma ghrelin levels after a standardized or fiber meal (even 2 h after the meal), representing an impaired ghrelin response to an acute meal (32). Presumably, the single meal is inadequate to restore energy homeostasis, and thus, ghrelin levels remain elevated to force an ongoing peripheral signal in the direction of energy intake. Nedvidkova et al. (32) suggest that these findings in anorexic patients represent an adaptive metabolic strategy secondary to prolonged food restriction and inadequate energy stores that attempts to restore normal feeding patterns by maintaining the drive to eat. When anorexic patients regain body weight and replenish energy stores, decreased ghrelin levels are observed (12), presumably indicating more adequate energy stores and weight regain that may possibly restore the normal acute ghrelin response to a meal. Whether amenorrheic athletes exhibit a similarly impaired ghrelin meal response remains to be determined.
Fasting ghrelin levels in obese and anorexic individuals are inversely correlated with body energy stores (7, 9, 11, 12). One possible explanation for this is that ghrelin acts as a compensatory mechanism to return individuals to a body weight set point. In this study, subjects in groups of differing menstrual status were similar in body weight, BMI, and body composition, perhaps limiting the opportunity to observe a correlation with ghrelin in such a homogenous subject sample. When compared with the results for insulin, leptin, and T3, the disproportionately high ghrelin levels in amenorrheic athletes suggest that ghrelin may be unique in reflecting a prolonged chronic state of chronic energy deficiency that is no longer effecting changes in body weight and composition but is associated with a strong signal to increase food intake and return body weight and body composition to its original state of energy homeostasis. Although detailed information about energy balance, weight, and dieting history was not gathered in the current study, it would be interesting to know whether the subjects in the amenorrheic group differed in their current state of energy balance, weight, level of body fat stores, or resting energy expenditure, representing deviations from earlier, higher levels. If the latter were true, it might indicate that ghrelin is acting to return an individual to some weight, metabolic, or body composition set point. In support of this, studies have reported that amenorrheic athletes report higher scores for cognitive restraint (33), a subscale of the Three Factor Eating Questionnaire (34) that indicates a conscious restriction of calories that presumably overrides normal physiological signals of hunger. Although data pertaining to estimates of energy balance are not available in our amenorrheic subjects, it is interesting to note that, in comparison to similar studies in amenorrheic athletes (20, 22), our subjects exhibit a lower maximum VO2 and a lower weekly training volume. In light of this, it is possible that chronic energy deficiency in our subjects may be more due to a lower than expected dietary intake that may be secondary to cognitive restraint (34) than a high exercise energy expenditure. In fact, data collected only in the amenorrheic subjects in this study revealed that the average score for this subscale (34) was in the clinical range, i.e. greater than 14. Whether a difference in how an energy deficit is created, i.e. increased exercise energy expenditure vs. decreased food intake, corresponds to differences in ghrelin concentrations is unknown.
The association of elevated fasting ghrelin levels with a state of inadequate energy availability in the amenorrheic athletes is supported by associated changes in insulin, T3, and leptin, and strong corroboration for disruptions in energy homeostasis with exercise-associated disturbances comes from numerous previous studies (18, 19, 20, 21, 23, 35, 36, 37). These studies support the existence of metabolic and endocrine adaptations to conserve energy in the face of inadequate energy intake. These adaptations include lower resting metabolic rates (35, 36), low plasma glucose levels (22), low T3 (20), low insulin (22), low leptin (38), low IGF-1 (22) and low IGF-1/IGF binding protein-1 (22) and increased levels of human GH (22, 37) and cortisol (39, 40). These hormonal and metabolic shifts are also observed in other nonathletic women with functional hypothalamic amenorrhea and are also secondary to self-imposed severe nutritional restrictions, particularly of dietary fat (41, 42).
Although many of the endocrine and metabolic alterations in exercise-associated amenorrhea represent changes in key metabolic signals that have been shown to modulate GnRH neuronal activity in human and animal studies examining the link between metabolism and reproduction (43), a direct causal relationship between one or several of these factors and exercise-associated amenorrhea has not been established. Interestingly, intracerebroventricular administration of ghrelin has been shown to rapidly suppress LH pulse frequency in ovariectomized rats (16). Ghrelin has also been found in the hypothalamus (44), and in the rat, GHS-R receptors have been found the arcuate nucleus (45, 46). If evidence for ghrelin as a modulator of the reproductive axis continues to mount, the finding in this study that elevated ghrelin levels uniquely discriminated the amenorrheic athletes from those with less severe menstrual disturbances may represent an important contribution to the potential role for ghrelin in the complete suppression of reproductive function in extreme states of chronic energy deficiency. Future studies examining whether changes in both fasting- and meal-related responses in ghrelin correlate with the development of exercise-associated menstrual disturbances will undoubtedly unravel the relationship between this important regulator of energy homeostasis and reproductive function.
|
Footnotes |
|---|
Received November 18, 2003.
Accepted March 1, 2004.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
-glucuronide in early morning urine samples to monitor ovarian function. J Biolumin Chemilumin 4:567–574[CrossRef][Medline]
This article has been cited by other articles:
 |
|
 |
|
  N. R Vulliemoz, E. Xiao, L. Xia-Zhang, J. Rivier, and M. Ferin Astressin B, a Nonselective Corticotropin-Releasing Hormone Receptor Antagonist, Prevents the Inhibitory Effect of Ghrelin on Luteinizing Hormone Pulse Frequency in the Ovariectomized Rhesus Monkey Endocrinology, March 1, 2008; 149(3): 869 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Z. Kasa-Vubu, A. Rosenthal, E. G. Murdock, and K. B. Welch Impact of Fatness, Fitness, and Ethnicity on the Relationship of Nocturnal Ghrelin to 24-Hour Luteinizing Hormone Concentrations in Adolescent Girls J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3246 - 3252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. I. Williams, S. L. Berga, and J. L. Cameron Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E270 - E276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Germain, B. Galusca, C. W Le Roux, C. Bossu, M. A Ghatei, F. Lang, S. R Bloom, and B. Estour Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin Am. J. Clinical Nutrition, April 1, 2007; 85(4): 967 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Kraemer and V. D. Castracane Exercise and Humoral Mediators of Peripheral Energy Balance: Ghrelin and Adiponectin Experimental Biology and Medicine, February 1, 2007; 232(2): 184 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M J De Souza, J Alleyne, J D Vescovi, N I Williams, J L VanHeest, and M P Warren Correction of misinterpretations and misrepresentations of the female athlete triad Br. J. Sports Med., January 1, 2007; 41(1): 58 - 59. [Full Text] [PDF]
|
|
|
|
|
|
A. B. Loucks The Response of Luteinizing Hormone Pulsatility to 5 Days of Low Energy Availability Disappears by 14 Years of Gynecological Age J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3158 - 3164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Vulliemoz, E. Xiao, L. Xia-Zhang, M. Germond, J. Rivier, and M. Ferin Decrease in Luteinizing Hormone Pulse Frequency during a Five-Hour Peripheral Ghrelin Infusion in the Ovariectomized Rhesus Monkey J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5718 - 5723. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
