Effects of short-term strenuous endurance exercise upon corpus luteum function.

PURPOSE: The present study tested whether short-term, abruptly initiated training can cause corpus luteum dysfunction when exercise is limited to either the follicular or luteal phase of the cycle. METHODS: Reproductive hormone excretion and menstrual characteristics were studied in sedentary women who exercised only during the follicular (N = 5) or the luteal (N = 4) phase. Six women served as controls, three of whom exercised at a low volume and three who remained sedentary. Weekly progressive increments in exercise volume continued until either ovulation (follicular group) or menses (luteal group) occurred. Physical activity and nutrient intake were closely monitored with the intent to maintain body weight. RESULTS: No luteal phase disturbances occurred in any of the control subjects, whereas 40% of follicular and 50% of luteal exercisers experienced luteal defects. The proportion of menstrual cycles disrupted was not different between luteal and follicular exercisers (50% vs 30%, respectively) but was significantly greater than the proportion of cycles disrupted in control subjects (P < 0.05). CONCLUSIONS: These results suggest that exposure to abrupt onset of training can alter luteal function, regardless of the menstrual cycle phase in which exercise occurs. This study also demonstrates that a relatively low volume of exercise suffices to induce mild disturbances in luteal function.

Strenuous exercise with caloric restriction: effect on luteinizing hormone secretion.

To test whether strenuous exercise with and without caloric restriction alters LH secretion, and whether these changes are apparent in the immediate post-exercise period, LH pulse parameters were studied in four moderately trained eumenorrheic women over three successive menstrual cycles. Blood samples were obtained 5 h before and 5 h after 90 min of running at 74% VO2max. Each test was preceded by a 7-d treatment of controlled diet and exercise (74% VO2max). During CONTROL, subjects were eucaloric on days 1-7, and performed no exercise on days 5-7. During STTI (short-term training increase), subjects were eucaloric and completed 90 min runs on days 5-7. During DIET/STTI, subjects consumed 60% of the calories necessary to maintain weight on days 1-7, and exercised as in STTI. A significant decrease in overall (0700-1830 h) LH pulse frequency during DIET/STTI compared with CONTROL and STTI treatments was observed. No changes were found in mean serum LH levels or peak amplitude. These results suggest that high-volume training combined with caloric restriction may predispose one to exercise-induced changes in LH pulse frequency, while adequate caloric intake may prevent these changes.

Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women.

OBJECTIVE: Current studies reveal little regarding the inception of exercise-induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic-pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period. SUBJECTS: All subjects were eumenorrhoeic, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid-luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise (VO2max = 38.0 +/- 1.8) (mean +/- SEM) ml/kg/min). DESIGN: All women completed a 13.5-hour pulsatility test which included three consecutive 20-minute runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake (n = 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4.5 hours before and 8 hours after one hour of exercise and or strolling. MEASUREMENTS: A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics. RESULTS: Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude (P < 0.05). Strolling produced no significant changes in LH secretion. CONCLUSION: Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post-exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulse.

Nalmefene enhances LH secretion in a proportion of oligo-amenorrheic athletes.

The influence upon LH secretion of doses of nalmefene, an orally effective congener of naloxone, and a placebo was compared in nine oligo-amenorrheic athletes with that in five regularly menstruating non-athletic women as a test for periodic elevations in hypothalamic opioid tone. After a 360-min control period, LH levels were followed for an additional 360 min following ingestion of the medications in random order approximately six weeks apart, 10-min blood sampling being employed throughout. The mean amplitude post-nalmefene in the athletes was significantly greater than pre (p < 0.05), although there were no differences in the frequency of LH pulses after placebo or nalmefene ingestion. Subjects were labelled as "responders" if their peak AUC after treatment exceeded their pretreatment AUC for LH by more than 1.96 SD (p < 0.05). There were no placebo responders, but 5/9 of the athletes and 1/5 of the menstruating controls were classified as nalmefene responders (p < 0.05). In addition, a variable proportion of the athletes (but none of the controls) experienced symptoms suggestive of narcotic withdrawal 1-4 h after ingesting nalmefene and again 12-18 h later. It appears that demonstrable increases in opioid tone occur at least transiently in a proportion of oligo-amenorrheic athletes.

Changes in body consciousness relate to regularity of exercise training.

Previous work has indicated improvement for scores on self-reported measures of body consciousness as aerobic fitness increased. To test whether exercise sufficient to improve aerobic fitness must be sustained on a regular basis to achieve positive changes in body consciousness, two separate periods of exercise training of 2 or 3 weeks duration were completed by nine female volunteers. The two exercise sessions were separated by 10 days of no exercise. Five women, as controls, did not exercise. Despite significant physiological improvement in the exercisers, no changes in self-perceived body self-consciousness were observed. Such changes may depend on the maintenance of a regular exercise regimen or the magnitude of physiological improvement.

Exercise induces two types of human luteal dysfunction: confirmation by urinary free progesterone.

We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase.

The effects of submaximal endurance exercise upon LH pulsatility.

The acute effects of submaximal endurance exercise (three consecutive 20-min runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake) upon the pulsatile release of LH were compared with those accompanying leisurely strolling for a similar period in seven normally menstruating young women. All trials were conducted during the early to mid-luteal phase, as determined by body temperature patterns, ultrasonic scans of the ovaries, detection of the LH surge in first morning urine specimens, and serial measurements of plasma progesterone. Blood was sampled every 10 min via an indwelling cannula for 8 h before and 12 h after exercise and serum LH measured by radioimmunoassay. LH pulsations were analysed by a time series method. Following cannulation, mean LH levels declined but then rose to reach a maximum 2 h before the beginning of the exercise bout. LH concentrations remained virtually unchanged during exercise itself, and exhibited a declining trend throughout the post-exercise period. The findings in the two groups were similar in all respects, except that in the control study the rate of LH pulsatility was significantly diminished (P less than 0.05) during the first 2 h of sampling as compared with the subsequent 2-h period. The approximate half-life of LH varied from 27 to 57 min, with a mean of 41 min.

The detection of peaks in luteinizing hormone secretion.

Fluctations in luteinizing hormone are believed to consist of irregularly spaced sharp increases separated by periods of exponential decay. A simple method is presented for analysing such fluctuations when the data consist of uniformly sampled observations of hormone. Specific allowance for the exponential decay in the absence of pulses is made via a time series model before assessing the number and extent of pulses. All calculations are done using MINITAB regression programs. The results have been compared with those obtained by three established models and are in general agreement.

Melatonin response to exercise training in women.

Previous human studies have indicated that daytime melatonin levels increase when the organism is subjected to the stress of fasting and exercise. Melatonin, epinephrine, and norepinephrine levels were measured during a mock run and in the course of treadmill exercise performed before (T-1), during (T-2), and following (T-3) a progressive conditioning (running) program. Hormonal responses to the training program were determined by comparing values at T-1 and T-3. Plasma melatonin, epinephrine, and norepinephrine levels rose significantly (P less than .01) from baseline values for each exercise intensity during all three treadmill runs. While a dose-response trend was observed in each of the norepinephrine and epinephrine trials, there appeared to be a progressive diminution of this relationship in melatonin between intensities. Further, as training progressed, the peak melatonin concentration was decreased by 52% from T-1 to T-3, while peak epinephrine and norepinephrine values diminished only 19% and 8%, respectively. These results suggest that vigorous exercise training may attenuate rather than augment the secretion of pineal melatonin. Development of a human model of pineal responsiveness to exercise may contribute to the elucidation of exercise-associated reproductive disorders.

Effects of endurance training on body-consciousness in women.

The Body Consciousness Questionnaire by Miller, Murphy, and Buss in 1981 was employed to assess the effects of intensive endurance training on changes in self-perception in 13 women volunteers aged 20 to 30 yr. The participants engaged in an intensive progressive running program for 6 to 8 wk. Additional moderate exercise (softball or volleyball) was engaged in for 3 1/2 hr. per day. Before and after the training subjects completed the questionnaire on self-perceived attributes of internal body consciousness, public body consciousness, and body competence. Aerobic fitness, measured pre- and posttraining, significantly increased while body fat and weight significantly decreased. In consonance with these physiological changes, rated self-perception of internal body consciousness and body competence increased significantly while public body consciousness remained unchanged. Self-report of internal body consciousness tended to increase in proportion to changes in fitness (r = 0.53). These results suggest that endurance and moderate exercise training contribute to increased self-perception specifically with regard to perceived internal and body competence.

Hormonal responses to short term fasting in postmenopausal women.

Urinary excretion of gonadotropins increases during fasting. We investigated whether this increase results from increased pituitary secretion of LH and FSH or from altered renal excretion of protein molecules. To this end, we studied urinary gonadotropin excretion, serum gonadotropin levels, and pituitary responsiveness of LHRH during control, 10-day fasting, and refeeding periods in 10 mildly obese postmenopausal women. Additionally, we measured urinary cortisol and estriol excretion and circulating levels of dehydroepiandrosterone sulfate, estradiol, estrone, melatonin, norepinephrine, epinephrine, and dopamine during the control, fasting, and refeeding periods. While urinary excretion of gonadotropins increased markedly during fasting, there were no significant changes in serum gonadotropin levels or in the pituitary sensitivity to LHRH. Plasma norepinephrine and serum melatonin increased significantly during fasting, but serum and urinary estrogens, indices of adrenal activity, and plasma levels of epinephrine and dopamine did not change. These results show that the stress of short term fasting selectively activates only certain components of the neuroendocrine system without any appreciable changes in the function of the gonadotropin-secreting system. Fasting-induced gonadotropinuria is probably explained by altered renal handling of gonadotropin molecules.

Effect of carbohydrate supplementation on reproductive hormones during fasting in men.

We previously demonstrated that during a 10-day fast in mildly obese men, urinary gonadotropin excretion significantly increased, and serum testosterone concentrations significantly decreased. The mechanisms by which these changes occur are unknown. We postulated that the mechanism of the gonadotropinuria might involve decreased proximal renal tubular reabsorption of gonadotropins during fasting and might be related to renal tubular reabsorption of ketones during fasting, a process that is enhanced by carbohydrate (CHO) administration. We studied the effects of CHO supplementation on ketosis, ketonuria, and reproductive hormone secretion and excretion in 14 mildly obese men, 24-54 yr old, who were 14-69% above ideal body weight. Group I (n = 6) received no CHO supplementation, group II (n = 4) received 15 g CHO, and group III (n = 4) received 45 g CHO daily during the 10-day fast (F). During the control (C) and refeeding (R) periods, all subjects received a 1500-cal diet. Daily 24-h urine collections were made for the measurement of total ketones (millimolar concentrations) and LH and FSH (expressed as international units of the Second International Reference Preparation of human menopausal gonadotropin). Values (mean +/- SE) for 3 representative days (control day 3, fasting day 8, and refeeding day 3) for all subjects are shown below: (table; see text) We also studied the effects of CHO supplementation on serum levels of pituitary gonadotropins, LH and FSH responses to exogenous LHRH stimulation, biological activity of LH, and circulating total and free testosterone levels. Neither dose of CHO prevented the decline in total and free testosterone levels. Serum LH concentrations, as measured by both the RIA and in vitro bioassay did not change significantly with fasting. Serum FSH concentrations in daily samples did not change significantly. The previously reported decline in the FSH response to LHRH stimulation with fasting was not prevented by CHO. We conclude that CHO supplementation prevents the gonadotropinuria of fasting in men. The effect appears to occur in the kidney. The mechanisms may be related to that by which CHO promotes the renal tubular reabsorption of ketones. The reduced serum testosterone level cannot be explained by a lack of biologically active LH. It appears that fasting has a direct effect on the testis, possibly by reducing its responsiveness to gonadotropic stimulation or by inhibiting steroidogenesis.

Induction of menstrual disorders by strenuous exercise in untrained women.

We performed a prospective study of 28 initially untrained college women with documented ovulation and luteal adequacy to determine whether strenuous exercise spanning two menstrual cycles would induce menstrual disorders. To ascertain the influence, if any, that weight loss might exert, we randomly assigned the subjects to weight-loss and weight-maintenance groups. Subjects were expected to run 4 miles (6.4 km) per day, progressing to 10 miles (16.1 km) per day by the fifth week, and to engage daily in 31/2 hours of moderate-intensity sports. The normalcy of the menstrual cycles during the period of exercise was judged independently according to clinical and hormonal criteria, the latter comprising serial measurements of gonadotropin and sex-steroid excretion. A higher percentage of abnormalities proved to be detectable by hormonal means (P less than 0.02). Only four subjects (three in the weight-maintenance group) had a normal menstrual cycle during training. In the weight-loss group, the number of women who had luteal abnormalities as compared with those who lost the surge in luteinizing hormone altered significantly over time, the latter occurring more frequently (P less than 0.01) as training progressed. Within six months of termination of the study, all subjects were again experiencing normal menstrual cycles. We conclude that vigorous exercise, particularly if compounded by weight loss, can reversibly disturb reproductive function in women.

Endorphins and exercise in females: possible connection with reproductive dysfunction.

Currently available measurements of beta-endorphin and beta-lipotropin in exercising women are in excellent agreement and indicate a 2-3 fold increase over basal levels. Possible effects of exercise upon the transfer of endorphins from the peripheral circulation to the brain are examined, and evidence is presented that suggests the occurrence of a concomitant exercise-related increase of endorphins in both humoral and central nervous system compartments. Steady-state measurements of circulating luteinizing hormone and follicle-stimulating hormone levels in oligo-amenorrheic athletes, on the other hand, do not agree. It is felt that the lack of consensus may be attributable partly to technical inadequacies and partly to lack of awareness of the need for frequent sampling. The bulk of the findings suggest a tendency for luteinizing hormone levels to be low and follicle-stimulating hormone levels to be normal or low, a pattern compatible with repeated activation of the CRH-ACTH-POMC system as a result of exercise.

Gonadotropin and prolactin pulsations in hyperprolactinemic women before and during bromocriptine therapy.

Pulsatile gonadotropin secretion and its relationship to PRL and estradiol (E2) secretion were investigated in 20 hyperprolactinemic amenorrheic women by obtaining serial blood samples for 6- to 24-h periods. Thirteen patients were restudied in the early follicular phase of the menstrual cycle (days 3-5) after ovulatory periods were established during bromocriptine therapy. In the hyperprolactinemic women, the number of LH peaks ranged from 0-12/24 h, and LH peak amplitude ranged from 0-1.7 mIU/ml. Serum E2 correlated with mean LH concentrations (P less than 0.001) and LH pulse frequency (P less than 0.05), but not with LH pulse amplitude. FSH pulsations were identified in 3 of the 20 women. There was no correlation between mean FSH concentrations and either serum E2 or PRL. There was a significant correlation between LH and FSH concentrations (P less than 0.001). During bromocriptine therapy, with comparable E2 concentrations, 5 of the 6 patients studied with blood sampling every 20 min for 24 h had a significant decrease (P less than 0.01) in the number of LH peaks per 24 h, with no change in LH peak amplitude. Mean FSH concentrations were unchanged in bromocriptine-treated patients; however, there was a significant (P less than 0.02) decrease in FSH levels during sleep. Serum PRL was normal in all bromocriptine-treated patients, but normal PRL secretory patterns were not reestablished, and there was no correlation between LH pulsations and serum PRL concentrations. We conclude that 1) hyperprolactinemic women have a heterogeneous pattern of pulsatile gonadotropin secretion; 2) serum E2 correlates with LH pulse frequency but not pulse amplitude; 3) LH pulsations and PRL pulsations are asynchronous in hyperprolactinemic women before and during bromocriptine therapy; and 4) normal PRL secretory patterns are not required for ovulatory function in hyperprolactinemic women treated with bromocriptine.

Release of beta endorphin and met-enkephalin during exercise in normal women: response to training.

Plasma beta endorphin and met-enkephalin concentrations were measured in response to treadmill exercises in 15 normal women before, during, and after an intensive programme of exercise training. Significant release of beta endorphin occurred in all three test runs, and the pattern and amount of release were not altered by training. Before training dramatic release of met-enkephalin was observed in seven subjects and smaller rises observed in a further four, and this response was almost abolished by training. This represents the first observed "physiological" stimulus to met-enkephalin release. Endogenous opioid peptides play a part in adaptive changes to exercise training and probably contribute to the menstrual disturbances of women athletes.

Endurance training effects on plasma hormonal responsiveness and sex hormone excretion.

A prospective study of the hormonal effects of a moderate exercise training program (4-wk control, 8-wk training) was conducted in seven young women. Sixty-minutes continuous bicycle ergometer tests of fixed relative intensity were performed at the beginning, middle, and end of the training period. The capacity of these acute bouts of exercise to affect circulating levels of stress markers, reproductive hormones, and hormones with possible antireproductive potential was measured. In addition, the urinary excretion of reproductive hormones was monitored continuously via serial overnight urine collections. Within testing sessions, plasma concentrations of all stress markers and antireproductive hormones rose significantly. Across testing sessions, only beta-endorphin + beta-lipotropin and cortisol exhibited an increment in peak responses as training progressed. Plasma reproductive hormone levels showed insignificant acute changes, and cyclic menstruation and preovulatory gonadotropin surges continued in all subjects. However, ovarian function was disturbed in four subjects as evidenced by a decreased excretion of estriol, free progesterone, or both. Transient infertility is a known clinical accompaniment of hormonal changes of comparable subtlety.

alpha-Subunit and gonadotropin responses to luteinizing hormone-releasing hormone in hyperprolactinemic women before and after bromocriptine.

alpha-Subunit and gonadotropin responses to a LHRH infusion (0.2 micrograms/min) for 4 h were studied in eight hyperprolactinemic amenorrheic women, ages 23-40, and in five normal women in the early follicular phase of the menstrual cycle. Basal alpha-subunit and LH concentrations were comparable to normal women; however, basal FSH concentrations were significantly (P less than 0.05) lower. Peak serum alpha, LH, and FSH concentrations during the LHRH infusion were significantly higher than controls (P less than 0.01, P less than 0.05, and P less than 0.01, respectively). Gel chromatography of serum confirmed the presence of both free alpha-subunit and intact LH which had normal biological activity. Six of the women were restudied in the early follicular phase of the cycle after return of normal ovulatory function and normalization of serum PRL concentrations. During bromocriptine therapy, peak serum alpha, LH, and FSH concentrations decreased significantly (P less than 0.02, P less than 0.05, and P less than 0.001, respectively) and were comparable to control subjects. The changes in serum alpha and gonadotropin responses to the LHRH infusion during bromocriptine therapy occurred independently of the serum estradiol concentrations. Abnormalities in the regulation of alpha-subunit and gonadotropin secretion are present in hyperprolactinemia. These abnormalities reverse with bromocriptine therapy and may occur independently of changes in gonadal steroids.

Exercise effect upon plasma melatonin levels in women: possible physiological significance.

The pattern of changes in plasma concentrations of melatonin was followed in 7 initially untrained young women subjected to periodic acute exercise testing during the course of an 8 weeks' progressive aerobic exercise training program. Training comprised cycle ergometry 2 days/week and running 4 days/week for increasingly prolonged periods of intense exercise eliciting 85% of maximum heart rate. Acute exercise tests consisted of one-hour graded submaximal endurance rides on a bicycle ergometer. After a mock ride for familiarization purposes, three test rides were conducted during the early follicular phase of three consecutive menstrual cycles at the beginning, middle and end of the training program. Blood was sampled atraumatically before the rides, at their conclusion and 30 minutes into recovery. During the rides, the plasma concentrations of melatonin rose significantly above baseline control values. Exercise-enhanced melatonin levels may contribute to impaired reproductive function in women engaging in endurance sports.