Correction of misinterpretations and misrepresentations of the female athlete triad.
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Biomedical subjects
Publications and source records attributed to M J De Souza.
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This paper provides new data on chromosomes of Brazilian vampire bats Desmodus rotundus and Diphylla ecaudata. These species were analyzed by GTG, CBG- and CB-DAPI banding, AgNO3/CMA3 sequential staining, base-specific fluorochrome dyes and in situ hybridization with 18S rDNA probe. C-banding (CBG) revealed constitutive heterochromatin in the pericentromeric regions in all autosomes and the X and Y chromosomes appeared entirely heterochromatic in both species. CB-DAPI revealed a coincident banding pattern to that obtained by CBG. Triple staining CMA3/DA/DAPI revealed an R-banding and a weak G-banding pattern in the karyotypes. Sequential AgNO3/CMA3 staining showed a NOR located interstitially on the long arm of pair 8 in D. rotundus and on the short arm of pair 13 in D. ecaudata. FISH with a rDNA probe confirmed the location and number of NORs; a difference neither in intensity nor in size of hybridization signal was detected between homologues for both species.
The purposes of this investigation were to evaluate the characteristics of three consecutive menstrual cycles and to determine the frequency ofluteal phase deficiency (LPD) and anovulation in a sample of sedentary and moderately exercising, regularly menstruating women. For three consecutive menstrual cycles, subjects collected daily urine samples for analysis of FSH, estrone conjugates (E1C), pregnanediol-3-glucuronide (PdG), and creatinine (Cr). Sedentary (n=11) and exercising (n=24) groups were similar in age (27.0+/-1.3 yr), weight (60.3+/-3.1 kg), gynecological age (13.8+/-1.2 yr), and menstrual cycle length (28.3+/-0.8 days). Menstrual cycles were classified by endocrine data as ovulatory, LPD, or anovulatory. No sedentary women (0%) had inconsistent menstrual cycle classifications from cycle to cycle, but 46% of the exercising women were inconsistent. The sample prevalence of LPD in the exercising women was 48%, and the 3-month sample incidence was 79%. In the sedentary women, 90% of all menstrual cycles were ovulatory (SedOvul; n=28), whereas in the exercising women only 45% were ovulatory (ExOvul; n=30); 43% were LPD (ExLPD; n=28), and 12% were anovulatory (ExAnov; n=8). In ExLPD cycles, the follicular phase was significantly longer (17.9+/-0.7 days), and the luteal phase was significantly shorter (8.2+/-0.5 days) compared to ExOvul (14.8+/-0.9 and 12.9+/-0.3 days) and SedOvul (15.9+/-0.6 and 12.9+/-0.4 days) cycles. Luteal phase PdG excretion was lower (P < 0.001) in ExLPD (2.9+/-0.3 microg/mg Cr) and ExAnov (0.8+/-0.1 microg/mg Cr) cycles compared to SedOvul cycles (5.0+/-0.4 microg/mg Cr). ExOvul cycles also had less (P < 0.01) PdG excretion during the luteal phase (3.7+/-0.3 microg/mg Cr) than the SedOvul cycles. E1C excretion during follicular phase days 2-5 was lower (P=0.05) in ExOvul, ExLPD, and ExAnov cycles compared to SedOvul cycles and remained lower (P < 0.02) in the ExLPD and ExAnov cycles during days 6-12. The elevation in FSH during the luteal-follicular transition was lower (P < 0.007) in ExLPD (0.7+/-0.1 ng/mg Cr) cycles compared to SedOvul and ExOvul cycles (1.0+/-0.1 and 1.1+/-0.1 ng/mg Cr, respectively). Energy balance and energy availability were lower (P < 0.05) in ExAnov cycles than in other menstrual cycle categories. The blunted elevation in FSH during the luteal-follicular transition in exercising women with LPD may explain their lower follicular estradiol levels. These alterations in FSH may act in concert with disrupted LH pulsatility as a primary and proximate factor in the high frequency of luteal phase and ovulatory disturbances in regularly menstruating, exercising women.
Several authors have suggested that estrogen may serve to protect skeletal muscle from exercise-induced damage. The present study examined the effects of regularly ingesting estrogen, in the form of oral contraceptives, on postexercise muscle damage following a bench-stepping regimen. Women currently ingesting oral contraceptives (OC) were compared with eumennorheic controls (CG). All subjects performed a 50-min stepping exercise during the midluteal phase of their menstrual cycle. Muscle damage was evaluated on 2, 3, and 5 days postexercise using several established indirect indicators: perceived soreness, strength and range of motion changes, girth measurements, and creatine kinase (CK) activity. Subjects on OC reported significantly lower quadriceps soreness (p < 0.05) relative to the CG (peak soreness = 4.0 and 7.8, respectively, on a scale of 1-10 where 1 is normal and 10 is very, very sore). These results indicate that oral contraceptive use attenuates soreness following an exhaustive stepping activity but cannot support a relationship between estrogen ingestion and other indices of exercise-induced muscle damage.
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The primary purpose of this study was to determine whether decreased ovarian progesterone production, associated with short and inadequate luteal phases in exercising women, was associated with decreased bone mineral density (BMD) and altered bone metabolism. Thirty-three eumenorrheic menstruating women participated in this study for 3 months. Subjects were required to collect daily urine samples for three consecutive menstrual cycles and have blood and urine collected weekly. Daily urine samples were analyzed for free LH, estrone conjugates (E1C), and pregnanediol 3-glucuronide (PdG), adjusted for creatinine, whereas weekly blood and urine samples were analyzed for bone markers, estradiol, progesterone, FSH, and LH. Based on the analyses of these samples, subjects were divided into three groups: sedentary ovulatory (SedOvul; n = 9), exercising ovulatory (ExOvul; n = 14), and exercising luteal phase defects (ExLPD; n = 10). The three groups were matched for age (27.6 +/- 1.0 yr), weight (60.6 +/- 1.9 cm), and reproductive maturity (14.5 +/- 1.0 yr), PdG production during the luteal phase was lower (P = 0.004) in the ExLPD women compared to that in the SedOvul group (2.4 +/- 0.4 vs. 5.1 +/- 0.6 ng/mL creatinine, respectively). The ExOvul group also had less (P < 0.01) PdG production during the luteal phase (3.5 +/- 0.3 ng/mL creatinine) compared to the SedOvul group. The total production of PdG, as assessed by area under the curve analysis, was also lower (P < 0.001) in the ExOvul and ExLPD groups compared to that in the SedOvul group. E1C production, however, was not different (P > 0.05) among the groups, except for E1C during the early follicular phase, which was lower (P = 0.043) in the ExLPD group than that in the SedOvul group. BMD and biochemical markers of bone metabolism were unaffected by and not associated with the compromised progesterone environment, but BMD values at the proximal femur (r = 0.354; P = 0.061) and total body (r = 0.359; P = 0.056) were associated with decreased early follicular E1C production. We conclude the following. 1) Luteal phase disturbances occur independent of training volume, and volume of training does not have to be severe to result in menstrual disturbances. 2) As a result of exercise, disturbance in progesterone production is not associated with decreased bone mass. 3) Long follicular phases are associated with reduced estrogen production during the early follicular phase, which are both associated with decreased bone mass. 4) Provided the estradiol status is adequately maintained, BMD is unaffected by decreased progesterone production associated with short and inadequte luteal phases in exercising women.
Investigations on reproductive function in male athletes are not as abundant in the literature as the research available on female athletes. The primary reason for this is the absence of an obvious clinical sign indicative of an alteration in reproductive function in male athletes. While alterations in the reproductive status of female athletes may be easily detected by the loss of menstrual regularity, a distinctive clinical sign reflective of reproductive dysfunction in the male is not apparent. In male runners, an effect of endurance training on reproductive function related to a specific 'volume threshold' of training is proposed. Data are supportive of this 'volume threshold' effect, provided careful and consistent definitions of volume of training are applied. In fact, if volume of training is carefully defined endurance-trained male runners exhibit a rather consistent range of subclinical modifications in the gonadal hormones and semen profile, and clinical (oligospermia) alterations in reproductive function. The precise mechanism responsible for these observed alterations remains unknown, although several peripheral and central mechanisms have been suggested. Clearly, more research is necessary to confirm, and to elucidate, the nature of the 'volume threshold' hypothesis in male runners.
The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG) ratio algorithm to identify anovulatory cycles was studied prospectively in two independent populations of women. Urinary hormone data from the first group was used to develop the algorithm, and data from the second group was used for its validation. PdG ratios were calculated by a cycles method in which daily PdG concentrations indexed by creatinine (CR) from cycle day 11 onward were divided by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the interval method, daily PdG/CR concentrations from day 1 onward were divided by baseline PdG (lowest 5-day average of PdG/CR values throughout the collection period). Evaluation of the first study population (n = 6) resulted in cycles with PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory; otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio algorithm to identify anovulatory cycles in the second population were 75% and 89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n = 40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n = 89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml progesterone. The sensitivity values for all cycles and for the first cycle using both methods were underestimated because of apparent misclassification of cycles using serum progesterone due to infrequent blood collection. Blood collection more than once a week would have greatly improved the sensitivity and modestly improved the specificity of the algorithm. The PdG ratio algorithm provides an efficient approach for screening urine samples collected in epidemiologic studies of reproductive health in women.
Metabolic efficiency was assessed in ovulatory eumenorrheic female distance runners and untrained control subjects of similar age, body weight, and fat-free mass (FFM). Energy intake (EI) was estimated from 3-d dietary records. Energy expenditure (EE) was determined during the same 3-d period from individual heart rate oxygen uptake (HR/VO2) curves during rest and exercise, 24-h HR records, and the thermic effect of meals. The runners and control subjects did not differ in resting metabolic rate statistically adjusted for FFM (kJ/min), the thermic effect of a test meal (kJ/3 h), the energy cost of submaximal physical activity, or EI. EE was higher (P = 0.01) in the runners. Reported EI was lower than EE in both the runners (P = 0.007) and control subjects, (P = 0.006), resulting in energy deficits of -4131 +/- 1185 kJ/d and -1652 +/- 456 kJ/d, respectively. These female runners did not exhibit an enhanced metabolic efficiency compared with the control subjects. It is possible that the energy deficit for both the runners and control subjects was due to both restricted eating and underreporting during the measurement period. Additional studies using longer measurement periods, more sophisticated technology (ie, doubly labeled water, more subjects, and subjects of varying menstrual and energy intake status) are needed to truly answer this question.
Eleven high mileage runners (HR) (108.0 +/- 4.5 km.wk-1), 9 moderate mileage runners (MR) (54.2 +/- 3.7 km.wk-1) and 10 sedentary controls (SC) of similar age (28.3 +/- 1.5 yr) were studied to evaluate the effects of volume of endurance training on reproductive function in male runners. Levels of reproductive, adrenal and thyroid hormones were measured during a 1-hr period of serial blood sampling (q20 min) and urinary excretion of 24-hr luteinizing hormone (uLH) was determined on two separate days. Semen exams and sperm penetration of standard cervical mucus (Penetrak) were performed 2-5 times. Levels of total testosterone (TT) and free testosterone (FT) were significantly lower in HR (15.3 +/- 1.3 nmol.l-1 and 60.2 +/- 5.1 pmol.l-1) compared to MR (21.4 +/- 1.6 nmol.l-1 and 86.0 +/- 6.1 pmol.l-1) and SC (19.5 +/- 0.9 nmol.l-1 and 75.9 +/- 3.6 pmol.l-1). No differences (p > 0.05) were found in uLH, serum LH, follicle-stimulating hormone (FSH), and prolactin (PRL) among the three groups. No other hormonal differences (p > 0.05) were observed among the groups. Total motile sperm count and density were lower (p < 0.05) in HR than SC. Decreased (p < 0.0006) sperm motility and an increased (p < 0.004) population of immature sperm and round cells were observed in HR compared to MR and SC. Sperm penetration of bovine cervical mucus was also decreased (p < 0.024) in HR compared to SC. Volume of training, defined by km.wk-1 run, was significantly correlated to sperm motility, density and number of round cells.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate mechanisms of blunted adrenocortical responsiveness to exercise and mild hypercortisolism in amenorrheic runners, adrenocorticotropic hormone [ACTH-(1-24) 0.25 mg Cortrosyn] stimulation tests were performed in the presence and absence of overnight dexamethasone (1 mg) suppression (DX and NDX condition, respectively) in six eumenorrheic sedentary women (ES), nine eumenorrheic runners (ER), and nine amenorrheic runners (AR). Before the NDX stimulation test, plasma cortisol was higher (P < 0.001) in AR than in ER and ES. The cortisol response to the NDX stimulation test was blunted (P < 0.001) in AR but reached similar (P > 0.7) peak levels in all groups. Dexamethasone suppressed (P < 0.001) cortisol to similar (P > 0.5) levels (approximately 20 nmol/l) in all groups. In AR, cortisol responses to the DX test were larger (P < 0.03) than to the NDX test and similar (P > 0.6) in the three groups, again reaching comparable (P > 0.8) peak levels. The blunted cortisol response to stimulation in AR in the presence of their mild hypercortisolism appears to be due to a normal limitation in maximal adrenal secretory capacity. Extrapituitary modulators of adrenal responsiveness to ACTH may explain the mild hypercortisolism observed in AR, but limitations of these tests prevent a central negative-feedback defect or an intrinsic adrenal abnormality from being excluded until results of additional studies with even lower doses of dexamethasone and submaximal doses of ACTH-(1-24) are available.
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Recent advances in the study of andrology are unfolding some of the idiopathic components of male factor infertility. The inclusion of exercise training as a component of male factor infertility has been proposed secondary to changes observed in the reproductive hormone and semen profile of some endurance trained male athletes. Evidence exists that a subset of endurance trained men, particularly runners, present with subclinical changes in their reproductive hormone profile. These changes include a reduction in total and free testosterone, alterations in luteinising hormone release and alterations in pituitary responses to gonadotrophin-releasing hormone and other pharmacological perturbations. Less attention has been directed towards identifying changes in spermatogenesis and fertility capacity as a result of endurance training. The semen ejaculate of some endurance trained athletes presents with nonspecific modifications including a low normal sperm count, decreased motility and several morphological changes that may compromise fertility. Thus, although a subset of high mileage endurance trained runners present with subclinical modifications in their reproductive hormone and semen profile, to date there is no evidence that endurance training causes male infertility. Future investigations should focus on the clinical impact these hormone and semen alterations may have on fertility capacity in endurance trained athletes.
STUDY OBJECTIVE: To investigate the effects of two forms of exercise, endurance training (running) and resistance training (weight lifting), on reproductive function in male athletes. DESIGN: Cross-sectional study. SETTING: Reproductive Endocrinology and Exercise Laboratory. SUBJECTS: Twenty-eight healthy male volunteers, 18 to 35 years of age, including 10 endurance-trained runners, 8 resistance-trained weight-lifters, and 10 sedentary controls. MAIN OUTCOME MEASURE(S): Hormonal evaluation included determination of plasma levels of total testosterone (T), serum levels of free T, luteinizing hormone (LH), follicle-stimulating hormone, prolactin, and estradiol, and urinary excretion of LH. Semen analyses included an evaluation of sperm characteristics in terms of density, count, motility, and morphology, and a determination of in vitro sperm penetration of standard bovine cervical mucus. RESULTS: Compared with sedentary controls, endurance-trained and resistance-trained athletes presented with significantly lower levels of total and free T. There were no significant differences in the serum levels of all other circulating and urinary hormone measurements among the three groups. Sperm density, motility, and morphology were significantly altered only in the endurance-trained runners. In vitro sperm penetration of standard cervical mucus was significantly reduced in the endurance-trained runners. CONCLUSION: Both endurance and resistance training modify the male reproductive hormone profile in a similar manner; however, only endurance training, in the form of running, is associated with subclinical modifications in semen characteristics.
In this prospective, double-blind study, we evaluated the efficacy and safety of low-dose estrogen and progestin replacement therapy in 36 postmenopausal women who were administered oral medroxyprogesterone acetate (MPA) cyclically or continuously in combination with conjugated equine estrogen (CEE) 0.625 mg daily. In the sequential group, MPA (5.0 mg) was administered daily for 12 days of each 25-day treatment cycle. In the two continuous groups, MPA was administered without interruption at a daily dose of either 2.5 mg or 5.0 mg for 12 treatment cycles. Of the 36 women in the study, 29 women completed the one-year protocol. The clinical and metabolic responses were assessed before and every three cycles during the 12 cycles of treatment. Endometrial biopsies and lumbar bone density scans were performed before and during the last week of the 12th treatment cycle. Vasomotor and urogenital symptoms improved in all women. Cyclic menstrual bleeding occurred in all patients on sequential therapy, and proliferative endometrium was noted in two of these women. All patients in both continuous treatment groups experienced amenorrhea after the fifth cycle of therapy, and all endometrial biopsies were atrophic or inactive. From the 3rd through the 12th month of cycle, favorable lipid and lipoprotein changes occurred in all treatment groups. Lumbar bone mineral density improved significantly (P < .05) by an average of 6.41% in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
To study the effects of exercise intensity and duration on excess postexercise oxygen consumption (EPOC), 8 men [age = 27.6 (SD 3.8) years, VO2max = 46.1 (SD 8.5) ml min-1 kg-1] performed four randomly assigned cycle-ergometer tests (20 min at 60% VO2max, 40 min at 60% VO2max, 20 min at 70% VO2max, and 40 min at 70% VO2max). O2 uptake, heart rate and rectal temperature were measured before, during, and for 1 h following the exercise tests. Blood for plasma lactate measurements was obtained via cannulae before, and at selected times, during and following exercise. VO2 rapidly declined to preexercise levels following each of the four testing sessions, and there were no differences in EPOC between the sessions. Blood lactate and rectal temperature increased (P < 0.05) with exercise, but had returned to preexercise levels by 40 min of recovery. The results indicate that VO2 returned to resting levels within 40 min after the end of exercise, regardless of the intensity (60% and 70% VO2max) or duration (20 min and 40 min) of the exercise, in men with a moderate aerobic fitness level.
Adrenocorticotropic hormone (ACTH), cortisol, and prolactin responses following maximal and submaximal (40 min at 80% maximal O2 consumption) running were studied in eumenorrheic (ER; n = 8, 29.0 +/- 1.5 yr) and amenorrheic (AR; n = 8, 24.5 +/- 2.0 yr) runners. ER were studied in the early follicular and midluteal phases of the menstrual cycle. Physical, training, and gynecological characteristics were similar, and cardiorespiratory and metabolic responses to the exercises were indistinguishable in the groups. ACTH, cortisol, and prolactin data from the follicular luteal phases in ER were combined for comparison to AR, because no differences were noted between the menstrual phases at rest. Similar preexercise ACTH levels and responses following exercise occurred in both groups, but preexercise cortisol levels were elevated (ER = 293.1 +/- 46.3, AR = 479.6 +/- 42.4 nmol/l) and cortisol responses blunted in AR. Adrenal sensitivity was blunted in AR compared with ER after submaximal (ER = 121.9 +/- 17.4, AR = 51.7 +/- 13.6) and maximal exercise (ER = 27.9 +/- 9.2, AR = 12.1 +/- 3.8). Preexercise prolactin levels were reduced (ER = 16.4 +/- 2.7, AR = 10 +/- 2.3 micrograms/l), and prolactin responses to maximal exercises were blunted in AR, despite high lactate levels (11.4 +/- 0.4 mmol/l). We conclude that 1) control for menstrual phase in ER is important in studies of prolactin responses following exercise but not in studies of ACTH and cortisol responses following exercise, 2) cortisol responses following submaximal and maximal exercise in AR are blunted at the adrenal level, 3) prolactin responses following submaximal and maximal exercise are also blunted in AR, and 4) prolactin responses following exercise may be mediated by adrenal activation.
Strenuous athletic training and anorexia are associated with a high incidence of amenorrhea. While the physiological and/or psychological stressors that contribute to the development of menstrual dysfunction in these individuals appear to differ, they both involve disorders of the reproductive system that originate in the hypothalamus. The available data suggest that both groups experience alterations in the pulsatile release of GnRH, which in turn produces perturbations in pituitary and ovarian function ultimately leading to menstrual dysfunction. In this review, the reproductive and "stress" hormone profiles in amenorrheic athletes and anorexic patients are compared, and the interaction of these hormonal axes in the occurrence of menstrual dysfunction is discussed.