Understanding the female athlete: molecular mechanisms underpinning menstrual phase differences in exercise metabolism.

Research should equitably reflect responses in men and women. Including women in research, however, necessitates an understanding of the ovarian hormones and menstrual phase variations in both cellular and systems physiology. This review outlines recent advances in the multiplicity of ovarian hormone molecular signaling that elucidates the mechanisms for menstrual phase variability in exercise metabolism. The prominent endogenous estrogen, 17-ß-estradiol (E2), molecular structure is bioactive in stabilizing plasma membranes and quenching free radicals and both E2 and progesterone (P4) promote the expression of antioxidant enzymes attenuating exercise-induced muscle damage in the late follicular (LF) and mid-luteal (ML) phases. E2 and P4 bind nuclear hormone receptors and membrane-bound receptors to regulate gene expression directly or indirectly, which importantly includes cross-regulated expression of their own receptors. Activation of membrane-bound receptors also regulates kinases causing rapid cellular responses. Careful analysis of these signaling pathways explains menstrual phase-specific differences. Namely, E2-promoted plasma glucose uptake during exercise, via GLUT4 expression and kinases, is nullified by E2-dominant suppression of gluconeogenic gene expression in LF and ML phases, ameliorated by carbohydrate ingestion. E2 signaling maximizes fat oxidation capacity in LF and ML phases, pending low-moderate exercise intensities, restricted nutrient availability, and high E2:P4 ratios. P4 increases protein catabolism during the luteal phase by indeterminate mechanisms. Satellite cell function supported by E2-targeted gene expression is countered by P4, explaining greater muscle strengthening from follicular phase-based training. In totality, this integrative review provides causative effects, supported by meta-analyses for quantitative actuality, highlighting research opportunities and evidence-based relevance for female athletes.

Skeletal site-specific effects of jump training on bone mineral density in adults: a systematic review and meta-analysis.

Preserving or preventing declines in bone mineral density (BMD) is imperative. As jumping is a high-impact bone-loading action, this meta-analysis evaluated the efficacy of jump training to improve BMD and bone turnover relative to non-jumping controls in men and women > 18 years, following Preferred Reported Items for Systematic Reviews and Meta-Analysis guidelines. PubMed and COCHRANE Library databases were searched until February 2022. Fifteen articles (19 jumping-trials) met the predetermined search criteria. Eighteen trials were included for BMD data (n = 666 participants). There was a significant small-moderate effect of jumping on femoral neck BMD (%mean difference: 95%CI, +1.50%: 0.83%; 2.17%, p < 0.0001), that remained significant after sub-analysis by age for both younger (+1.81%: 0.98%; 2.65%) and older adults (+1.03%: 0.02%; 2.03%). BMD of total hip (+1.26%: 0.56%; 1.96% vs + 0.06%: -0.96%; 1.08%), and trochanter (+0.84%: 0.20%; 1.48% vs -0.16%: -1.08%; 0.76%) increased significantly with jump training only in younger adults and non-significantly at the lumbar spine (+0.84%: -0.02%; 1.7% vs -0.09%: -0.96%; 0.77%) only in younger but not older adults, respectively. The BMD response to jump training appears to be site-specific, with the highest sensitivity at the femoral neck. No dose-response effect suggests moderate certainty of a gain in femoral neck BMD when performing the median jump-load of 50 jumps four times weekly.

Carbohydrate-Restricted Exercise With Protein Increases Self-Selected Training Intensity in Female Cyclists but Not Male Runners and Cyclists.

ABSTRACT: Oosthuyse, T, Florence, GE, Correia, A, Smyth, C, and Bosch, AN. Carbohydrate-restricted exercise with protein increases self-selected training intensity in female cyclists but not male runners and cyclists. J Strength Cond Res 35(6): 1547-1558, 2021-Carbohydrate-restricted training challenges preservation of euglycemia and exercise intensity that precludes ergogenic gains, necessitating countering strategies. We investigated the efficacy of ingesting casein protein hydrolysate in overnight-fasted male runners, male cyclists, and female cyclists. Twenty-four overnight-fasted athletes ingested 15.8 g·h-1 casein hydrolysate or placebo-water during exercise (60-80 minutes) comprising an incremental test to exhaustion, steady-state exercise (70% Vmax or 60% peak power output, 87 ± 4% HRmax), and 20-minute time trial (TT) in a double-blind randomized crossover design, with p < 0.05 accepted as significant. Ingesting protein vs. placebo increased metabolic demand {oxygen consumption, +4.7% (95% confidence interval [CI] ± 4%), p = 0.0297; +3.2% (95% CI ± 3.4%), p = 0.061}, heart rate (p = 0.0083; p = 0.007) and rating of perceived exertion (RPE) (p = 0.0266; p = 0.0163) in male cyclists and runners, respectively, but not female cyclists. Protein vs. placebo increased carbohydrate oxidation (+0.26 [95% CI ± 0.13] g·min-1, p = 0.0007) in female cyclists alone. Cyclists reported +2 ± 1 higher RPE than runners (p = 0.0062). Glycemia was maintained only in runners and increased with protein vs. placebo after 20 minutes of steady-state exercise (+0.63 [95% CI ± 0.56] mmol·L-1, p = 0.0285). TT performance with protein vs. placebo ingestion was modestly compromised in runners (-2.8% [95% CI ± 2.2%], p = 0.0018), unchanged in male cyclists (+1.9% [95% CI ± 5.6%], p = 0.5794), and modestly improved in female cyclists (+2.5% [95% CI ± 1.8%], p = 0.0164). Casein hydrolysate ingestion during moderate to hard carbohydrate-restricted exercise increases glycemia in runners, but not cyclists. Casein hydrolysate increases metabolic demand in male athletes and carbohydrate oxidation in female cyclists and is suitable for improving carbohydrate-restricted training intensity in female but not male endurance athletes.

Mountain Bike Racing Stimulates Osteogenic Bone Signaling and Ingesting Carbohydrate-Protein Compared With Carbohydrate-Only Prevents Acute Recovery Bone Resorption Dominance.

ABSTRACT: Oosthuyse, T, Bosch, AN, Kariem, N, and Millen, AME. Mountain bike racing stimulates osteogenic bone signaling and ingesting carbohydrate-protein compared with carbohydrate-only prevents acute recovery bone resorption dominance. J Strength Cond Res 35(2): 292-299, 2021-Mountain biking, unlike road cycling, includes vibrational accelerations but whether it stimulates osteogenic signaling remains unknown. Furthermore, exercise nutrition influences bone turnover, and the effect of ingesting protein during multiday racing was investigated. We measured plasma bone turnover markers, C-terminal telopeptide of type1-collagen (ß-CTX) and N-terminal propeptides of type1-procollagen (P1NP), and osteocyte mechanosensory signaling factor, sclerostin (SOST), corrected for plasma volume change, before (pre-day 1) and 20-60 minutes after (post-day 3) a multiday mountain bike race in 18 male cyclists randomly assigned to ingest carbohydrate-only (CHO-only) or carbohydrate-with-casein protein hydrolysate (CHO-PRO) during racing. Fourteen cyclists (n = 7 per group) completed the race, and data were analyzed with p < 0.05 accepted as significant. Plasma SOST decreased similarly in both groups (mean ± SD, CHO-only: 877 ± 451 to 628 ± 473 pg·ml-1, p = 0.004; CHO-PRO: 888 ± 411 to 650 ± 443 pg·ml-1, p = 0.003), suggesting that osteocytes sense mountain biking as mechanical loading. However, the bone formation marker, P1NP, remained unchanged in both groups, whereas the bone resorption marker, ß-CTX, increased in CHO-only (0.19 ± 0.034 to 0.31 ± 0.074 ng·ml-1, p = 0.0036) but remained unchanged in CHO-PRO (0.25 ± 0.079 to 0.26 ± 0.074 ng·ml-1, p = 0.95). Mountain bike racing does stimulate osteogenic bone signaling but bone formation is not increased acutely after multiday mountain biking; investigation for a delayed effect is warranted. The acute recovery increase in bone resorption with CHO-only is prevented by ingesting CHO-PRO during racing.

Effect of ingesting carbohydrate only or carbohydrate plus casein protein hydrolysate during a multiday cycling race on left ventricular function, plasma volume expansion and cardiac biomarkers.

PURPOSE: Multiday racing causes mild left ventricular (LV) dysfunction from day 1 that persists on successive days. We evaluated ingesting casein protein hydrolysate-carbohydrate (PRO) compared with carbohydrate-only (CHO) during a 3-day mountain bike race. METHODS: Eighteen male cyclists were randomly assigned to ingest 6.7% carbohydrate without (CHO) or with 1.3% casein hydrolysate (PRO) during racing (~ 4-5 h/day; 68/71/71 km). Conventional LV echocardiography, plasma albumin content, plasma volume (PV) and blood biomarkers were measured before day 1 and post race on day 3. RESULTS: Fourteen cyclists (n = 7 per group) completed the race. PV increased in CHO (mean increase (95% CI), 10.2% (0.1 to 20.2)%, p = 0.045) but not in PRO (0.4% (- 6.1 to 6.9)%). Early diastolic transmitral blood flow (E) was unchanged but deceleration time from peak E increased post race (CHO: 46.7 (11.8 to 81.6) ms, p = 0.019; PRO: 24.2 (- 0.5 to 48.9) ms, p = 0.054), suggesting impaired LV relaxation. Tissue Doppler mitral annular velocity was unchanged in CHO, but in PRO septal early-to-late diastolic ratio decreased (p = 0.016) and was compensated by increased lateral early (p = 0.034) and late (p = 0.012) velocities. Systolic function was preserved in both groups; with increased systolic lateral wall velocity in PRO (p = 0.002). Effect size increase in serum creatine kinase (CK) activity, CK-MB and C-reactive protein concentrations was less in PRO than CHO (Cohen's d mean ± SD, PRO: 2.91 ± 2.07; CHO: 7.56 ± 4.81, p = 0.046). CONCLUSION: Ingesting casein hydrolysate with carbohydrate during a 3-day race prevented secondary hypervolemia and failed to curb impaired LV relaxation despite reducing tissue damage and inflammatory biomarkers. Without PV expansion, systolic function was preserved by lateral wall compensating for septal wall dysfunction.

Carbohydrate mouth rinse does not affect performance during a 60-min running race in women.

This study examined the effect of carbohydrate mouth rinsing on endurance running performance in women. Fifteen female recreational endurance runners, who used no oral contraceptives, ran two races of 1-h duration on an indoor track (216-m length) at 18:00 h after an 8-h fast with a 7-days interval between races, corresponding to the 3rd-10th day of each premenopausal runner's menstrual cycle, or any day for the postmenopausal runners. In a double-blind random order, participants rinsed their mouth with 25 ml of either a 6.4% carbohydrate (RCHO) or a placebo solution (RP). No fluid was ingested during exercise. Serum 17ß-Εstradiol (P = 0.59) and Progesterone (P = 0.35) did not differ between treatments. There was no difference in 1-hour running performance (RCHO: 10,621.88 ± 205.98 m vs. RP: 10,454.00 ± 206.64 m; t = 1.784, P = 0.096). Furthermore, the mean percentage effect (±99%CI) of RCHO relative to RP, 1.67% (-1.1% to 4.4%), and Cohen's effect size (d = 0.21) support a trivial outcome of RCHO for total distance covered. In conclusion, carbohydrate mouth rinsing did not improve 60-min track running performance in female recreational runners competing in a low ovarian hormone condition, after an 8-h fast and when no fluid was ingested during exercise.

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Changes in substrate utilisation and protein catabolism during multiday cycling in well-trained cyclists.

There is a paucity of studies that have evaluated substrate utilisation and protein catabolism during multiday strenuous exercise in athletes. Eleven well-trained male cyclists completed 3 h of race-simulated cycling on 4 consecutive days. Cyclist exercised 2 h postprandially and with carbohydrate supplementation (~50 g · h(-1)) during exercise. Whole body substrate utilisation was measured by indirect calorimetry, protein catabolism from sweat and urine urea excretion, and blood metabolite concentration was evaluated. Protein catabolism during exercise was significantly greater on days 2-4 (29.9 ± 8.8; 34.0 ± 11.2; 32.0 ± 7.3 g for days 2, 3, and 4, respectively) compared to day 1 (23.3 ± 7.6 g), P < 0.05. Fat oxidation was greater at 21 km (~45 min) on days 2-4 (1.06 ± 0.23; 1.08 ± 0.25; 1.12 ± 0.29 g · min(-1)) compared to day 1 (0.74 ± 0.23 g · min(-1), P < 0.05), but the rate of carbohydrate and fat oxidation was similar between days at 50 and 80 km. Whole body substrate utilisation is altered on subsequent days of multiday prolonged strenuous cycling that includes a quicker transition to greater fat utilisation from exercise onset and a 28-46% greater reliance on endogenous protein catabolism on all successive days.

Ingesting Isomaltulose Versus Fructose-Maltodextrin During Prolonged Moderate-Heavy Exercise Increases Fat Oxidation but Impairs Gastrointestinal Comfort and Cycling Performance.

Certain commercial carbohydrate replacement products include slowly absorbed carbohydrates such as isomaltulose. Few studies have investigated the metabolic effects of ingesting isomaltulose during exercise and none have evaluated exercise performance and gastrointestinal comfort. Nine male cyclists participated postprandially during three trials of 2-h steady-state (S-S) exercise (60%Wmax) followed by a 16 km time trial (TT) while ingesting 63 g·h-1 of either, 0.8:1 fructose: maltodextrin (F:M) or isomaltulose (ISO) or placebo- flavored water (PL). Data were analyzed by magnitude-based inferences. During S-S exercise, ISO and PL similarly increased plasma nonesterified fatty acid (NEFA) concentration (mean change ISO versus F:M: 0.18, 90%CI ±0.21 mmol·L-1, 88% likelihood) and fat oxidation (10, 90%CI ±9 g, 89% likelihood) while decreasing carbohydrate oxidation (-36, 90%CI ±30.2 g, 91% likelihood) compared with F:M, despite equal elevations in blood glucose concentration with ISO and F:M. Rating of stomach cramps and bloating increased progressively with ISO (rating: 0-90 min S-S, weak; 120 min S-S, moderate; TT, strong) compared with F:M and PL (0-120 min S-S and TT, very weak). TT performance was substantially slower with ISO (mean change: 1.5, 90%CI ±1.4 min, 94% likely harmful) compared with F:M. The metabolic response of ISO ingestion during moderate exercise to increase NEFA availability and fat oxidation despite elevating blood glucose concentration is anomalous for a carbohydrate supplement. However, ingesting isomaltulose at a continuous high frequency to meet the recommended carbohydrate replacement dose, results in severe gastrointestinal symptoms during prolonged or high intensity exercise and negatively affects exercise performance compared with fructose-maltodextrin supplementation.

Anaerobic power in road cyclists is improved after 10 weeks of whole-body vibration training.

Whole-body vibration (WBV) training has previously improved muscle power in various athletic groups requiring explosive muscle contractions. To evaluate the benefit of including WBV as a training adjunct for improving aerobic and anaerobic cycling performance, road cyclists (n = 9) performed 3 weekly, 10-minute sessions of intermittent WBV on synchronous vertical plates (30 Hz) while standing in a static posture. A control group of cyclists (n = 8) received no WBV training. Before and after the 10-week intervention period, lean body mass (LBM), cycling aerobic peak power (Wmax), 4 mM lactate concentration (OBLA), VO2peak, and Wingate anaerobic peak and mean power output were determined. The WBV group successfully completed all WBV sessions but reported a significant 30% decrease in the weekly cycling training time (pre: 9.4 ± 3.3 h·wk(-1); post: 6.7 ± 3.7 h·wk(-1); p = 0.01) that resulted in a 6% decrease in VO2peak and a 4% decrease in OBLA. The control group reported a nonsignificant 6% decrease in cycling training volume (pre: 9.5 ± 3.6 h·wk(-1); 8.6 ± 2.9 h·wk(-1); p = 0.13), and all measured variables were maintained. Despite the evidence of detraining in the WBV group, Wmax was maintained (pre: 258 ± 53 W; post: 254 ± 57 W; p = 0.43). Furthermore, Wingate peak power increased by 6% (668 ± 189 to 708 ± 220 W; p = 0.055), and Wingate mean power increased by 2% (553 ± 157 to 565 ± 157 W; p = 0.006) in the WBV group from preintervention to postintervention, respectively, without any change to LBM. The WBV training is an attractive training supplement for improving anaerobic power without increasing muscle mass in road cyclists.

Progression of changes in left ventricular function during four days of simulated multi-stage cycling.

This study investigated the effect of multi-stage cycling on left ventricular function with optimal carbohydrate and fluid replacement. Eleven well-trained cyclists completed 4 days of 3 h race-simulated cycling at an average intensity of 51.8 ± 2.8 %W (max) with carbohydrate supplements (50 g h(-1)). Left ventricular function was assessed by conventional echocardiography and tissue-Doppler imaging before and immediately after exercise on each day and a final recovery measurement on day 5. The rate of passive ventricular filling was persistently suppressed during repeated days of strenuous cycling (change in Septal E' wave pre to post-exercise: -3.9 ± 3.2; -1.0 ± 1.7; -1.9 ± 2.1; -2.2 ± 2.4 cm s(-1) for day 1-4, respectively) and was not completely restored before the subsequent exercise bout. Ejection fraction was significantly reduced post-exercise on day 1 and 2 (by -6.3 ± 7.1 and -6.8 ± 7.6%, respectively), whereas the change was not significant on day 3 and 4 (-3.8 ± 8.5 and -5.5 ± 10.6%, respectively), and may be partly due to the augmented rate of late diastolic filling (Septal A' wave) noted only on day 3 and 4. Finally, resting end-diastolic volume on day 5 (recovery day) was increased compared to day 1 before exercise (127 ± 23 and 108 ± 25 ml, respectively) and may indicate secondary hypervolemia; induced to further compensate for the cardiovascular strain of multi-day exercise. Strenuous prolonged cycling even with carbohydrate replacement is sufficiently stressful to impair cardiac function. As a multi-day cycling event progresses, cardiovascular strain is mitigated by adaptations that assist in restoring systolic function, while diastolic function remains impaired.

The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running.

Serum creatine kinase (CK) activity reflects muscle membrane disruption. Oestrogen has antioxidant and membrane stabilising properties, yet no study has compared the CK and muscle soreness (DOMS) response to unaccustomed exercise between genders when all menstrual phases are represented in women. Fifteen eumenorrhoeic women (early follicular, EF (n = 5); late follicular, LF (n = 5); mid-luteal, ML (n = 5) phase) and six men performed 20 min of downhill running (-10% gradient) at 9 km/h. Serum CK activity and visual analogue scale rating of perceived muscle soreness were measured before, immediately, 24-h, 48-h and 72-h after exercise. The 24-h peak CK response (relative to pre-exercise) was similar between women and men (mean change (95% confidence interval): 58.5 (25.2 to 91.7) IU/L; 68.8 (31.3 to 106.3) IU/L, respectively). However, serum CK activity was restored to pre-exercise levels quicker in women (regardless of menstrual phase) than men; after 48-h post exercise in women (16.3 (-4.4 to 37.0) IU/L; 56.3 (37.0 to 75.6) IU/L, respectively) but only after 72-h in men (14.9 (-14.8 to 44.6) IU/L). Parallel to the CK response, muscle soreness recovered by 72-h in men. Conversely, the women still reported muscle soreness at 72-h despite CK levels being restored by 48-h; delayed recovery of muscle soreness appeared mainly in EF and LF. The CK and DOMS response to downhill running is gender-specific. The CK response recovers quicker in women than men. The CK and DOMS response occur in concert in men but not in women. The DOMS response in women is prolonged and may be influenced by menstrual phase.

Radial and tibial bone indices in athletes participating in different endurance sports: a pQCT study.

Low magnitude bone-loading sports may benefit bone structure and strength in the exercised limbs. This study compared peripheral quantitative computed tomography measures of radial and tibial diaphyseal strength (strength-strain index, SSI), structure (total area (ToA) and cortical area (CoA), density (CoD) and thickness (CT), and circumferences), muscle cross-sectional area (MCSA) and strength (one-repetition maximum, 1-RM) in male endurance athletes taking part in (i) non-weight-bearing and non-impact sports: swimmers (SWIM, n = 13) and road cyclists (RC, n = 10), (ii) non-weight-bearing, impact sport: mountain bikers (MB, n = 10), (iii) weight bearing and impact sport: runners (RUN, n = 9). All athlete groups were also compared to sedentary controls (CON, n = 10). Arm MCSA, 1-RM and radial bone size and strength tended to be greater in SWIM than CON and/or RC (ToA, %difference ± 95%CI, SWIM-CON: 14.6% ± 12.7%; SWIM-RC: 12.9% ± 10.7%) but not different to MB and RUN. RUN had bigger tibial CoA than CON, SWIM and RC (CoA, RUN-CON: 12.1% ± 10.7%; RUN-SWIM: 10.9% ± 9.4%; RUN-RC: 15.8% ± 9.5%) without marked changes in tibial strength indices, lower-limb MCSA or 1-RM. Both MB and RC failed to display any difference in tibial indices, lower-limb MCSA and 1-RM compared to CON. In swimmers, the bone structure and strength of the primary exercised limbs, the arms, is greater than controls and road cyclists. Conversely, although runners experience impact and weight-bearing loading, tibial structure is greater without a substantial difference in tibial strength compared to controls and non-impact sports. Failure to observe a difference in tibial indices in MB and RC compared to controls is unexpected.

Comparison of energy supplements during prolonged exercise for maintenance of cardiac function: carbohydrate only versus carbohydrate plus whey or casein hydrolysate.

Cardiac function is often suppressed following prolonged strenuous exercise and this may occur partly because of an energy deficit. This study compared left ventricular (LV) function by 2-dimensional echocardiography and tissue Doppler imaging (TDI) before and after ∼2.5 h of cycling (2-h steady-state 60% peak aerobic power output plus 16 km time trial) in 8 male cyclists when they ingested either placebo, carbohydrate-only (CHO-only), carbohydrate-casein hydrolysate (CHO-casein), or carbohydrate-whey hydrolysate (CHO-whey). No treatment-by-time interactions occurred, but pre-to-postexercise time effects occurred selectively. Although diastolic function measured by pulsed-wave Doppler early-to-late (E/A) transmitral blood flow velocity was suppressed in all trials from pre- to postexercise (mean change post-pre exercise: -0.53 (95% CI -0.15 to -0.91)), TDI early-to-late (e'/a') tissue velocity was significantly suppressed pre- to postexercise only with placebo, CHO-only, and CHO-whey (septal and lateral wall e'/a' average change: -0.62 (95% CI -1.12 to -0.12); -0.69 (95% CI -1.19 to -0.20); and -0.79 (95% CI -1.28 to -0.29), respectively) but not with CHO-casein (-0.40 (95% CI -0.90 to 0.09)). LV contractility was, or tended to be, significantly reduced pre- to postexercise with placebo, CHO-only, and CHO-whey (systolic blood pressure/end systolic volume change, mm Hg·mL(-1): -0.8 (95% CI -1.2 to -0.4), p = 0.0003; -0.5 (95% CI -0.9 to -0.02), p = 0.035; and -0.4 (95% CI -0.8 to 0.04), p = 0.086, respectively), but not with CHO-casein (-0.3 (95% CI -0.8 to 0.1), p = 0.22). However, ejection fraction (EF) and ventricular-arterial coupling were significantly reduced pre- to postexercise only with placebo (placebo change: EF, -4.6 (95% CI -8.4 to -0.7)%; stroke volume/end systolic volume, -0.3 (95% CI -0.6 to -0.04)). Despite no treatment-by-time interactions, pre-to-postexercise time effects observed with specific beverages may be meaningful for athletes. Tentatively, the order of beverages with least-to-most variables displaying a time effect indicating suppression of LV function following exercise was CHO-casein < CHO-only and CHO-whey < placebo, and calls for further verification.

Radial bone size and strength indices in male road cyclists, mountain bikers and controls.

Mountain biking (MB), unlike road cycling (RC) involves exposure to ground impact bone strain and requires upper-body muscle forces to maintain stability over uneven terrain and therefore may have differential effects on radial bone structure and strength. This study aimed to compare serum bone turnover marker concentration, 1-repetition maximum muscle strength and the radial proximal (diaphysis) and distal (metaphysis) bone structure [bone mineral content, total and cortical area (CoA), density and thickness, diameter and circumference], strength strain indices and muscle cross-sectional area (MCSA) using peripheral quantitative computed tomography (pQCT) between 30 male cyclists (18-34 years) MB (n = 10), RC (n = 10) and non-athletes controls (CON, n = 10). Differences were assessed by ANOVA and an ANCOVA (adjusting for body mass and height) where appropriate. MB radii were characterised by significantly stronger (14-16%), denser (9-27%) and larger (10%) metaphyses and stronger (22-23%) and larger (11-13%) diaphyses compared to RC and CON. RC had significantly 7% higher strength indices and 4% greater CoA and thickness than CON at the diaphysis, with no differences for other bone measurements. Serum C-terminal telopeptides of type-1 collagen concentration (bone resorption marker) was higher in RC than MB (p < 0.05) and above the age-reference range. MCSA and strength were greater in MB than RC (p < 0.05). Muscle forces generated during RC appear to produce an osteogenic stimulus to increase radial bone strength indices with minimal improvement in bone structure. However greater resorptive activity in RC suggests inadequate loading to support bone maintenance. In conclusion, bone loading, muscle size and strength of MB are superior to RC.

Bone resorption is suppressed immediately after the third and fourth days of multiday cycling but persistently increased following overnight recovery.

Previous studies suggest that seasoned cyclists may incur a low bone mineral density. This study investigated the effect of multiday cycling on bone turnover. Ten male cyclists completed 4 consecutive days of cycling for 3 h·day(-1). Sweat calcium excretion during exercise and serum calcium, cortisol, bone formation marker (bone alkaline phosphotase (bone-ALP)), bone resorptive marker (C-terminal telopeptide of type I collagen (ß-CTX)), and parathyroid hormone concentration were measured before and immediately postexercise each day. Serum ß-CTX concentration increased from pre- to postcycling on days 1 and 2 (p = 0.01) (day 1: 0.31 ± 0.14 to 0.60 ± 0.4 ng·mL(-1); day 2: 0.58 ± 0.26 to 0.87 ± 0.42 ng·mL(-1)), while serum bone-ALP concentration remained unchanged. Conversely, on days 3 and 4 both serum ß-CTX (day 3: 0.60 ± 0.26 to 0.43 ± 0.26 ng·mL(-1), p < 0.05; day 4: 0.63 ± 0.21 to 0.43 ± 0.22 ng·mL(-1), p < 0.001) and bone-ALP (p < 0.01) response to exercise was suppressed. Interestingly, calcium lost to sweat and postexercise serum cortisol concentration were also significantly lower on days 3 and 4 than on day 1 (p < 0.05). However, both serum ß-CTX (102%-124%) and bone-ALP (25%-29%) remained persistently elevated after 21 h of overnight recovery on all successive days compared with day 1 pre-exercise, where the percentage increase was greater for ß-CTX (p < 0.05). Bone resorption, immediately following prolonged cycling, is acutely reduced by the third and fourth consecutive days and is coincident to reduced sweat calcium excretion and cortisol concentration. However, multiday cycling imposes a persistent increase in bone resorption following overnight recovery.

Oestrogen's regulation of fat metabolism during exercise and gender specific effects.

Early animal, menstrual phase and gender comparative studies inconsistently support an oestrogen-induced increase in fat oxidation during exercise. Recent advances from studies of cellular signalling and gene expression provide evidence for inter-tissue and intramuscular mechanisms that demonstrate oestrogen's promotion of skeletal muscle fat oxidative capacity. Oestrogen or oestrogen-analogues act mainly through oestrogen receptor-alpha in skeletal muscle to stimulate the genomic expression of certain other nuclear hormone receptors and downstream targets to promote long chain fatty acid (LCFA) uptake, mitochondrial shuttling and ß oxidation. Oestrogen increases the availability of LCFA substrate by enhancing adipocyte lipolysis and expression of genes promoting intramyocellular lipid storage. Oestrogen acts by non-genomic means to increase the activation of AMPK that may reinforce some direct genomic actions.

The effect of the menstrual cycle on exercise metabolism: implications for exercise performance in eumenorrhoeic women.

The female hormones, oestrogen and progesterone, fluctuate predictably across the menstrual cycle in naturally cycling eumenorrhoeic women. Other than reproductive function, these hormones influence many other physiological systems, and their action during exercise may have implications for exercise performance. Although a number of studies have found exercise performance - and in particular, endurance performance - to vary between menstrual phases, there is an equal number of such studies reporting no differences. However, a comparison of the increase in the oestrogen concentration (E) relative to progesterone concentration (P) as the E/P ratio (pmol/nmol) in the luteal phase in these studies reveals that endurance performance may only be improved in the mid-luteal phase compared with the early follicular phase when the E/P ratio is high in the mid-luteal phase. Furthermore, the late follicular phase, characterized by the pre-ovulatory surge in oestrogen and suppressed progesterone concentrations, tends to promote improved performance in a cycling time trial and future studies should include this menstrual phase. Menstrual phase variations in endurance performance may largely be a consequence of changes to exercise metabolism stimulated by the fluctuations in ovarian hormone concentrations. The literature suggests that oestrogen may promote endurance performance by altering carbohydrate, fat and protein metabolism, with progesterone often appearing to act antagonistically. Details of the ovarian hormone influences on the metabolism of these macronutrients are no longer only limited to evidence from animal research and indirect calorimetry but have been verified by substrate kinetics determined with stable tracer methodology in eumenorrhoeic women. This review thoroughly examines the metabolic perturbations induced by the ovarian hormones and, by detailed comparison, proposes reasons for many of the inconsistent reports in menstrual phase comparative research. Often the magnitude of increase in the ovarian hormones between menstrual phases and the E/P ratio appear to be important factors determining an effect on metabolism. However, energy demand and nutritional status may be confounding variables, particularly in carbohydrate metabolism. The review specifically considers how changes in metabolic responses due to the ovarian hormones may influence exercise performance. For example, oestrogen promotes glucose availability and uptake into type I muscle fibres providing the fuel of choice during short duration exercise; an action that can be inhibited by progesterone. A high oestrogen concentration in the luteal phase augments muscle glycogen storage capacity compared with the low oestrogen environment of the early follicular phase. However, following a carbo-loading diet will super-compensate muscle glycogen stores in the early follicular phase to values attained in the luteal phase. Oestrogen concentrations of the luteal phase reduce reliance on muscle glycogen during exercise and although not as yet supported by human tracer studies, oestrogen increases free fatty acid availability and oxidative capacity in exercise, favouring endurance performance. Evidence of oestrogen's stimulation of 5'-AMP-activated protein kinase may explain many of the metabolic actions of oestrogen. However, both oestrogen and progesterone suppress gluconeogenic output during exercise and this may compromise performance in the latter stages of ultra-long events if energy replacement supplements are inadequate. Moreover, supplementing energy intake during exercise with protein may be more relevant when progesterone concentration is elevated compared with menstrual phases favouring a higher relative oestrogen concentration, as progesterone promotes protein catabolism while oestrogen suppresses protein catabolism. Furthermore, prospective research ideas for furthering the understanding of the impact of the menstrual cycle on metabolism and exercise performance are highlighted.

Cycling time trial performance during different phases of the menstrual cycle.

Submaximal exercise performance has not previously been assessed in the late follicular phase of the menstrual cycle, which is associated with a pre-ovulatory surge in oestrogen. Therefore, we compared cycling time trial performance during the early follicular (EF), late follicular (LF) and mid-luteal (ML) phase of the menstrual cycle in trained and untrained eumenorrhoeic women who cycled 30 and 15 km, respectively, in a non-fasted state. The women completed the three cycling time trials on a conventional racing bicycle mounted on an air-braked ergometer. We required resting oestrogen to increase by at least twofold above EF phase values in both the LF and ML phases and this resulted in a number of exclusions reducing the sample size of each group. No significant difference was noted in the finishing time between the different menstrual phases in trained (n=5) or untrained (n=8) group, albeit limited by sample size. However, analysis of the combined trained and untrained group data (n=13) revealed a trend for a faster finishing time (P=0.027) in the LF phase compared to the EF phase as 73% of the subjects showed improvements with an average of 5.2+/-2.9% (or 2.1+/-1.1 min) in the LF phase (for alpha=0.05 requires P<0.017). Combined group analysis yielded no difference between performance in the EF and ML phase or between the LF and ML phase. Thus, further research is encouraged to confirm the tendency for a faster time trial in the LF phase, which coincides with the pre-ovulatory surge in oestrogen.

Effect of menstrual phase on the acetate correction factor used in metabolic tracer studies.

The acetate correction factor is used to account for retention of carbon label in exchange reactions of the tricarboxylic acid cycle in studies estimating free fatty acid oxidation with carbon-labeled tracers. Previous evidence indicates that substrate utilisation and metabolic rate vary across the menstrual cycle, which may alter the correction factor. We therefore derived the acetate correction factor for each of three menstrual phases (early follicular [EF], late follicular [LF], and midluteal [ML] phase) from the fractional recovery of 13CO2 from a constant infusion of sodium-[1-13C] acetate during 90 min of submaximal exercise (60% VO2-max) in sedentary eumenorrhoeic women. There was no difference in the correction factor between the EF and LF or the LF and ML phases, but the correction factor derived in the ML phase was significantly lower than in the EF phase (p < 0.05). Neither energy expenditure nor whole body substrate utilisation during exercise varied significantly between menstrual phases and therefore cannot explain the observed difference in the correction factor. The lower correction factor in the ML phase, compared to the EF phase, would result in only a small increase of -6% in the calculated plasma free fatty acid oxidation rate.