What we know about primary dysmenorrhea today: a critical review.

BACKGROUND: Primary dysmenorrhea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynecological condition that affects between 45 and 95% of menstruating women. Despite the high prevalence, dysmenorrhea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. This review reports on current knowledge, particularly with regards to the impact and consequences of recurrent menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhea. METHODS: Comprehensive literature searches on primary dysmenorrhea were performed using the electronic databases PubMed, Google Scholar and the Cochrane Library. Full-text manuscripts published between the years 1944 and 2015 were reviewed for relevancy and reference lists were cross-checked for additional relevant studies. In combination with the word 'dysmenorrhea' one or more of the following search terms were used to obtain articles published in peer-reviewed journals only: pain, risk factors, etiology, experimental pain, clinical pain, adenomyosis, chronic pain, women, menstrual cycle, hyperalgesia, pain threshold, pain tolerance, pain sensitivity, pain reactivity, pain perception, central sensitization, quality of life, sleep, treatment, non-steroidal anti-inflammatory drugs. RESULTS: Women with dysmenorrhea, compared with women without dysmenorrhea, have greater sensitivity to experimental pain both within and outside areas of referred menstrual pain. Importantly, the enhanced pain sensitivity is evident even in phases of the menstrual cycle when women are not experiencing menstrual pain, illustrating that long-term differences in pain perception extend outside of the painful menstruation phase. This enhanced pain sensitivity may increase susceptibility to other chronic pain conditions in later life; dysmenorrhea is a risk factor for fibromyalgia. Further, dysmenorrheic pain has an immediate negative impact on quality of life, for up to a few days every month. Women with primary dysmenorrhea have a significantly reduced quality of life, poorer mood and poorer sleep quality during menstruation compared with their pain-free follicular phase, and compared with the menstruation phase of pain-free control women. The prescribed first-line therapy for menstrual pain remains non-steroidal anti-inflammatory drugs, which are effective in relieving daytime and night-time pain. CONCLUSION: Further study is needed to determine whether effectively blocking dysmenorrheic pain ameliorates risk for the development of chronic pain disorders and to explore whether it is possible to prevent the development-and not just treat-severe dysmenorrheic pain in adolescent girls. In conclusion, we demonstrate the extensive multi-factorial impact of dysmenorrhea and we encourage and direct researchers to necessary future studies.

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.

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.

Reduced quality of life when experiencing menstrual pain in women with primary dysmenorrhea.

Primary dysmenorrhea is the most common gynecological condition among women of reproductive age. Although dysmenorrhea has been reported to affect the ability of women to carry out daily activities, the impact of primary dysmenorrheic pain specifically on quality of life (QoL), has yet to be elucidated. We investigated whether QoL varies between women with and without severe primary dysmenorrhea, and whether QoL is impaired only during menstruation or also during pain-free phases of the menstrual cycle. Twelve women with severe primary dysmenorrhea and nine control women completed the quality of life enjoyment and satisfaction questionnaire (Q-LES-Q-SF) during menstruation and during the late follicular phase. Women with dysmenorrhea had a significant reduction in Q-LES-Q-SF scores (mean ± SD: 54 ± 18%, percentage of the total maximum possible score) when they were experiencing severe menstrual pain compared with their own pain-free follicular phase (80 ± 14%, p < 0.0001) and compared with controls during menstruation (81 ± 10%, p < 0.0001). They also rated their overall life satisfaction and contentment as poorer during menstruation. Severe menstrual pain associated with primary dysmenorrhea, therefore, impacts health-related of QoL.

The 24-h progression of menstrual pain in women with primary dysmenorrhea when given diclofenac potassium: a randomized, double-blinded, placebo-controlled crossover study.

PURPOSE: Primary dysmenorrhea, which refers to painful, spasmodic cramping in the lower abdomen just before/or during menstruation, is the most common gynecological complaint in women of reproductive age. Non-steroidal anti-inflammatory drugs have been prescribed as the first-line therapy for pain relief from dysmenorrhea. We aimed to investigate the efficacy of the daily recommended dose (150 mg) of diclofenac potassium, administered at set intervals across the first 24 h of menstruation, in treating severe menstrual pain in 24 women with severe primary dysmenorrhea. METHODS: In a randomized, placebo-controlled, double-blind cross-over study, women rated their menstrual pain intensity on a 100-mm visual analog scale across set time intervals over a 24-h period. RESULTS: Menstrual pain intensity was significantly reduced after taking the first capsule of diclofenac, and remained consistently lower (P < 0.0001), compared with initial pain intensity, in the morning (before treatment), throughout the day, evening, and into the next morning. Also, women rated their pain intensity as significantly lower (P < 0.001) at each time point across the 24-h time interval of the cycle when receiving diclofenac compared with the cycle when they received placebo. No woman required rescue medication when taking diclofenac potassium compared with six women taking rescue medications during the placebo trial. When taking only placebo, women rated their menstrual pain intensity as persistently severe across the first 24 h of menstruation. CONCLUSION: These results show that the recommended daily dose of diclofenac potassium, in three 50 mg doses across the day and evening, offers effective menstrual pain relief across 24 h, compared with placebo, in women with severe primary dysmenorrhea.

Effects of short-term exercise training on tissue Doppler indices of left ventricular diastolic function in overweight and obese individuals.

Although exercise training is unable to improve obesity-associated decreases in left ventricular (LV) diastolic function, as assessed using chamber function measurements, the effects on LV diastolic myocardial function, as assessed using tissue Doppler imaging (TDI), are uncertain. In 32 overweight (n = 11) or obese (n = 21), sedentary or recreationally active men and women (30-57 years), we assessed the effects of 6 weeks of exercise training either preceded (n = 16) or followed (n = 16) by a 6-week control period on TDI indices of LV diastolic function (e', e'/a' and E/e') (echocardiography). Diastolic function at baseline was comparable to that noted in overweight and obese participants from a community sample (n = 245), and 56% (n = 18) had e' values below the lower 95% CI of a lean and healthy cohort (n = 60) of the community sample. Exercise training increased peak oxygen consumption (27.4 ± 4.9 to 29.4 ± 5.8 mL · kg(-1) · min(-1), P = 0.0001), but had no effect on body mass index (P = 0.99). No changes in TDI indices of diastolic function were observed after exercise training in all the participants (e': P = 0.74, a': P = 0.98, e'/a': P = 0.85, E/e': P = 0.26), participants with abnormal e' values (n = 18)(e': P = 0.99, a': P = 0.96, e'/a': P = 0.91, E/e': P = 0.97) or obese participants (n = 21)(e': P = 0.67, a': P = 1.00, e'/a': P = 0.78, E/e': P = 0.11). In conclusion, exercise training, despite increasing cardiorespiratory fitness, is unable to improve obesity-associated decreases in LV diastolic myocardial function.

A two-year history of high bone loading physical activity attenuates ethnic differences in bone strength and geometry in pre-/early pubertal children from a low-middle income country.

We examined the interplay between ethnicity and weight-bearing physical activity on the content and volumetric properties of bone in a pre- to early pubertal South African Black and White population. Sixty six children [Black boys, 10.4 (1.4)yrs, n=15; Black girls, 10.1 (1.2)yrs, n=27; White boys, 10.1 (1.1)yrs, n=7; White girls, 9.6 (1.3)yrs, n=17] reported on all their physical activities over the past two years in an interviewer administered physical activity questionnaire (PAQ). All participants underwent a whole body and site-specific DXA scan and we also assessed bone structure and estimated bone strength with pQCT. Children were classified as being either high or low bone loaders based on the cohort's median peak bone strain score estimated from the PAQ. In the low bone loading group, Black children had greater femoral neck bone mineral content (BMC) (2.9 (0.08)g) than White children (2.4 (0.11)g; p=0.05). There were no ethnic differences in the high bone loaders for femoral neck BMC. At the cortical site, the Black low bone loaders had a greater radius area (97.3 (1.3) vs 88.8 (2.6)mm(2); p=0.05) and a greater tibia total area (475.5 (8.7) vs. 397.3 (14.0)mm(2); p=0.001) and strength (1633.7 (60.1) vs. 1271.8 (98.6)mm(3); p=0.04) compared to the White low bone loaders. These measures were not different between the Black low and high bone loaders or between the Black and White high bone loaders. In conclusion, the present study shows that there may be ethnic and physical activity associations in the bone health of Black and White pre-pubertal children and further prospective studies are required to determine the possible ethnic specific response to mechanical loading.

Women with dysmenorrhea are hypersensitive to experimental deep muscle pain across the menstrual cycle.

UNLABELLED: Primary dysmenorrhea is a common painful condition in women that recurs every month across the reproductive years. The recurrent nociceptive input into the central nervous system that occurs during menstruation each month in women with dysmenorrhea is hypothesized to lead to increased sensitivity to painful stimuli. We investigated whether women with primary dysmenorrhea are hyperalgesic to deep muscle pain induced by a cleanly nociceptive method of hypertonic saline injection. Pain stimulation was applied both within an area of referred menstrual pain (lower back) and at a remote site outside of referred menstrual pain (forearm) in 12 healthy women with severe dysmenorrhea and 9 healthy women without dysmenorrhea, at 3 phases of the menstrual cycle: menstruation and follicular and luteal phases. Women rated their pain severity on a 100-mm visual analog scale every 30 seconds after injection until the pain subsided. In both groups of women, menstrual cycle phase had no effect on the reported intensity and duration of muscle pain. However, women with dysmenorrhea had increased sensitivity to experimental muscle pain both at the site of referred pain and at a remote nonpainful site, as assessed by peak pain severity visual analog scale rating, area under the visual analog scale curve, and pain duration, compared to women without dysmenorrhea. These data show that women with severe primary dysmenorrhea, who experience monthly menstrual pain, are hyperalgesic to deep muscle pain compared to women without dysmenorrhea. PERSPECTIVE: Our findings that dysmenorrheic women are hyperalgesic to a clinically relevant, deep muscle pain in areas within and outside of referred menstrual pain indicates lasting changes in pain sensitivity outside of the painful period during menstruation.

The clinical utility of accelerometry in patients with rheumatoid arthritis.

OBJECTIVES: To assess habitual physical activity levels in patients with RA compared with healthy control participants and to compare these measures with health-related quality of life and disease activity in the RA patients. METHODS. Fifty RA patients [age 48 (13) years] and 22 BMI, sex and geographically matched control participants were recruited. Habitual physical activity was measured using an Actical accelerometer worn on the hip for 2 consecutive weeks. Patients completed the Short Form-36 (SF-36) and modified Health Assessment Questionnaires (HAQ-DI). Disease activity was assessed using the Simplified Disease Activity Index (SDAI). RA patients were further categorized as more physically active (n = 25) and less physically active (n = 25) according to their average activity counts. RESULTS: The RA group spent more time in sedentary activity than the control group (71% vs 62% of the day respectively, P = 0.002) and had bimodal decreases in diurnal physical activity compared with the control group in the morning (P < 0.001) and late afternoon (P < 0.001). HAQ-DI, when adjusted for age and disease duration, was negatively correlated with physical activity in the RA group (r = -0.343, P = 0.026). The more physically active patients scored better than the less physically active patients on every component of the SF-36. CONCLUSION: Patients with RA lead a significantly more sedentary lifestyle than healthy controls and show diurnal differences in physical activity due to morning stiffness and fatigue. Higher levels of habitual physical activity may be protective of functional capacity and are highly associated with improved health-related quality of life in RA patients.

Effects of short-term exercise-training on aortic systolic pressure augmentation in overweight and obese individuals.

To determine whether exercise training-induced decreases in blood pressure (BP) can be explained by decreases in aortic systolic pressure augmentation in overweight or obese individuals. Thirty-five sedentary or recreationally active men and women (30-57 years) who were either overweight (40 %) or obese (60 %) completed 6 weeks of exercise training (≥3 days/week; stationary bike and/or treadmill) either preceded (n = 19) or followed (n = 16) by a 6-week control period of no exercise. Aortic augmentation pressure (AP), aortic and peripheral augmentation indices (AIx), and central aortic BP (SphygmoCor) were determined before and after exercise training and a control period. Peak oxygen consumption increased (p = 0.0001) from 27.0 ± 5.1 to 28.8 ± 5.8 mL/(kg min) after 6 weeks of exercise. Exercise training decreased brachial systolic (SBP) and diastolic BP from 142 ± 8/94 ± 8 to 134 ± 11/86 ± 11 mmHg (p < 0.005/p < 0.005); whereas no changes were observed after the control period (141 ± 11/91 ± 9 mmHg, p = 0.81/p = 0.34). Neither AP (baseline: 9.2 ± 4.2 mmHg; after 6 weeks training: 8.7 ± 6.1 mmHg), aortic AIx (baseline: 24.6 ± 11.0 %; after 6 weeks training: 22.7 ± 11.1 %), nor peripheral AIx (baseline: 81.4 ± 16.7 mmHg; after 6 weeks training: 76.4 ± 16.5 mmHg) were modified by exercise training. Although aortic SBP decreased after exercise (132 ± 8 to 124 ± 12 mmHg, p < 0.002), these changes were accounted for by decreases in mean arterial pressure. In overweight or obese individuals, although short-term aerobic exercise training, which improved cardiorespiratory fitness, may produce marked decreases in aortic and brachial BP; these effects are not attributed to alterations in aortic systolic pressure augmentation.

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.

Diclofenac potassium restores objective and subjective measures of sleep quality in women with primary dysmenorrhea.

STUDY OBJECTIVES: Primary dysmenorrhea is a common gynecological disorder that disrupts daytime functioning and nighttime sleep quality. We determined the effectiveness of diclofenac potassium, compared to placebo, in alleviating nighttime pain and restoring sleep architecture in women with primary dysmenorrhea. DESIGN: Randomized, double-blind, crossover study. SETTING: Sleep laboratory. PARTICIPANTS: Ten healthy women (21 +/- 1 years) with a history of primary dysmenorrhea. INTERVENTIONS: Placebo or diclofenac potassium (150 mg per day) for menstrual pain. MEASUREMENTS AND RESULTS: We assessed objective measures of sleep (polysomnography) and subjective measures of sleep quality, mood, and intensity of menstrual pain. Compared to a pain-free phase of the menstrual cycle (mid-follicular), women receiving placebo for their menstrual pain had a poorer mood (P < 0.01), decreased sleep efficiency (P < 0.05), less REM sleep (P < 0.05), more stage 1 sleep (P < 0.01), and more sleep stage changes per hour of sleep during the night. Administration of diclofenac potassium compared to placebo not only attenuated the women's menstrual pain (P < 0.05), but also increased sleep efficiency (P < 0.05) and percentage of REM sleep (P < 0.01), decreased percentage of stage 1 sleep (P < 0.05) and number of sleep stage changes per hour of sleep (P < 0.05), and improved subjective ratings of sleep quality and morning vigilance (P < 0.05). CONCLUSION: Diclofenac potassium effectively attenuates nighttime dysmenorrheic pain and restores subjective and objective measures of sleep quality to values recorded in a pain-free phase of the menstrual cycle.