Psychosocial predictors of healthy behaviours in women

The link between psychosocial factors and various health problems may be partially explained by the relationships of these factors to healthy behaviours. The relationships of anger experience, anger expression, hostility and hardiness to healthy behaviours was investigated in 97 healthy women. In multiple regression analysis, 25% of the variance in healthy behaviour was accounted for by hostility (12.5%), education (added 7.5%), and the combination of high anger experience/high anger-out (added an additional 5%). This was especially significant in view of the significant relationship of hostility to both anger experience and anger out. Although hardiness showed a significant positive correlation (r = 0.23 P less than 0.05) with healthy behaviours, it did not enter the multiple regression equation. The negative effects of hostility and chronic experience and overt expression of anger emerged as stronger than any positive association between hardiness and healthy behaviours. Implications for nursing include anger recognition and constructive management as areas of education and support. These interventions should assist women in managing their health better and will provide fruitful areas for further study.     

对围绝经期妇女心理干预的研究进展

围绝经期是女性卵巢功能从成熟到逐渐衰退的一个过渡期.医学科学认为,卵巢功能的逐渐衰退,引起丘脑-垂体-卵巢内分泌轴的功能失调,从而出现阵发性潮热、出汗、易疲劳等植物神经系统功能紊乱症候群,并出现焦虑、人际关系紧张、敏感多疑、抑郁等许多心理问题.本文对固绝经期妇女的心理特点和心理干预进行综述,为提高围绝经期妇女的健康水平提供依据.     

Electronic momentary assessment in chronic pain II: pain and psychological pain responses as predictors of pain disability

OBJECTIVES AND METHODS: More than 7,100 electronic diaries from 80 patients with chronic pain (mean: 89.3, range 30-115) entered multilevel analyses to establish the statistical prediction of disability by pain intensity and by psychological functioning (fear avoidance, cognitive, and spousal pain responses). We also tested the differences between pre-chronic, recently chronic, and persistently chronic pain in the prediction of disability (impaired physical and mental capacity, pain interference with activities, immobility due to pain). RESULTS: Pain intensity explained 8% to 19% of the disability variance. Beyond this psychological functioning explained 7% to 16%: particularly fear-avoidance and cognitive pain responses predicted chronic pain disorder disability; spousal responses predicted immobility better than other aspects of disability. Immobility due to actual pain occurred infrequently. When it did, however, it was better predicted by avoidance behavior in the patient and by spousal discouragement of movement than by actual pain intensity. The prediction of immobility due to pain by, respectively, avoidance behavior and catastrophizing was better in chronic pain (>6 months) and that of physical impairment by catastrophizing better in persistently chronic pain (>12 months) than in pain of shorter duration. DISCUSSION: The psychological prediction of chronic pain disorder disability was determined beyond that accounted for by pain intensity. Nonetheless, psychological functioning explained substantial variance in chronic pain disorder disability. The psychological prediction of immobility and physical impairment was stronger with longer pain duration. Patient characteristics and momentary states of disability-and in particular of immobility-should be carefully distinguished and accounted for in chronic pain disorder.     

Rapid suppression of S-PTH by oral calcitriol and calcium in healthy premenopausal women

The influence of oral calcium +/- cholecalciferol or calcitriol on S-PTH and whole blood ionized calcium (B-Ca++) in the very short term has not been elucidated. B-Ca++ and S-PTH were measured after overnight fast every 5 or 15 min for 4-h in 7 healthy premenopausal women (30-45 years) in a crossover design where the subjects were studied on 4 different days. Study 1: (control), 125-ml tap water (also given in studies 2-4); study 2: 1000 mg calcium, as calcium carbonate; study 3: 1000 mg calcium and 400 IU (5 microg) cholecalciferol; and study 4: 0.5 microg calcitriol plus 1000 mg calcium. Calcium plus 1,25(OH)2 vitamin D3 induced a rapid and significant fall in S-PTH compared to the control period (p < 0.02). Calcium alone or calcium plus cholecalciferol did not change the PTH levels significantly compared to control (water). B-Ca++ increased significantly after calcium plus 1,25(OH)2 vitamin D3 (p<0.01) and calcium plus cholecalciferol (p<0.05) compared to the control period. The B-Ca++ elevation was significantly higher after calcium plus 1,25 vitamin D3 than after calcium plus cholecalciferol (p<0.05). In conclusion, oral calcitriol plus calcium causes a rapid elevation in B-Ca++ and suppression of the PTH secretion also in the short term (hours).     

Electronic momentary assessment in chronic pain I: psychological pain responses as predictors of pain intensity

OBJECTIVES AND METHODS: Electronic momentary assessment was employed to substantiate the relevance of psychological functioning in chronic pain. More than 7,100 electronic diaries from 80 patients with varying IASP classified types of chronic pain served to investigate to what extent fear-avoidance, cognitive and spousal solicitous and punishing pain responses explained fluctuations in pain intensity and whether patients with pre-chronic, recently chronic and persistently chronic pain differed in this regard. RESULTS: Psychological pain responses explained 40% of the total variance in pain intensity: almost 24% concerned pain variance that occurred between the CPD patients and 16% pertained to pain variance due to momentary differences within these patients. Separately tested fear-avoidance and cognitive responses each explained about 28% of the total pain variance, while spousal responses explained 9%. Catastrophizing emerged as the strongest pain predictor, followed by pain-related fear and bodily vigilance. Results did not differ with the duration of chronicity. DISCUSSION: Exaggerated negative interpretations of pain, and fear that movement will induce or increase pain strongly predicted CPD pain intensity. Spousal responses-assessed only when the spouse was with the patient who at that moment was in actual pain-may more strongly affect immobility due to pain than pain intensity per se (see part II of the study). The findings substantiate the importance of catastrophizing, fear and vigilance identified primarily in low back pain and extend this to other forms of chronic pain. The compelling evidence of momentary within-patients differences underscores that these must be accounted for in chronic pain research and practice.     

Adrenocortical and hemodynamic predictors of pain perception in men and women

Research has demonstrated that women report more pain than men, and clinical observations suggest that attenuated adrenocortical activity is associated with high pain sensitivity. The extent to which cortisol concentrations and hemodynamics contribute to gender differences in pain sensitivity has not been investigated. Thirty-four women and 31 men performed the hand cold pressor test (CPT). Participants rated their pain every 15 s during a 90-s CPT and a 90-s post-CPT recovery period and reported pain using the McGill Pain Questionnaire (MPQ). Salivary cortisol samples and cardiovascular measures were collected prior to, during, and after the CPT. Women reported greater pain than men during and after the CPT and on the MPQ (Ps<0.01). CPT disrupted the expected diurnal decline in cortisol, as shown by a significant increase in cortisol concentration post-CPT (P<0.01) in men and women. Regression analyses revealed that pre-CPT cortisol concentrations predicted lower pain reports during and after CPT in men only (P<0.01). Systolic blood pressure (BP) and stroke volume correlated negatively with pain reports only in women (Ps<0.05). Controlling for potential confounding variables did not alter these relationships. The negative association between pre-CPT cortisol and pain perception in men and the association between BP and pain in women demonstrate different physiological predictors of pain perception in men and women.     

Relationship of regional fat distribution and obesity to electrocardiographic parameters in healthy premenopausal women

Abdominal obesity is an independent cardiovascular risk factor. The coexistence of abdominal obesity and electrocardiographic abnormalities may facilitate the development of cardiac arrhythmias and sudden death. We determined the relationship of body fat distribution and obesity to ECG indices in 27 obese premenopausal women on an isocaloric diet. Intra-abdominal fat distribution was assessed by computerized tomography, and obesity was assessed by hydrostatic weighing. The PR, QRS, and QTc intervals, the P and QRS axes, and the P-QRS angle were determined from a resting electrocardiogram. Cardiovascular risk profile was assessed by systolic and diastolic blood pressure and plasma cholesterol and triglyceride levels. Increased deposition of intra-abdominal fat was significantly associated with prolongation of the QTc interval independent of obesity and other cardiovascular risk factors. The prolongation of the QTc interval seen with increasing intra-abdominal fat distribution may enhance susceptibility to cardiac arrhythmias. These subjects should have electrocardiographic monitoring during periods of weight loss achieved by intensive regimens.     

Effect of insulin sensitivity on SHBG levels in premenopausal versus postmenopausal obese women

This study was performed to evaluate the impact of insulin sensitivity on sex hormone-binding globulin (SHBG) and sex steroids in premenopausal and postmenopausal euthyroid obese women. A total of 227 women were eligible for this study. All were euthyroid, obese, and overweight; ages ranged from 25 to 69 years. Women were divided into premenopausal (n=151) and postmenopausal (n=76) groups. SHBG, sex steroids, thyrotropin, fasting and postprandial glucose, lipid profile, uric acid, serum insulin, and blood pressure were measured. No significant difference was found in mean SHBG levels between premenopausal and postmenopausal women. The investigators observed that during transition from premenopause to postmenopause, SHBG levels increased in insulin-sensitive women in the postmenopausal group; however, SHBG levels decreased in insulinresistant women. It was concluded that SHBG blood concentration factors are likely to change during transition from premenopause to postmenopause. The positive effect of estradiol on SHBG levels is probably stronger in premenopausal women than in postmenopausal women. It has been noted that after menopause, the impact of insulin resistance on SHBG level seems more important than the effect of estradiol.     

Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans

Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.6 ± 1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4 ng/kg) or saline on 2 otherwise identical study days. Blood samples were collected 15 min before and 1, 2, 3, 4, and 6h after injection to characterize changes in immune parameters including proinflammatory cytokines. Rectal sensory and pain thresholds and subjective pain ratings were assessed with barostat rectal distensions 2h after injection. LPS administration induced an acute inflammatory response indicated by transient increases in tumor necrosis factor alpha, interleukin 6, and body temperature (all P<.001). The LPS-induced immune activation increased sensitivity to rectal distensions as reflected by significantly decreased visceral sensory and pain thresholds (both P<.05) compared to saline control. Visceral stimuli were rated as more unpleasant (P<.05) and inducing increased urge to defecate (P<.01). Pain thresholds correlated with interleukin 6 at +1h (r=0.60, P<.05) and +3h (r=0.67, P<.05) within the LPS condition. This report is novel in that it demonstrates that a transient systemic immune activation results in decreased visceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders.     

Investigating the effects of anxiety sensitivity and coping on the perception of cold pressor pain in healthy women.

Research indicates that anxiety sensitivity may be related to the negative experience of pain, especially amongst women. Further evidence with chronic pain patients indicates that anxiety sensitivity may result in avoidance pain-coping strategies. However, this effect has not yet been experimentally investigated in healthy groups. Therefore, the current study sought to investigate the effect of anxiety sensitivity and coping on women's responses to pain. Thirty women who were classified as high in anxiety sensitivity and 30 women classified as low in anxiety sensitivity participated. Within each anxiety sensitivity group, half the participants (n = 15) were randomly instructed to either focus on or avoid cold pressor pain sensations. As expected, women high in anxiety sensitivity were found to report higher levels of sensory and affective pain. Also, and consistent with previous research into anxiety sensitivity, no differences were found between anxiety sensitivity groups for measures of pain threshold or pain tolerance. The pain coping instruction manipulation was found to moderate pain experience, in that the avoidance strategy resulted in higher pain ratings compared to when instructed to focus. Finally, high anxiety sensitive women reported greater pain when instructed to avoid rather than focus on cold pressor pain. These results are discussed in light of previous research and future directions for pain management.     

Effects of elagolix on the pharmacokinetics of omeprazole and its metabolites in healthy premenopausal women

This study evaluated the effect of repeated doses of elagolix on the pharmacokinetics (PK) of omeprazole and its metabolites in healthy premenopausal female subjects. Adult premenopausal female subjects (N = 20) received a single oral dose of omeprazole (40 mg) on day 1 and day 11 and oral doses of elagolix (300 mg) twice‐daily on days 3–11. Serial blood samples for assay of omeprazole and its metabolites were collected for 24 h after dosing on days 1 and 11. PK parameters were calculated for omeprazole, 5‐hydroxyomeprazole and omeprazole sulfone; and were compared between day 1 and day 11. Pharmacogenetic testing was performed for CYP2C19 variant alleles and the results were used to compare the magnitude of elagolix–omeprazole drug–drug interaction (DDI) between the different genotype subgroups. Administration of elagolix 300 mg twice‐daily for 9 days increased omeprazole exposure by 1.8‐fold and decreased the metabolite‐to‐parent ratio for 5‐hydroxyomeprazole by ~60%. Conversely, there was an increase in the metabolite‐to‐parent ratio for omeprazole sulfone by 25%. Elagolix increased omeprazole exposures by 2‐ to 2.5‐fold in CYP2C19 extensive (EM) and intermediate (IM) metabolizer subjects, but decreased omeprazole exposures by 40% in poor metabolizer subjects. Exposures of 5‐hydroxyomeprazole decreased by 20%–30% in all genotype subgroups, and omeprazole sulfone exposures increased by ~3‐fold in EM and IM subjects. Elagolix is a weak inhibitor of CYP2C19 and exposure of CYP2C19 substrates may be increased upon coadministration with elagolix. Omeprazole may exhibit drug interactions due to multiple mechanisms other than CYP2C19‐mediated metabolism; complicating the interpretation of results from omeprazole DDI studies.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Elagolix is an inhibitor of P‐glycoprotein (P‐gp) and a weak‐to‐moderate inducer of cytochrome P450 3A (CYP3A4). In vitro, elagolix was identified as a possible inhibitor of CYP2C19 with potential to increase plasma concentrations of drugs that are substrates of CYP2C19 if they are coadministered with elagolix.

• WHAT QUESTION DID THIS STUDY ADDRESS?

What are the effects of elagolix on the pharmacokinetics of omeprazole and its metabolites in healthy subjects with different CYP2C19 genotypes and are P‐gp and/or CYP3A4 potentially involved in the interaction between elagolix and omeprazole?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study suggests that elagolix is a weak inhibitor of CYP2C19 and exposure of other CYP2C19 substrates may be increased upon coadministration with elagolix. These results also suggest P‐gp, CYP3A4, and/or another unknown mechanism may also be potential mechanisms for drug interactions with omeprazole.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Future DDI studies with omeprazole as a CYP2C19 substrate should consider that omeprazole may exhibit complex drug interactions due to multiple mechanisms mediating metabolism and transport, which may confound the interpretation of study results.     

Age-related increase in visceral adipose tissue and body fat and the metabolic risk profile of premenopausal women.

OBJECTIVE: Age-related differences in body fat and, more specifically, in the accumulation of abdominal visceral adipose tissue (AT) were examined as potential covariates of the age-related difference in the metabolic profile predictive of cardiovascular disease (CVD) risk observed in young, as compared with middle-aged, premenopausal women. RESEARCH DESIGN AND METHODS: Body composition, AT distribution, plasma lipoprotein-lipid levels, glucose tolerance, and plasma insulin concentrations were assessed in a sample of 122 young women (27.4+/-7.5 years, mean +/- SD) and compared with a sample of 52 middle-aged premenopausal women (49.5+/-5.3 years) who still had a normal menstrual cycle. RESULTS: Middle-aged women were characterized by elevated levels of total abdominal and visceral AT and greater body fat mass and waist circumference, as well as by higher plasma levels of total cholesterol, LDL cholesterol, apolipoprotein (apo)B, and LDL-apoB compared with younger women. Furthermore, middle-aged women showed a greater glycemic response to a 75-g oral glucose load than young women (P < 0.01). In both young and middle-aged subjects, visceral AT accumulation was significantly correlated with plasma triglyceride, apoB, and LDL-apoB levels and with the cholesterol/HDL cholesterol ratio, as well as with plasma glucose, insulin, and C-peptide levels measured in the fasting state and after the oral glucose load, and negatively correlated with HDL cholesterol levels (-0.41 < or = r < or = 0.65, P < 0.05). When variables were adjusted for levels of visceral AT and fat mass, age-related differences that were initially found in plasma apoB and LDL-apoB levels, as well as in fasting glycemia and glucose tolerance, were eliminated. CONCLUSIONS: Results of the present study suggest that even before the onset of menopause there is an age-related deterioration in the metabolic risk profile and an increase in visceral AT deposition in middle-aged women compared with young control subjects. Furthermore, our results provide support for the notion that the age-related increase in visceral AT accumulation is a significant factor involved in the deterioration of the CVD risk profile noted in premenopausal women with age.     

Sex hormone-binding globulin levels in middle-aged premenopausal women. Associations with visceral obesity and metabolic profile.

OBJECTIVE: Low sex hormone-binding globulin (SHBG) levels in women are associated not only with hyperinsulinemia, increased risk for cardiovascular disease, and type 2 diabetes but also with excess body fatness and abdominal obesity. We tested the hypothesis that an elevated total or intra-abdominal adipose tissue accumulation mediates the relationship between low SHBG levels and an altered metabolic profile. RESEARCH DESIGN AND METHODS: We measured body composition (dual-energy X-ray absorptiometry [DEXA]) and body fat distribution (computed tomography) in 52 middle-aged (46.7 +/- 0.4, mean +/- SEM) premenopausal women. Insulin and glucose responses to a 75-g oral glucose load and plasma lipid-lipoprotein levels were also measured. RESULTS: Low plasma SHBG concentrations were associated with increased total body fat mass (r = -0.41, P < 0.005) and subcutaneous abdominal (r = -0.39, P < 0.005) and intra-abdominal (r = -0.37, P < 0.008) adipose tissue area. Low SHBG was also associated with a greater insulin response to oral glucose (r = -0.40, P < 0.005), higher triglyceride levels (r = -0.29, P < 0.05), higher cholesterol/HDL cholesterol ratio (r = -0.51, P < 0.005), but lower HDL cholesterol concentrations (r = 0.65, P < 0.005). When matched for intra-abdominal fat or total fat mass, subjects with either low or high SHBG showed no difference in the insulin response to an oral glucose challenge. Statistical adjustment for differences in intra-abdominal adipose tissue accumulation or total body fat mass also eliminated the associations between SHBG levels and metabolic variables, with the exception of the association between SHBG and HDL cholesterol levels (r = 0.52, P < 0.005). CONCLUSIONS: Our results suggest that the previously reported relationship between low SHBG levels and increased metabolic disease risk in women is mediated, to a large extent, by concomitant variation in body fatness and intra-abdominal adipose tissue accumulation.     

Attentional and emotional mechanisms related to pain as predictors of chronic postoperative pain: A comparison with other psychological and physiological predictors

The present prospective longitudinal study on chronic postoperative pain was conducted to assess the predictive power of attentional and emotional variables specifically assumed to augment pain, such as pain hypervigilance, pain-related anxiety, pain catastrophizing and attentional biases to pain. Their relevance was determined in comparison with other psychological and physiological predictors (depression, anxiety, somatization, cortisol reactivity, pain sensitivity). In 84 young male patients the predictor variables were assessed one day before surgery (correction of chest malformation). Postoperative outcome (subjective pain intensity and pain-related disability) was assessed three (N = 84) and six months (N = 78) after surgery. Patients were classified into good and poor outcome groups. Patients with high pain intensity three (25%) or six months (14%) after surgery, differed significantly from those low in pain with regard to their preoperative performance in the dot-probe task (high attentional bias towards positive words). A sizeable portion (54%) of patients still felt disabled due to pain after three months and a few patients after six months (13%). These patients were those with high preoperative ratings in the Pain Vigilance and Awareness Questionnaire. The few subjectively disabled patients after six months could be identified in addition by low pressure pain and high cold pain thresholds before surgery. An attentional bias towards positive stimuli prior to surgery may indicate a maladaptive coping style, which avoids necessary confrontation with pain and predisposes patients to chronic postoperative pain. Lasting subjectively felt pain-related disability occurs predominantly in patients with high levels of pain hypervigilance before surgery.     

Patient-controlled analgesia: psychological predictors of pain experience,analgesic consumption and satisfaction

Introduction. The present study examines the relationship between different psychological variables (including anxiety, depression, locus of control, expectations of pain intensity and social support) and postoperative pain, analgesic consumption and satisfaction with the pain management in a study sample of 67 patients. Methods. Intravenous patient-controlled analgesia was used for postoperative analgesia. Pain intensity was assessed by numerical rating scales and obtained from the PCA-report. On the fourth day after surgery, the patients estimated retrospectively the pain intensity of the first day. Results. The results show that postoperative pain experience correlates significantly with several variables raised preoperatively. The retrospective variables were predicted by psychological measures. There was no relationship to the pain measurements of the PCA-report. Conclusions. While pain experience could be predicted by stable psychological traits, satisfaction was associated with the state variables, like anxiety and depression. It is precisely satisfaction with the pain therapy that could be improved by special preoperative psychological training and/or general information about the postoperative pain intensity.     

Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women

Premenopausal women may be most vulnerable to acute coronary syndromes at a point in their menstrual cycle when their plasma estrogen levels are the lowest during and immediately after menstruation. Metoprolol is a first-line drug in the management of patients with acute coronary syndrome; however, when metoprolol was marketed in 1982, women were largely excluded from clinical trials. Furthermore, the over-the-counter antihistamine diphenhydramine inhibited the metabolism of the CYP2D6 substrate metoprolol in healthy, young men with pharmacokinetic and pharmacodynamic consequences. The pharmacokinetics and pharmacodynamics of metoprolol and its interaction with diphenhydramine were investigated in a randomized, double-blind, crossover, placebo-controlled manner in healthy, premenopausal extensive (EM; n = 16) and poor metabolizer (PM; n = 4) women immediately after menstruation. During the placebo phase, EMs had between 5.2- and 8.4-fold higher total clearance (CL/F) of R- and S-metoprolol compared with PMs, whereas the latter had a 35% greater area under the effect curve (AUEC) and 60% greater EC(50) value for heart rate reduction than EMs (all P < 0.05). Diphenhydramine coadmininstration caused a 2.2- to 3.2-fold decrease in CL/F of metoprolol enantiomers with a resulting 21% increase in AUEC and 29% increase in EC(50) value for heart rate reduction in EMs (all P < 0.05). This is the first study to report an in-depth elucidation of metoprolol's pharmacokinetics and hemodynamics in premenopausal EM and PM women at a point in their menstrual cycle when vulnerability for acute coronary events may be greatest. Caution is warranted when the over-the-counter antihistamine diphenhydramine is part of a chronic therapeutic regimen.