Middle-aged Premenopausal Women Research Articles

Association between Bone-Specific Physical Activity Scores and Measures of Areal and Volumetric Bone Mineral Density and Bone Markers in Middle-Aged Premenopausal Women

The bone-specific physical activity questionnaire (BPAQ) has been shown to be related to areal bone mineral density (aBMD), but its relation to bone architecture and bone markers has not been well studied. PURPOSE: The purpose of this study was to investigate the relationship between a total BPAQ score (tBPAQ), aBMD, volumetric BMD (vBMD, mg/cm3), and bone markers in middle-aged premenopausal women. METHODS: Thirty-four premenopausal women (44.4 ± 4.1 years; 161.7 ± 5.4 cm; 69.9 ± 11.1 kg) were recruited for this study. aBMD of L1-L4 and dual proximal femur (TH; total hip, FN; femoral neck) were measured using Dual Energy X-ray Absorptiometry. We assessed vBMD of tibia 4% (ToD; total vBMD, trabecular vBMD), 38% (ToD, CoD; cortical vBMD, SSI; strength strain index), and 66% (ToD, CoD, SSI) by peripheral quantitative computed tomography. Bone formation (Bone ALP) and bone resorption (TRAP5b) markers were assessed. The tBPAQ was used to obtain a comprehensive account of lifetime physical activity related to bone health. RESULTS: Spearman’s correlation showed significant (p<0.05) positive relationships between tBPAQ and aBMD of right FN(r=.370) and left femur (TH, r=.373; FN, r=.372) and L1-L4 (r=.371), but no significant relationship was found for the right TH (p>0.05). There were no significant correlations between vBMD variables and tBPAQ. Also, no relationships were found between tBPAQ and bone ALP and TRAP5b (p>0.05). When tBPAQ, bone free lean body mass (BFLBM), calcium intake, and age were included in a stepwise multiple linear regression analysis, BFLBM was the only predictor of tibia 38% and 66% SSI, accounting for 16% (p=0.012) and 27% of the variance (p=0.001), respectively. CONCLUSION: The tBPAQ score-derived physical activity had positive relationships with FN, TH, and L1-L4 aBMD in healthy middle-aged premenopausal women, but no significant associations were found between tBPAQ and both vBMD and bone markers. Table 1. tBPAQ and aBMD (g/cm2).Table: No title available.

Effect of short-term aerobic and combined training program on body composition, lipids profile and psychological health in premenopausal women

Summary Purpose The purpose of this study was to investigate the effect of short-term (eight weeks) aerobic and combined training program on the body composition, lipids profile and psychological health (depression), and to compare which training method is more effective in middle-aged premenopausal sedentary women. Methods Sixty-four women aged 35–45 years (age = 38.8 ± 3.0 years) were divided into three groups: Aerobic training, Combined training and the control group and women exercised during eight weeks. The subjects’ body composition was measured with anthropometric tape and skinfold caliper and also body fat percentage, fat mass and lean body mass were estimated using BIA. Total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein and also Beck Depression Inventory scores were registered at before and after eight weeks training. Results Aerobic training and combined training showed significant differences in fat percentage (−2.6%Δ, −4.2%Δ, and 0.2%Δ, P = 0.044 respectively) and fat mass (−5.5%Δ, −5.7%Δ, and 1.1%Δ, P = 0.034 respectively) compared to the control group. Considering the waist circumference, there was a significant difference only between the combined training and control group (−1.3%Δ, −2.6%Δ, and 0.5%Δ, P = 0.048 respectively). Aerobic training and combined training groups showed significant differences in total cholesterol (−7.9%Δ, −9.7%Δ, and 0.9%Δ, P = 0.022 respectively), triglyceride (−5.8%Δ, −6.9%Δ, and 2.0%Δ, respectively, P = 0.012), atherogenic index (−13.5%Δ, −16.0%Δ, and 2.3%Δ, P = 0.000 respectively) and Beck Depression Inventory score (−26.2%Δ, −24.7%Δ, and 8.7%Δ, P = 0.047 respectively) compared to the control group. Conclusion The results of this study suggest that both training methods could be used for loosing body weight, fat mass and fat percentage for middle-aged women. Although the combined training seems a little more efficient, aerobic training is also practically easier in order to control and maintain in a large scale training groups.

Screening for Cardiometabolic Risk Profile in Middle Aged Premenopausal Indian women

Background: Prevalence of several cardio metabolic risk factors, especially central obesity and dyslipidemia, places women in high risk group for development of insulin resistance and atherosclerosis. Physiological and hormonal in women acts as an additional risk factor for such disease. The burden of cardio metabolic risk in middle aged pre-menopausal women need to evaluated thoroughly. Objective: The study was designed to assess cardio metabolic risk profile and to evaluate association of traditional risk factors of metabolic syndrome with obesity and atherogenic markers in middle aged pre-menopausal Indian women. Materials and Methods: One hundred and thirty seven randomly selected female subjects ( age 25-45 years) were evaluated for prevalence of various cardio metabolic risk factors. The parameters studied included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), blood pressure, ECG, fasting blood glucose level and lipid profile of the subject. The association between various traditional risk factors of metabolic syndrome and the obesity and atherogenic markers of the subject was evaluated. Results: The overall prevalence rate of metabolic syndrome in middle aged pre-menopausal women was found to be 28.99%. The rate of incidence of metabolic syndrome increases with advancement of age. The most common individual component of metabolic syndrome in subject was central obesity followed by altered lipid profile. All the traditional risk factors of metabolic syndrome were found to very with WC, WHR and TG/HDL-C ratio of the subject. Conclusion: The result of the present study suggest that central obesity followed by altered lipid profile are the main causative factors for development of metabolic syndrome in pre-menopausal middle aged Indian women. Obesity markers like waist circumference and waist –hip ratio and TG/HDL-C ratio can be used to predict metabolic syndrome in this group of subjects. Key words: Metabolic syndrome, Premenopausal women , TG/HDL-C, WC, WHR.

A rare inguinal mass: Round ligament leiomyoma

INTRODUCTIONLeiomyoma of the round ligament is a rare condition and usually appears like an inguinal hernia. PRESENTATION OF CASEWe report a case of a 40 year-old women found to have an inguinal mass which it was finally diagnosed as leiomyoma.The patient was admitted to our hospital with a history of painless groin mass. The mass was thought to be irreducible inguinal hernia. Surgical exploration demonstrated a round ligament leiomyoma. DISCUSSIONA smooth muscle tumor in the round ligament of the uterus in the inguinal region is a rare entity and can be mistaken for an irreducible inguinal hernia. It is a rare condition occurring predominantly in premenopausal middle-aged women. Abdominal, inguinal, and vulvar locations have been described. Surgical excision is the curative treatment. CONCLUSIONLeiomyoma of the round ligament should be entertained as a possible etiology of inguinal mass.

Vocal Characteristics of Middle-Aged Premenopausal Women

Aging influences the laryngeal anatomy and physiology, leading to altered vocal quality. In middle-aged women, the voice is affected by a combination of aging and menopausal transition. However, in many studies about vocal aging, the menopausal transition is not taken into account. The purpose of this study was to measure and describe the effect of aging on the vocal characteristics by comparing young women (between 20 and 28 years) and middle-aged premenopausal women (between 45 and 52 years). To determine the vocal characteristics in both groups, objective (aerodynamic measurements, vocal performance measurements, acoustic analysis, and a determination of the Dysphonia Severity Index) and subjective assessment techniques (perceptual evaluation, videostroboscopic evaluation, and Voice Handicap Index) were used. The middle-aged premenopausal women showed a smaller frequency and intensity range, a lower habitual fundamental frequency, and a higher soft phonation index compared with the young women. The results of this study are important when studying the voices of middle-aged women. Vocal characteristics of middle-aged women differ from young women, and these changes cannot only be because of hormonal changes during the menopause.

Plasma adiponectin and insulin sensitivity in overweight and normal-weight middle-aged premenopausal women

Adiponectin has been reported to regulate systemic insulin sensitivity as a part of a broader control mechanism in energy balance. However, it is not clear whether adiponectin exerts its positive effects on insulin sensitivity equally in a wide range of obesity. We investigated the association of plasma adiponectin concentration with insulin resistance (IR) in a cross-sectional sample of 98 middle-aged premenopausal women with a wide range of obesity. In addition, we studied the relationship between adiponectin, body composition, and blood biochemical and cardiorespiratory fitness variables. Body composition and fat distribution were measured via dual-energy x-ray absorptiometry in normal-weight (NW) (n = 41, body mass index [BMI] <25 kg/m 2) and overweight (OW) (n = 57, BMI ≥25 kg/m 2) women. Fasting blood samples were obtained; adiponectin, leptin, insulin, glucose, and insulin-like growth factor–I were measured; and IR index was calculated. The IR index from fasting plasma insulin and plasma glucose levels was estimated using the homeostasis model assessment (HOMA), as follows: fasting plasma insulin (in microliter units per milliliter) × fasting plasma glucose (in millimoles per liter)/22.5. Adiponectin was significantly higher ( P = .0001) in NW (14.7 ± 4.7 μg/mL) compared with OW (9.9 ± 3.1 μg/mL) women. Significant differences ( P < .003) in body mass, BMI, percentage of fat mass, fat mass, trunk fat, trunk fat–leg fat ratio, leptin, insulin, and HOMA were also observed between NW and OW groups. Leptin was independently related to plasma adiponectin ( β = −.259, P = .001) in the overall study group. Plasma adiponectin was only related to trunk fat–leg fat ratio ( β = −.242, P = .002) among NW subjects, whereas plasma adiponectin was related to fat-free mass ( β = .182, P = .0001) and HOMA ( β = −.576, P = .002) among OW women. The inverse relationship between adiponectin and leptin concentrations suggests that leptin may be involved in the regulation of adiponectin in middle-aged premenopausal women. Our data also demonstrate that adiponectin may play an important role in sustaining insulin sensitivity only in OW middle-aged premenopausal women.

Effects of Self-Foot Reflexology on Stress, Fatigue and Blood Circulation in Premenopausal Middle-Aged Women

This study was to examine the effects of self-foot reflexology on stress, fatigue and blood circulation in premenopausal middle-aged women. A quasi-experimental nonequivalent control group, pretest-posttest design was used. Participants were 59 premenopausal, middle-aged women in their 40s and 60s living in G city: 30 in the experiment group and 29 in the control group. Data were collected from May to August 2008. Self-foot reflexology was performed three times a week for 6 weeks for 40 min at each session. The results showed that self-foot reflexology was effective in reducing perceived stress and fatigue and helped blood circulation in premenopausal middle-aged women. Self-foot reflexology may be an effective nursing intervention in reducing perceived stress and fatigue and in improving blood circulation.

Association between bone mineral density, lean mass, and fat mass among healthy middle-aged premenopausal women: a cross-sectional study in southern Sri Lanka

Associations between lean mass, fat mass, and bone mass have been reported earlier; however, most of those studies have been done in Caucasian populations, and data from Asian countries, especially those in South Asia, are limited. We examined the associations between lean mass, fat mass, bone mineral density (BMD), and bone mineral content (BMC), determined by dual-energy X-ray absorptiometry technology, in a group of healthy, middle-aged, premenopausal female volunteers. The mean (SD) age of the women (n = 106) was 42.1 (6.1) years and the mean (SD) body mass index was 24.3 (3.6) kg/m(2). Total body BMD, total body BMC, and BMD in total spine, total hip, and femoral neck showed statistically significant partial correlations (adjusted for age) with total fat mass (r = 0.19-0.43, P < 0.05) and lean body mass (r = 0.28-0.54, P < 0.05). Truncal fat mass correlated positively with total body BMC and BMD at total hip and femoral neck (r = 0.33-0.40, P < 0.001). When a stepwise regression model was fitted, lean mass remained the strongest predictor of total body BMD, total body BMC, and total spine BMD (regression coefficients = 0.004-0.008 g/cm(2) per 1-kg change in lean mass, P < 0.001). Similarly, crude BMD and BMC increased across the tertiles of lean mass (P trend < 0.05). We show that lean mass is the strongest predictor of total body BMC and BMD at different sites, although positive correlations with fat mass also exist.

24-Hour Serum Levels of Growth Hormone, Prolactin, and Cortisol in Pre- and Postmenopausal Women: The Effect of Combined Estrogen and Progestin Treatment

Our objective was to study the 24-h profiles of GH, prolactin (PRL), and cortisol concentrations in older postmenopausal and middle-aged premenopausal women, before and after estrogen-progestin treatment (EPT). The study was a randomized, placebo-controlled, double-blind trial. GH, PRL, and cortisol were sampled every 20 min for 24 h in 18 postmenopausal (aged 58-70 yr) and 17 premenopausal (aged 45-51 yr) women before and after 6 months of EPT. The mean 24-h GH (1.0 vs. 1.8 mU/liter, P = 0.033) and PRL (6.8 vs. 10.0 ng/ml, P = 0.009) concentrations were lower in postmenopausal than in premenopausal women. After EPT, the postmenopausal GH and PRL did not differ from premenopausal baseline levels. Postmenopausal mean 24-h GH (P < 0.001) and PRL (P = 0.002), daytime GH (P < 0.001) and nighttime PRL (P = 0.004) were higher during EPT compared with placebo. Cortisol levels did not differ. Premenopausal mean nighttime PRL (P = 0.026) and cortisol (P = 0.018) were higher during EPT compared with placebo. Postmenopausal PRL and premenopausal GH and PRL concentrations were higher at night than during the day. EPT did not alter this pattern. Menopause was associated with decreased 24-h levels of GH and PRL, which were reversible with EPT. In contrast, cortisol levels were not affected by menopause or EPT. In middle-aged premenopausal women, the studied effects of EPT were limited to nighttime increases of PRL and cortisol.

Adiponectin is a predictor of bone mineral density in middle-aged premenopausal women

Adipose-modulated biochemical signal that explains some of the association between fat mass and bone mineral density (BMD) is adiponectin. The results demonstrated an independent association between adiponectin and BMD, while the influence of adiponectin on bone mineral content is mediated by fat free mass in middle-aged women. Positive association between fat mass (FM) and bone mineral density (BMD) is mediated by biochemical factors. The relationship between plasma adiponectin concentration and BMD in 98 sedentary premenopausal women aged 38-49 years with a body mass index range of 20.0-42.1 kg/m(2) was examined. Different body composition and blood biochemical parameters were measured to adjust for possible confounding variables. The association between adiponectin and BMD values (total BMD: beta = -0.919; p = 0.0001, femoral neck BMD: beta = -0.925; p = 0.0001 and lumbar spine BMD: ss = -0.912; p = 0.0001) was independent of the influences that measured body composition, hormonal and insulin resistance factors may exert on BMD (p < 0.02). However, adiponectin explained only 3-12% of the variations in measured BMD variables. Similarly, adiponectin was associated with total bone mineral content (BMC; beta = -0.911; p = 0.0001) and remained associated in different analyses that controlled for possible confounding parameters (p < 0.01). However, the association between adiponectin and total BMC was no longer significant when adjusted for fat free mass (FFM; p > 0.21). Adiponectin is an independent predictor of BMD, while its independent contribution to the interindividual variance in measured values is only modest. The influence of adiponectin on total BMC is mediated or confounded by FFM in middle-aged premenopausal women.

Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables

The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but <7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) <30 kg/m(2). Adiponectin values were higher (P < 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/- 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P < 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P < 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle-aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status.

Middle-Aged Premenopausal Women With Type 1 Diabetes Have Lower Bone Mineral Density and Calcaneal Quantitative Ultrasound Than Non-diabetic Women

Middle-Aged Premenopausal Women With Type 1 Diabetes Have Lower Bone Mineral Density and Calcaneal Quantitative Ultrasound Than Non-diabetic Women

Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy

The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissues. Because fat-free mass is largely determined by its protein content, ovarian hormones would exert control through their effects on protein balance. Thus, we examined the effect of menopausal status and hormone replacement therapy on protein turnover. Healthy, middle-aged premenopausal (n=15; 49 ± 1 yr) and postmenopausal (n=18; 53 ± 1 yr) women were studied. Premenopausal women were tested at one timepoint. Post-menopausal women were tested before and two months following treatment with oral conjugated estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg; HRT; n=9) or placebo (n=9). Whole body protein breakdown, oxidation and synthesis were measured under postabsorptive conditions using [13C]leucine. No differences in whole body protein breakdown, oxidation or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when sub-groups (n=10) of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on body composition or whole body protein breakdown, synthesis or oxidation. Thus, our results suggest no detrimental effects of ovarian hormone deficiency coincident with the postmenopausal state and no beneficial effect of ovarian hormone repletion with HRT on whole body protein turnover. Grant support NIH AG 15821, AG13978, AG021602.

Middle-Aged Premenopausal Women With Type 1 Diabetes Have Lower Bone Mineral Density and Calcaneal Quantitative Ultrasound Than Nondiabetic Women

To determine whether middle-aged premenopausal women with type 1 diabetes had more self-reported fractures and lower bone mineral density (BMD) compared with nondiabetic women. Participants were premenopausal women aged 35-55 years with type 1 diabetes (n = 67; 32.2 +/- 5.3 years duration) and without diabetes (n = 237). Total hip, femoral neck, whole-body, and spine BMD were measured by dual X-ray absorptiometry. Calcaneal broadband ultrasound attenuation (BUA) was assessed with quantitative ultrasound. Women with type 1 diabetes were more likely to report a fracture after age 20 years compared with nondiabetic women (33.3 vs. 22.6%; age-adjusted odds ratio 1.89 [95% CI 1.02-3.49]). Type 1 diabetes was associated with lower total hip BMD (0.890 vs. 0.961 g/cm2; P < 0.001), femoral neck BMD (0.797 vs. 0.847 g/cm2; P = 0.001), whole-body BMD (1.132 vs. 1.165 g/cm2; P < 0.01), and lower calcaneal BUA (71.6 vs. 84.9 dB/MHz; P < 0.001) after multivariate adjustment. BMD was 3-8% lower in type 1 diabetic compared with control women and calcaneal BUA was 15% lower. Spine BMD and biomarkers of bone remodeling were not significantly different between groups. In the type 1 diabetic women, reduced monofilament detection and blindness were both associated with lower BMD. Lower BMD in premenopausal women with type 1 diabetes may substantially increase their risk of developing osteoporosis after menopause. Type 1 diabetic women should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause.

Plasma Adrenal Androgens and Risk of Breast Cancer in Premenopausal Women

Abstract Objectives: Plasma DHEA and its sulfate (DHEA-S) are positively associated with breast cancer risk in postmenopausal women; but the relationships have not been studied in detail in premenopausal women. We prospectively evaluated relationships between plasma levels of DHEA and DHEA-S in blood samples provided by a group of primarily premenopausal women and subsequent breast cancer, by use of case-control sampling from the Nurses' Health Study cohort. Method: Blood samples were collected from 1989 to 1990. Among women who were not postmenopausal at blood collection, 302 were diagnosed with breast cancer between blood collection and June 1998. Two controls were selected per case and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at blood collection. Statistical analyses using conditional logistic regression were done to adjust for potential confounders. Results: At time of blood collection, the median age was 49 (10th to 90th percentiles 45 to 53). In multivariable analyses, the highest quartile of DHEA was associated with an odds ratio of breast cancer of 0.92 (95% confidence interval, 0.59-1.43) relative to the lowest quartile (P value for log-linear trend 0.11). A similar analysis revealed an odds ratio of 1.08 (0.69-1.69) for DHEA-S (P value for log-linear trend 0.83). No statistically significant interactions were noted according to certainty of menopausal status, age, or past oral contraceptive use. Discussion: Our analysis did not reveal a relationship between DHEA or DHEA-S and subsequent breast cancer in middle-aged premenopausal women. In the future, this relationship should be studied in younger women.

Adherence to Hormone Replacement Therapy: A Longitudinal Study Using the Theory of Planned Behaviour

The aim of this longitudinal study was to assess the stability and determinants of the intention to adopt HRT over a one-year period using the Theory of Planned Behaviour. At baseline, a total of 644 middle-aged premenopausal women who had never used HRT, were recruited. At follow-up, 417 women completed an interview to assess any change in their reproductive status and in their behavioural intention. Among women who stayed premenopausal (n = 172) and among those who became perimenopausal (n = 209), the intention to adopt HRT was quite stable over the one-year period. However, being perimenopausal had a significant effect on the intention to adopt HRT at follow-up, as did subjective norm, perceived behavioural control and moral norm measured at baseline. Attitude towards HRT did not have a significant effect on the intention to adopt HRT one year later. Therefore, interventions to support women's decision-making about HRT should be tailored to their menopausal status and take into account their perception of social pressure to perform, control over this behaviour and moral obligation.

Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women.

Studies in animal models suggest that ovarian hormone deficiency is associated with the development of insulin resistance. In women, ovarian hormone levels are dramatically reduced after the menopause transition. However, the effect of the menopause transition on insulin sensitivity is unclear. Thus, we examined the effect of menopausal status on insulin sensitivity. Insulin-stimulated glucose disposal was measured in 43 middle-aged premenopausal women (47 +/- 3 years of age) during the luteal phase of the menstrual cycle and 40 early postmenopausal women (51 +/- 4 years; time since menopause, 21 +/- 13 months) using the hyperinsulinemic-euglycemic clamp technique. Body composition was measured by dual-energy X-ray absorptiometry and abdominal fat distribution by computed tomography No difference in fat-free mass (FFM) was found between groups. Total body (P < 0.01), subcutaneous abdominal (P < 0.05), and intra-abdominal (P < 0.01) adiposity were greater in postmenopausal women compared with premenopausal women. No differences in insulin-stimulated glucose disposal were found between premenopausal and postmenopausal women on an absolute basis (pre, 436 +/- 130 vs. post, 446 +/- 120 mg/min), when expressed relative to FFM (pre, 10.7 +/- 3.0 vs. post, 11.5 +/- 3.6 mg x kg(-1) FFM x min(-1)) or when statistically adjusted for FFM (pre, 436 +/- 125 vs. post, 445 +/- 126 mg/min). These results suggest that menopausal status does not affect insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique.

A natural experiment on the effects of ovarian hormones on cardiovascular risk factors and stress reactivity: bilateral salpingo oophorectomy versus hysterectomy only.

To test the effects of declining ovarian hormone levels on cardiovascular risk factors, blood pressure, lipids, weight, and physiological responses to stress were evaluated in 29 middle-aged premenopausal women prior to and following elective hysterectomy and/or bilateral salpingo oophorectomy (BSO). Prior to surgery, there were no group differences in standard or putative risk factors, with the exceptions of body composition measures and total cholesterol level. After surgery, women who had undergone BSO (n = 10) had higher levels of atherogenic lipids and stress-induced lipids and tended to have higher circulating levels of epinephrine and stress-induced systolic and diastolic blood pressure than women who had undergone hysterectomy only (n = 19). This study is consistent with the hypothesis that presence of ovarian hormones plays a key role in determining women's risk factor status.

EFFECT OF GENDER AND MENOPAUSAL STATUS ON THE PHARMACOKINETICS OF TIRILAZAD MESYLATE IN HEALTHY SUBJECTS

The pharmacokinetics of tirilazad were assessed in men ages 40--60 years, women <40 years of age, premenopausal women ages 40--60, and postmenopausal ages 40--60. Eight subjects in each group received single 3.0 mg kg(minus sign1) intravenous infusions of tirilazad mesylate over 10 min. Plasma concentrations of tirilazad and U-89678, an active metabolite, were measured by high-performance liquid chromatography. Tirilazad administration was well tolerated in all groups. Mean tirilazad clearance was 59.6% higher in young women compared to the middle-aged men (35.6 plus minus 8.04 L h(minus sign1) vs. 22.3 plus minus 8.40 L h(minus sign1)). Mean tirilazad clearance in middle-aged women was 30.7% higher than in middle-aged men. Mean clearance in postmenopausal women (26.1 plus minus 4.21 L h(minus sign1)) was not significantly different than that in middle-aged men, but clearance corrected for body weight was significantly different between the men and postmenopausal women. Clearance in premenopausal middle-aged women (32.2 plus minus 7.60 L h(minus sign1)) was not significantly different from that in young women and was 44% greater than that in middle-aged men. Mean AUC(0minus signinfty infinity) and C(max) values for U-89678 were significantly higher in men than in all of the female groups. Among the women, values for U-89678 AUC(0minus signinfty infinity) were lowest in young women (467 plus minus 345 ng h ml(minus sign1), 8.8% of male value) and highest in postmenopausal women (1565 plus minus 1382 ng h ml(minus sign1), 29.4% of male value). The absolute values for U-89678 AUC(0minus signinfty infinity) must be interpreted with caution, as limited assay sensitivity and low plasma concentrations in the latter portion of the concentration-time profile in women precluded accurate determination of the terminal half-life and AUC(0minus signinfty infinity). Regardless, these results show that women, particularly premenopausal women, have lower concentrations of U-89678, an active metabolite of tirilazad, than are achieved in men. The gender differences in tirilazad and U-89678 pharmacokinetics are of sufficient magnitude that they may impact the clinical response of male and female patients to tirilazad treatment.

Influence of the Perimenopause on Cardiovascular Risk Factors and Symptoms of Middle-Aged Healthy Women

Matthews, Karen A.; Wing, Rena R.; Kuller, Lewis H.; Meilahn, Elaine N.; Plantinga, PamAuthor Information