Premenopausal Control Subjects Research Articles

Alterations in Haematological and Clotting Profile of Post-Menopausal Women in Benin City, Nigeria

Background: The cessation of ovarian functions at menopause and the accompanying decline in the production of ovarian steroid hormones creates a unique set of health concerns for women. Reductions in sex steroid levels, particularly oestrogen, have been associated with various diseases and conditions, including bleeding disorders, coronary heart disease (CHD), osteoporosis, cognitive dysfunction, urinary incontinence, hot flushes, and mood changes, among others.
 Objective: To determine changes in haemorheological and clotting profile in post-menopausal women.
 Methods: Two hundred participants comprising one hundred and fifty post-menopausal women and fifty healthy pre-menopausal control subjects were studied. The investigations carried out include whole blood viscosity, plasma viscosity, fibrinogen concentration, Prothrombin time (PT), Activated partial thromboplastin time with kaolin (APTTK) levels and complete blood count using standard methods.
 Results: The mean age (p = 0.01), platelet count (p = 0.013), neutrophil (p = 0.03), neutrophil to lymphocyte ratio (p = 0.045) and platelet to lymphocyte ratio (p = 0.044) in postmenopausal women were significantly higher while lymphocyte count (p = 0.004) was significantly lower in postmenopausal compared to premenopausal women. Similarly, plasma oestradiol (p = 0.001), plasma viscosity (p = 0.03), relative blood viscosity (p = 0.03), whole blood viscosity (p = 0.03) and PTTK (p = 0.04) were significantly lower among postmenopausal women compared to premenopausal control subjects.
 Conclusion: Relative plasma viscosity correlated positively with age. There were significantly lower levels of haemorheological and clotting profile in post-menopausal women. These changes may be due to age or a decline in circulating oestrogen levels.

Antioxidant Status of Breast, Cervical and Ovarian Cancer Patients at Various Menopausal Stages in Lagos State, Nigeria

Cancer is a collection of diseases which involves the abnormal growth of cells with the potential to invade or spread to other parts of the body. The aim of this study is to access the antioxidant status of women with female predominant cancer (breast, cervical and ovarian) in relationship with their menopausal stages. Blood samples were collected from 180 freshly diagnosed female patients of breast, cervical and ovarian cancer at Lagos State University Teaching Hospital, Idi- Araba, Mushin, Lagos and Lagos State University Teaching Hospital Ikeja, Lagos and 60 relatively healthy subjects at different menopausal stages. Serum catalase (CAT), Superoxide dismutase (SOD) activites, Reduced Glutathione (GSH), Vitamin C and E concentrations were evaluated in subject’s blood sample using standard established methods. The results obtained were subjected to statistical analysis (p<0.05). However, the results of the female cancer patients at each menopausal stage were compared to premenopausal, menopausal and postmenopausal control groups, while the results obtained from the menopausal and postmenopausal control subjects were compared to the premenopausal control subjects. There was significant decrease (p<0.05) in the activities of CAT, SOD and in the concentrations of GSH, Vitamins C and E in all the menopausal stages when compared to the control groups. However, MDA concentrations showed significant increase (p<0.05) in all the menopausal stages in comparison to the corresponding control groups. These findings suggest that cancer patients might be at risk from oxidative cell damage. Therefore, further research is required in this field with a view of improving the management of cancers predominant in females.

MicroRNAs 182 and 375 Sera Expression as Prognostic Biochemical Markers in Breast Cancer

IntroductionBreast cancer (BC) is the most common malignancy among women; supporting the need for identification of novel prognostic biomarkers, circulating microRNAs (miRNAs) could serve as such in various cancers. The aim of this study was to explore the association between miRNAs 182 and 375 with BC stages and its receptors, based on their expression using real time PCR. Materials and MethodsDetailed medical history was taken and blood samples were withdrawn from 80 female subjects divided over the studied groups. Patients ranged in age from 24 to 80 years and were classified as follows: group I included 10 noncancerous postmenopausal control subjects; group II included 32 postmenopausal patients with BC; group III included 10 noncancerous premenopausal control subjects; group IV included 24 premenopausal patients with BC; and group V included 6 patients with benign breast tumors. ResultsmiRNA 182 expression was significantly higher in group II, group IV, and group V (3.36 ± 0.14, 2.52 ± 0.34, and 4.93 ± 0.3,9 respectively); miRNA 375 expression was significantly higher in group II, group IV, and group V (4.41 ± 0.40, 3.12 ± 0.35, and 11.28 ± 2.37, respectively) (P < .05). Both miRNAs were significantly associated with each other and with receptors used for the prognosis of BC even after multiple regression analysis. ConclusionAccordingly, miRNAs 182 and 375 could be potential noninvasive markers used for the follow up of BC patients.

Genetic polymorphisms of insulin-like growth factor 1 and insulin-like growth factor binding protein 3, xenoestrogen, phytoestrogen, and premenopausal breast cancer.

Previous studies suggest a combined effect of insulin-like growth factor 1 (igf-1) and igf binding protein 3 (igfbp-3) gene polymorphisms, xenoestrogen, and phytoestrogen on the igf-1 signalling pathway and serum concentrations in the igf system, which are associated with premenopausal breast cancer (bca) risk. Between 2010 and 2012, our study recruited 140 premenopausal bca patients and 160 community-based premenopausal control subjects. Participants were surveyed about oral contraceptive (oc) use, dietary habits, and other bca risk factors. TaqMan assays were used to determine igf-1 rs1520220 and igfbp-3 rs2854744 genotypes. Daily intakes of energy-adjusted soy isoflavones (easis) were calculated by the residual method. Multivariate logistic regression was applied to estimate the adjusted odds ratios (ors) and 95% confidence intervals (cis) of the igf-1 rs1520220 and igfbp-3 rs2854744 genotypes, oc use, and intake of easis. Stratified analyses were performed to detect the gene-environment combined effect, and multivariate logistic regression was used to estimate interaction coefficients (iors) by the multiplicative model, with 95% cis. The delta method was used to calculate interaction coefficients by the additive model [relative excess risk of interaction (reri), attributable proportions of interaction (apis)] and 95% cis. The igf-1 and igfbp-3 genotypes, oc use, and easis were not found to be associated with bca risk (p > 0.05). Stratified analysis showed that the risk of bca was markedly increased in women carrying the igfbp-3C allele and using ocs compared with women either carrying the igfbp-3C allele or using ocs (or: 3.02; 95% ci: 1.04 to 8.79). The interaction coefficients ior, reri, and api were 4.89 (95% ci: 1.09 to 21.90), 2.42 (95% ci: -0.76 to 5.61), and 0.80 (95% ci: 0.46 to 1.67) respectively. The igfbp-3 rs2854744 polymorphism and oc use might synergistically increase premenopausal bca risk.

Increased Serum Osteocalcin Levels in Elderly Females with Vitamin D Deficiency

Serum levels of osteocalcin (OC), a 49 amino acid bone matrix protein, have been found to be a biochemical parameter of bone formation. In order to study bone metabolism in aging subjects we measured serum levels of OC, parathyroid hormone (PTH) and 25 hydroxy-vitamin D (25 OH Vit D) in 36 institutionalized elderly females (age range: 80-93 years) and in 21 premenopausal control subjects. Serum levels of 25 OH Vit D were significantly decreased in the elderly subjects (p less than 0.0001), whereas serum levels of OC and PTH were significantly higher in the elderly subjects than in the controls (p less than 0.0025 and p less than 0.0001, respectively). Serum OC levels correlated significantly with the serum PTH levels (p less than 0.009). Our data demonstrate that in elderly females with vitamin-D deficiency secondary hyperparathyroidism is associated with increased serum OC levels indicating an increased bone formation; these conditions might contribute to the bone disease of geriatric patients.

Premenopausal advantages in postprandial lipid metabolism are lost in women with type 2 diabetes.

Women with type 2 diabetes appear to lose the protection against cardiovascular disease afforded by estrogens. We examined the effects of menopausal status on postprandial clearance of dietary fat in healthy and diabetic women. Fasting subjects (premenopausal and postmenopausal control subjects, premenopausal and postmenopausal diabetic women, all n = 8) were given a meal containing the stable isotope 1,1,1-(13)C-tripalmitin, with blood and breath sampled for 6 and 24 h, respectively, in the postprandial period. Lower levels of (13)C-palmitic acid ((13)C-PA) in the triglyceride fraction implies more efficient chylomicron clearance, lower levels of (13)C-PA in the nonesterified fatty acid (NEFA) fraction implies improved dietary NEFA entrapment, and higher levels of (13)CO(2) in the breath denote more efficient of oxidation of dietary-derived lipid. In diabetic women, there were no differences between the pre- and postmenopausal groups for any of these parameters. In contrast, premenopausal control subjects, compared with postmenopausal control subjects, had lower (13)C-PA in the triglyceride fraction area under the curve (AUC) (premenopausal median [range] 25.2 [12.1-49.4 mmol/l] per 6 h, postmenopausal 48.5 [15.5-77.2 mmol/l] per 6 h; P < 0.01) and higher (13)CO(2) levels in the breath AUC (premenopausal 22.5 [18.0-31.5%] of administered dose, postmenopausal 17.2 [11.2-31.5%] of administered dose; P < 0.01) with no difference between groups in levels of (13)C-PA in the NEFA fraction AUC. The premenopausal advantage in clearance of dietary lipid is not seen in premenopausal diabetic women. This is likely to promote an atherogenic lipoprotein profile and may contribute to the loss of cardiovascular disease protection seen in diabetic women.

Determinants of increased energy expenditure in HIV-infected women

Little is known about sex-specific effects of HIV infection on energy expenditure. We investigated the determinants of energy expenditure in HIV-infected women. Resting energy expenditure (REE), body composition, and hormonal and nutritional indexes were compared in 33 ambulatory, premenopausal HIV-infected women and 26 weight-matched, healthy premenopausal control subjects. REE was determined by indirect calorimetry and body composition by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis, and skinfold-thickness analysis. Hormonal indexes included leptin, testosterone, estradiol, and insulin-like growth factor I. HIV-infected subjects had a higher REE than control subjects [6794 +/- 1374 compared with 6011 +/- 607 kJ/d (1624 +/- 329 compared with 1437 +/- 145 kcal/d), P = 0.0096]. On average, REE was 119 +/- 23% of Harris-Benedict predictions in HIV-infected subjects compared with 102 +/- 9% for control subjects (P = 0.0007). In HIV-infected subjects, REE was highly correlated with fat-free mass (FFM) by DXA (R = 0.641, P < 0.001), but not with weight or disease status. The slope of the regression equation for REE and FFM was significantly greater (P = 0.027, analysis of covariance) for HIV-infected subjects [REE (kJ/d) = 203.5 (kg FFM) - 1237] than for control subjects [REE (kJ/d) = 77.4 (kg FFM) + 2923]. In a stepwise regression analysis, FFM was the most significant variable (P = 0.005), followed by free testosterone (P = 0.029), which together explained 49% of the variation in REE. The final equation was REE (kJ/d) = 230.8 (kg FFM) + 395.9 (free testosterone, pmol/L) - 3304. Energy expenditure was higher in HIV-infected women than in control women. FFM is the primary determinant of REE in HIV-infected women, but energy expenditure is greater per kg FFM in HIV-infected subjects than in control subjects, which may contribute to the wasting syndrome.

Estrogen receptor expression in benign breast epithelium and breast cancer risk.

Estrogen exposure is a major risk factor for breast cancer. Increased estrogen responsiveness of breast epithelium may enhance this effect. We examined the relationship between breast cancer diagnosis and 1) the presence and absence of estrogen receptor expression in benign breast epithelium, 2) the level of expression and 3) its variation during the menstrual cycle, and 4) other established risk factors. e.g., age, age at menarche, parity, and family history. We measured estrogen receptor expression (as % of positive cells) by immunohistochemistry in normal breast epithelium from 376 women undergoing diagnostic or therapeutic breast surgery. Data on established risk factors were collected prior to surgery and those on menstrual cycle dates at the time of surgery. Logistic regression was used to assess risks (odds ratios [ORs]). The crude OR for breast cancer in women with estrogen receptor-positive breast epithelium versus those without was 3.16 (95% confidence interval [CI] = 1.89-5.28), with an OR of 2.49 (95% CI = 1.25-4.96) for premenopausal and an OR of 3.32 (95% CI = 1.43-7.68) for postmenopausal women. The ORs remained high and statistically significant after controlling for age and other breast cancer risk factors. The level of estrogen receptor expression was higher in patients with breast cancer than in control subjects and it was related to breast cancer risk in postmenopausal women (P trend <.005). Expression declined as expected in premenopausal control subjects as the menstrual cycle progressed but rose in breast cancer patients (P trend <.015). The overexpression of estrogen receptors in normal breast epithelium may augment estrogen sensitivity and hence the risk of breast cancer.

Bone mineralization in women following successful treatment of Hodgkin's disease

Purpose: Women with Hodgkin's disease in whom a cure has been achieved may be at risk for osteoporosis because of therapy-induced premature menopause. Our objective was to gather information regarding the integrity of bone mass in such long-term cancer survivors. SUBJECTS AND METHODS: Bone mineral density was measured using photon absorptiometry in five groups of women: 11 patients with Hodgkin's disease and ovarian failure (Group I); six patients with Hodgkin's disease and ovarian failure who received estrogen replacement (Group II); 15 patients with Hodgkin's disease and normal ovarian function (Group III); 16 premenopausal control subjects (Group IV); and 11 postmenopausal control subjects (Group V). All patients with Hodgkin's disease were in remission and had completed treatment more than five years earlier. Results: Subjects in Group I were found to have significantly decreased radial (p = 0.0009), lumbar spine (p = 0.002), and femoral neck (p = 0.0001) bone mineral density measurements compared with those in subjects in Group IV; the bone mineral density measurements at all sites of subjects in Group I were no different than those of subjects in Group V. Subjects in Group III had bone density measurements that were similar to those in Group IV, although the radial bone mineral density value was significantly lower (p = 0.0004). Determination of serum gonadotropins and estradiol was consistent with the menstrual status defining the five groups. No secondary causes for decreased bone mineral density values could be detected, since the mean serum levels of parathyroid hormone, calcium, phosphorus, and vitamin D metabolites were similar among the groups, and all prolactin levels were normal. Conclusion: We have identified a new population of patients with a high risk of osteoporosis, and these results emphasize the importance of treatment-related ovarian failure in the pathogenesis of osteoporosis.

Elevations in skin temperature of the finger as an objective index of postmenopausal hot flashes: Standardization of the technique

The present study was designed to validate and standardize a technique of continuous recording of skin temperature of the finger as an objective index of hot flashes. Significant skin temperature rises (>1° C) were recorded in close temporal relationship to 69% of subjective hot flashes experienced by seven postmenopausal women. The temperature elevations occurred at an interval of 54 ± 10 minutes (mean ± standard error) and lasted an average of 31 minutes. The mean increase was 2.7° ± 0.2° C. The extent of the temperature elevations found in the postmenopausal subjects was significantly greater than in premenopausal control subjects (P < 0.05) and was reduced by estrogen treatment (P < 0.02). This study substantiates that the recording of skin temperature changes of the finger provides and objective index of hot flashes. This should assist in the investigation of the underlying disturbance and provide more accurate evaluation of modes of therapy.