Konstantinos Panoulis

Mammographic changes associated with raloxifene and tibolone therapy in postmenopausal women : A prospective study

Objective The prolonged use of estrogen therapy is associated with a slightly increased risk of breast cancer. Alternative therapies that are effective in the prevention of menopause, having associated morbidities but no unwanted effects, are of primary interest in the pharmacologic research. The aim of this study was to evaluate the effect of two alternative to estrogens drugs, the selective estrogen receptor modulator raloxifene and the tissue-specific tibolone, on the mammographic appearance of the breast. Design The study group comprised 131 postmenopausal women aged 41 to 67 years. The women were at least 2 years postmenopausal, free of climacteric symptoms, and at the time of entry to the study had not had therapy for at least 9 months. Women with risk factors for osteoporosis or cardiovascular disease were allocated either to tibolone (n = 56) or raloxifene (n = 48) therapy. Women with no risk factors and women who either did not qualify for or denied treatment (n = 27) served as controls. The study duration was 12 months. Women received a baseline mammogram before commencing therapy and a repeat mammogram at the end of the study period. Mammogram findings were classified according to the modified Wolfe criteria by two expert radiologists. Results No difference was identified between groups with respect to baseline characteristics associated with breast cancer risk. Similarly, no difference was detected between groups concerning the modified Wolfe classification of baseline mammographic findings. In the tibolone group, 10.7% of the women showed an increase in breast density in the 12-month reevaluation. The respective figure in the raloxifene group was 6.3%, whereas no woman in the control group showed an increase in breast density. Differences in the increase in breast density between groups did not, however, reach statistical significance. Accordingly, 10.7% of women in the tibolone group and 18.8% of women in the raloxifene group exhibited involutionary changes in the repeat mammogram, whereas 25.9% of women in the control group revealed a decrease in breast density in the 12-month examination. The percentages were not significantly different between groups. Conclusions Breast density as shown by mammography was stable in a majority of patients and changed in a minority of cases for both tibolone and raloxifene. In most patients, these drugs are not likely to interfere with mammogram interpretation. Larger long-term studies are needed to confirm the impact of prolonged tibolone or raloxifene administration on mammography.

The effect of various regimens of hormone replacement therapy on mammographic breast density

OBJECTIVES To evaluate the effect of three distinct hormone replacement therapy regimens on mammography. METHODS 121 postmenopausal women who had never received or were past users of hormone replacement therapy were studied prospectively. Women with an intact uterus were randomly allocated either to conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, n=34) or to 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E(2)/NETA, n=35). Hysterectomized women received CEE 0.625 mg (CEE, n=25). Women who either declined or did not qualify for treatment served as controls (n=27). Treatment was continuous and the study period lasted 12 months. Main outcome measures were the changes according to Wolfe classification between baseline and 12-month-mammograms. RESULTS No increase in breast density was identified in any of the women in the control group. Two women (8%) in the CEE group showed an increase in breast density. Four women (11.8%) in the CEE/MPA and 11 women (31.4%) in the E(2)/NETA group revealed an increase in breast density. No woman in the therapy groups showed an involution of fibroglandular tissue while seven women (25.9%) in the control group exhibited involution of breast parenchyma. CONCLUSIONS Our study suggests that hormone replacement therapy may suspend breast involution but does not increase breast density in the majority of patients. In the minority of patients who show a density increase, the magnitude of this increase varies according to the regimen employed.

Perinatal mortality in diabetic pregnancy

Perinatal mortality rate (PMR) is one of the most important perinatal health indicators. PMR in diabetic pregnancies varies throughout the world and is higher than the background PMR. The prevalence of pregestational diabetes is increasing and is associated with an elevated risk of congenital malformations, macrosomia, preeclampsia, and preterm delivery. The incidence of PMR in preexisting diabetes mellitus ranges considerably, with congenital abnormalities and preterm labor the main factors contributing to the higher PMR. Women with gestational diabetes mellitus or impaired glucose tolerance are a mixed group that may have low to a high PMR, especially if they require insulin in their pregnancy. All the known diabetic women should plan their pregnancies and optimize glycemic control periconceptually and throughout pregnancy, as this reduces the frequency of congenital abnormalities, obstetric complications, and perinatal mortality.

Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype.

Objective: The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. Methods: This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima–media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Results: Women with the PCOS phenotype (N = 43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46 ± 1.74 vs. 8.60 ± 1.51 m/s, P = 0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Conclusion: Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life.

Association between serum tumor necrosis factor-α and corticotropin-releasing hormone levels in women with preterm labor

Aim:  To evaluate the association of serum corticotropin‐releasing hormone (CRH) and tumor necrosis factor‐α (TNF‐α) in preterm labor.

Maternal serum levels of neutrophil gelatinase‐associated lipocalin (NGAL), matrix metalloproteinase‐9 (MMP‐9) and their complex MMP‐9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study

The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase‐associated lipocalin (NGAL), matrix metalloproteinase‐9 (MMP‐9), and MMP‐9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA).

Prevalence of vasomotor, psychological, psychosomatic and sexual symptoms in perimenopausal and recently postmenopausal Greek women: association with demographic, life-style and hormonal factors

Aim: To assess the prevalence of climacteric symptoms and their association with demographic, life-style and hormonal parameters in Greek peri- and recently postmenopausal women. Methods: 1025 Greek women who were either perimenopausal or within their first 5 postmenopausal years participated in this cross-sectional observational study. Menopausal symptoms were assessed by the Greene Climacteric Scale and were tested for associations with demographic, anthropometric, life-style and hormonal parameters. Results: 29.8% Of the women reported moderate to severe menopausal symptoms. More specifically, 39.2% reported vasomotor, 21.3% psychological, 6.3% psychosomatic and 34.5% sexual symptoms. Years since menopause (r = 0.13, p < 0.01), waist circumference (r = 0.11, p < 0.05) as well as serum FSH, LH and estradiol (r = 0.15, r = 0.118, r = −0.157; p < 0.01) correlated with the intensity of menopausal symptoms. In the multivariate analysis years since menopause and serum estradiol were the only significant predictors of menopausal symptoms (b = −0.158 and b = −0.198, p < 0.001, respectively), explaining though only 4.8% of the variance. Conclusion: One out of three Greek women has moderate to severe climacteric symptoms during the menopause transition or the first postmenopausal years. This frequency is comparable to other White populations. Menopausal age and endogenous estrogens are significant predictors of climacteric symptoms.

Greek-origin royal jelly improves the lipid profile of postmenopausal women.

Abstract Aim: Menopause transition is associated with chronic conditions such as osteoporosis and cardiovascular disease. Concerns about the long-term safety of menopausal hormone therapy make alternative natural methods an appealing approach to management. The aim of this study was to examine the effect of royal jelly (RJ) on cardiovascular and bone turnover markers in clinically healthy postmenopausal women. Methods: A total of 36 postmenopausal healthy women were studied in a prospective follow-up study. Participants received 150 mg of RJ daily for three months. Circulating cardiovascular risk markers [lipid profile, antithrombin-III (ATIII), Protein C, Protein S, Plasminogen Activator Inhibitor-1 (PAI-1)] and bone turnover parameters [Total calcium, phosphate (P), parathormone (PTH), total type-1 Procollagen N-terminal (P1NP), Osteocalcin and serum collagen type 1 cross-linked C-telopeptide (CTX)] were compared between the baseline and the three-month visit. Results: The RJ used in this study was particularly rich in medium chain fatty acids, compounds with hypolipidemic properties, which comprised 63% of the dry weight fatty content. RJ treatment resulted in a significant increase in high density lipoprotein – cholesterol (HDL-C 60.2 mg/dL ± 12.3 versus 64.7 mg/dL ± 13.9, 7.7% increase, p = 0.0003), as well as in a significant decrease in low density lipoprotein – cholesterol (LDL-C, 143.9 ± 37.5 versus 136.2 ± 32, 4.1% decrease, p = 0.011) and in total cholesterol (224.4 ± 38.6 to 216.1 ± 36.5, 3.09% decrease, p = 0.018). No statistical significant changes were found in the remaining cardiovascular or the bone turnover parameters. Conclusions: The intake of RJ 150 mg for three months is associated with significant improvements of the lipid profile of postmenopausal women. RJ supplementation may offer an alternative method of controlling the menopause – associated dyslipidemia.

Indices of adiposity and thyroid hormones in euthyroid postmenopausal women

OBJECTIVE We aimed to evaluate the association between thyroid hormones and indices of obesity in a sample of euthyroid postmenopausal women. DESIGN Cross-sectional study. METHODS Serum levels of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) as well as BMI and waist:hip ratio (WHR) were evaluated in 194 healthy euthyroid postmenopausal women. Ultrasonography was used to assess abdominal fat layers (subcutaneous fat (SF), preperitoneal fat (PF), and SF:PF ratio). Indices of adiposity were defined as high vs low depending on the median value of the assessed parameters. RESULTS After multivariate adjustment for traditional risk factors, lower FT4 levels and a higher FT3:FT4 ratio predicted higher SF mass (FT4, Exp(β)=0.035, P=0.020 and FT3:FT4, Exp(β)=2.374, P=0.018), whereas higher FT3 predicted higher PF mass (Exp(β)=2.815, P=0.032). Women with FT3:FT4 above the highest quartile had a significantly higher SF mass as compared to women in the lowest quartile (1.81 ± 0.62 cm vs 1.54 ± 0.46 cm, P=0.027). BMI had a positive independent association with TSH (Exp(β)=1.829, P=0.018). Finally, FT3 was significantly associated with SF mass among women with higher BMI (FT3, β=0.259, P=0.040) and women with higher WHR (β=0.309, P=0.020) but not among women with lower BMI or WHR values. CONCLUSION Thyroid hormone levels, and in particular FT3, were independently associated with SF and PF in euthyroid postmenopausal women, and this association was mainly evident in women with higher BMIs. On the other hand, among traditional indices of adiposity, only TSH was positively associated with BMI. Larger prospective studies are needed to evaluate the significance of the present findings.

Intrauterine HPV transmission: a systematic review of the literature

PurposeTo evaluate the percentage of intrauterine vertical human papillomavirus (HPV) transmission among HPV-positive mothers and the relative risk of intrauterine vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women.MethodsThis systematic review was made according to the PRISMA statement. We searched PubMed and Scopus and the final articles were selected by two reviewers. Data from the selected articles were plotted, and the pooled percentage of antenatal vertical HPV transmission among HPV-positive mothers as well as the pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women were calculated.Results9 studies including 421 HPV-positive mothers and their offsprings were selected from 434 potential papers. Following meta-analysis, the pooled percentage of antenatal vertical HPV transmission was 4.936% (95% CI 1.651–9.849), with moderate heterogeneity between the studies (I2 = 72.22%). The pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women was 0.912, with no statistical significance (95% CI 0.226–3.674) and homogeneity between the studies (I2 = 24.48%).