The LADY study: epidemiological characteristics of prevalent and new genitourinary syndrome of menopause cases in Greece.

OBJECTIVE: The genitourinary syndrome of menopause (GSM) is often underdiagnosed and undertreated despite its significant impact on postmenopausal quality of life. We assessed the prevalence of GSM and associated symptoms in Greek perimenopausal/postmenopausal women attending gynecology clinics. METHODS: Four hundred and fifty women, aged 40-70 years (93.1% postmenopausal), attending three gynecology clinics at university hospitals completed a validated questionnaire and underwent pelvic examination. RESULTS: GSM was diagnosed in 87.6% of the women at the study visit, whereas only 16% of the overall sample had been previously diagnosed with the condition. Vaginal dryness (72.7%), vulvar burning sensation or itching (58.0%) and dyspareunia (52.7%) were the most prevalent symptoms. Pelvic signs consisted of vaginal dryness (89.1%), loss of vaginal rugae (80.6%) and vulvovaginal pallor (86.9%). However, only 31.3% of the participants had discussed genitourinary symptoms with their health-care professionals (HCPs). Regarding management, only 11.1% of women had prior experience with any form of therapy, and currently only 8.7% were receiving treatment. CONCLUSION: GSM is highly prevalent in this Greek perimenopausal/postmenopausal population. Nevertheless, the majority of women remain undiagnosed and untreated. Education for both women and HCPs regarding GSM will lead to improved diagnosis and better management of this syndrome.

Site specific differences in vBMD and geometry in postmenopausal women with primary hyperparathyroidism.

PURPOSE: Primary Hyperparathyroidism (PHPT) is associated with catabolic effects at both trabecular and cortical bone. Mechanical loading is one of the most important natural anabolic stimuli for bone at all ages. The present study was designed to assess the impact of PHPT on vBMD and bone geometry using peripheral quantitative computed tomography (pQCT) at the radius and tibia, sites with similar structural characteristics, but subject to different loading conditions. METHODS: We evaluated the impact of PHPT on bone, by comparing the z-scores of volumetric Bone Mineral Density (vBMD) and indices of bone geometry simultaneously at the tibia and the radius by pQCT, skeletal sites with similar structure, but subject to different loading conditions. Forty-one postmenopausal women with PHPT and 79 controls, comprised the study group. RESULTS: At both trabecular and cortical sites, vBMD and bone geometry indices were significantly lower in patients compared with controls. In patients with PHPT, apart from a lower z-score for total vBMD (p = 0.01) at the radius, there was no other difference between the radius and the tibia at the trabecular sites. On the contrary, at cortical sites, the z-scores of cortical bone mineral content (p = 0.02), cortical vBMD (p = 0.01) and cortical cross-sectional area (p = 0.05) were significantly lower at the radius compared with the tibia, indicating that cortical bone at the weight bearing tibia might be less affected by the catabolic actions of continuous parathyroid hormone (PTH) exposure. PTH levels were positively associated with the difference in z-scores of cort BMD (r = 0.439, p < 0.01) indicating that in more severe cases, as expressed by higher PTH levels, the deleterious effects at the non-weight bearing radius might be accentuated. CONCLUSION: We found that in postmenopausal women with PHPT, both trabecular and cortical bone are adversely affected. However, at the weight bearing tibia as compared with the radius, the deleterious effects, especially on cortical bone, seem to be attenuated. TRIAL REGISTRATION NUMBER: NCT05426512, 21/06/2022, "retrospectively registered".

Understanding of and clinical approach to cardiometabolic transition at the menopause.

Cardiovascular disease (CVD) represents the leading cause of death and accounts for almost 50% of all deaths in women worldwide. The menopausal transition is associated with central body fat accumulation, a decrease in energy expenditure, weight gain, insulin resistance and a pro-atherogenic lipid profile. Moreover, menopause is independently associated with an adverse effect on functional and structural indices of subclinical atherosclerosis. Women with premature ovarian insufficiency have heightened CVD risk compared to women of natural age at menopause. Furthermore, women with severe menopausal symptoms may have a more adverse cardiometabolic profile than those without symptoms. We reviewed the latest evidence on the cardiovascular management of perimenopausal or postmenopausal women. Clinicians should aim for cardiovascular risk stratification, followed by dietary and lifestyle advice as required based on individual needs. The medical management of cardiometabolic risk factors at midlife should always be individualized, focusing on hypertension, diabetes and dyslipidemia. Menopausal hormone therapy, when prescribed for the management of bothersome menopausal symptoms or for the prevention of osteoporosis, has also a beneficial effect on cardiometabolic risk factors. This narrative review aims to summarize the cardiometabolic alternations occurring during the menopausal transition and to outline the appropriate prevention strategies to prevent future cardiovascular adverse outcomes.

Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones.

The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT.

Cardiometabolic health in premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is an increasing public health problem with a prevalence now approaching 4%. POI results in adverse effects on the skeleton and central nervous system as well as disturbances of metabolic and cardiological factors that predispose to a major increased risk of cardiovascular disease (CVD). This article reviews the effects of the premature loss of ovarian function on lipids and lipoproteins, glucose and insulin metabolism, body composition, hemostasis and blood pressure, together with effects on the development of metabolic syndrome and diabetes mellitus. The article examines the effects of POI on vascular endothelial function and inflammation that result in arterial disease, and reviews the effects of hormone replacement therapy (HRT) on these various metabolic processes and on cardiovascular outcomes. It is essential that women with POI receive hormonal treatment to help prevent the development of CVD, and that this treatment is continued at least until the normal age of menopause. It appears that HRT has a more favorable effect than the combined oral contraceptive, but larger clinical trials are needed to establish the optimal treatment. Other therapeutic measures may need to be added to correct existing metabolic abnormalities and, in particular, attention to lifestyle factors such as diet and exercise must be encouraged.

Premature ovarian insufficiency: a toolkit for the primary care physician.

Premature ovarian insufficiency (POI) refers to the loss of ovarian activity before the age of 40 years, which leads to hypoestrogenism and amenorrhea. The diagnosis of POI in a young woman has potentially life-changing physical and emotional consequences for both the patient and her family. Therefore, it is very important that the diagnosis is correct and that it is made in a timely manner. Unfortunately, the diagnosis and therefore the effective treatment of POI are often delayed, which underlines the need for education of the broad medical community on the issue. A panel of menopause experts reviewed and critically appraised the literature, and present: (1) the diagnostic approach to POI, (2) the investigation of the etiology of this condition, (3) the therapeutic strategy regarding both hormone replacement therapy and fertility, and (4) the long-term follow-up and management for ensuring quality of life, as well as urogenital, cardiovascular, bone and mental health. The ultimate goal of this article is to provide a complete toolkit for the primary care physician to have easy access to all the information needed for the optimal management of women with POI, in the context of evidence-based and personalized medicine.HIGHLIGHTSPremature ovarian insufficiency occurs in 1% of the female population of reproductive age, yet the diagnosis is often delayed, with severe physical and emotional consequences for the patient.Primary care physicians should be aware of the possibility of premature ovarian insufficiency in young women presenting with menstrual irregularity.Prompt initiation of hormone replacement therapy ensures quality of life and prevents osteoporosis and cardiovascular disease.Women seeking fertility should be referred to specialists to discuss assisted reproduction options.

How we treat endocrine complications of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are antibodies that target certain immune checkpoints (ICs), such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) or its ligand (PD-L1), and have emerged as a powerful new tool for oncologists. As these immune checkpoints are crucial for immunological self-tolerance, such therapies can trigger autoimmune adverse effects. Endocrine complications are among the most common, including hypophysitis, thyroid dysfunction, diabetes mellitus and primary adrenal insufficiency, while autoimmune polyendocrine syndrome type 2 (APS-2) may also present. The aim of this article is to critically appraise the literature and present (i) the biological role and function of the main ICs, (ii) the use of ICIs in the treatment of various cancer types, (iii) the endocrine complications of cancer immunotherapy with ICIs and (iv) practical recommendations for screening and management of patients with such endocrinopathies in everyday clinical practice.

Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis?

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.

Dietary patterns and cardiovascular risk in postmenopausal women: Protocol of a cross-sectional and prospective study.

OBJECTIVE: Aging and menopause are associated with an adverse cardiometabolic profile, predisposing to cardiovascular disease. Diet may also affect their cardiometabolic risk. The aim of this study is to assess dietary habits and patterns of postmenopausal women and their association with adiposity measures, cardiometabolic parameters and subclinical atherosclerosis. STUDY PROTOCOL: The study will include two parts. The first part consists of cross-sectional evaluation of 750 postmenopausal women recruited consecutively from the Menopause Unit of an academic hospital. Dietary intake will be assessed by a food frequency questionnaire. Nutrient and food group intake will be calculated and adherence to the Mediterranean diet and other dietary patterns will be evaluated. A-priori and a-posteriori defined dietary patterns will be tested for associations with major and minor outcome measures. The second part consists of a prospective follow-up of all women recruited at baseline and re-assessment of the same variables after 3 years. Adherence to predefined or a-posteriori defined dietary patterns over these 3 years will be evaluated in association with changes in obesity indices and lipid levels, as well as in the progression of subclinical atherosclerosis. MAJOR OUTCOME MEASURES: Body mass index, lipid profile, carotid and femoral artery intima-media thickness and plaques. MINOR OUTCOME MEASURES: Waist circumference, waist-to-hip ratio, abdominal fat layers, incident hypertension and diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), c-reactive protein and markers of subclinical arterial disease, including flow-mediated dilation, pulse wave velocity, augmentation index and ankle-brachial index. RESULTS: The study is expected to complete baseline enrolment by the end of 2018 and follow-up assessment by the end of 2021. The results of the study will address the question of whether dietary patterns and eating habits are associated with cardiometabolic risk as well as with accelerated subclinical arterial disease and arterial aging in postmenopausal women.

Comparative effects of denosumab or bisphosphonate treatment on bone mineral density and calcium metabolism in postmenopausal women.

OBJECTIVES: To clarify potential differences between denosumab (DNS) and bisphosphonates (BIS) in terms of bone density and bone metabolism, in a sample of postmenopausal women. METHODS: A total of 113 postmenopausal women aged 53-66 years were treated with either DNS or BIS for 12 months. Bone densitometry and laboratory tests were compared between baseline and follow-up. RESULTS: Femoral neck BMD increased in both treatment-arms (FN-BMD, DNS: 0.69±0.07 g/cm2 to 0.75±0.09 g/cm2; BIS: 0.69±0.06 g/cm2 to 0.71±0.07 g/cm2; p≤0.001 in both cases). Lumbar spine BMD (LS-BMD) increased significantly only in the DNS-group (0.83±0.14 g/cm2 to 0.89±0.14 g/cm2, p=0.0001). Only women under treatment with DNS had a significant increase in serum parathyroid hormone (PTH: 44.87±17.54 pg/mL to 53.27±15.77 pg/mL, p=0.04), independently of baseline vitamin D levels. DNS-administration resulted in higher increase from baseline in FN-BMD compared to BIS (DNS vs BIS: 8.7%±8.5 vs 3.8%±7.3, p=0.004). Finally, baseline 25OH vitamin D levels did not determine the extent of PTH-increase following administration of DNS- or BIS-treatment. CONCLUSIONS: Both treatments increased BMD, however, the effect of DNS on FN-BMD was superior compared to that of BIS. DNS-treatment increased serum PTH. Baseline 25OH vitamin D levels did not predict the extent of PTH increase at follow-up.

Prolactin as a predictor of endothelial dysfunction and arterial stiffness progression in menopause.

Postmenopausal women are at increased risk for progression of arteriosclerosis and hypertension. Recent cross-sectional evidence suggests that high normal circulating prolactin levels may accelerate vascular ageing in menopause. Postmenopausal women (n=201) were consecutively recruited from a Menopause Clinic and re-evaluated in at least one follow-up visit within the next 3 years. Baseline circulating prolactin levels were measured while both baseline and follow-up vascular and biochemical measurements were performed. Endothelial function was assessed by flow-mediated dilation (FMD), aortic stiffness by pulse-wave velocity (PWV) and arterial wave reflections by applanation tonometry. Baseline prolactin significantly correlated with lower FMD at follow-up (P=0.005). After multivariable adjustment for age, follow-up time, blood pressure (BP), body mass index, smoking and medication, this correlation remained significant (P=0.003). In addition, baseline circulating prolactin levels were independently associated with changes in mean BP (ß=0.131, P=0.021), peripheral diastolic BP (ß=0.169, P=0.004) and new-onset hypertension (OR=1.235, P=0.001). Owing to significant interaction between baseline prolactin and age for changes in PWV over time (P=0.036), a subgroup analysis based on median age was performed. This analysis revealed that in women younger than 55 years, prolactin was an independent predictor of changes in PWV over time (P=0.008). In conclusion, high normal circulating prolactin levels predict changes in haemodynamic indices and worsening endothelial function in healthy postmenopausal women. Particularly in young postmenopausal women, prolactin predicts accelerated arterial stiffening.

The intensity of menopausal symptoms is associated with episodic memory in postmenopausal women.

OBJECTIVE: The adaptation of the brain to aging is subject to the impact of psychological and environmental factors and possibly climacteric symptomatology. We aimed to determine the association of climacteric symptomatology with different aspects of episodic memory in a sample of Greek menopausal women. METHODS: This cross-sectional study included 39 postmenopausal women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT) and the revised Brief Visuospatial Memory Test (BVMT), assessing verbal and visuospatial episodic memory, respectively. We evaluated general cognitive status using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Menopausal symptoms were assessed using Greene's Climacteric scale. RESULTS: In the multivariate approach, vasomotor symptoms predicted independently HVLT (retained percentage and delayed recall: b-coefficient = -0.568, p = 0.009 and b-coefficient = -0.563, p = 0.012, respectively). Psychological symptoms predicted independently MMSE (b-coefficient = -0.391, p = 0.024); and in combination with free estrogens (logFEI), psychological symptoms predicted BVMT (total and delayed recall: b-coefficient = -0.558, p = 0.001 and b-coefficient = -0.474, p = 0.005) and HVLT discrimination index (b-coefficient = -0.390, p = 0.023). Combined symptomatology predicted independently MMSE (b-coefficient = -0.457, p = 0.006) and HVLT total (b-coefficient = -0.557, p = 0.034); combined symptomatology predicted in combination with logFEI scores of BVMT total (b-coefficient = -0.593, p < 0.001), BVMT delayed recall (b-coefficient = -0.492, p = 0.002). CONCLUSION: The intensity of psychological, vasomotor and combined climacteric symptoms predicted cognitive performance in this sample of postmenopausal women. A differential contribution of vasomotor symptoms to episodic memory is described, with the negative impact being more pronounced in visuospatial rather than verbal episodic memory.

Increased Maternal Serum Interleukin-6 Concentrations at 11 to 14 Weeks of Gestation in Low Risk Pregnancies Complicated with Gestational Diabetes Mellitus: Development of a Prediction Model.

The aim of the study was to examine interleukin-6 (IL-6) maternal serum concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit. Study population included 40 GDM cases and 94 controls. Maternal characteristics, first trimester ultrasound markers, biochemical indices, and IL-6 levels were used for our analysis. IL-6 was related to maternal weight among the maternal characteristics, (R(2)=0.0679, p=0.01). IL-6 was increased (p=0.001) in the GDM group (median=2 pg/ml) compared to the control group (median=1.5 pg/ml) even after adjustment for maternal weight. IL-6 was inversely related to birth weight adjusted for gestational age at delivery (r=-0.3382, p<0.001) and glucose levels at oral glucose test. Maternal weight and age were the only predictors of GDM among the maternal characteristics [Detection Rate (DR)=59.4%; for 25% False Positive Rate (FPR); Area Under the Curve (AUC)=0.7291; Model R(2)=0.1096, p<0.001]. IL-6 alone was a significant predictor of GDM (DR=51.3%; for 25% FPR; AUC=0.6731; Model R(2)=0.0616, p<0.001). Combination of maternal characteristics with IL-6 yielded an improved prediction (DR=67.5%; for 25% FPR; AUC=0.7586; Model R(2)=0.1521, p<0.001). IL-6 concentrations are increased at 11-14 weeks in pregnancies with GDM. Combination of maternal characteristics and maternal serum IL-6 levels may provide effective first trimester screening for GDM.

Circulating androgens are associated with mood disturbances in young postmenopausal women.

OBJECTIVES: We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women. METHODS: Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens. RESULTS: The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = -0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = -0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens. CONCLUSION: Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.

Psychological but not vasomotor symptoms are associated with temperament and character traits.

OBJECTIVE: Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. METHODS: One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. RESULTS: In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. CONCLUSIONS: Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms.

Efficacy and safety of DT56a compared to hormone therapy in Greek post-menopausal women.

BACKGROUND: Hormone therapy (HT) is the treatment of choice for the alleviation of menopausal symptoms; concerns, however, about its concomitant long-term health risks have limited its use. DT56a is a unique enzymatic isolate of soybeans. The purpose of our study was to evaluate the efficacy and safety of DT56a, compared to HT, in symptomatic post-menopausal women. SUBJECTS AND METHODS: Eighty-nine post-menopausal women were studied prospectively. Women with climacteric symptoms were randomly assigned to receive eitherDT56a (no.=27) or oral low dose continuous combined HT (no.=26). Symptomatic women not wishing to receive any treatment served as controls (no.=36). Menopausal symptoms as assessed through the Kupperman index, serum lipids and lipoproteins, calcium, as well as bone mineral density (BMD), endometrial thickness, and mammography were assessed at baseline and at 12 months. RESULTS: Patients receiving HT and DT56a showed a significant and independent decrease in menopausal symptoms (mean difference in Kupperman score, DT56a group: -3.98, HT group -5.601, no treatment group +1.76, p-value <0.001). Lumbar spine BMD T-score was significantly lower in women receiving no treatment, as opposed to the two treatment arms which showed no significant change (No treatment, baseline: -0.60, final: -0.85, p=0.001; HT, baseline: -84, final -0.99, p=0.79; DT56a, baseline -0.51, final: -0.76, p=0.75). No differences in femoral bone density, ET or mammography classification were detected in any of the treatment arms. Likewise, serum lipids or lipoproteins did not differ between the three groups. CONCLUSIONS: DT56a decreased menopausal symptoms significantly and in the same degree as HT.

Effect of tibolone and raloxifene on serum markers of apoptosis in postmenopausal women.

OBJECTIVES: To investigate the effect of tibolone and raloxifene on the serum apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c (cyt-c) in postmenopausal women. METHODS: A total of 89 healthy postmenopausal women, attending the University Menopause Clinic, were randomly allocated to tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. RESULTS: Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8±28.3 pg/ml, 6 months: 40.45±19.2 pg/ml, p =0.001), whilst sFas levels did not significantly change in this group. Serum sFas or sFasL did not change either in the raloxifene group or in the control group. Serum cyt-c concentrations were under the detection limit of the assay in all women assessed. CONCLUSIONS: Tibolone use resulted in a significant decrease in serum sFasL, but not in serum sFas. Raloxifene had no effect on either sFas or sFasL. These results may indicate that tibolone use is associated with a decrease in receptor-mediated apoptosis.

MTHFR C677T polymorphism modifies the effect of HRT on metabolic parameters in postmenopausal women.

OBJECTIVE: To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. METHODS: In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). RESULTS: The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. CONCLUSION: While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women.

Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress.

INTRODUCTION: Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. MATERIALS AND METHODS: The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder. CONCLUSIONS: In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.