Promising Role of Alkaloids in the Prevention and Treatment of Thyroid Cancer and Autoimmune Thyroid Disease: A Comprehensive Review of the Current Evidence.

Thyroid cancer (TC) and thyroid autoimmune disorders (AITD) are among the most common diseases in the general population, with higher incidence in women. Chronic inflammation and autoimmunity play a pivotal role in carcinogenesis. Some studies, indeed, have pointed out the presence of AITD as a risk factor for TC, although this issue remains controversial. Prevention of autoimmune disease and cancer is the ultimate goal for clinicians and scientists, but it is not always feasible. Thus, new treatments, that overcome the current barriers to prevention and treatment of TC and AITD are needed. Alkaloids are secondary plant metabolites endowed with several biological activities including anticancer and immunomodulatory properties. In this perspective, alkaloids may represent a promising source of prophylactic and therapeutic agents for TC and AITD. This review encompasses the current published literature on alkaloids effects on TC and AITD, with a specific focus on the pathways involved in TC and AITD development and progression.

Flexibility and Strength Effects of Adapted Nordic Walking and Myofascial Exercises Practice in Breast Cancer Survivors and Analysis of Differences.

Breast cancer treatments can elicit negative kinesiological side effects concerning both the posture and functional status of breast cancer survivors. As our body is functionally organized in myofascial meridians, physical exercise practice should favor a whole-body approach rather than a local one. The aim of the study was to investigate and compare the effects of two whole-body disciplines, i.e., adapted Nordic Walking and myofascial exercise, on the flexibility and strength performances in BCS. One hundred and sixty breast cancer survivors were trained three times per week for 12 weeks through adapted Nordic Walking or myofascial exercise. Handgrip, sit and reach, back scratch, and single leg back bridge tests and body composition were assessed at the beginning and completion of the training period. Linear mixed models showed no significant changes in body composition, whereas flexibility (p < 0.001), strength (p < 0.001), and muscle quality index (p = 0.003) changed independently from the treatment. When data modification has been analyzed according to sub-sample membership, no significant differences have been observed. Age, radiation therapy, and chemotherapy seem to have independent effects on several investigated variables. Twelve weeks of adapted myofascial exercise and Nordic Walking led to significant changes in flexibility, strength, and muscle quality in breast cancer survivors, with no apparent superiority of one approach over the other.

The Effects of Combined Exposure to Bisphenols and Perfluoroalkyls on Human Perinatal Stem Cells and the Potential Implications for Health Outcomes.

The present study investigates the impact of two endocrine disruptors, namely Bisphenols (BPs) and Perfluoroalkyls (PFs), on human stem cells. These chemicals leach from plastic, and when ingested through contaminated food and water, they interfere with endogenous hormone signaling, causing various diseases. While the ability of BPs and PFs to cross the placental barrier and accumulate in fetal serum has been documented, the exact consequences for human development require further elucidation. The present research work explored the effects of combined exposure to BPs (BPA or BPS) and PFs (PFOS and PFOA) on human placenta (fetal membrane mesenchymal stromal cells, hFM-MSCs) and amniotic fluid (hAFSCs)-derived stem cells. The effects of the xenobiotics were assessed by analyzing cell proliferation, mitochondrial functionality, and the expression of genes involved in pluripotency and epigenetic regulation, which are crucial for early human development. Our findings demonstrate that antenatal exposure to BPs and/or PFs may alter the biological characteristics of perinatal stem cells and fetal epigenome, with potential implications for health outcomes at birth and in adulthood. Further research is necessary to comprehend the full extent of these effects and their long-term consequences.

Cardiometabolic Profile, Physical Activity, and Quality of Life in Breast Cancer Survivors after Different Physical Exercise Protocols: A 34-Month Follow-Up Study.

BACKGROUND: Breast cancer (BC) and cardiovascular (CV) disease share many risk factors associated with worse outcomes, in terms of cancer relapse, CV events, and quality of life (QoL), that could be counteracted by physical exercise (PE). We aimed to assess the impact of a 12-week differential PE protocol on cardiometabolic profile, QoL, CV- and BC-related long-term outcomes, and physical activity (PA) in a cohort of BC survivors (BCS) not treated with chemotherapy. METHODS: 57 BCS participated in a 12-week PE protocol [aerobic exercise training (AET) or resistance exercise training (RET)]. Anthropometric and CV evaluation, health-related (HR)-QoL, daily PA, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels were assessed before (T0) and after (T1) PE. We assessed BC and CV outcomes, HR-QoL, CV-QoL, and PA at the follow-up. RESULTS: RET improved waist circumference, DHEA-S, cortisol/DHEA-S, systolic and mean blood pressure, and ventricular/arterial coupling; AET ameliorated sagittal abdomen diameter and pulse wave velocity. Regarding HR-QoL, physical function improved only in AET group. At a mean 34 ± 3.6-month follow-up, we documented no significant differences in CV-QoL, HR-QoL, and PA or CV and BC outcomes. CONCLUSIONS: AET and RET determine specific, positive adaptations on many parameters strongly related to CV risk, CV and BC outcomes, and QoL, and should be included in any cardio-oncology rehabilitation program.

Impact of Maternal Lifestyle and Dietary Habits during Pregnancy on Newborn Metabolic Profile.

Expanded newborn screening (NBS) is a preventive program that allows for the early identification of over 40 congenital endocrine-metabolic diseases by analyzing dried blood spot samples collected from the newborn's heel within 48-72 h of birth. The determination of amino acids and acyl-carnitines by Flow Injection Analysis Tandem Mass Spectrometry (FIA-MS/MS) may also highlight metabolic alterations resulting from external factors, such as maternal nutrition. In the present study, we developed a questionnaire to investigate the eating habits of 109 women during pregnancy and statistically correlated the results from the investigation on dietary habits with the data obtained by the NBS laboratory of Abruzzo region (Italy). Parameters such as smoking, physical activity, and the intake of iodized salt, drugs, and supplements were analyzed. This study aimed to highlight how maternal lifestyle, diet, and drug intake during pregnancy may affect the neonatal metabolic profile, possibly generating false positive or false negative results in the NBS test. The results pointed out how the knowledge of maternal nutrition and lifestyle may also be precious in preventing misinterpretations of the neonatal metabolic profile, thereby reducing unnecessary stress for newborns and their parents and limiting costs for the health system.

Relationships between daily physical activity combinations and psychophysical health status of Italian breast cancer survivors.

In breast cancer survivors (BCS), the contemporaneous increase of sedentary time and reduction of physical activity (PA) requires early attention because it has negative consequences for their health. Aims of the study were to investigate: a) the correlations between PA, sedentarism, and health-related measures; b) the association between different patterns of daily activity and health-related outcomes. Two hundred and nineteen BCS (50.98 ± 6.28) were selected for this study. Psychological, anthropometric, endocrine, sleeping, and both daily sedentary time and PA variables were considered. Sedentarism and PA have opposite correlations with anthropometric variables, anxiety, depression, morning salivary cortisol, and sleeping characteristics. The first favors pathological values and the latter favors normal values. Regression tree analysis showed the impact of different daily sedentary time and PA combinations on the investigated variables and allowed the individualization of their optimal combination for health. Our results could be useful to healthcare providers and BCS.

Hormonal Regulation of the MHC Class I Gene in Thyroid Cells: Role of the Promoter "Tissue-Specific" Region.

In previous studies we have demonstrated that the expression of the Major Histocompatibility Complex (MHC) class I gene in thyrocytes is controlled by several hormones, growth factors, and drugs. These substances mainly act on two regions of the MHC class I promoter a "tissue-specific" region (-800 to -676 bp) and a "hormone/cytokines-sensitive" region (-500 to -68 bp). In a previous study, we have shown that the role of the "tissue-specific" region in the MHC class I gene expression is dominant compared to that of the "hormone/cytokines-sensitive" region. In the present report we further investigate the dominant role of the "tissue-specific" region evaluating the effect of thyroid stimulating hormone (TSH), methimazole (MMI), phenylmethimazole (C10), glucose and thymosin-α1. By performing experiments of electrophoretic mobility shift assays (EMSAs) we show that TSH, MMI and C10, which inhibit MHC class I expression, act on the "tissue-specific" region increasing the formation of a silencer complex. Glucose and thymosin-α1, which stimulate MHC class I expression, act decreasing the formation of this complex. We further show that the silencer complex is formed by two distinct members of the transcription factors families activator protein-1 (AP-1) and nuclear factor-kB (NF-kB), c-jun and p65, respectively. These observations are important in order to understand the regulation of MHC class I gene expression in thyroid cells and its involvement in the development of thyroid autoimmunity.

Resveratrol Enhances the Cytotoxic Activity of Lymphocytes from Menopausal Women.

Nutraceuticals and functional foods are the main sources of antioxidants and have positive effects on health through regulation of the redox balance. Accordingly, they represent a useful nutritional source for the prevention of noncommunicable diseases (NCDs). Menopausal women have an increased risk of developing NCDs due to hormonal dysregulation and the ongoing aging process. Accordingly, a healthy lifestyle and good nutritional habits are of utmost importance in this population. Resveratrol (RSV) is a natural polyphenol, and it is used as a nutraceutical given its estrogenic, anti-inflammatory, and antioxidant properties. The aim of this study was to analyze the effects of RSV on the lymphocyte cytotoxicity in menopausal women. Lymphocytes from 13 healthy menopausal women (56.18 ± 4.24 years) were isolated, and then cocultured with hTERT-HME1, a breast cell line with a precancerous phenotype. The results showed that, when treated with RSV, lymphocytes significantly increased the TNF-α production (p < 0.001), the formation of immune synapses (p = 0.009), and the target cell lysis (p = 0.002). No effects were detected in the lymphocyte total antioxidant capacity. In conclusion, RSV might enhance the immune surveillance in menopausal women by increasing the cytotoxic activity of lymphocytes.

Non-Conventional Clinical Uses of TSH Receptor Antibodies: The Case of Chronic Autoimmune Thyroiditis.

Anti TSH receptor antibodies (TSHrAb) are a family of antibodies with different activity, some of them stimulating thyroid function (TSAb), others with blocking properties (TBAb), it is a common finding that antibodies with different function might coexist in the same patient and can modulate the function of the thyroid. However, most of the labs routinely detect all antibodies binding to the TSH receptor (TRAb, i.e. TSH-receptor antibodies detected by binding assay without definition of functional property). Classical use of TSHr-Ab assay is in Graves' disease where they are tested for diagnostic and prognostic issues; however, they can be used in specific settings of chronic autoimmune thyroiditis (CAT) as well. Aim of the present paper is to highlight these conditions where detection of TSHr-Ab can be of clinical relevance. Prevalence of TSHrAb is different in in the 2 main form of CAT, i.e. classical Hashimoto's thyroiditis and in atrophic thyroiditis, where TBAb play a major role. Simultaneous presence of both TSAb and TBAb in the serum of the same patient might have clinical implication and cause the shift from hyperthyroidism to hypothyroidism and vice versa. Evaluation of TRAb is recommended in case of patients with Thyroid Associated Orbitopathy not associated with hyperthyroidism. At present, however, the most relevant recommendation for the use of TRAb assay is in patients with CAT secondary to a known agent; in particular, after treatment with alemtuzumab for multiple sclerosis. In conclusion, the routine use of anti-TSH receptor antibodies (either TRAb or TSAb/TBAb) assay cannot be suggested at the present for diagnosis/follow up of patients affected by CAT; there are, however, several conditions where their detection can be clinically relevant.

The Potential of Steroid Profiling by Mass Spectrometry in the Management of Adrenocortical Carcinoma.

Radiological and endocrinological work up of adrenal neoplasms is aimed at distinguishing between frequent non-functioning adenomas and rare but very aggressive adrenocortical carcinoma (ACC). Relevant research has addressed the identification of molecular, genetic and hormonal markers that could have clinical significance for malignancy, as well as a prognostic value. Regarding endocrine aspects, attention has been paid to the pattern of steroid secretion that can be affected by altered steroidogenic pathway in ACC. The advent of mass spectrometry techniques has overcome many limitations usually associated with immunoassays, allowing the determination of both common and rarely measured steroids in a single analysis with high specificity and sensitivity. Indeed, mass spectrometry strategies may be able to identify an individualized steroid profile of ACC, allowing a rapid diagnosis and a specific follow-up. In this review, insights, strengths and limitations of mass spectrometry-based approaches in steroid profiling, as well as of immunoassay in steroid measurements, will be specifically discussed. Moreover, the latest findings on steroid profiling by mass spectrometry-based techniques, the most promising analytical tool, will be summarized to evaluate if steroid profiling might be the clue for solving the clinical dilemma in differentiating ACC from non-functioning adrenocortical adenomas (ACA).

Inositol and antioxidant supplementation: Safety and efficacy in pregnancy.

Pregnancies complicated by diabetes have largely increased in number over the last 50 years. Pregnancy is characterized by a physiologic increase in insulin resistance, which, associated with increased oxidative stress and inflammations, could induce alterations of glucose metabolism and diabetes. If not optimally controlled, these conditions have a negative impact on maternal and foetal outcomes. To date, one can resort only to diet and lifestyle to treat obesity and insulin resistance during pregnancy, and insulin remains the only therapeutic option to manage diabetes during pregnancy. However, in the last years, in a variety of experimental models, inositol and antioxidants supplementation have shown insulin-sensitizing, anti-inflammatory, and antioxidant properties, which could be mediated by some possible complementary mechanism of action. Different isomers and multiple combinations of these compounds are presently available: Aim of the present review article is to examine the existing evidence in order to clarify and/or define the effects of different inositol- and antioxidant-based supplements during pregnancy complicated by insulin resistance and/or by diabetes. This could help the clinician's evaluation and choice of the appropriate supplementation regimen.

The Role of the Transcription Factor Nuclear Factor-kappa B in Thyroid Autoimmunity and Cancer.

Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor that is involved in inflammatory and immune responses, as well as in regulation of expression of many other genes related to cell survival, proliferation, and differentiation. In mammals, NF-κB comprises five subunits that can bind to promoter regions of target genes as homodimers or heterodimers. The most common dimer is the p50/p65 heterodimer. The several combinations of dimers that can be formed contribute to the heterogeneous regulation of NF-κB target genes, and this heterogeneity is further increased by interactions of the NF-κB dimers with other transcription factors, such as steroid hormone receptors, activator protein-1 (AP-1), and cAMP response element binding protein (CREB). In the thyroid, several studies have demonstrated the involvement of NF-κB in thyroid autoimmunity, thyroid cancer, and thyroid-specific gene regulation. The role of NF-κB in thyroid autoimmunity was hypothesized more than 20 years ago, after the finding that the binding of distinct NF-κB heterodimers to the major histocompatibility complex class I gene is hormonally regulated. Further studies have shown increased activity of NF-κB in thyroid autoimmune diseases and in thyroid orbitopathy. Increased activity of NF-κB has also been observed in thyroid cancer, where it correlates with a more aggressive pattern. Of particular interest, mutation of some oncogenes or tumor suppressor genes involved in thyroid carcinogenesis results in constitutive activation of the NF-κB pathway. More recently, it has been shown that NF-κB also has a role in thyroid physiology, as it is fundamental for the expression of the main thyroid-specific genes, such as sodium iodide symporter, thyroid peroxidase, thyroglobulin, Pax8, and TTF-1 (NKX2-1).

Walking training and cortisol to DHEA-S ratio in postmenopause: An intervention study.

The literature indicates that the plasma cortisol-to-dehydroepiandrosterone-sulfate (DHEA-S) ratio is a marker of health status after menopause, when a decline in both estrogen and DHEA-S and an increase in cortisol occur. An increase in the cortisol-to-DHEA-S ratio has been positively correlated with metabolic syndrome, all-cause mortality, cancer, and other diseases. The aim of this study was to investigate the effects of a walking program on the plasma cortisol-to-DHEA-S ratio in postmenopausal women. Fifty-one postmenopausal women participated in a 13-week supervised walking program, in the metropolitan area of Pescara (Italy), from June to September 2013. Participants were evaluated in April-May and September-October of the same year. The linear mixed model showed that the variation of the log10Cortisol-to-log10DHEA-S ratio was associated with the volume of exercise (p = .03). Participants having lower adherence to the walking program did not have a significantly modified log10Cortisol or log10DHEA-S, while those having the highest adherence had a significant reduction in log10Cortisol (p = .016) and a nearly significant increase in log10DHEA-S (p = .084). Walking training appeared to reduce the plasma log10Cortisol-to-log10DHEA-S ratio, although a minimum level of training was necessary to achieve this significant reduction.

Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance.

Graves' disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves' hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves' disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves' disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves' disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves' disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves' disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves' disease in pregnancy focusing on the role of the TRAbs in maternal and fetal function.

Resveratrol has anti-thyroid effects both in vitro and in vivo.

Resveratrol is a natural polyphenol with antioxidant, anti-inflammatory, and antiproliferative properties. We have shown previously that resveratrol decreases sodium/iodide symporter expression and iodide uptake in thyrocytes, both in vitro and in vivo. In the present study, we further investigated the effects of resveratrol, with evaluation of the expression of additional thyroid-specific genes in the FRTL-5 rat thyroid cell line: thyroglobulin, thyroid peroxidase, TSH receptor, Nkx2-1, Foxe1 and Pax8. We observed decreased expression of these genes in FRTL-5 cells treated with 10 µM resveratrol. The effects of resveratrol was further evaluated in vivo using Sprague-Dawley rats treated with resveratrol 25 mg/kg body weight intraperitoneally, for 60 days. No clinical signs of hypothyroidism were seen, although the treated rats showed significant increase in thyroid size. Serum TSH and thyroid hormone levels were in the normal range, with significantly higher TSH seen in resveratrol-treated rats, compared with control rats. Histological and immunohistochemical analyses confirmed increased proliferative activity in the thyroid from resveratrol-treated rats. These data suggest that resveratrol acts as a thyroid disruptor and a goitrogen, which indicates the need for caution as a supplement and for therapeutic uses.

Psychophysical health status of breast cancer survivors and effects of 12 weeks of aerobic training.

The aim of this study was to analyse the health status of breast cancer survivors and the effects of 12 weeks of aerobic training. Twenty-three breast cancer survivors (51.71 ± 3.17 years) and 23 healthy women (50.73 ± 2.97 years) were investigated for body composition, daily physical activity, quality of life, salivary cortisol, and DHEA-S. Breast cancer survivors were then aerobically trained for 12 weeks. Breast cancer survivors have a worse psychophysical health than healthy women. Aerobic training increased salivary DHEA-S, aerobic fitness, self-reported health, and nocturnal sleeping time and reduced salivary cortisol in breast cancer survivors. Salivary cortisol variation correlated with change of sleeping time and self-reported health. Salivary DHEA-S correlated with change of self-reported physical pain and general health as well. Breast cancer survivors can live in a situation of continuous distress, requiring a multidisciplinary approach. Twelve weeks of aerobic training improve the psychophysical health of breast cancer survivors.

Physical exercises for breast cancer survivors: effects of 10 weeks of training on upper limb circumferences.

[Purpose] The aims of this study were to verify the effects on upper limb circumferences and total body extracellular water of 10 weeks of Nordic Walking (NW) and Walking (W), both alone and combined with a series of exercises created for breast cancer survivors, the ISA method. [Subjects and Methods] Twenty breast cancer survivors were randomly assigned to 4 different training groups and evaluated for upper limb circumferences, total body and extracellular water. [Results] The breast cancer survivors who performed NW, alone and combined with the ISA method, and Walking combined with the ISA method (but not alone) showed significantly reduced arm and forearm circumferences homolateral to the surgical intervention. [Conclusion] For breast cancer survivors, NW, alone and combined with the ISA method, and Walking combined with the ISA method should be prescribed to prevent the onset and to treat light forms of upper limb lymphedema because Walking training practiced alone had no significant effect on upper limb circumference reduction.

Nordic Walking and the Isa Method for Breast Cancer Survivors: Effects on Upper Limb Circumferences and Total Body Extracellular Water - a Pilot Study.

BACKGROUND: The negative side effects of breast cancer treatments can include upper limb lymphoedema. The growing literature indicates that Nordic walking is an effective discipline against several disease symptoms. The aim of this study was to determine whether introduction to Nordic walking alone is effective against total body extracellular water and upper limb circumferences in breast cancer survivors compared to its combination with a series of specifically created exercises (i.e. the Isa method). METHODS: 16 breast cancer survivors (49.09 ± 2.24 years) were recruited and randomly assigned to 1 of 2 different training groups. RESULTS: 10 lessons on Nordic walking technique plus the Isa method significantly reduced both extracellular body water and the extracellular-to-total body water ratio (p = 0.01 for both), and also the circumference of the upper limb, (both relaxed arm and forearm circumferences) (p = 0.01 for all), whereas Nordic walking alone did not. CONCLUSIONS: Introduction to Nordic walking does not seem to affect lymphoedema in breast cancer survivors. This might be because novice Nordic Walkers do not adequately generate an effective muscular pump through coordination of the alternated bimanual open-close cycle. The Isa method appears to close this gap.

Resveratrol inhibits sodium/iodide symporter gene expression and function in rat thyroid cells.

Resveratrol is a polyphenol found in grapes and berries that has antioxidant, antiproliferative and anti-inflammatory properties. For these reasons, it is available as a dietary supplement, and it is under investigation in several clinical trials. Few data are available regarding the effects of resveratrol on thyroid function. A previous study showed that resveratrol transiently increases iodide influx in FRTL-5 rat thyroid cells. Indeed, this increase arises after short treatment times (6-12 h), and no further effects are seen after 24 h. The aim of the present study was to investigate the effects of resveratrol on iodide uptake and sodium/iodide symporter expression in thyroid cells after longer times of treatment. For this purpose, the effects of resveratrol were evaluated both in vitro and in vivo using the rat thyroid FRTL-5 cell line and Sprague-Dawley rats, respectively. In FRTL-5 cells, resveratrol decreased the sodium/iodide symporter RNA and protein expression as a function of time. Furthermore, resveratrol decreased cellular iodide uptake after 48 h of treatment. The inhibitory effect of resveratrol on iodide uptake was confirmed in vivo in Sprague-Dawley rats. This study demonstrates that with longer-term treatment, resveratrol is an inhibitor of sodium/iodide symporter gene expression and function in the thyroid. These data suggest that resveratrol can act as a thyroid disruptor, which indicates the need for caution as a supplement and in therapeutic use.

Walking training affects dehydroepiandrosterone sulfate and inflammation independent of changes in spontaneous physical activity.

OBJECTIVE: We hypothesized that physical exercise in postmenopausal women could interfere with the molecular interrelationship of the immune-endocrine system and be effective even in women in whom training determined a reduction of spontaneous physical activity (SPA). For this reason, we investigated the effects of an aerobic program on plasma dehydroepiandrosterone sulfate (DHEA-S) and cytokine levels in relationship to SPA modification. METHODS: Thirty-two postmenopausal women (mean [SD] age, 56.38 [4.33] y) were enrolled in the study. Inclusion criteria were as follows: age younger than 65 years, body mass index higher than 18.5 and lower than 35 kg/m2, no pharmacological treatments, and no history of chronic, cardiovascular, or orthopedic diseases. Before and after 3 months of walking training at moderate intensity (40-50 min, 4 d/wk), they were evaluated for SPA, body composition, energy intake, and levels of plasma cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1α, IL-1ß, IL-2, IL-8, and IL-10), C-reactive protein, DHEA-S, cortisol, and estrogen. RESULTS: At baseline, SPA did not correlate with either DHEA-S level or cytokine levels. There was negative correlation between DHEA-S and both TNF-α and IL-2. After the intervention program, 16 women showed increased SPA, and 16 women showed decreased SPA. Independent of these changes in SPA, both TNF-α levels and cortisol-to-DHEA-S ratio decreased, whereas DHEA-S levels increased. CONCLUSIONS: In postmenopausal women, walking training, rather than SPA, influences DHEA-S and cytokine concentrations and their correlations, thus interfering with adrenal steroids and the inflammatory markers network. Physical exercise acts in parallel on menopausal neuroendocrine alterations and on the systemic inflammatory profile independent of SPA changes.