Adherence to the Mediterranean diet is associated with handgrip strength in postmenopausal women.

OBJECTIVE: This study aimed to assess the possible association of adherence to the Mediterranean diet (MD) with muscle strength and body composition. METHODS: The cross-sectional study evaluated 112 postmenopausal women (aged 41-71 years). Fasting blood samples were obtained for biochemical/hormonal assessment. The Mediterranean Dietary Score (MedDietScore) was calculated and used to stratify adherence by tertiles (low [T1], moderate [T2] or high [T3]). Handgrip strength (HGS) was measured by dynamometry and body composition with dual-X-ray absorptiometry. RESULTS: Women with low-moderate MedDietScore (T1/T2) had lower HGS values than those with higher scores (19.5 ± 4.9 kg vs. 21.9 ± 3.9 kg, p = 0.023). A linear stepwise increase of HGS values per MedDietScore tertile was found (T1 vs. T2 vs. T3: 18.4 ± 4.4 kg vs. 20.6 ± 5.2 kg vs. 21.9 ± 3.9 kg, ANOVA p-value for linear trend = 0.009, ANCOVA p-value = 0.026). Multivariable models confirmed that HGS values were independently associated with the MedDietScore (ß-coefficient = 0.266, p = 0.010). Lean mass values were associated with the MedDietScore (ß-coefficient = 0.205, p = 0.040). All models were adjusted for age and cardiometabolic risk factors. CONCLUSIONS: The data suggest that the higher the adherence to the MD, the better the muscle strength and lean mass in postmenopausal women. Prospective studies are required to evaluate the significance of these observations in cardiovascular prevention strategies at midlife.

Seliciclib: A New Treatment for Cushing's Disease?

Previous studies have suggested that corticotroph tumours are associated with the overexpression of cyclin E and that the inactivation of cyclin-dependent kinases, which activate cyclin E, may have antisecretory and antiproliferative effects. Seliciclib, also known as R-roscovitine, is a pituitary-targeting agent shown to inhibit the growth of corticotroph tumour cells via cyclin E and retinoblastoma protein-mediated pathways. A recent study investigated the role of seliciclib in regulating biochemical parameters in a small number of patients with Cushing's disease, providing preliminary data on its possible therapeutic effectiveness in treating this disorder.

EMAS position statement: Thyroid disease and menopause.

INTRODUCTION: Thyroid diseases are common in women in their late reproductive years; therefore, thyroid disease and menopause may co-exist. Both conditions may present with a wide range of symptoms, leading to diagnostic challenges and delayed diagnosis. Aim To construct the first European Menopause and Andropause Society (EMAS) statement on thyroid diseases and menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion (EMAS executive board members/experts on menopause and thyroid disease). SUMMARY RECOMMENDATIONS: This position paper highlights the diagnostic and therapeutic dilemmas in managing women with thyroid disease during the menopausal transition, aiming to increase healthcare professionals' awareness of thyroid disorders and menopause-related symptoms. Clinical decisions regarding the treatment of both conditions should be made with caution and attention to the specific characteristics of this age group while adopting a personalized patient approach. The latter must include the family history, involvement of the woman in the decision-making, and respect for her preferences, to achieve overall well-being.

Postmenopausal women with higher TSH values within the normal range present improved handgrip strength: a pilot study.

OBJECTIVE: To evaluate the possible association between thyroid function within the euthyroid range and musculoskeletal parameters as well as body composition in a sample of postmenopausal women. METHODS: This cross-sectional study included 96 postmenopausal women with serum thyroid-stimulating hormone (TSH) within the normal laboratory reference range. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Bone status and body composition were measured using Dual Energy X-ray absorptiometry (DXA). Physical activity was quantified using the International Physical Activity Questionnaire (IPAQ) index. RESULTS: Serum TSH correlated with handgrip strength (HGS, r-coefficient = 0.233, p = .025), and total body bone mineral density (BMD) T-score values (r-coefficient = 0.321, p = .003). HGS measures were associated with BMD (r-coefficient = 0.415, p < .001), with bone mineral content (BMC, r-coefficient = 0.427, p < .001), and lean mass (r-coefficient = 0.326, p = .003). Women with low muscle strength, defined as HGS < 16 kg, had lower TSH levels than women with normal muscle strength (low vs. normal muscle strength, ANCOVA 1.13 ± 0.49 mU/L vs. 1.60 ± 0.83 mU/L, p = 0.024) independently of age, BMD, percentage of body fat or absolute lean mass. Multivariable linear regression analysis showed that HGS values were associated with TSH measurements (ß-coefficient = 0.246, p = .014) and BMD T-score values (ß-coefficient = 0.306, p = .002). All models were adjusted for age, body mass index (BMI), vitamin D, low-density lipoprotein cholesterol, current smoking, physical activity, and homeostasis model assessment of insulin resistance. CONCLUSIONS: In this sample of postmenopausal women, lower serum TSH values, within normal range, were associated with lower muscle strength compared to higher normal TSH values. Further research is needed to elucidate the significance of our preliminary findings.

Statin use and incident type 2 diabetes mellitus in women after menopause.

Menopause is associated with adverse cardiometabolic changes which increase the risk of new-onset type 2 diabetes (T2DM) and cardiovascular disease (CVD). Statins are widely used for primary and secondary CVD prevention, given their beneficial effects on the lipid profile and the vessel wall. On the other hand, statins increase the risk of T2DM. This association has been evaluated mainly in mixed-gender studies, without gender-specific evaluation. This narrative review evaluates the use of statins and the related risk of new-onset T2DM among postmenopausal women. Studies that incorporated a gender-specific analysis report a higher risk of new-onset T2DM in women than in men on treatment with statins. Fewer studies evaluated female-only samples; these confirm the observed association between statin use and new-onset T2DM. Factors influencing the association between statin use and T2DM include the type and dose of statin and the baseline metabolic status. Women may benefit from stratification of their metabolic risk before initiating a statin for CVD prevention.

Lower Urinary Tract Symptoms in Greek Women After Menopause: The LADY Study.

INTRODUCTION AND HYPOTHESIS: The genitourinary syndrome of menopause (GSM), apart from symptoms related to vulvovaginal atrophy (VVA), also consists of lower urinary tract symptoms (LUTS). Based on the common embryological origin of the genital and lower urinary system, the presence of estrogen receptors, and the high prevalence of VVA and LUTS in the menopausal population, the two conditions can coexist. This study is aimed at investigating the prevalence and risk factors of LUTS in a sample of Greek peri- and postmenopausal women. METHODS: Four hundred and fifty (450) women, aged 40-70 years, attending three outpatient gynecology clinics for routine examination, completed a structured interview and responded to a validated questionnaire (International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms, ICIQ-FLUTS). RESULTS: Urinary urgency or frequency affected 51.6% and dysuria 43.6% of the participants. Mild urgency or frequency was described by 25.6%, moderate by 14.4%, and severe by 11.6% of the women. Mild dysuria was reported by 26.26%, moderate by 5.8%, and severe by 11.6%. Age, weight, BMI, and number of pregnancies and abortions correlated with a higher ICIQ-FLUTS score. Women with moderate/severe symptoms of VVA, such as irritation, a burning sensation, and pruritus of the vulva or vagina, had a higher ICIQ-FLUTS score than women without such symptoms (beta coefficient 2.42, CI 1.204, 3.635, p < 0.001). CONCLUSIONS: Lower urinary tract symptoms are very common among peri- and postmenopausal women and are linked to symptoms of VVA. Our data support the need for prompt evaluation of women transitioning to menopause, as these symptoms compromise the quality of life.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

The Effect of Fat Supplementation on the Appearance of Symptoms Associated With Dumping Syndrome in Patients Having Undergone Gastric Surgery: Preliminary Results.

BACKGROUND/OBJECTIVES: Data on the effect of dietary fat on dumping syndrome (DS) symptoms are limited. The aim of this study was to assess the effect of the addition of fat to a carbohydrate meal on the appearance of DS symptoms and glycemic response, in patients who had undergone gastric surgery. SUBJECTS/METHODS: This was an interventional crossover study. Patients scheduled for gastric surgical procedures related to DS at two surgical units of two public hospitals (General University Hospital of Larissa and General Hospital of Larissa) were considered for study inclusion. Patients presenting symptoms suggestive of diagnosis (n = 12), after the ingestion of a carbohydrate meal, were used as both intervention and control groups. During the intervention process, a fat supplement was added to the carbohydrate meal that was previously used for diagnosis. Glycemic response and the amount and intensity of DS symptoms provoked by the two meals were assessed at both appointments. RESULTS: Blood glucose levels were significantly lower in the group that consumed the added fat meal compared with the group that consumed the carbohydrate meal 60 minutes after ingestion (p = 0.028). Furthermore, a significant reduction was noted in the amount of late dumping symptoms (p = 0.021) and the intensity of both early and late dumping symptoms (p = 0.007 and p = 0.012 respectively), after fat addition.  Conclusions: Incorporating fat into a carbohydrate meal seems to attenuate postprandial blood glucose rises and reduce the amount and intensity of DS symptoms, in patients who had undergone gastric surgery.

EMAS position statement: Testosterone replacement therapy in older men.

INTRODUCTION: Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. AIM: To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12 months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

The severity of menopausal symptoms is associated with diabetes, and cardiometabolic risk factors in middle-aged women.

BACKGROUND: Ovarian senescence is associated with increased cardiovascular risk. We aimed to evaluate the association between menopausal symptoms and cardiometabolic risk factors in a cohort of apparently healthy middle-aged women. METHODS: The cohort included 2793 peri- and postmenopausal women not on menopausal hormone therapy. Demographic/anthropometric and biochemical/hormonal data were assessed. The severity of menopausal symptoms was evaluated by the Greene Climacteric Scale (GCS). RESULTS: GCS-Total Score was associated with BMI (b=0.12, 95% CI: 0.04 to 0.20), T2DM (b=2.10, 95% CI: 0.06 to 4.15), and late-postmenopause (b=-1.24, 95% CI: -2.17 to -0.33). GCS-psychological score was associated with BMI (b=0.06, 95% CI: 0.00 to 0.11). GCS-Physical Score was associated with BMI (b=0.06, 95% CI: 0.03 to 0.09), central obesity (b=0.18, 95% CI: 0.02 to 0.34), and postmenopause (early-/late-postmenopause vs. perimenopause, b=-0.36, 95% CI: -0.59 to -0.13 and b=-0.65, 95% CI: -0.97 to -0.34, respectively). All GCS-scores were negatively associated with age. GCS-Sexual Score was associated with early-postmenopause (incidence rate ratio (IRR)=1.53, 95% CI: 1.21 to 1.94), central obesity (IRR=1.18, 95% CI: 1.00 to 1.39), smoking, diastolic blood pressure, age. Cox-regression analysis showed that incident T2DM was positively associated with increasing age, BMI, daily alcohol consumption, moderate-to-severe vasomotor symptoms (VMS, OR=1.045, 95% CI: 1.011 to 1.079), and negatively with moderate-to-strenuous physical activity. These associations persisted in lean but not in obese women. CONCLUSIONS: The severity of menopausal symptoms is associated with T2DM, obesity, and smoking in a cohort of peri-/postmenopausal women. VMS were associated with incident T2DM, especially in lean women. These associations must be considered in implementing primary and secondary prevention strategies.

Primary Pituitary Carcinoids Do Not Exist: A Reappraisal in the Era of Pituitary Neuroendocrine Tumours.

The World Health Organization classification of pituitary tumours, published in 2022, supported a change in the terminology from "pituitary adenoma" to "pituitary neuroendocrine tumour" (PitNET). The neuroendocrine cells represent an integral part of the diffuse neuroendocrine system, including, among others, thyroid C cells, the parathyroid chief cells, and the anterior pituitary. Normal and neoplastic adenohypophyseal neuroendocrine cells have light microscopic, ultrastructural features and an immunoprofile compatible with the neuroendocrine cells and neuroendocrine tumours from other organs. Moreover, neuroendocrine cells of pituitary origin express transcription factors which indicate their cell-lineage origin. Thus, pituitary tumours are now considered as a continuum with other neuroendocrine tumours. PitNETs may occasionally be aggressive. In this context, the term "pituitary carcinoid" has no specific meaning: it either represents a PitNET, or a metastasis to the pituitary gland of a neuroendocrine tumour (NET). An accurate pathological evaluation, combined where necessary with functional radionuclide imaging, can define the origin of the tumour. We recommend that clinicians liaise with patient groups to understand the terminology to define primary tumours of adenohypophyseal cells. It is incumbent upon the responsible clinician to explain the use of the word "tumour" in a given clinical context.

Antimüllerian Hormone as a Tool to Predict the Age at Menopause.

This study aimed to assess an eligible cut-off value of anti-Müllerian hormone (AMH) to detect ovarian senescence in a group of premenopausal Greek women to evaluate the possible link between AMH-values and the severity of climacteric symptoms during a follow-up of 24 months. This study included 180 women (group A, 96 women of late reproductive stage/early perimenopause; group B, 84 women in late perimenopause). We measured AMH blood levels and assessed climacteric symptoms using the Greene scale. Log-AMH is inversely associated with postmenopausal status. The AMH cut-off of 0.012 ng/mL predicts the postmenopausal status with a sensitivity of 24.2% and specificity of 30.5%. The postmenopausal stage associated with age (OR = 1.320, 95%CI: 1.084-1.320) and AMH (values ≥ vs. <0.012 ng/mL, OR = 0.225, 95%CI: 0.098-0.529, p-value < 0.001). Moreover, the severity of vasomotor symptoms (VMS) was only associated inversely with AMH (b-coefficient = -0.272, p-value = 0.027). In conclusion, AMH levels measured in the late premenopausal period are inversely associated with the time to ovarian senescence. In contrast, AMH levels measured in the perimenopausal period are inversely associated only with the severity of VMS. Therefore, a cut-off of 0.012 ng/mL predicts menopause with low sensitivity and specificity, making it challenging to use in a clinical setting.

Vasomotor symptoms and risk of cardiovascular disease in peri- and postmenopausal women: A systematic review and meta-analysis.

INTRODUCTION: Vasomotor symptoms (VMS) are the symptoms most frequently experienced by women transitioning to menopause and are a primary indication for menopausal hormone therapy. A growing body of evidence has associated the presence of VMS with future risk for cardiovascular disease (CVD) events. This study aimed to systematically evaluate, qualitatively and quantitatively, the possible association between VMS and the risk for incident CVD. METHODS: This systematic review and meta-analysis included 11 studies evaluating peri- and postmenopausal women in a prospective design. The association between VMS (hot flashes and/or night sweats) and the incidence of major adverse cardiovascular events, including coronary heart disease (CHD) and stroke, was explored. Associations are expressed as relative risks (RR) with 95 % confidence intervals (CI). RESULTS: The risk for incident CVD events in women with and without VMS differed according to the age of participants. Women with VSM younger than 60 years at baseline had a higher risk of an incident CVD event than women without VSM of the same age (RR 1.12, 95 % CI 1.05-1.19, I2 0%). Conversely, the incidence of CVD events was not different between women with and without VMS in the age group >60 years (RR 0.96, 95 % CI 0.92-1.01, I2 55%). CONCLUSION: The association between VMS and incident CVD events differs with age. VMS increases the incidence of CVD only in women under 60 years of age at baseline. The findings of this study are limited by the high heterogeneity among studies, pertaining mainly to different population characteristics, definitions of menopausal symptoms and recall bias.

Climacteric symptoms, age, and sense of coherence are associated with sexual function scores in women after menopause.

BACKGROUND: Postmenopausal sexual function presupposes the integration of hormonal, neural, and vascular interactions and is subject to optimal crosstalk among psychological, interpersonal, cultural, and environmental factors. Sense of coherence (SOC) reflects a person's ability to cope with stressors and may influence the occurrence of menopausal symptoms and sexual dysfunction. AIM: To investigate the association of severity of climacteric symptoms, cardiometabolic risk factors, and SOC with sexual function in postmenopausal women. METHODS: Overall 281 sexually active postmenopausal women without significant psychopathology or cardiovascular disease attending the Menopause Unit of Aretaieion Hospital were evaluated by the Female Sexual Function Index (FSFI), Greene Climacteric Scale, Beck Depression Scale, and Sense of Coherence Scale. Hormonal and biochemical parameters and cardiometabolic risk factors were evaluated. FSFI scores <26.5 were considered pathologic. OUTCOMES: Total and subdomain scores of sexual response were determined. RESULTS: Pathologic FSFI scores were found in 79.7% of the sample. Linear models of multivariable regression analysis showed that FSFI scores were associated with (1) Beck scores (b = -0.200; 95% CI, -0.472 to -0.073, P = .001), vasomotor symptom severity (b = -0.324; 95% CI, -0.985 to 0.051; P < .001), and age and (2) SOC (b = 0.150, 95% CI, 0.036-0.331; P = .008), vasomotor symptom severity (b = -0.361; 95% CI, -0.743 to 0.245; P < .001), and age. Both models were adjusted for menopausal age, diabetes mellitus, hypertension, type of menopause, and menopausal hormone therapy intake. SOC was associated with Beck depression scores (ß = -0.487, P < .001; Greene Climacteric Scale total scores, ß = -0.199, P < .001). FSFI score <26.5 vs >26.5 was associated with SOC (odds ratio, 0.982; 95% CI, 0.563 to 1.947; P = .006) and moderate to severe vasomotor symptom severity (odds ratio, 2.476; 95% CI, 1.478 to 3.120; P = .009) independent of age, diabetes mellitus, hypertension, menopausal hormone therapy intake, type of menopause, or Beck depression classification. CLINICAL IMPLICATIONS: The results indicate the importance of psychometric assessment of postmenopausal women when presenting with scores of low sexual function. The severity of vasomotor symptoms should also be addressed in any case. STRENGTHS AND LIMITATIONS: This is the first study investigating the relationship between SOC and sexuality in menopause in a carefully selected homogenous population. Limitations included the cross-sectional design and the fact that sexual distress was not assessed. CONCLUSIONS: Pathologic FSFI scores were highly prevalent in this sample of postmenopausal women. FSFI is associated positively with age and severity of vasomotor symptoms and negatively with SOC.

Objective Measurements of Physical Function to Predict Survival in Patients with Metastatic Cancer.

BACKGROUND/OBJECTIVES: Physician-reported performance status (PS) constitutes the established method for stratifying oncologic patients in therapeutic decision-making. Objective measurements of physical function may further refine prognostication. SUBJECTS/METHODS: In this prospective observational study, 103 patients with metastatic cancer who were referred for systemic therapy initiation were evaluated. PS was evaluated using the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and five objective physical function measurements (handgrip strength [HGS], chair stand test [CST], timed up and go [TUG] test, 4-m gait speed [GS] test, and short physical performance battery [SPPB] test). Overall survival and treatment complications were recorded from the medical records. RESULTS: Patients with low PS according to ECOG-PS (hazard ratio [HR]: 3.80, 95% confidence interval [CI]: 1.84, 7.80), HGS (HR: 2.37, 95% CI: 1.24, 4.55), SPPB (HR: 3.43, 95% CI: 1.55, 7.57), GS (HR: 3.03, 95% CI: 1.44, 6.38), and TUG (HR: 5.16, 95% CI: 2.19, 12.14) had shorter overall survival after adjustment for sex, age, symptomatology, comorbidity, percentage of weight loss, and tumor localization. CONCLUSIONS: Among the studied objective physical function measurements, HGS, SPPB, GS, and TUG were independent predictors of survival in a sample of patients with metastatic cancer, with TUG showing the highest effect size.

The Spectrum of Familial Pituitary Neuroendocrine Tumors.

Hereditary pituitary tumorigenesis is seen in a relatively small proportion (around 5%) of patients with pituitary neuroendocrine tumors (PitNETs). The aim of the current review is to describe the main clinical and molecular features of such pituitary tumors associated with hereditary or familial characteristics, many of which have now been genetically identified. The genetic patterns of inheritance are classified into isolated familial PitNETs and the syndromic tumors. In general, the established genetic causes of familial tumorigenesis tend to present at a younger age, often pursue a more aggressive course, and are more frequently associated with growth hormone hypersecretion compared to sporadic tumors. The mostly studied molecular pathways implicated are the protein kinase A and phosphatidyl-inositol pathways, which are in the main related to mutations in the syndromes of familial isolated pituitary adenoma (FIPA), Carney complex syndrome, and X-linked acrogigantism. Another well-documented mechanism consists of the regulation of p27 or p21 proteins, with further acceleration of the pituitary cell cycle through the check points G1/S and M/G1, mostly documented in multiple endocrine neoplasia type 4. In conclusion, PitNETs may occur in relation to well-established familial germline mutations which may determine the clinical phenotype and the response to treatment, and may require family screening.

Menopause, androgens, and cardiovascular ageing: a narrative review.

Cardiovascular disease is the leading cause of death worldwide; however, women tend to be less affected than men during their reproductive years. The female cardiovascular risk increases significantly around the time of the menopausal transition. The loss of the protective action of ovarian oestrogens and the circulating androgens has been implicated in possibly inducing subclinical and overt changes in the cardiovascular system after the menopausal transition. In vitro studies performed in human or animal cell lines demonstrate an adverse effect of testosterone on endothelial cell function and nitric oxide bioavailability. Cohort studies evaluating associations between testosterone and/or dehydroepiandrosterone and subclinical vascular disease and clinical cardiovascular events show an increased risk for women with more pronounced androgenicity. However, a mediating effect of insulin resistance is possible. Data on cardiovascular implications following low-dose testosterone treatment in middle-aged women or high-dose testosterone supplementation for gender affirmatory purposes remain primarily inconsistent. It is prudent to consider the possible adverse association between testosterone and endothelial function during the decision-making process of the most appropriate treatment for a postmenopausal woman.

Dietary patterns are associated with arterial stiffness and carotid atherosclerosis in postmenopausal women.

PURPOSE: The increase in cardiovascular risk after the menopausal transition remains partly explained until today. Further research is needed to identify risk factors potentially modifiable by primary prevention practices. This cross-sectional study, part of a larger prospective project, aims to investigate possible associations between dietary patterns and indices of vascular structure and function among healthy postmenopausal women. METHODS: Postmenopausal women (n = 310) without clinically overt cardiovascular disease were recruited consecutively from a University Menopause Clinic over three years. Dietary intake was assessed by a validated food frequency questionnaire and the MedDietScore. In addition, we assessed anthropometric/biochemical parameters, including the Triglyceride-glucose index (TyG-Index), body fat distribution [triceps skinfold (TSF), mid-upper arm circumference (MUAC)] and physical activity. The vascular assessment included carotid-femoral pulse wave velocity (PWV), carotid and femoral-artery intima-media thickness (IMT) and atheromatous plaques presence. RESULTS: Consumption of non-refined cereals was associated with carotid-bulb IMT (R2 = 5.5% b-coefficient = -0.142; p = 0.011), adjusting for age, physical activity, lipids, systolic blood pressure, smoking, body mass index, insulin resistance, and daily energy intake. PWV was associated with the intake of total dairy products (R2 = 27.3%, b-coefficient = -0.117; p = 0.017). Higher red meat consumption was related to a greater TyG-index (Model 1, R2 = 14.3%, b-coefficient=0.121; p = 0.048), an association mediated by total daily energy intake. Higher consumption of alcohol, as well as the MedDietScore, were inversely associated with TSF measurements, significant after Bonferroni correction. CONCLUSION: Dietary patterns are associated with metabolic indices and subclinical atherosclerosis in postmenopausal women independently of traditional cardiovascular risk factors, total energy intake or physical activity.