The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

Bone Health in Patients with Dyslipidemias: An Underestimated Aspect.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength.

Anterior femoral notching ≥ 3 mm is associated with increased risk for supracondylar periprosthetic femoral fracture after total knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Anterior femoral notching (AFN) may be associated with a higher risk for supracondylar periprosthetic fracture (sPPF) after total knee arthroplasty (TKA), although studies have yielded inconclusive results. We aimed to systematically investigate and meta-analyze the best available evidence regarding the association between AFN and the risk of sPPF after TKA. METHODS: A comprehensive search of PubMed, Scopus, Mendeley, Google Scholar and Cochrane databases was performed, from conception to February 29, 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). I2-index was employed for heterogeneity. Newcastle-Ottawa scale was implemented for quality assessment of the included studies. RESULTS: Nine studies fulfilled the eligibility criteria, including a total of 3264 patients subjected to TKA. Among them, there were 150 patients who sustained a sPPF. Overall, patients exposed to AFN (AFN group) demonstrated an increased risk for sPPF compared to those not exposed (control group) (OR 3.91, 95% CI 1.22-12.58, p = 0.02; I2 68.52%). Subgroup analysis based on AFN depth with a cut-off value of 3 mm further clarified this association. Patients with AFN ≥ 3mm were at higher risk for sPPF compared to patients with AFN < 3 mm and control group (OR 4.85, 95% CI 2.08-11.33, p = 0.00; I2 0.0%). On the contrary, fracture risk was not significant for patients with AFN < 3 mm compared to the control group (OR 5.0, 95% CI 0.44-56.82, p = 0.19; I2 42.99%). CONCLUSION: Patients, exposed to AFN ≥ 3 mm in depth, are at higher risk for sustaining a sPPF.

Menopausal hormone therapy and women's health: An umbrella review.

BACKGROUND: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). CONCLUSIONS: MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

Teriparatide Treatment in Patients with Pregnancy- and Lactation-Associated Osteoporosis.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 µg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3-9) vs. 2.5 VFs (1-10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9  ±  11.9% vs. 6.2  ±  4.8% at the LS (p < 0.001), 10.0  ±  11.6% vs. 5.8  ±  2.8% at the TH (p = 0.43), and 6.7  ±  6.9% vs. 0.9  ±  3.7% in TBS (p = 0.09), respectively. At 24 months, seven patients on TPTD and six controls achieved a mean LS aBMD increase of 32.9  ±  13.4% vs. 12.2  ±  4.2% (p = 0.001). P1NP levels during the first month of TPTD treatment were positively correlated with the 1-year LS aBMD change (r = 0.68, p = 0.03). No new clinical fractures occurred while on-treatment. In patients with PLO, TPTD treatment resulted in significantly greater increases in LS aBMD compared with calcium and vitamin D supplementation at 12 and 24 months.

Serum anti-Mullerian hormone, prolactin and estradiol concentrations in infertile women with endometriosis.

OBJECTIVE: Endometriosis is a benign gynecological disease, which significantly impairs fertility. However, the contribution of specific hormonal parameters to the proper diagnosis of endometriosis in infertility states has not been adequately determined. The aim of this study was to compare ant-Mullerian hormone (AMH), prolactin and estradiol concentrations between infertile women with and without endometriosis, as well as to estimate the effect of endometrioid heterotopia on ovarian reserve. METHODS: In this cross-sectional study, mean baseline serum AMH, prolactin and estradiol levels were assessed in infertile women with and without endometriosis. Descriptive statistics are presented in the form of arithmetic mean ± standard deviation (SD). The comparison of indicators was performed by using parametric (t-test) and non-parametric criteria (Mann-Whitney). RESULTS: Seventy-two infertile women with endometriosis (group A; mean age: 32 ± 4.3 years) and 77 infertile women without endometriosis (group B; mean age: 32.4 ± 3.7 years) were studied. Mean baseline prolactin concentrations were higher in group A (16.9 ± 5.7 ng/mL) compared with group B (15 ± 4.3 ng/mL; p = .023), whereas mean AMH concentrations were lower (2.8 ± 1.9 ng/mL and 3.5 ± 1.8 ng/mL, respectively; p = .018). The highest prolactin and the lowest AMH concentrations were found in women with ovarian endometriomas than in those with deep infiltrative endometriosis and adenomyosis. There was no difference in estradiol levels between groups. CONCLUSIONS: Infertile women with endometriosis demonstrated higher prolactin and lower AMH concentrations, compared with infertile women without endometriosis. The highest prolactin and the lowest AMH concentrations were observed in patients with ovarian endometriomas.

Type 2 Diabetes Mellitus is Associated with Increased Risk of Sarcopenia: A Systematic Review and Meta-analysis.

Diabetes mellitus (DM) is associated with an increased risk of fractures, mainly due to impaired bone architecture and microvascular complications. Whether DM is also associated with increased risk of sarcopenia is not yet known, with studies yielding inconclusive results. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between DM and sarcopenia risk. A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. Only studies which had implemented at least two of the three criteria for sarcopenia diagnosis (low muscle mass, muscle strength and/or muscle performance), as defined by the international studying groups, were included. Fifteen studies fulfilled eligibility criteria, yielding a total of 1832 patients with type 2 DM (T2DM) and 1159 cases of sarcopenia. Patients with T2DM demonstrated a higher risk of sarcopenia compared with euglycemic subjects (OR 1.55, 95% CI 1.25-1.91, p < 0.001; I2 34.6%). This risk remained significant when analysis was restricted to studies matched for age and sex. Sarcopenia risk was independent of disease definition or study design. Notably, T2DM patients presented lower muscle performance and strength compared with euglycemic subjects, whereas no difference in muscle mass was observed between groups. Patients with T2DM have an increased risk of sarcopenia compared with euglycemic subjects.

Do Near-Infrared Intra-Operative Findings Obtained Using Indocyanine Green Correlate with Post-Thyroidectomy Parathyroid Function? the Icgpredict Study.

OBJECTIVE: Postoperative hypoparathyroidism (hypoPT) still remains a significant complication after thyroidectomy. Intra-operative imaging modalities, such as near-infrared fluorescence using indocyanine green (ICG), may assist in identifying and preserving the parathyroid glands (PGs). The purpose of this study was to test the association between the intra-operative ICG staining scoring system and 24-hour postoperative parathyroid hormone (PTH) levels, as well as its capability for intra-operative PG identification. METHODS: This was a prospective study, recruiting patients scheduled for total thyroidectomy by the same surgical team, from December 2018 to April 2019. Intra-operative angiography was performed after infusion of ICG solution (5 mg). Two minutes later, images were acquired using the near-infrared system. RESULTS: Sixty patients fulfilled the eligibility criteria. The percentage of temporary postoperative hypoPT (defined as PTH <14 pg/mL) was 11.66%. No association between intra-operative ICG staining score (expressed as the number of PGs scoring <2 per patient) and 24-hour postoperative PTH (r = 0.011; P = .933) or serum calcium concentrations (r = 0.127; P = .335) was observed. There was also no correlation between the location of PGs scoring ≤2 and postoperative PTH (P = .257) or serum calcium levels (P = .950). Moreover, with regard to secondary endpoint, ICG correctly identified PGs in 98.3% of cases. ICG score was not affected by age, gender, duration of operation, or thyroid gland pathology. No allergic reactions attributed to ICG administration were observed. CONCLUSION: The intra-operative ICG staining scoring system did not predict 24-hour postoperative PTH and serum calcium levels. However, this modality may assist in intra-operative PG identification during a total thyroidectomy.

Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. METHODS: Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. RESULTS: This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-CM/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). CONCLUSION: LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.

Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials.

OBJECTIVE: Increased oxidative stress has been identified as a pathogenetic mechanism in female infertility. However, the effect of specific antioxidants, such as coenzyme Q10 (CoQ10), on the outcomes after assisted reproductive technologies (ART) has not been clarified. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of CoQ10 supplementation on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) compared with placebo or no-treatment in women with infertility undergoing ART. METHODS: A comprehensive literature search was conducted in PubMed (MEDLINE), Cochrane, and Scopus, from inception to March 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Five randomized-controlled trials fulfilled eligibility criteria (449 infertile women; 215 in CoQ10 group and 234 in placebo/no treatment group). Oral supplementation of CoQ10 resulted in an increase of CPR when compared with placebo or no-treatment (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30-4.59, p = 0.006; I2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding LBR (OR 1.67, 95% CI 0.66-4.25, p = 0.28; I2 34%) and MR (OR 0.61, 95% CI 0.13-2.81, p = 0.52; I2 0%). CONCLUSIONS: Oral supplementation of CoQ10 may increase CPR when compared with placebo or no-treatment, in women with infertility undergoing ART procedures, without an effect on LBR or MR.

Genetic Predisposition to Developmental Dysplasia of the Hip.

BACKGROUND: The etiopathogenesis of developmental dysplasia of the hip (DDH) has not been clarified. This systematic review evaluated current literature concerning all known chromosomes, loci, genes, and their polymorphisms that have been associated or not with the prevalence and severity of DDH. METHODS: Following the established methodology of Meta-analysis of Observational Studies in Epidemiology guidelines, MEDLINE, EMBASE, and Cochrane Register of Controlled Trials were systematically searched from inception to January 2019. RESULTS: Forty-five studies were finally included. The majority of genetic studies were candidate gene association studies assessing Chinese populations with moderate methodological quality. Among the most frequently studied are the first, third, 12th,17th, and 20th chromosomes. No gene was firmly associated with DDH phenotype. Studies from different populations often report conflicting results on the same single-nucleotide polymorphism (SNP). The SNP rs143384 of GDF5 gene on chromosome 20 demonstrated the most robust relationship with DDH phenotype in association studies. The highest odds of coinheritance in linkage studies have been reported for regions of chromosome 3 and 13. Five SNPs have been associated with the severity of DDH. Animal model studies validating previous human findings provided suggestive evidence of an inducing role of mutations of the GDF5, CX3CR1, and TENM3 genes in DDH etiopathogenesis. CONCLUSION: DDH is a complex disorder with environmental and genetic causes. However, no firm correlation between genotype and DDH phenotype currently exists. Systematic genome evaluation in studies with larger sample size, better methodological quality, and assessment of DDH patients is necessary to clarify the DDH heredity. The role of next-generation sequencing techniques is promising.

Successful management of tertiary hyperparathyroidism associated with hypophosphataemic rickets in an adult.

Tertiary hyperparathyroidism (THP) is a rare complication in patients with hypophosphataemic rickets (HR), usually related to long-term management with active vitamin D analogues and oral phosphate salts. If left untreated, THP may aggravate bone and renal disease. We report a case of THP, which developed during the course of HR. Preoperatively, cinacalcet administration along with gradual increase in alphacalcidol dose, led to almost normalization of serum calcium and decrease in parathyroid hormone (PTH) concentrations. The patient underwent an uneventful subtotal parathyroidectomy, resulting in PTH normalization and stabilization of eucalcaemia during 18 months of follow-up. We conclude that, except for optimal dosage of elementary phosphate and alphacalcidol, cinacalcet prior to parathyroidectomy may be an effective option in patients with HR complicated with THP.

Could Lipid Profile be Used as a Marker of Autonomous Cortisol Secretion in Patients with Adrenal Incidentalomas?

Adrenal incidentalomas (AIs) have been associated with an increased risk of metabolic syndrome and dyslipidemia, though evidence regarding the latter is limited. Lipid abnormalities in patients with AIs have been associated with subclinical hypercortisolism. The current study aims to test whether lipid profile in patients with AIs predicts "autonomous cortisol secretion" (ACS). Patients with AIs found on either computerized tomography (CT) or magnetic resonance imaging (MRI), were included in a prospective cohort study. All patients were followed up for at least three years. Alterations in their hormonal and lipid profiles were recorded. Ninety-four patients (69 women) harboring 111 AIs were included. There were no differences between patients with ACS and those without, with respect to their baseline lipid profile [total cholesterol, low-density-lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C] and blood pressure (systolic and diastolic). Non-HDL-C concentrations decreased over time (Repeated Measures ANOVA, p=0.013), despite patients' body mass index (BMI) remaining unchanged. Logistic regression analysis revealed that the only predictor of ACS was the size of AIs, as calculated by CT or MRI. The current study demonstrated that lipid profile at baseline or during follow-up cannot predict ACS in patients with AIs. However, larger AIs may have a greater probability of ACS.

Enduring remission of active and sight-threatening Graves' orbitopathy with rituximab: report of two cases.

Intravenous (i.v.) glucocorticosteroids (GCs) constitute the first-line treatment for active and moderate-to-severe Graves' orbitopathy (GO). In cases of persistent disease, rituximab, a monoclonal anti-CD20 antibody, may be used, although studies have yielded conflicting results. In case 1, a 50-year-old female heavy smoker presented with severe bilateral disfiguring eyelid edema of four months, bilateral exophthalmos and a clinical activity score (CAS) of 5/7. Laboratory investigation showed thyrotoxicosis and high thyroid-stimulating immunoglobulin (TSI) levels [32 IU/L (normal <1.75]. After minor improvement by i.v. methylprednisolone and standard retrobulbar radiotherapy (20 Gy), her visual acuity progressively declined to "hand motion". Rituximab was administered (two pulses of 500 mg, two weeks apart), with significant response. At 3 1/2 years of follow-up, CAS is 0/7 and CD20+ lymphocytes remain at the lower normal range. In case 2, a 78-year-old non-smoker male was referred for management of severe active GO, one month after total thyroidectomy for Graves' thyrotoxicosis (TSI: 6.74 IU/L). Over the preceding two-three months, severe GO manifested with chemosis, constant diplopia, loss of color vision and acuity of 1/10 bilaterally (CAS: 7/7). Following partial response to i.v. methylprednisolone and concomitant radiotherapy, rituximab (two pulses of 500 mg each, two weeks apart), was administered. Vision partially recovered and GO remains in remission one year later, even after 131I (100 mCi) administration for papillary thyroid carcinoma (TSI: 0.9 IU/L and CD20+ count at the lower normal range). In conclusion, rituximab may be an effective second-line therapy in GO patients, providing long-lasting remission.

Effects of gender, age and menopausal status on serum apolipoprotein concentrations.

OBJECTIVE: To undertake a comprehensive evaluation of apolipoprotein risk markers for cardiovascular disease (CVD) according to gender, age and menopausal status. DESIGN: Cross-sectional analysis of independent associations of gender, age and menopause with serum apolipoproteins. PARTICIPANTS: Apparently healthy Caucasian premenopausal (n = 109) and postmenopausal (n = 252) women not taking oral contraceptives or hormone replacement, and Caucasian men (n = 307). MEASUREMENTS: Serum apolipoprotein (apo) B, A-I and A-II concentrations were measured, plus serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), triglycerides, cholesterol in HDL subfractions and the apoB/apoA-I, LDL-C/apoB, HDL-C/apoA-I and HDL-C/apoA-II ratios. Analyses were undertaken with and without standardization for confounding characteristics and in 5-year age ranges. RESULTS: Overall, apoB concentrations were highest in men but in women rose with age and menopause to converge, in the age range of 50-55 years, with concentrations in men. The LDL-C/apoB ratio was generally higher in women than in men. ApoA-I concentrations were highest in postmenopausal women and lowest in men (standardized median (IQR) 144 (130, 158) vs 119 (108, 132) g/l, respectively, P < 0·001). ApoA-II concentrations were also highest in postmenopausal women but were lowest in premenopausal women (40·3 (37·5, 44·5) vs 32·9 (30·5, 35·7) g/l, respectively, P < 0·001). Nevertheless, postmenopausal women had HDL-C/apoA-I and HDL-C/apoA-II ratios approaching the lowest ratios, which were seen in men. CONCLUSIONS: Consistent with adverse effects on CVD risk, male gender, ageing in women and menopause were associated with increased apoB concentrations, and menopause and male gender were associated with a decreased cholesterol content of HDL particles.

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options.

INTRODUCTION: Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. METHODS: PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause"). RESULTS: Only hormone replacement therapy (mainly oral estrogens) and tibolone have been specifically studied in postmenopausal women and can reduce Lp(a) concentrations by up to 44%, although evidence indicating a concomitant reduction in CVD risk associated with Lp(a) is lacking. As alternative treatments for women who cannot, or will not, take hormonal therapies, niacin and the upcoming proprotein convertase subtilisin / kexin type 9 (PCSK-9) inhibitors are effective in reducing Lp(a) concentrations by up to 30%. Statins have minimal or no effect on Lp(a). However, data for these and other promising Lp(a)-lowering therapies including mipomersen, lomitapide, cholesterol-ester-transfer protein inhibitors and eprotirome are derived from studies in the general, mainly high CVD risk, population, and include only subpopulations of postmenopausal women. CONCLUSIONS: Past, present and emerging therapies can reduce Lp(a) concentrations to a varying extent. Overall, it remains to be proven whether the aforementioned reductions in Lp(a) by these therapeutic options are translated into CVD risk reduction in postmenopausal women.

Expression of gonadal steroid receptors in the ovaries of post-menopausal women with malignant or benign endometrial pathology: a pilot study.

This pilot study aimed to investigate the expression of estrogen (ER) and progesterone receptors (PR), as well as their subtypes [alpha (ERα), beta (ERß)], in the ovaries of postmenopausal women with benign or malignant endometrial pathology. Twenty postmenopausal women (age 66.2 ± 7.4 years) were included, diagnosed with benign (n = 10) or malignant [(serous/papillary (n = 4), endometrioid (n = 6)] endometrial lesions. Higher ERß and PR ovarian expressions were observed comparing women with endometrioid versus non-endometrioid endometrial carcinoma (p = 0.022 and p = 0.029, respectively). Age, age at menarche and presence of hypertension were negatively associated with ERs and PR expression. The expression of ERα and ERß was inversely correlated with menopausal age, which was not verified for PR. No significant association was observed between ERs or PR expression and benign or malignant endometrial pathology. Higher expression of ERß and PR in the postmenopausal ovary is associated with the presence of a less aggressive type of endometrial cancer, comparing women with endometrioid versus non-endometrioid lesions. The expression pattern of ovarian receptors did not differ regarding the development of benign or malignant endometrial lesions. Larger observational studies are necessary to confirm the significance of our findings.

Genetic basis of familial isolated hyperparathyroidism: a case series and a narrative review of the literature.

Primary hyperparathyroidism is a heterogeneous clinical entity. In the clinical setting, the diagnosis and management of familial isolated hyperparathyroidism (FIHP) and other familial hyperparathyroidism (FHPT) forms continue to rely on clinical, laboratory, and histological findings, with careful examination of the family. In this article, we report a case series of FIHP in a four-generation Greek family, with no identifiable gene mutations. Clinical approach and long-term follow-up are discussed and a narrative review of the genetic basis of this entity has been performed.