Reliable reference intervals for sex hormones are indispensable in evaluations of the hypothalamo-pituitary-gonadal axis. This study established reference intervals for estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and prolactin with the immunoassay platforms Advia Centaur and Immulite 2000XP (Siemens Healthcare, Germany). We recruited healthy men (n=220), women in the follicular (n=139) or luteal (n=87) phases of the menstrual cycle, and postmenopausal women (n=103). Data was analyzed according to CLSI EP28-A3c guidelines. Although reference intervals established with both platforms showed good agreement with ranges quoted by the assay manufacturer, two discrepancies were noted. First, intervals for prolactin in women were influenced by hormonal status, and the partition analysis supported their separation into subgroups based on menstrual cycle. Second, the upper limit for estradiol in the follicular phase was nearly a half of that provided by the manufacturer. This discrepancy was attributed to the stringent definition of the follicular phase (consistently set at days 3-5 after menstruation onset). Our findings suggest that reference values for prolactin should both be gender specific and account for menstrual cycle phase. The results also emphasize that clear-cut selection criteria are required when assembling populations for establishing endocrine reference intervals.
Adult ; Aged ; Female ; Follicular Phase ; Gonadal Steroid Hormones/*blood ; Humans ; Immunoassay ; Luteal Phase ; Male ; Middle Aged ; Postmenopause ; Reference Values ; Sex Factors

PURPOSE: Up to 71% of South Korean postmenopausal women have vitamin D deficiency {serum 25-hydroxyvitamin D [25(OH) D] level <50 nmol/L}. Data on vitamin D supplementation was collected during the screening phase of an efficacy/safety study of denosumab in Korean postmenopausal women with osteoporosis. This report describes the effect of vitamin D supplementation on repletion to 25(OH)D levels ≥50 nmol/L in Korean postmenopausal women with osteoporosis. MATERIALS AND METHODS: Vitamin D levels of Korean postmenopausal women (60-90 years old) were measured by extracting 25(OH)D2 and 25(OH)D3 from serum samples via protein precipitation and using liquid chromatography with tandem mass spectrometry detection. Calibration curves were constructed from the mass chromatograms to obtain total vitamin D levels. Subjects with serum 25(OH)D levels <50 nmol/L were supplemented with 1000 IU of vitamin D tablets during the 2.5-month-long screening period. Dose, frequency, and duration were determined by the investigator. If repletion was achieved (≥50 nmol/L) on retest, subjects were eligible to be rescreened for study entry. RESULTS: Of 371 subjects screened, 191 (52%) required vitamin D supplementation, and 88% (168 of 191) were successfully repleted. More than half of the subjects (58%) who were successfully repleted received doses of 2000 IU daily. The mean time to successful repletion was 31 days (standard deviation 8.4 days; range 11-48 days). CONCLUSION: Supplementation with daily median doses of 2000 IU vitamin D successfully repleted 88% of Korean postmenopausal women with osteoporosis within 48 days to a serum vitamin D level of 50 nmol/L.
Aged ; Aged, 80 and over ; *Asian Continental Ancestry Group ; Bone Density Conservation Agents/*therapeutic use ; *Dietary Supplements ; Double-Blind Method ; Female ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal/*complications/drug therapy/ethnology ; Postmenopause/blood ; Republic of Korea ; Vitamin D/analogs & derivatives/blood/*therapeutic use ; Vitamin D Deficiency/diagnosis/*drug therapy/ethnology

BACKGROUNDMenopausal hormone therapy (MHT) has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen (CEE) and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women.

METHODSA prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups: Group A received CEE 0.3 mg/micronized progesterone (MP) 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student's t-test and analysis of variance.

RESULTSA total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline (all P < 0.05). Among the three groups, only Group C showed significantly increased triglycerides compared with baseline (1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P = 0.026). Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups.

CONCLUSIONSAmong Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01698164; https://clinicaltrials.gov/ct2/show/NCT01698164?term=NCT01698164&rank=1.

Apolipoproteins B ; blood ; Blood Pressure ; drug effects ; Body Composition ; drug effects ; Dydrogesterone ; administration & dosage ; therapeutic use ; Estrogens, Conjugated (USP) ; administration & dosage ; therapeutic use ; Female ; Humans ; Insulin ; blood ; Lipoprotein(a) ; blood ; Metabolic Syndrome ; blood ; drug therapy ; Middle Aged ; Postmenopause ; Progesterone ; administration & dosage ; therapeutic use ; Triglycerides ; blood

It has been well established that women generally have lower incidence rates of hypertension than men at similar ages and these differences may vary with age. It also has been observed in many studies that after menopause, blood pressure (BP) increases in women to levels even higher than in men. The lack of estrogens may not be suggested as the only component involved in the development of postmenopausal hypertension. Thus, in this mini-review, the possible mechanisms by which sex hormones may influence the BP are discussed. This review also examines the renal regulatory mechanisms for gender differences in BP and explores the effects of salt intake on BP (salt-sensitivity) in pre and post-menopausal women. Estrogen has been shown to stimulate nitric oxide (NO) production, thus female sex hormones have a beneficial effect on BP control. Evidences that angiotensin type 2 receptor (AT2R) is up-regulated by estrogen support the favorable effects on BPs in women than men. The kidney plays an integral role in the regulation of arterial pressure through the mechanism of pressure-natriuresis, which has been shown to be modulated by the RAS. The prevalence of salt-sensitivity increases with age and low-salt diets has shown to help reduce systolic BP (SBP) and diastolic BP. While oral hormone replacement therapy has yielded only a neutral or minimal effect on the elevation of SBP, both the transdermal route replacement and a novel progestin with anti-aldosterone activity (drospirenone) has also shown to reduce SBP.
Arterial Pressure ; Blood Pressure ; Diet, Sodium-Restricted ; Estrogens ; Female ; Gonadal Steroid Hormones ; Hormone Replacement Therapy ; Humans ; Hypertension* ; Incidence ; Kidney ; Male ; Menopause ; Nitric Oxide ; Postmenopause ; Prevalence ; Receptor, Angiotensin, Type 2 ; Sodium*

OBJECTIVETo analyze the relationship between normal serum uric acid (SUA) levels and nonalcoholic fatty liver disease (NAFLD) among postmenopausal women, and determine the possible risk factors of NAFLD in this patient population.

METHODSChinese postmenopausal women who participated in the annual health check-up program from March 2009 to February 2010 were retrospectively assessed to identify individuals with SUA within normal range for study inclusion. For the total 1425 study participants, the recorded data of anthropometric parameters, metabolic factors, and serum biochemical parameters were collected. Results from abdominal ultrasonography examination were used to group participants according to presence of fatty liver. Women with fatty liver were divided into NAFLD and non-NAFLD groups. Further sub-grouping was performed according to SUA quartiles, as follows: Q1 group: less than 226.1 mumol/L); Q2 group: 226.1 mumol/L less than or equal to SUA less than 267.8 mumol/L; Q3 group: 267.8 mumol/Lless than or equal to SUA less than 303.5 mumol/L); Q4 group: 303.5 mumol/Lless than or equal toSUAless than or equal to357.0 mumol/L. The independent-sample t-test was used to compare normally distributed variables between groups, and the Mann-Whitney U test was used to analyze variables with skewed distribution. Categorical variables were examined by the R * C x2 test. Binary logistic analysis was used to determine the risk factors for fatty liver and to adjust for possible confounders. The multiple non-parameter independent-sample test (Kruskal-Wallis test) was used to compare the differences of SUA levels among NAFLD groups with different disease severity.

RESULTSThe prevalence of NAFLD among Chinese postmenopausal women with normal SUA was 32.8%, with NAFLD prevalences of 20.4% (70/343) in women with Q1 SUA, 26.3% (104/395) with Q2 SUA, 35.2% (128/364) with Q3 SUA, and 51.4% (166/323) with Q4 SUA. The prevalence of fatty liver showed a significant increasing trend according to the SUA quartile (x2 = 76.470, P-trend less than 0.01). Women in the SUA Q3 and Q4 groups had significantly higher risk of fatty liver presence than women in the Q1 group (P less than 0.01 for both, with or without adjustment of confounders). Disease severity did not appear to be related to disease severity, as the SUA levels in women with mild, moderate or severe fatty liver were not significantly different (286.8+/-48.2 mumol/L vs. 277.9+/-53.0 mumol/L vs. 281.4+/-48.2 mumol/L, respectively; x2 = 3.025, P more than 0.05).

CONCLUSIONSUA levels were independently correlated with NAFLD in Chinese postmenopausal women. SUA levels in the higher quartiles of the normal range may be an independent risk factor of NAFLD.

Aged ; Female ; Humans ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; blood ; diagnosis ; Postmenopause ; Retrospective Studies ; Risk Factors ; Uric Acid ; blood

OBJECTIVESolanum xanthocarpum Schrad. & Wendl. (Solanaceae) is present in many Ayurveda compound formulations including Chavanaprasha and Dasamoolarishta. The whole plant is used in conditions such as inflammation, constipation and promoting conception in females. In the present study, we carried out different tests to evaluate the effect of aqueous extract of Solanum xanthocarpum (SXE) in postmenopausal syndrome.

METHODSThe study was carried out in bilaterally ovariectomized one-month-old Wistar rats (40-50 g). Bilaterally ovariectomized (OVX) Wistar rats were divided into four groups (n=6) receiving different treatments, consisting of a vehicle (distilled water), aqueous extract of Solanum xanthocarpum at two different doses (200 and 400 mg/kg) administered orally daily for 90 d and standard drug β estradiol at a dose of 1 mg/kg administered subcutaneously biweekly for 90 d. Estrogenic activity was assessed by vaginal cornification, sexual behavior, serum estradiol and uterine weight to body weight ratio. Antiosteoporotic activity was assessed on the basis of biomechanical and biochemical parameters followed by histopathological studies, and antidepressant activity was assessed by forced swim test.

RESULTSSXE showed presence of steroids. At the dose of 200 mg/kg, it significantly improved all the parameters of sexual behavior (P<0.01), caused vaginal cornification, and increased serum estradiol and uterine weight (P<0.01). It also significantly improved all the parameters of bone strength as well as depression (P<0.01). Histopathology of bones confirmed the above findings.

CONCLUSIONThe study indicated that SXE may provide an effective treatment in the prevention of postmenopausal symptoms.

Animals ; Antidepressive Agents ; pharmacology ; Estradiol ; blood ; Estrogens ; pharmacology ; Female ; Femur ; drug effects ; metabolism ; Humans ; Male ; Mice ; Osteoporosis, Postmenopausal ; prevention & control ; Ovariectomy ; Plant Extracts ; pharmacology ; Postmenopause ; drug effects ; Rats ; Rats, Wistar ; Sexual Behavior, Animal ; drug effects ; Solanum

BACKGROUNDAs an adipocytokine, resistin has been proposed as a link between inflammation, metabolic disorder and atherosclerosis. The aim of the study is to evaluate whether serum resistin is associated with acute coronary syndrome (ACS) and major adverse cardiovascular events (MACEs) among postmenopausal women with ACS undergoing percutaneous coronary intervention (PCI).

METHODSA total of 106 consecutive postmenopausal women who underwent coronary angiography for evaluation of suspected myocardial ischemia were enrolled. Pre-procedure serum resistin, inflammatory and metabolic biomarkers were measured. All participants were followed for seven years for MACEs, including cardiovascular death, recurrent nonfatal myocardial infarction, and re-PCI.

RESULTSPatients with ACS (n = 69) had significantly higher resistin levels than those without coronary artery disease (CAD) (n = 37) (4.61 (1.79 - 10.80) ng/ml vs. 2.36 (0.85 - 4.15) ng/ml, P = 0.002). Correlation analysis revealed positive correlations between resistin levels and inflammatory and metabolic factors (P < 0.05). A follow-up of a mean of 83.4 months showed that patients with ACS suffered more MACEs than those without (13.0% vs. 2.7%, P = 0.05). Adjusted for cardiovascular risks, inflammatory and metabolic factors, multiple Logistic regression analysis indicated that an elevated resistin level was an independent predictor of ACS onset (OR = 1.139, 95%CI 1.024 - 1.268, P = 0.017) and of MACEs after PCI (OR = 1.099, 95%CI 1.015 - 1.189, P = 0.019). To clarify the association between resistin levels and MACEs, ACS patients were divided into two subgroups on the basis of resistin levels. Compared with the low resistin subgroup (≤ 4.35 ng/ml, n = 32), patients in the high resistin subgroup (> 4.35 ng/ml, n = 37) were more prone to suffer MACEs (21.6% vs. 3.1%, P = 0.015). Kaplan-Meier analysis showed a significantly lower event-free survival rate in ACS patients with high resistin levels than in the low resistin subgroup (78.4% vs. 96.9%, Log rank 5.594, P = 0.018).

CONCLUSIONAn elevated serum resistin level is associated with ACS and cardiovascular events and acts as a predictor in progression of ACS in postmenopausal women.

Acute Coronary Syndrome ; blood ; pathology ; therapy ; Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Postmenopause ; Resistin ; blood

Primary vaginal cancer combined with uterine prolapse is very rare. We present a case of 80-year-old postmenopausal women complaints of something coming out per vagina for the past 20 years, along with blood stained discharge, foul odor leukorrhea, and severe pelvic pain for the last 3 months. A 4 x 5 cm ulcer was present on middle third of vaginal wall with marked edema and ulceration of surrounding tissue. The prolapse was reduced under intravenous sedation in operating room. On gynecologic examination, uterus was normal in size, no adnexal mass was examined, and both parametrium were thickened. Papanicolaou smear was normal. Biopsy of the ulcer at vaginal wall revealed invasive squamous cell carcinoma of vagina. Magnetic Resonance Imaging of abdomen and pelvis showed left hydronephrosis and liver metastasis. Positron emission tomography (PET)/computed tomography (CT) revealed metastasis to lung, liver and iliac bone. She died from progression of disease one month after diagnosis.
Abdomen ; Aged, 80 and over ; Biopsy ; Blood Stains ; Carcinoma, Squamous Cell ; Diagnosis ; Edema ; Female ; Humans ; Hydronephrosis ; Leukorrhea ; Liver ; Lung ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Odors ; Operating Rooms ; Papanicolaou Test ; Pelvic Pain ; Pelvis ; Positron-Emission Tomography ; Postmenopause ; Prolapse ; Ulcer ; Uterine Prolapse* ; Uterus ; Vagina ; Vaginal Neoplasms*

OBJECTIVETo study relationships between serum ferritin and bone metabolism in patients with hip fragility fractures.

METHODSThis cross-sectional study included 76 postmenopausal women with hip fracture from Feburary 2011 to June 2012. The mean age of the women was (73 ± 10) years (range, 55-93 years) and the mean duration of menstruation was (22 ± 10)years (range, 5-50 years). Serum concentrations of ferritin, transferrin, alkaline phosphatase (ALP), amino-terminal extension peptide of type I collagen (P1NP), C-terminal telopeptides of type I collagen (β-CTX)and femoral and lumbar bone mineral density by dual-energy X-ray absorptiometry were measured. Bone metabolism was compared between normal and elevated ferritin groups with t-test, Pearson linear, partial correlation and multiple regression analysis examined associations between iron- and bone-related markers.

RESULTSSerum ferritin concentration raised to (230 ± 146)µg/L, transferrin concentration reduced to (1.89 ± 0.33)g/L. P1NP concentration raised to (61 ± 32) ng/L when the concentration of serum ALP and β-CTX were in the normal range. T-scores for bone mineral density in the femoral neck (-2.0 ± 1.1) and lumbar (-2.1 ± 1.2) were below the normal ranges(-1.0-1.0). The subjects were divided into two groups according to serum ferritin concentration, normal group(serum ferritin concentration ≤ 150 µg/L, n = 25) and elevated group(serum ferritin concentration > 150 µg/L, n = 51). Patients of elevated group had lower bone mineral density in femoral neck and lumbar than normal group(t = 3.13,2.89, P < 0.01), and higher P1NP, β-CTX concentration (t = -2.38, -3.59, P < 0.05) . In partial correlation analysis adjusted for confounders, serum ferritin concentration was correlated negatively with bone mineral density in both femoral neck and lumbar (r = -0.335,-0.295, P < 0.05), and positively with P1NP and β-CTX (r = 0.467,0.414, P < 0.05), but not correlated with ALP (r = 0.188, P > 0.05). Transferrin concentration tended to be correlated positively with bone mineral density in both femoral neck and lumbar (r = 0.444, 0.262, P < 0.05) and negatively with ALP, P1NP and β-CTX(r = -0.326,-0.285,-0.278, P < 0.05).

CONCLUSIONSIron overload has a high prevalence in postmenopausal women with fragility fracture. Increased iron stores, which might lead to bone loss and lower bone mineral density by enhancing the activity of bone turnover, could be an independent factor to take effects on bone metabolism on postmenopausal women.

Aged ; Aged, 80 and over ; Bone Density ; Bone Remodeling ; Collagen Type I ; blood ; Cross-Sectional Studies ; Female ; Hip Fractures ; metabolism ; Humans ; Iron Overload ; Iron-Binding Proteins ; metabolism ; Middle Aged ; Osteoporosis, Postmenopausal ; metabolism ; Postmenopause ; Retrospective Studies

Osteopontin (OPN) is an acidic, noncollagenous matrix protein produced by the bone and kidneys. It is reportedly involved in bone resorption and formation. We examined the association between serum OPN levels and bone mineral density in postmenopausal women. Premenopausal women (n=32) and postmenopausal women (n=409) participated in the study. We measured serum osteopontin levels and their relationships with bone mineral density and previous total fragility fractures. The postmenopausal women had higher mean serum OPN levels compared to the premenopausal women (43.6+/-25.9 vs 26.3+/-18.6 ng/mL; P<0.001). In the postmenopausal women, high serum OPN levels were negatively correlated with mean lumbar bone mineral density (BMD) (r=-0.113, P=0.023). In a stepwise multiple linear regression model, serum OPN levels were associated with BMD of the spine, femoral neck, and total hip after adjustment for age, body mass index, smoking, and physical activity in postmenopausal women. However, serum OPN levels did not differ between postmenopausal women with and without fractures. Postmenopausal women exhibit higher serum OPN levels than premenopausal women and higher serum OPN levels were associated with low BMD in postmenopausal women.
Aged ; Bone Density/*physiology ; Female ; Femur Neck/metabolism ; Fractures, Bone/metabolism/pathology ; Humans ; Linear Models ; Middle Aged ; Osteopontin/*blood ; Postmenopause ; Premenopause ; Spine/metabolism