Menopause (MENOPAUSE)

Publications in this journal

• Article: Hyperresistinemia is associated with postmenopausal breast cancer

  Dalamaga M, Karmaniolas K, Papadavid E, Pelekanos N, Sotiropoulos G, Lekka A
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  ABSTRACT: OBJECTIVE: The constellation of obesity, insulin resistance, and serum adipocytokine levels is associated with the risk and prognosis of postmenopausal breast cancer (PBC). Altered secretion of resistin may underlie the association between overweight/obesity and PBC. We thus explored the association of serum resistin with PBC, taking into account established risk factors, including adipokines and anthropometric, metabolic, and inflammatory markers. METHODS: In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control participants matched on age and time of diagnosis between 2003 and 2010 at the Veterans' Administration General Hospital of Athens (NIMTS Hospital). Serum resistin, adiponectin, leptin, metabolic (homeostasis model assessment score of insulin resistance) and inflammatory (tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein) parameters, and tumor markers (carcinoembryonic antigen and CA 15-3) were determined. RESULTS: The mean serum resistin level was significantly higher in case participants than in control participants (P < 0.001) in both univariate and multivariable analyses, adjusting for age, date of diagnosis, education, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, physical activity, reproductive markers, metabolic markers, anthropometric (body mass index and weight circumference) markers, inflammatory markers, and adipokines (odds ratio, 1.17; 95% CI, 1.03-1.34; P = 0.02). In case participants, resistin level correlated significantly with tumor markers and inflammatory parameters, but not with metabolic and anthropometric variables. CONCLUSIONS: Further prospective, longitudinal, and mechanistic studies are needed to determine whether hyperresistinemia is involved in the development of PBC or reflects changes during PBC progression and therefore could be used as a biomarker for PBC. Targeting resistin inhibition could be an effective therapeutic strategy in breast cancer by down-regulating the inflammatory microenvironment in breast tissue.
  Menopause 03/2013;
• Article: Overexpression of PGRMC-1 possible mechanism for increased breast cancer risk using norethisterone in hormone therapy

  Helen Schneck, Harald Seeger, Michael A. Cahill, Yayun Liang, Benford Mafuvadze, Salman Hyder, Tanja Fehm, Alfred O. Mueck
  Menopause 12/2012;
• Article: Depressive symptoms are increased in the early perimenopausal stage in ethnically diverse human immunodeficiency virus infected and human immunodeficiency virus uninfected women.

  Maki, P.M, Rubin, L.H, Cohen, M.C, Golub, E.T, Greenblatt, R.M, Young, Schwartz, Anastos, Cook
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  ABSTRACT: Objective: The risk of clinically significant depressive symptoms increases during perimenopause. With highly active antiretroviral treatment (HAART), more human immunodeficiency virus (HIV)-infected women survive to transition through menopause. In a cross-sectional analysis, we evaluated the association of menopausal stage and vasomotor symptoms with depressive symptoms in an ethnically diverse cohort of women with a high prevalence of HIV. Methods: Participants included 835 HIV-infected women and 335 HIV-uninfected controls from the Women's Interagency HIV Study (63% African American). The Center for Epidemiologic Studies Depression Scale was used to screen for elevated depressive symptoms. Menopausal stages were defined according to standard definitions. Logistic regression analysis was used to identify predictors of elevated depressive symptoms. Results: Compared with premenopausal women, early perimenopausal women (OR [odds ratio], 1.74; 95% CI, 1.17-2.60), but not late perimenopausal or postmenopausal women, were more likely to show elevated depressive symptoms in adjusted analyses. The odds were similar in HIV-infected and HIV-uninfected women. Persistent vasomotor symptoms also predicted elevated depressive symptoms in HIV-infected and HIV-uninfected women (OR, 1.45; 95% CI, 1.02-2.06). In HIV-infected women, menopausal stage interacted with antiretroviral use (P = 0.02); the likelihood of elevated depressive symptoms in early perimenopause compared with premenopause was especially high in HAART-untreated women (OR, 3.87; 95% CI, 1.57-9.55). Conclusions: In HIV-infected and HIV-uninfected women, the odds of elevated depressive symptoms were significantly higher during early perimenopause. Elevated depressive symptoms were associated with nonadherence to HAART, underscoring the importance of screening and treating depressive symptoms in HIV-infected women who have experienced a change in the regularity of their menstrual cycles.
  Menopause 11/2012; 19(11):1215-1223.
• Article: Ovarian Volume and Menopausal Status

  Jodi A. Flaws, Julia C. Rhodes, Patricia Langenberg, Anne N. Hirshfield, Kristen Kjerulff, Fady I. Sharara
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  ABSTRACT: Objective: The purposes of this study were to (1) examine whether ovarian volume differs by age and menopausal status in healthy women; (2) evaluate whether ovarian volume could be a sensitive and specific predictor of menopausal status; and (3) assess whether ovarian volume is affected by cigarette smoke, oral contraceptives (OCs), and hormone replacement therapy (HRT). Design: Each participant (527 women) completed an extensive in-home interview that assessed age, menopausal status, smoking history, OC use, and HRT use. Each participant also received a transvaginal ultrasound that measured ovarian volume. Geometric means for ovarian volume were compared between premenopausal and postmenopausal women using t tests. Tests for trends were conducted using linear regression analyses. Results: Ovarian volume declined with age (p <= 0.0001) and also differed by menopausal status; postmenopausal women had smaller ovarian volumes than premenopausal women of the same age (p <= 0.0001). Ovarian volume was not associated with smoking history or HRT use. However, it was significantly smaller in current users of OCs compared with past users of or those who never used OCs (p <= 0.0001). Ovarian volume was a sensitive and specific predictor of postmenopausal status. Conclusions: The data suggest that age, menopausal status, and OC use may be determinants of ovarian volume. They also suggest that ovarian volume may be useful for predicting menopausal status in women. (Menopause 2000;7:53-61. (C) 2000, The North American Menopause Society.) (C)2000The North American Menopause Society
  Menopause 08/2012; 7(1).
• Article: Phytoestrogens and breast cancer in postmenopausal women: a case control study

  Alice Murkies, Fabien S. Dalais, Esther M. Briganti, Henry G. Burger, David L. Healy, Mark L. Wahlqvist, Susan R. Davis
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  ABSTRACT: Objective: To examine the association between isoflavones, androgens, and dietary composition and the risk of breast cancer in Australian postmenopausal women. Design: Eighteen women with recently diagnosed breast cancer before surgery and 20 controls were recruited over a 12-month period. Both cases and controls were similarly assessed for urinary isoflavones, serum and urinary sex steroids, and dietary intake. Results: Women with breast cancer had lower 24-h urinary daidzein compared with controls (cases: 31 [95% CI: 4, 234] nmol/day; controls: 427 [95% CI: 4, 234] nmol/day; p = 0.03), and there was a trend to lower urinary genistein excretion (cases: 25 [95% CI: 5, 132] nmol/day; controls: 155 [95% CI: 43, 550] nmol/day; p = 0.08). Total testosterone was higher in women with breast cancer compared with controls (cases: 1.3 [95% CI: 1.1, 1.5] nmol/L; controls: 1.0 [95% CI: 0.8, 1.1] nmol/L; p = 0.05). No significant differences were found for serum sex hormone binding globulin, free androgen index, dehydroepiandrosterone sulphate, estradiol and progesterone, or in urinary androgen metabolites, or in dietary intake with regard to fat, carbohydrate, protein, or fiber consumption between cases and controls. Conclusions: This preliminary study is the first report of low urinary daidzein and genistein in postmenopausal women with breast cancer. These findings are in keeping with the increasing observational data demonstrating a protective effect from phytoestrogens on breast cancer risk. (Menopause 2000;7;289-296. (C) 2000, The North American Menopause Society.) (C)2000The North American Menopause Society
  Menopause 08/2012; 7(5).
• Article: Relationship Among Leptin, Neuropeptide Y, and Galanin in Young Women and in Postmenopausal Women

  Bogusølawa Baranowska, Malgorzata Radzikowska, Elzbieta Wasilewska-Dziubínska, Krzysztof Roguski, Artur Pølonowski
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  ABSTRACT: Objective: To determine whether hormonal status may affect neuropeptide Y (NPY), galanin, and leptin release in postmenopausal women and in young women. Design: Forty-eight postmenopausal women aged 47-65 years and 35 young women aged 26-39 years were investigated. Results: Plasma leptin concentrations increased with increasing body mass index in both young and postmenopausal women and were significantly higher in obese postmenopausal women than in obese young women (p < 0.01). Plasma NPY levels in obese young and postmenopausal women were significantly higher than in lean women (p < 0.01 and p < 0.01, respectively) and were significantly higher in obese and nonobese postmenopausal women than in young women (p < 0.05 and p < 0.001, respectively). Plasma galanin levels in postmenopausal women, both lean and overweight, were significantly lower than in young women (p < 0.01 and p < 0.01, respectively). In obese postmenopausal women, plasma galanin concentrations were lower without differing significantly from those in obese young women. However, they were significantly higher than that in lean postmenopausal women (p < 0.001). Conclusions: Our results suggest that the differences is plasma leptin, NPY, and galanin between postmenopausal women and young women may be related to body mass index rather than to differences in hormonal status and that the higher NPY levels in both lean and obese postmenopausal women than in young women indicate that factors other than body mass index may be involved. (Menopause 2000;7:149-155. (C) 2000, The North American Menopause Society.) (C)2000The North American Menopause Society
  Menopause 07/2012; 7(3).
• Article: Bone resorption levels by age and menopausal status in 5,157 women.

  L L Lewis, J F Shaver, N F Woods, M J Lentz, K C Cain, V Hertig, S Heidergott
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  ABSTRACT: The purpose of this study was to describe bone resorption activity using a biochemical marker according to the categories of age, menopausal status, and selected drug/supplement use in middle-aged and elderly community-based women. This was a cross-sectional study that assessed urinary cross-linked N-telopeptide of type I collagen (NTx) and used self-report data to group women as premenopausal (Pre), perimenopausal (Peri), postmenopausal without hormone replacement therapy (Post), and postmenopausal with hormone replacement therapy (HRT). Mean NTx values were found to be significantly different by group and controlling for age (p = 0.001), with post hoc tests showing all pairwise group comparisons as significantly different (p = 0.001), except that the Pre and HRT groups were not significantly different. Both the Peri and the Post NTx levels were significantly higher than the Pre and the HRT groups'. NTx values in the Peri group varied with age-the youngest Peri women were similar to Pre women, and the oldest Peri women were similar to Post women. Significantly lower NTx levels were found only in the Post (p = 0.009) and HRT (p < 0.001) groups using diuretics compared with nonuse and only in the HRT group using calcium supplements compared with nonuse (p = 0.006). No differences by thyroid use were found. With a biochemical marker, the results showed that bone resorption activity differences could be demarcated in women according to age, estimated menopausal stage, and selected drug/supplement use. These results support the usefulness of NTx assessment for indicating bone resorption activity and therefore the potential for osteoporosis or for monitoring the efficacy of antiresorptive therapies.
  Menopause 07/2012; 7(1):42-52.
• Article: Transdermal Administration of Estradiol and Norethisterone: Effect on the Uterus and Uterine Arteries *

  Angelo Cagnacci, Serenella Arangino, Francesca Paola Draetta, Marco Angiolucci, Annibale Volpe, Gian Benedetto Melis
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  ABSTRACT: Objective: To evaluate the short- and long-term effect on the uterus, endometrium, and vascular reactivity of uterine arteries of sequential transdermal estradiol (50 [mu]g/day) and norethisterone (0.25 mg/day in the last 14 days of each cycle). Design: An intravaginal ultrasound evaluation was performed in 48 postmenopausal women before and at the 3rd and 12th month of treatment, during the last 3 days of both estradiol alone and estradiol plus norethisterone. An endometrial biopsy was also performed before and at the end of treatment. In 11 participants, intravaginal ultrasound and endometrial biopsy were repeated after 48 months of treatment. Results: Uterine volume (33.7 +/- 3.3 cm3 to 56.8 +/- 3.7 cm3; p = 0.001) and endometrial thickness (3.07 +/- 0.48 mm to 5.74 +/- 0.41 mm; p = 0.001) increased within 3 months, with no further increases. Thickness was similar in the estradiol and estradiol-norethisterone phase. Endometrial hyperplasia was found in one participant at 12 months of treatment. A significant decrease (p = 0.002) in the pulsatility index of uterine arteries was observed only during the estradiol phase. After 48 months of treatment, the pulsatility index of uterine arteries was lower than at baseline (2.78 +/- 0.24 vs. 2.23 +/- 0.33; p = 0.044) even when evaluated in the combined phase. Conclusions: The transdermal administration of sequential estradiol and norethisterone reduces uterine artery resistance and induces a self-limiting growth of the uterus and endometrium. (Menopause 2000;7:117-122. (C) 2000, The North American Menopause Society.) (C)2000The North American Menopause Society
  Menopause 07/2012; 7(2).
• Article: García-Arenzana N, Navarrete-Muñoz EM, Peris M, Salas D, Ascunce N, Gonzalez I, Sánchez-Contador C, Santamariña C, Moreo P, Moreno MP, Carrete JA, Collado-García F, Pedraz-Pingarrón C, Ederra M, Miranda-García J, Vidal C, Aragonés N, Pérez-Gómez B, Vioque J, Pollán M. Diet quality and related factors among Spanish female participants in breast cancer screening programs. Menopause. 2012 Jul 2. [Epub ahead of print] PubMed PMID: 22760085.

  García-Arenzana N, Navarrete-Muñoz EM, Peris M, Salas D, Ascunce N, Gonzalez I, Sánchez-Contador C, Santamariña C, Moreo P, Moreno MP, Carrete JA, Collado-García F, Pedraz-Pingarrón C, Ederra M, Miranda-García J, Vidal C, Aragonés N, Pérez-Gómez B, Vioque J, Pollán M
  Menopause 07/2012;
• Article: Construction and validation of an instrument that breaks the silence: the impact of domestic and/or sexual violence on women’s health, as shown during climacterium

  Sandra D. Teixeira de Araújo Moraes, Ângela Maggio da Fonseca, José M. Jr Soares, Vicente R. Bagnoli, Marilena A. Souza, Wilson Maça Yuki Ariê, Edmund Chada Baracat
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  ABSTRACT: Objective: The aim of this study was to construct and to validate a measure of the consequences of domestic violence on women’s health during climacterium. Methods: A questionnaire was administered at the Outpatient Climacterium Clinic to 124 women aged 40 to 65 years who were the victims of domestic and/or sexual violence (experimental group). They were divided into three groups: (1) those who were victims of violence exclusively during childhood/adolescence, (2) those who were victims of violence exclusively during adulthood, and (3) those who were victims of violence throughout their lives. The instrument included 34 items evaluating the beginning, frequency, and type of violence; the search for health assistance and reporting of the violence; the violence and the number of comorbidities; and violence and the Kupperman Menopausal Index. We also included a control group composed of perimenopausal and postmenopausal women who did not experience any violence (n = 120). Results: The instrument presented a Cronbach α = 0.82, good reliability among the examiners (+0.80), and a good possibility of reproducibility. The mean age of menopause was 45.4 years, and the mean age in the control group was 48.1 years. Group 1 showed a mean of 5.1 comorbidities, Group 2 had 4.6, and Group 3 had 4.4. Sexual violence (43.5%) and other types of violence both presented average comorbidities (4.60) but represented a significant impairment in the victim’s sexual life. There were significant associations in group 3 and a high Kupperman Menopausal Index score. In the experimental group, 80.6% did not seek health services for the violence they experienced. Conclusions: The questionnaire presented good internal consistency and a validated construction. It can be easily reproduced and is indicated to evaluate the consequences of domestic and/or sexual violence on women’s health during climacterium.
  Menopause 12/2011; 19(1):16–22.
• Source

  Available from: menopause.org

  Article: JoAnn E. Manson, MD, DrPH, NCMP 2011-2012 NAMS President

  The Editors
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  ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
  Menopause 11/2011; 18(12):1263–1264.
• Article: Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative

  Margery L.S. Gass, Barbara B. Cochrane, Joseph C. Larson, JoAnn E. Manson, Vanessa M. Barnabei, Robert G. Brzyski, Dorothy S. Lane, June LaValleur, Judith K. Ockene, Charles P. Mouton, David H. Barad
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  ABSTRACT: Objective: The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI). Methods: Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined. Results: Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01). Conclusions: Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction.
  Menopause 10/2011; 18(11):1160-1171.
• Article: Protective effect of Sideritis euboea extract on bone mineral density and strength of ovariectomized rats

  Ismene A. Dontas, Pavlos P. Lelovas, Stavros K. Kourkoulis, Nektarios Aligiannis, Anna Paliogianni, Sofia Mitakou, Antony Galanos, Eva Kassi, Athanasios Mitousoudis, Theodore T. Xanthos, Nikolaos Papaioannou, George P. Lyritis
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  ABSTRACT: Objective: The aim of this study was to investigate the potential protective effect of Sideritis euboea extract (SID), commonly consumed as "mountain tea," on bone mineral density (BMD) and the strength of the ovariectomized (OVX) rat model of osteoporosis. Methods: Thirty-two 10-month-old Wistar rats were separated into controls (sham operated), OVX, and OVX plus SID in their drinking water (dose, 330 mg/kg body weight per day), starting immediately after OVX for 6 months. Tibial BMD at baseline and at 3 and 6 months post-OVX, three-point-bending of the femur, and body and uterine weight at the study end were examined. Results: BMD percentage change from baseline of the whole tibia was similar in control and OVX + SID rats at 3 months (−3.02% vs −4.67%, P = not significant), revealing a strong osteoprotective effect. At 6 months, the corresponding changes were −6.02% versus −14.37%, P < 0.05, indicating a greater bone loss in treated rats, albeit significantly less than the OVX change (−20.46%; OVX vs OVX + SID, P < 0.05). The proximal (metaphyseal) tibial BMD percentage change from baseline to 3 and 6 months between the OVX and OVX + SID groups (−26.47% vs −15.57% and −31.22% vs −16.57%, respectively) was statistically significant, demonstrating that SID preserved the proximal tibial BMD of the OVX + SID group significantly. Three-point-bending showed a significant increase in the treated compared with the OVX groups. Body and uterine weights were similar in the OVX and treated groups. Conclusions: SID significantly protected tibial bone loss and improved femoral biomechanical strength in OVX + SID rats compared with OVX rats.
  Menopause 07/2011; 18(8):915-922.
• Article: Antioxidant enzymes GSR, SOD1, SOD2, and CAT gene variants and bone mineral density values in postmenopausal women

  Mlakar SJ, Osredkar J, Prezelj J, Marc J.
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  ABSTRACT: OBJECTIVE: Oxidative stress participates in decreasing bone formation and stimulating bone resorption. Furthermore, antioxidant enzymes have been observed to have low protective activity in women with osteoporosis. The aim of the present study was to examine any association of selected gene polymorphisms of the glutathione S-reductase (GSR), superoxide dismutase (SOD1 and SOD2), and catalase (CAT) genes, alone or in combination, with the bone mineral density (BMD) values of femoral neck (fn), lumbar spine (ls), and total hip (th) in Slovenian postmenopausal women. METHODS: The gene polymorphisms of CAT, GSR, SOD1, and SOD2 genes in 468 postmenopausal women were analyzed using restriction fragment length polymorphism and a fluorescent 5'-exonuclease genotyping method. BMD_fn, BMD_ls, and BMD_th were measured using dual-energy x-ray absorptiometry. Moreover, univariate statistic analysis and two-way analysis of variance for interaction testing were performed. RESULTS: A significant association of BMD_th values (P = 0.027) was found in genotype subgroups of 423-287G>A GSR polymorphism located in the third intron among postmenopausal women. Furthermore, women with at least one G allele showed significantly higher levels of BMD_fn (P = 0.044), BMD_th (P = 0.009), and BMD_ls (P = 0.043) than those that are AA homozygotes. Interestingly, the 423-287G>A_GSR*1154-393T>A_GSR combination was significantly associated with BMD_fn (P = 0.013) and BMD_th (P = 0.002) in postmenopausal women. CONCLUSIONS: The results of our study demonstrate for the first time that antioxidant enzyme GSR gene polymorphisms are significantly associated with BMD, suggesting that the A allele of 423-287G>A GSR polymorphism could contribute to decreased BMD values in postmenopausal women.
  Menopause 01/2011;
• Article: Kenneth William Kleinman (1946-2010)

  Wulf H. Utian
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  ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
  Menopause 12/2010; 18(1):1-2.
• Article: Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk

  Susanne M. Veltman-Verhulst, Bas B. van Rijn, H. Egbertine Westerveld, Arie Franx, Hein W. Bruinse, Bart C.J.M. Fauser, Angelique J. Goverde
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  ABSTRACT: Objective: Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. Methods: We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. Results: Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m2. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. Conclusions: Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.
  Menopause 08/2010; 17(5):990-996.
• Article: Differential effects of 17[beta]-estradiol and raloxifene on bone and lipid metabolism in rats with chronic kidney disease and estrogen insufficiency

  Manuel Naves-Díaz, Natalia Carrillo-López, Aránzazu Rodríguez-Rodríguez, Socorro Braga, Teresa Fernández-Coto, Jose Miguel Lopez-Novoa, Francisco López-Hernández, Jorge B. Cannata-Andía
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  ABSTRACT: Objective: The aim of this study was to evaluate the effect of 17β-estradiol, raloxifene, and 1-α,25-dihydroxycholecalciferol or calcitriol on bone and lipid metabolism in chronic kidney disease and estrogen insufficiency. Methods: Six-month-old female Sprague-Dawley rats (n = 48) were ovariectomized and nephrectomized (seven eighths). One week after surgery, the rats were divided into six groups and treated with (1) placebo, (2) 17β-estradiol 10 μg kg−1 day−1, (3) raloxifene 1 mg kg−1 day−1, (4) calcitriol 10 ng kg−1 day−1, (5) 17β-estradiol + calcitriol, and (6) raloxifene + calcitriol. A group of untreated animals with chronic kidney disease and normal ovarian function was used as a control group (n = 5). The rats were killed after 8 weeks of treatment. Blood samples were drawn for serum analyses; the right tibia was removed to perform histomorphometric analyses, uteri were used as tissue markers of estrogen replacement, and paraffin-embedded sections of the uterus and the fourth breast were used for histopathologic evaluation. Results: Raloxifene, alone or combined with calcitriol, and 17β-estradiol combined with calcitriol significantly diminished total cholesterol level compared with placebo. Qualitative histological and histomorphometric analyses showed that both the single treatments and their combinations were able to increase the trabecular connectivity compared with placebo. The less beneficial results were obtained with 17β-estradiol alone, whereas the more beneficial results were obtained with the combined treatments, particularly with raloxifene and calcitriol. Conclusions: In summary, this experimental study demonstrates the advantages of replacing both hormonal deficiencies together. The combination of calcitriol and raloxifene, a selective estrogen receptor modulator, showed a better lipid, uterus, and bone profile.
  Menopause 06/2010; 17(4):766-771.
• Article: Similar phenotype characteristics comparing familial and sporadic premature ovarian failure

  Femi Janse, Erik A.H. Knauff, Martinus F. Niermeijer, Marinus J. Eijkemans, Joop S.E. Laven, Cornelius B. Lambalk, Bart C.J.M. Fauser, Angelique J. Goverde, on behalf of the Dutch Premature Ovarian Failure Consortium
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  ABSTRACT: Objective: Premature ovarian failure (POF) is characterized by secondary amenorrhea before the age of 40 years, along with repeated increased follicle-stimulating hormone and low estrogen concentrations. POF is considered a complex genetic disease with a familial presentation in 12% to 50% of cases. POF may originate from different genes and various gene-environment interactions. The aim of this study was to identify possible differences in phenotype comparing women with familial and women with sporadic POF. Methods: A multicenter study was initiated in the Netherlands using standardized phenotyping. For each woman, medical history, menstrual cycle, and fertility and smoking status were assessed and a standardized examination was performed. Based on a detailed three-generation family history, women were identified as having either familial (defined as having at least one relative with POF) or sporadic POF. Results: A total of 58 familial cases and 142 sporadic cases of POF were identified. Maternal age at menopause was significantly lower in the women with familial compared with the women with sporadic POF (41.0 ± 7.5 and 49.7 ± 2.6 y, respectively; P < 0.001). Sex hormone-binding globulin concentration was significantly higher in the women with familial than in the women with sporadic POF (73.6 ± 37.1 and 55.2 ± 26.9 nmol/L, respectively; P = 0.002). All other characteristics, such as parity, bone mineral density, and serum follicle-stimulating hormone and lipid levels were similar, as was the incidence of autoimmunity and cytogenetic abnormalities. Conclusions: Familial and sporadic POF do not differ in phenotype except for maternal menopause age and sex hormone-binding globulin concentration. Future studies are needed to unravel the genotype-phenotype interactions in POF.
  Menopause 06/2010; 17(4):758-765.
• Article: Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction

  Lucinar J. Flores, Diego Figueroa, Iris C. Sanches, Luciana Jorge, Maria-Cláudia Irigoyen, Bruno Rodrigues, Kátia De Angelis
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  ABSTRACT: Objective: The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. Methods: Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. Results: Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 μg/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = −0.7, P < 0.005) and sympathetic (r = 0.7, P < 0.001) effects. Conclusions: These results indicate that exercise training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women.
  Menopause 06/2010; 17(4):712-717.