Selección de Resúmenes de Menopausia

Agosto de 2009

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 Semana del 29 de Julio al 4 de Agosto de 2009

 

Hum Reprod. 2009 Jul 30. [Epub ahead of print]

Anti-Mullerian hormone and inhibin B levels as markers of premature ovarian aging and transition to menopause in type 1 diabetes mellitus.

Soto N, Iñiguez G, López P, Larenas G, Mujica V, Rey RA, Codner E.

Endocrinology and Diabetes Unit, San Borja-Arriarán Hospital, Santiago, Chile.

BACKGROUND Serum anti-Müllerian hormone (AMH) levels decrease early during the transition to menopause and women with type 1 diabetes mellitus (DM1) experience menopause at a younger age. We hypothesized that older women with DM1 will have lower AMH levels than controls. METHODS We studied ovarian function in women with DM1 (n = 66) and healthy controls (n = 58), all <45 years old. Steroids, gonadotrophins, AMH and inhibin B levels were measured during the follicular phase. RESULTS Piece-wise regression analysis demonstrated that AMH levels begin to decrease at 33 years of age in both groups. This age limit was used to compare data in both groups. AMH levels were lower in DM1 women than in controls >33 years (4.1 +/- 4.2 versus 9.5 +/- 7.9 pmol/l, mean +/- SD, P = 0.006). A higher proportion of women with DM1 showed AMH levels in the menopausal range compared with controls (16.7% versus 3.4%, respectively, P = 0.02). For all patients, those with DM1 exhibited lower inhibin B levels than controls (89.3 +/- 51.7 versus 113.2 +/- 76.0 ng/ml, P < 0.05). FSH and estradiol were similar in both groups. Regression analysis showed an earlier decline in AMH levels in women with DM1 than controls. Even after age adjustment, DM1 was a significant factor for the determination of inhibin B and AMH levels. CONCLUSIONS Lower AMH levels in women with DM1 during the fourth decade of life suggest the presence of an earlier decline in the ovarian follicle pool in these women. Further studies are needed to evaluate the mechanism of this complication.

 

Int J Cancer. 2009 Jul 29. [Epub ahead of print]

Birth weight and mammographic density among postmenopausal women in Sweden.

Tamimi RM, Eriksson L, Lagiou P, Czene K, Ekbom A, Hsieh CC, Adami HO, Trichopoulos D, Hall P.

Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.

Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.

 

J Relig Health. 2009 Jul 30. [Epub ahead of print]

Spirituality and Severity of Menopausal Symptoms in a Sample of Religious Women.

Steffen PR.

Clinical Psychology, Brigham Young University, 284 TLRB, Provo, UT, 84602, USA, steffen@byu.edu.

Menopause represents an important life change, particularly for religious women whose identity is significantly related to family. Two competing hypotheses are examined: one, because religious women have their identity focused on family and child rearing, spirituality will be related to increased menopausal symptoms because menopause represents a loss of identity and purpose; and two, because spirituality can provide strength and comfort during difficult times, it will, therefore, be related to decreased menopausal symptoms. To test these competing hypotheses, questionnaires were administered to 218 women (average age 55, 35% premenopausal, 26% peri-menopausal, 39% postmenopausal) who were members of the Church of Jesus Christ of Latter Day Saints. Regression analyses indicated that higher levels of spiritual strength were related to decreased levels of reported menopausal symptoms. Spiritual strength was also related to increased benefit finding during menopause, decreased concern with body appearance, and increased use of adaptive coping strategies. We conclude that finding strength in spirituality may help religious women cope better with the life changes associated with menopause.

 

Expert Opin Pharmacother. 2009 Jul 29. [Epub ahead of print]

Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy.

Gennari L.

University of Siena, Department of Internal Medicine, Siena, Italy.

 Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. The purpose of this article is to review the effects of lasofoxifene, a new-generation SERM that has completed the Phase III development program for the prevention and treatment of osteoporosis and vaginal atrophy in postmenopausal women. This compound selectively binds to both ERs with high affinity. Lasofoxifene also has a remarkably improved oral bioavailability with respect to other SERMs such as raloxifene and tamoxifen, owing to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term clinical studies, this compound showed a favorable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. More recently, Phase III clinical trials have confirmed the efficacy and safety of this new SERM in the prevention of bone loss and vertebral and nonvertebral fractures. Moreover, in postmenopausal women with osteoporosis, lasofoxifene treatment also reduced ER positive breast cancer risk and the occurrence of vaginal atrophy. With its increased potency and efficacy on the prevention of nonvertebral fractures and its positive effects on the vagina, this new SERM may represent an alternative therapy for osteoporosis in postmenopausal women.

 

Climacteric. 2009 Jul 28:1-6. [Epub ahead of print]

Breast arterial calcification is a predictive factor of cardiovascular disease in Brazilian postmenopausal women.

Ferreira JA, Pompei LM, Fernandes CE, Azevedo LH, Peixoto S.

ABC School of Medicine, Santo Andre, Brazil.

Objective The objectives of this study were to evaluate the association between cardiovascular disease (CVD) and breast arterial calcification (BAC), as well as the prevalence rates of these conditions in Brazilian postmenopausal women. Methods A cross-sectional study was performed in 307 women over 40 years of age who were receiving care at the gynecology clinic of the Center for Women's Integrated Healthcare (CAISM), ABC School of Medicine. All these women had been amenorrheic for at least 12 months and had undergone mammography in the preceding 12 months. Cardiovascular disease and its subtypes were evaluated, as well as its association with BAC. Means and standard deviations, absolute frequencies and percentages were calculated, and univariate analysis and multiple logistic regression were performed. Results The mean age of the patients was 55.2 +/- 6.8 years; age at menopause was 48.5 +/- 4 years. Time since menopause was 80.2 +/- 75.4 months; 96.1% of the patients were non-smokers and 46.3% were using hormone therapy. Of the patients, 33.6% had systemic arterial hypertension, 4.9% had diabetes mellitus and 5.2% had hypercholesterolemia. The mean body mass index was 27.3 +/- 4.3 kg/m(2). CVD was found in 6.8% and BAC in 8.5% of the women. Significantly more women with BAC had CVD compared to the women who did not have this condition (23.1% vs. 5.3%, p = 0.0006). BAC was associated with an odds ratio of 8.13 (95% confidence interval 2.68-24.64) for predicting CVD. Conclusions In postmenopausal women, breast arterial calcification may represent a higher likelihood of cardiovascular disease.

 

Fertil Steril. 2009 Jul 22. [Epub ahead of print]

Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women.

Lindsay R, Christopher Gallagher J, Kagan R, Pickar JH, Constantine G.

Department of Medicine, Helen Hayes Hospital, West Haverstraw, and Columbia University, New York.

Objetive: To evaluate the efficacy of the tissue-selective estrogen complex, bazedoxifene/conjugated estrogens (BZA/CE), for postmenopausal osteoporosis prevention. Design: Multicenter, randomized, double-blind, placebo- and active-controlled, phase 3 trial (Selective estrogen Menopause And Response to Therapy [SMART]-1). Setting: Outpatient clinical study. Patient: Women (n = 3,397) more than 5 years and 1-5 years postmenopause were enrolled in the Osteoporosis Prevention I and II Substudies, respectively. Intervention: Single tablets of BZA (10, 20, or 40 mg) each with CE (0.625 or 0.45 mg), raloxifene (60 mg), or a placebo taken daily for 2 years. Main outcomes: The primary outcome for both substudies was change in bone mineral density of the lumbar spine; bone mineral density was also measured at the hip. Results: In both substudies, bone mineral density increased significantly more with all BZA/CE doses compared with placebo at the lumbar spine and total hip, and for most BZA/CE doses compared with raloxifene at the lumbar spine. Osteocalcin and N-telopeptide significantly decreased with all BZA/CE doses vs. placebo and most BZA/CE doses vs. raloxifene. Conclusion: BZA/CE combinations decreased bone turnover and bone loss in postmenopausal women at increased risk for osteoporosis.

 

Fertil Steril. 2009 Jul 22. [Epub ahead of print]

Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile.

Lobo RA, Pinkerton JV, Gass ML, Dorin MH, Ronkin S, Pickar JH, Constantine G.

Columbia University Medical Center, New York, New York.

OBJECTIVE: To evaluate the effects of a tissue-selective estrogen complex (TSEC) composed of bazedoxifene/conjugated estrogens (BZA/CE) on menopausal symptoms, metabolic parameters, and overall safety. DESIGN: Multicenter, double-blind, placebo- and active-controlled phase 3 trial (Selective estrogens, Menopause, And Response to Therapy [SMART]-1). SETTING: Outpatient clinical. PATIENT(S): Healthy, postmenopausal women (n = 3,397) age 40 to 75 with an intact uterus. INTERVENTION(S): Single tablets of BZA (10, 20, or 40 mg), each with CE (0.625 or 0.45 mg); raloxifene 60 mg; or placebo taken daily for 2 years. MAIN OUTCOME MEASURE(S): Hot flushes, breast pain, vaginal atrophy, metabolic parameters, and adverse events. RESULT(S): BZA (20 mg)/CE (0.625 or 0.45 mg) significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy compared with placebo. At week 12, the daily number of hot flushes decreased by 51.7% to 85.7% with all BZA/CE doses vs. 17.1% for placebo. BZA/CE improved lipid parameters and homocysteine levels, did not significantly change carbohydrate metabolism, and had only minor effects on some coagulation parameters. The incidences of breast pain and adverse events were similar between BZA/CE and placebo. CONCLUSION: The TSEC composed of BZA (20 mg)/CE (0.625 or 0.45 mg) is an effective and safe treatment for menopausal symptoms.

 

Fertil Steril. 2009 Jul 22. [Epub ahead of print]

Bazedoxifene/conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women.

Archer DF, Lewis V, Carr BR, Olivier S, Pickar JH.

CONRAD Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia.

OBJECTIVE: To evaluate the effect of bazedoxifene/conjugated estrogens (BZA/CE), a tissue selective estrogen complex, on uterine bleeding in postmenopausal women. DESIGN: International, multicenter, randomized, double-blind, placebo- and active-controlled, phase III study (Selective estrogen Menopause And Response to Therapy [SMART]-1). SETTING: Outpatient clinical. PATIENT(S): Healthy, postmenopausal women (N = 3,397) aged 40 to 75 years with an intact uterus. INTERVENTION(S): Daily oral therapy with BZA 10, 20, or 40 mg, each with CE 0.625 or 0.45 mg, raloxifene 60 mg, or placebo. MAIN OUTCOME MEASURE(S): Cumulative amenorrhea profiles and the incidence of bleeding or spotting over 2 years. RESULT(S): Treatment with BZA 20 or 40 mg with CE 0.625 or 0.45 mg was associated with rates of cumulative amenorrhea (>83% during cycles 1-13 and >93% during cycles 10-13) and bleeding or spotting that were comparable to those with placebo. Subjects who received BZA 10 mg/CE 0.625 mg experienced slightly lower cumulative amenorrhea rates throughout the study compared with placebo-treated subjects. CONCLUSION(S): Postmenopausal women treated with BZA 20 or 40 mg with CE 0.625 or 0.45 mg had high rates of cumulative amenorrhea that were similar to those reported with placebo. This new menopausal therapy may offer a favorable bleeding and tolerability profile.

 

Fertil Steril. 2009 Jul 22. [Epub ahead of print]

Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conjugated estrogens as a menopausal therapy.

Pickar JH, Yeh IT, Bachmann G, Speroff L.

Wyeth Research, Collegeville, Pennsylvania.

OBJECTIVE: To evaluate the endometrial safety of a tissue selective estrogen complex (TSEC; pairing of a selective estrogen receptor modulator [SERM] with estrogens) composed of bazedoxifene/conjugated estrogens (BZA/CE) in postmenopausal women. DESIGN: Randomized, double-blind, multicenter, placebo- and active-controlled, phase 3 study (Selective estrogen Menopause And Response to Therapy [SMART]-1). SETTING: Outpatient clinical. PATIENT(S): Healthy, postmenopausal women (n = 3,397) age 40-75 with an intact uterus. INTERVENTION(S): Single tablets of BZA (10, 20, or 40 mg) combined with CE (0.625 or 0.45 mg); raloxifene (60 mg); or placebo daily for 2 years. MAIN OUTCOME MEASURE(S): Incidence of endometrial hyperplasia at 12 months in the efficacy evaluable population. RESULT(S): Treatment with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was associated with low rates (<1%) of endometrial hyperplasia that were not significantly different from those reported with placebo over 24 months. Endometrial thickness with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was not significantly different from that with placebo. CONCLUSION(S): When combined with CE (0.625 mg or 0.45 mg), BZA (20 mg) was the lowest effective dose that prevented endometrial hyperplasia over 2 years of study, creating the possibility for a new, progestin-free menopausal therapy.

 

Ann Med. 2009 Jul 24:1-8. [Epub ahead of print]

Cannabinoids and the skeleton: From marijuana to reversal of bone loss.

Bab I, Zimmer A, Melamed E.

Bone Laboratory, the Hebrew University of Jerusalem, Jerusalem, Israel.

The active component of marijuana, Delta(9)-tetrahydrocannabinol, activates the CB1 and CB2 cannabinoid receptors, thus mimicking the action of endogenous cannabinoids. CB1 is predominantly neuronal and mediates the cannabinoid psychotropic effects. CB2 is predominantly expressed in peripheral tissues, mainly in pathological conditions. So far the main endocannabinoids, anandamide and 2-arachidonoylglycerol, have been found in bone at 'brain' levels. The CB1 receptor is present mainly in skeletal sympathetic nerve terminals, thus regulating the adrenergic tonic restrain of bone formation. CB2 is expressed in osteoblasts and osteoclasts, stimulates bone formation, and inhibits bone resorption. Because low bone mass is the only spontaneous phenotype so far reported in CB2 mutant mice, it appears that the main physiologic involvement of CB2 is associated with maintaining bone remodeling at balance, thus protecting the skeleton against age-related bone loss. Indeed, in humans, polymorphisms in CNR2, the gene encoding CB2, are strongly associated with postmenopausal osteoporosis. Preclinical studies have shown that a synthetic CB2-specific agonist rescues ovariectomy-induced bone loss. Taken together, the reports on cannabinoid receptors in mice and humans pave the way for the development of 1) diagnostic measures to identify osteoporosis-susceptible polymorphisms in CNR2, and 2) cannabinoid drugs to combat osteoporosis.

  

Maturitas. 2009 Jul 24. [Epub ahead of print]

The menopause and the female larynx, clinical aspects and therapeutic options: A literature review.

D'haeseleer E, Depypere H, Claeys S, Van Borsel J, Van Lierde K.  Ghent University Hospital, Belgium.

During lifetime the female larynx is very sensitive to sex hormone fluctuations. The menopause forms a critical event in a women's life and also affects the laryngeal tissues. The present report gives an overview of the recent literature about the impact of the menopause on the female larynx and vocal quality. The article discusses the symptoms, aetiology and different treatment options for laryngeal changes during the menopause. The literature pertaining to the impact of the menopause on the voice and the larynx was reviewed to provide a critical summary about the menopausal voice, aetiology and therapeutic options. In postmenopausal women laryngeal changes like oedema and muscular and mucosal dystrophy and atrophy were found. For the voice, the most important acoustic changes in postmenopausal women are a decreased vocal frequency range, decreased fundamental frequency and a higher frequency perturbation. Potential direct and indirect causes for these changes are discussed. Hormone replacement therapy is prescribed in some women for the treatment of menopausal complaints. The first reports in the literature point out a tendency towards a positive, organ-conserving effect of hormone treatment on the larynx and probably the voice. The type and the form of application of hormone therapy seem to be important in the outcome of the studies.

 

 

Semana del 5 al 11 de Agosto de 2009

 

Climacteric. 2009 Aug 3:1-8. [Epub ahead of print]

Hormone therapy in Brazilian postmenopausal women with chronic hepatitis C: a pilot study.

Padua MA, Fonseca AM, Deguti MM, Bagnoli VR, Farias AQ, Maciel GA, Soares JM Jr, Carilho FJ, Baracat EC.

Departments of Obstetrics and Gynecology.

Objective To evaluate liver function and hemostatic parameters in postmenopausal women who have chronic infection with the hepatitis C virus and climacteric symptoms and are undergoing hormone therapy (HT) (standard dose of transdermal continuous combined hormone therapy). Design Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 mug estradiol plus 170 mug norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment. Results No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling. Conclusions There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

 

Climacteric. 2009 Aug 4:1-8. [Epub ahead of print]

LEI (Lack of tEstosterone Impact) survey in a clinical sample with surgical menopause.

Nappi RE, Lello S, Melis GB, Albani F, Polatti F, Genazzani AR.

Research Center for Reproductive Medicine, Department of Morphological, Eidological & Clinical Sciences, University of Pavia, Pavia.

Objectives To assess perception of sexuality and awareness of the impact of testosterone on sexual desire in a clinical sample of Italian women with surgical menopause. Methods In the present cross-sectional study, a structured interview on sexuality-related menopausal symptoms, attitudes towards sexuality and menopausal profile was administered to 568 women (age range 35-69 years) with bilateral oophorectomy with and without hysterectomy for benign conditions. Results The majority of women (58% yes; 36% most of the time) reported they were satisfied with their sexual life before surgical menopause. After oophorectomy, 79.3% noted the appearance/worsening of vaginal dryness, whereas the reduction of sexual desire was reported by 78.7%. Women with low sexual desire (n = 436) were significantly distressed (59.7%) and reported an impairment (24.8% yes/yes, very much) in the relationship with their partner. Sexual reactions of the partner reported by women included reduced sexual desire (17.8%), sexual dysfunction (5.1%) and fears of giving pain/lack of pleasure (28.3%). A high number of women (88.2%) would be willing to discuss sexual matters with their doctors and would consider therapeutic options. Only 36.8% were aware that a lack of testosterone might impact on sexual desire but 71% would like to know more about the role of testosterone. Hormone replacement therapy was used by 38.4% of the women. Conclusions These data suggest that women experience significant vaginal dryness and low sexual desire and report a significant distress in the relationship with their partner after surgical menopause. Sexual counseling is mandatory in order to discuss potential therapeutic strategies, including testosterone use.

 

J Cereb Blood Flow Metab. 2009 Aug 5. [Epub ahead of print]

Frontal cerebral blood flow changes after hormone replacement therapy in depressed postmenopausal women.

Yao WJ, Pan HA, Wang ST, Yang YK, Yu CY, Lin HD.

Department of Nuclear Medicine, National Cheng Kung University, Tainan, Taiwan.

We investigated the effects of hormone replacement therapy (HRT) on frontal cerebral blood flow (CBF), depressive symptoms, and cognitive function in depressed postmenopausal women. Fourteen postmenopausal women with depressive symptoms underwent HRT, and seven controls not undergoing HRT were studied. We evaluated frontal CBF, expressed as frontal/cerebellum (F/C) ratio, using Tc-99m hexamethyl propylene amine oxime single photon emission computed tomography (Tc-99m HMPAO SPECT), cognitive function using the Mini-Mental Status Examination (MMSE), and depression using the HAD (Hospital Anxiety and Depression) scale. All studies were carried out at initial status and after 9 months. Single photon emission computed tomography was performed at rest and at activation during the Wisconsin Card Sorting Test (WCST). Initial frontal CBF was not different between groups. After 9 months, resting frontal CBF was similar between groups. However, activated frontal CBF was significantly higher in the HRT group than in controls (F/C ratio: 0.924+/-0.04 versus 0.853+/-0.05, P=0.007). Furthermore, the increase in the activated F/C ratio was inversely associated with years since menopause. Mini-Mental Status Examination scores improved after HRT, but depression scores did not. Hormone replacement therapy improved frontal CBF and cognitive function but not depression in postmenopausal women. The changes in frontal CBF were detected only during WCST activation and were most apparent during early postmenopausal years.

CMAJ. 2009 Aug 4. [Epub ahead of print]Click here to read

Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study.

Ioannidis G, Papaioannou A, Hopman WM, Akhtar-Danesh N, Anastassiades T, Pickard L, Kennedy CC, Prior JC, Olszynski WP, Davison KS, Goltzman D, Thabane L, Gafni A, Papadimitropoulos EA, Brown JP, Josse RG, Hanley DA, Adachi JD.

BACKGROUND: Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality. METHODS: A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and "other"). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death. RESULTS: Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4-7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1-12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2-8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjust ed HR 3.0, 95% CI 1.0-8.7). INTERPRETATION: Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.

 

Mol Nutr Food Res. 2009 Aug 3. [Epub ahead of print]

Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review.

Jacobs A, Wegewitz U, Sommerfeld C, Grossklaus R, Lampen A.

Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany. Fax: +49 30 8412 37 15.

This review assessed the efficacy of isoflavone supplements to reduce vasomotor symptoms in menopausal women by reviewing all published randomized controlled trials. Systematic literature searches were carried out in 70 databases. Randomized and placebo controlled studies were included if they investigated the treatment of isoflavone supplements derived from soy or red clover on vasomotor symptoms in peri- or postmenopausal women for at least 12 wks. Data were analyzed concerning outcome and methodological quality of the study. Twenty-three trials met the inclusion criteria, thereof 17 investigated soy isoflavones and 6 red clover isoflavones. Without exception, selected trials examining the effect of red clover isoflavones were already assessed in several meta-analyses and were therefore excluded from this evaluation. As the soy isoflavone studies were very heterogeneous concerning interventions and outcome measures, meta-analysis could not be performed and trials were systematically assessed in a structured approach. Included soy isoflavone studies had numerous quality deficiencies and did not consistently show a reduction of flushes after treatment with soy isoflavones. Therefore, there is no conclusive evidence, but only some indication of a benefit of soy isoflavones on hot flush frequency or severity.

 

Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2207-13.

The use of herbal preparations to alleviate climacteric disorders and risk of postmenopausal breast cancer in a German case-control study.

Obi N, Chang-Claude J, Berger J, Braendle W, Slanger T, Schmidt M, Steindorf K, Ahrens W, Flesch-Janys D.

Institute for Cancer Epidemiology eV, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany. Nadia.Obi@uk-sh.de

BACKGROUND: The use of herbal preparations (HEP) to alleviate climacteric disorders is expected to increase as women seek alternatives to menopausal hormone therapy to avoid the associated breast cancer risk. Data are sparse on the long-term effects of HEP containing phytoestrogens and black cohosh on breast cancer risk. METHODS: Within a German case-control study, associations between patterns of HEP use and incident breast cancer were investigated in 10,121 postmenopausal women (3,464 cases, 6,657 controls). Information on HEP use was collected in face-to-face interviews supported by a list of brand names. Multivariate logistic and polytomous regression analyses were done. FINDINGS: Ever use of HEP (9.9%) was inversely associated with invasive breast cancer [odds ratio (OR), 0.74; 95% confidence interval (CI), 0.63-0.87] in a dose-dependent manner (OR, 0.96 per year of use; P = 0.03). Classes of HEP did not differ significantly (P(heterogeneity) = 0.81). Risks for invasive ductal (OR, 0.72; 95% CI, 0.60-0.87) and combined lobular/mixed/tubular tumors (OR, 0.76; 95% CI, 0.58-1.01) were similarly reduced by any HEP use but not for in situ carcinomas (1.34; 95% CI, 0.86-2.09). There were no substantial differences in associations of HEP use by estrogen receptor status (ER(+) OR, 0.74; 95% CI, 0.62-0.89; ER- OR, 0.68, 95% CI, 0.50-0.93) and progesterone receptor status of the tumor. INTERPRETATION: Our findings support the hypothesis that HEP use protects from invasive breast cancer in postmenopausal women. Among conceivable modes of action, those independent of estrogen receptor-mediated pathways seem to be involved (i.e., cytotoxicity, apoptosis).

 

Contraception. 2009 Aug;80(2):187-93. Epub 2009 Apr 22

Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old.

De Groote D, d'Hauterive SP, Pintiaux A, Balteau B, Gerday C, Claesen J, Foidart JM.

PROBIOX SA, Campus Universitaire du Sart-Tilman, Avenue de l'hôpital, Tour GIGA, Bât. B34, B-4000 Liège, Belgium. d.degroote@probiox.com

BACKGROUND: Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. STUDY DESIGN: A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. RESULTS: Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of beta-carotene (-41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log(2) fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log(2) fold change=-0.24, p<.05) in the OCU compared to the NCU. CONCLUSIONS: The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk.

 

 

 Semana del 12 al 18 de Agosto de 2009

 

Arch Gynecol Obstet. 2009 Aug 14. [Epub ahead of print]

Severe menopausal symptoms in middle-aged women are associated to female and male factors.

Chedraui P, Pérez-López FR, Mendoza M, Morales B, Martinez MA, Salinas AM, Hidalgo L.

Hospital Gineco-Obstétrico Enrique C. Sotomayor, Guayaquil, Ecuador, pchedraui@jbgye.org.ec.

BACKGROUND: The frequency and intensity of menopausal symptoms within a given population, as assessed by several tools, may vary and depend on several factors, such as age, menopausal status, chronic conditions and personal and partner socio-demographic profile. OBJECTIVE: To determine the frequency and intensity of menopausal symptoms and related risk factors among middle-aged women. METHODS: In this cross-sectional study a total of 404 women aged 40 to 59 years, visiting inpatients at the Enrique C. Sotomayor Gynecology and Obstetrics Hospital, Guayaquil, Ecuador, were requested to fill out the menopause rating scale (MRS) and a questionnaire containing personal and partner data. RESULTS: Mean age of surveyed women (n = 404) was 48.2 +/- 5.7 years, 85.1% had 12 or less years of schooling and 44.8% were postmenopausal. None was on hormonal therapy (HT) for the menopause or psychotropic drugs. Regarding their partner, erectile dysfunction was present in 23.8%, premature ejaculation in 21.2% and 43.5% abused alcohol. The four most frequently found symptoms of those composing the MRS were muscle and joint problems (80%), depressive mood (73.5%), physical and mental exhaustion (71.3%) and irritability (68%). Mean total MRS score was 18 +/- 10.6 (median 17) and for subscales: 7.2 +/- 4.5 (somatic); 6.9 +/- 4.8 (psychological) and 3.9 +/- 3.4 (urogenital). Women presented severe scores in 53, 36.1, 48.3 and 49.8% for total MRS and somatic, psychological and urogenital subscales, respectively. After adjusting for confounding factors, logistic regression analysis determined that female higher parity and partner premature ejaculation increased the risk for presenting severe total MRS scores (impaired female quality of life), whereas women who had a positive perception of their health status were at decreased risk. CONCLUSION: In this middle-aged series psychological menopausal symptoms were the most frequent in which severity was associated to parity and partner sexual dysfunction.

 

Int J Gynaecol Obstet. 2009 Aug 8. [Epub ahead of print]

Assessment of bone mineral density should be considered earlier in perimenopausal women with vasomotor symptoms.

Tural A, Yoldemir T, Erenus M.

Marmara University School of Medicine, Department of Obstetrics and Gynecology, Istanbul, Turkey.

OBJECTIVE: To investigate the relationship between vasomotor symptoms (hot flashes) and osteopenia or osteoporosis in perimenopausal women. METHOD: In this cross-sectional study 79 perimenopausal women aged between 45 and 55years and seen at the Gynecology or Menopause Outpatient Clinic of Marmara University School of Medicine were allotted to one of 2 groups according to the presence or absence of hot flashes. The groups were then compared for bone mineral density (BMD) of the lumbar vertebrae, as measured by dual energy X-ray absorptiometry. RESULTS: The mean BMD measurement for vertebrae L2 to L4 was 0.32+/-0.19 for the group with no hot flashes and -0.53+/-0.21 for the group with hot flashes (P=0.007). In the former, 6.1% of the women and in the latter, 32.6% of the women had a BMD value less than a 1.5 standard deviation from the mean (P=0.005). CONCLUSION: Women with vasomotor symptoms are more prone to have osteopenia or osteoporosis.

 

N Engl J Med. 2009 Aug 11. [Epub ahead of print]

Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis.

Cummings SR, Martin JS, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, et al.

California Pacific Medical Center Research Institute and University of California, San Francisco, CA, USA.

BACKGROUND: Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis. METHODS: We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures. RESULTS: As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001) - a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04) - a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) - a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab. CONCLUSIONS: Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis.

 

Circulation. 2009 Aug 10. [Epub ahead of print]

Optimism, Cynical Hostility, and Incident Coronary Heart Disease and Mortality in the Women's Health Initiative.

Tindle HA, Chang YF, Kuller LH, Manson JE, Robinson JG, Rosal MC, Siegle GJ, Matthews KA.

Brigham and Women's Hospital and Harvard Medical School, Boston, Mass

BACKGROUND: -Trait optimism (positive future expectations) and cynical, hostile attitudes toward others have not been studied together in relation to incident coronary heart disease (CHD) and mortality in postmenopausal women. Methods and Results-Participants were 97 253 women (89 259 white, 7994 black) from the Women's Health Initiative who were free of cancer and cardiovascular disease at study entry. Optimism was assessed by the Life Orientation Test-Revised and cynical hostility by the cynicism subscale of the Cook Medley Questionnaire. Cox proportional hazard models produced adjusted hazard ratios (AHRs) for incident CHD (myocardial infarction, angina, percutaneous coronary angioplasty, or coronary artery bypass surgery) and total mortality (CHD, cardiovascular disease, or cancer related) over approximately 8 years. Optimists (top versus bottom quartile ["pessimists"]) had lower age-adjusted rates (per 10 000) of CHD (43 versus 60) and total mortality (46 versus 63). The most cynical, hostile women (top versus bottom quartile) had higher rates of CHD (56 versus 44) and total mortality (63 versus 46). Optimists (versus pessimists) had a lower hazard of CHD (AHR 0.91, 95% CI 0.83 to 0.99), CHD-related mortality (AHR 0.70, 95% CI 0.55 to 0.90), cancer-related mortality (blacks only; AHR 0.56, 95% CI 0.35 to 0.88), and total mortality (AHR 0.86, 95% CI 0.79 to 0.93). Most (versus least) cynical, hostile women had a higher hazard of cancer-related mortality (AHR 1.23, 95% CI 1.09 to 1.40) and total mortality (AHR 1.16, 95% CI 1.07 to 1.27; this effect was pronounced in blacks). Effects of optimism and cynical hostility were independent. Conclusions-Optimism and cynical hostility are independently associated with important health outcomes in black and white women. Future research should examine whether interventions designed to change attitudes would lead to altered risk.

 

Menopause. 2009 Aug 12. [Epub ahead of print]

Osteoporosis treatment and atrial fibrillation: alendronate versus raloxifene.

Huang WF, Tsai YW, Wen YW, Hsiao FY, Kuo KN, Tsai CR.

Institute of Health and Social Welfare Policy, National Yang-Ming University, Taipei, Taiwan.

OBJECTIVES:: Concerns have been raised about bisphosphonate use and risk of atrial fibrillation (AF) in women with osteoporosis. This study compares the risk of AF and of flutter or acute myocardial infarction (AMI) in women with osteoporosis taking alendronate or raloxifene. METHODS:: Using Taiwan's National Health Insurance database to conduct a population-based retrospective cohort study, we reviewed the medical and prescription histories of 27,257 women with osteoporosis (21,037 receiving alendronate and 6,220 receiving raloxifene) between 2001 and 2007. Mean (SD) follow-up was 303.62 (422.87) days. For the main outcome measures, we calculated the adjusted relative risk of AF and AMI using the Cox proportional hazards model, adjusting for various confounders. RESULTS:: Incidence rates (per patient-year) of AF in the alendronate group (1.00%) and the raloxifene group (1.02%) were similar. Alendronate use was not associated with risk of AF (hazard ratio [HR], 1.06; 95% CI, 0.85-1.32) and AMI (HR, 1.02; 95% CI, 0.86-1.19) compared with raloxifene use. However, alendronate users who had previous cardiovascular events and had taken their medications for more than 1 year were at significantly greater risk of AMI than were the group taking raloxifene (HR, 2.24; 95% CI, 1.07-4.71). Users who received 70 mg of alendronate once a week were at significantly lower risk of AF than were those taking 10 mg daily (HR, 0.56; 95% CI, 0.47-0.68). CONCLUSIONS:: Compared with raloxifene, alendronate did not increase the risk of AF and flutter in women with osteoporosis. Medical history contributed most to the development of AF or AMI in the women who received either raloxifene or alendronate. Long-term treatment with alendronate is not suggested for women with a history of cardiovascular events because they are at increased risk of AMI

 

Bone. 2009 Aug 10. [Epub ahead of print]

Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years.

Reginster JY, Bruyère O, Sawicki A, Roces-Varela A, Fardellone P, Roberts A, Devogelaer JP.

Department of Public Health Sciences, University of Liège, Liège, Belgium.

Objectives. Strontium ranelate 2g/day has proven efficacy against vertebral and nonvertebral fracture over 5 years in postmenopausal osteoporosis, though many women require longer-term treatment. This article describes the efficacy, safety, and tolerability of this agent over 8 years. Methods. Postmenopausal osteoporotic women having participated in the 5-year efficacy trials SOTI and TROPOS were invited to enter a 3-year open-label extension study. The results presented here focus on patients who received strontium ranelate for 8 years. Results. At the extension baseline, the population treated for 8 years (n=879; 79.1+/-5.6 years) had femoral neck T-score of -2.61+/-0.71. The cumulative incidences of new vertebral and nonvertebral fractures (13.7% and 12.0% respectively) over years 6 to 8 were non statistically different from the cumulative incidences in the first 3 years of the original studies (11.5% and 9.6%). Lumbar spine, femoral neck, and total hip Bone Mineral Density (BMD) increased throughout the 8-year period. Annual relative change in BMD was significant at every visit, except the 8-year visit for femoral neck and total hip BMD. Strontium ranelate was safe and well tolerated over 8 years. Conclusions. Long-term treatment with strontium ranelate 2g/day in postmenopausal osteoporotic women leads to continued increases in BMD at all sites. The data also provide some evidence for a sustained antifracture efficacy.

 

Menopause. 2009 Aug 11. [Epub ahead of print]

Daily vasomotor symptoms, sleep problems, and mood: using daily data to evaluate the domino hypothesis in middle-aged women.

Burleson MH, Todd M, Trevathan WR.

Arizona State University, Phoenix, AZ.

Objetive: The aim of this study was to investigate the relationships among daily reports of vasomotor symptoms (hot flashes and/or sweats), same-day sleep problems, and next-day mood reports in middle-aged women. METHODS: Fifty-five healthy middle-aged women were recruited to keep daily records for up to 5 years or until menopause. For each participant, the first 252 days of contiguous data with the highest weekly frequency of vasomotor symptoms was selected for the current analyses. Multilevel structural equation modeling was used to test whether changes in daily vasomotor symptom occurrence predicted changes in occurrence of same-day sleep problems and changes in next-day positive and negative mood ratings and whether sleep problems mediated any predictive effect of symptoms on next-day mood. RESULTS: Controlling for initial depression, daily vasomotor symptoms predicted same-day sleep problems (b = 0.59, P < 0.001) and next-day positive mood (b = -0.07, P < 0.01), although significant direct relationships between vasomotor symptoms and mood were found primarily in women with initial depression scores in the low to moderate range. Sleep problems predicted next-day positive (b = -0.08, P < 0.01) and negative (b = 0.10, P < 0.001) mood more robustly than vasomotor symptoms did. CONCLUSIONS: Sleep problems predicted worse mood on the following day and accounted for only a small portion of the relationship between vasomotor symptoms and mood. These findings suggest that any effect of vasomotor symptoms on mood may occur largely through a mechanism other than sleep disruption.

 

Menopause. 2009 Aug 11. [Epub ahead of print]

A randomized controlled study of taper-down or abrupt discontinuation of hormone therapy in women treated for vasomotor symptoms.

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Objetive: The aim of this study was to investigate whether tapering down of combined estrogen plus progestogen therapy (EPT) reduced the recurrence of hot flashes and resumption of therapy compared with abrupt discontinuation. A secondary aim was to evaluate whether health-related quality of life (HRQoL) was affected after discontinuation of EPT and to investigate the possible factors predicting resumption of EPT. Methods: Eighty-one postmenopausal women undergoing EPT because of hot flashes were randomized to tapering down or abrupt discontinuation of EPT. Vasomotor symptoms were recorded in self-registered diaries, and resumption of hormone therapy (HT) was asked for at every follow-up. The Psychological General Well-being Index was used to assess HRQoL. Results: Neither the number nor the severity of hot flashes or HRQoL or frequency of resumption of HT differed between the two modes of discontinuation of EPT during up to 12 months of follow-up. About every other woman had resumed HT within 1 year. Women who resumed HT after 4 or 12 months reported more deteriorated HRQoL and more severe hot flashes after discontinuation of therapy than did women who did not resume HT. Conclusions Women who initiate EPT because of hot flashes may experience recurrence of vasomotor symptoms and impaired HRQoL after discontinuation of EPT regardless of the discontinuation method used, abrupt or taper down. Because, in addition to severity of flashes, decreased well-being was the main predictor of the risk to resume HT, it seems important to also discuss quality of life in parallel with efforts to discontinue HT.

 

Climacteric. 2009 Aug 11:1-14. [Epub ahead of print]

The effects of hormone replacement therapy on myocardial performance in early postmenopausal women.

Duzenli MA, Ozdemir K, Sokmen A, Gezginc K, Soylu A, Celik C, Altunkeser BB, Tokac M.

Objectives The results of the studies in which the effect HRT on cardiac function have been evaluated are rather disputable. In these studies, cardiac function was evaluated with conventional echocardiographic methods. This study was planned in order to investigate the effects of HRT on myocardial velocities and myocardial performance index (MPI) in healthy early postmenopausal women. Method In a prospective, controlled study, 60 healthy postmenopausal women were assigned to two groups (32 in the HRT group and 28 in the control group). After conventional echocardiographic parameters were measured, tissue Doppler echocardiography recordings were obtained from the mitral and tricuspid annulus. Systolic myocardial velocity (Sm), early and late diastolic myocardial velocities (Em and Am) and time intervals were measured and MPI was calculated. Then the symptom-limited exercise stress test using the Bruce protocol was performed. After 3 and 6 months of HRT (oral 0.625 mg conjugated estrogen + 2.5 mg medroxyprogesterone acetate/day), the same examinations were repeated. The effects of HRT on myocardial velocities, MPI and exercise time were evaluated at the 3rd and 6th months. Results The parameters of the control group remained statistically unchanged during the study. HRT did not have any effect on segmental and mean left ventricular (LV) Sm or right ventricular (RV) Sm. However, LV Em/Am and RV Em/Am ratios significantly increased at the 6th month of HRT, and LV and RV MPI values were observed to decrease significantly as compared to basal values. Additionally, a significant increase was observed in exercise duration and metabolic equivalent values after 3 months of HRT, and this increase continued at the 6th month as well. The favorable changes in all parameters in the HRT group were significantly different from those of the control group. Conclusion Data obtained in this study suggest that HRT is not only effective for treating menopausal complaints but also increases cardiovascular performance by improving especially diastolic functions in early postmenopausal women.

 

Eur J Endocrinol. 2009 Aug 11. [Epub ahead of print]

Hyperthyroid Levels of TSH correlate with low bone mineral density: The HUNT 2 -Study.

Svare A, Nilsen T, Bjøro T, Forsmo S, Schei B, Langhammer A.

Objective: To study the relation between TSH and forearm bone mineral density (BMD) in a general female population. Design: Cross sectional, population-based study. Methods: In a substudy of the Nord-Trøndelag Health Study (HUNT 2), 5,778 women without and 944 with self-reported thyroid disease aged >/=40 years had their serum TSH and distal and ultra distal forearm BMD measured. In range-based categories of TSH, excluding women with previous thyroid disease, a general linear model was used to calculate adjusted mean BMD, and a logistic regression model to compute adjusted odds ratio for osteopenia and osteoporosis. Corresponding models were used to compare BMD in women with self-reported hypothyroidism or hyperthyroidism to euthyroid women. Results: In women without self-reported thyroid disease, those with TSH <0.5 mU/l had 10.7 mg/cm(2) (95% CI 0.2 - 21.1) lower distal and 9.1 mg/cm(2) (95% CI -0.7 - 18.9) lower ultra distal BMD than women in the reference category (TSH 0.50-1.49 mU/l). No differences were found between the categories with TSH >/=0.50 mU/l. Compared to self-reported euthyroid women, self-reported hyperthyroid women had increased odds for osteoporosis both distally (OR 1.35, 95% CI 1.00 - 1.82) and ultra distally (OR 1.48, 95% CI 1.10 - 1.99). Conclusion: Women with the lowest TSH (<0.5 mU/l) had lower forearm BMD than the reference category. No differences were observed between the TSH categories >/=0.50 mU/l. The prevalence of osteoporosis was higher in women who reported hyperthyroidism than in women without self-reported thyroid disease.

 

 

Semana del 19 al 25 de Agosto de 2009

 

Methods Inf Med. 2009 Aug 20;48(5). [Epub ahead of print]

Physical Activity and Postmenopausal Breast Cancer.

Schmidt ME, Chang-Claude J, Slanger T, Obi N, Flesch-Janys D, Steindorf K.

PD Dr. Karen Steindorf, Unit of Environmental Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Objectives: Epidemiological evidence suggests an inverse association between physical activity (PA) and postmenopausal breast cancer risk. Breast cancer is a heterogeneous disease, influenced by reproductive factors, lifestyle pattern, and predispositions. We investigated whether these risk factors modify the effect of PA on breast cancer risk. Methods: We analyzed data from 2004 hormone-receptor-positive postmenopausal breast cancer cases and 6569 controls from the population-based MARIE study conducted 2002-2005 in Germany. Interaction was statistically tested using adjusted unconditional logistic regression models. Results: The inverse association between leisure-time PA and risk of postmenopausal hormone-receptor-positive breast cancer was not heterogeneous by family history of breast cancer or by hormone therapy. PA showed a significant interaction with benign breast diseases (p = 0.023) and with breastfeeding (p = 0.045) but not with parity (p = 0.94), with clear risk reductions only for women who ever had breastfed or who ever had a benign breast disease (among ever breastfed: odds ratio = 0.63; 95% confidence interval = (0.52, 0.77), highest vs. lowest PA quartile). Interaction with BMI was weak (p = 0.053). Conclusions: Breastfeeding and benign breast diseases modified the effect of PA on postmenopausal breast cancer risk. If other studies find similar modifications, increasing knowledge about these risk factors may contribute to a better understanding of the mode of action of PA on breast cancer risk. For women who are at higher risk for breast cancer due to family history or due to hormone therapy use, it is encouraging that they might lower their risk by being physically active.

 

Clin Rheumatol. 2009 Aug 14. [Epub ahead of print]

Relationship between historical height loss and vertebral fractures in postmenopausal women.

Bennani L, Allali F, Rostom S, Hmamouchi I, Khazzani H, El Mansouri L, Ichchou L, Abourazzak FZ, Abouqal R, Hajjaj-Hassouni N.

Laboratory of Information and Research on Bone Diseases (LIRPOS), Department of Rheumatology, El Ayachi hospital, University Hospital of Rabat-Sale, Rabat, Morocco, loubnabennani29@yahoo.fr.

The aim of this study was to evaluate the relationship between historical height loss (HHL) and prevalent vertebral fractures (VF) in postmenopausal Moroccan women and to estimate its accuracy as a clinical test for detecting VF. Two hundred eighty-eight postmenopausal women were studied. All subjects had bone density measurements and spinal radiographs. Vertebral bodies (T4-L4) were graded using the semi-quantitative method of Genant. HHL was calculated as the difference between a patient's tallest recalled height and the current measured height. The mean age was 58.4 +/- 7.8 years. Thirty-one percent of patients were osteoporotic, and 46.5% had VF. Patients with VF had lost more height than those without VF (median, 2.0 cm (0.26-3.3) vs 0.96 cm (0.33-2.4), p < 0.05). In univariate analysis, HHL was positively correlated to both number and grade of prevalent VF (p < 0.05). The area under the receiver operating characteristics curve for the ability of HHL to detect VF was 0.60 (95% confidence interval (CI), 0.52, 0.69). Our HHL threshold for detecting VF was >1.5 cm, its sensitivity was 58%, and its specificity was 61%. The positive predictive value was 53%, and the negative predictive value was 65%. With HHL >1.5 cm, positive likelihood ratio was 1.49 with 95% CI, 1.07, 2.06. Our results demonstrate significant positive associations between HHL, VF, number of VF, and grade of VF. However, this relationship is not clinically pertinent. Consequently, HHL cannot be used as a reliable clinical test for detecting VF in postmenopausal Moroccan women.

 

Spine (Phila Pa 1976). 2009 Aug 15;34(18):1984-9.

The relationship between back pain and future vertebral fracture in postmenopausal women.

Kuroda T, Shiraki M, Tanaka S, Shiraki Y, Narusawa K, Nakamura T.

Department of Gynecology and Obstetrics, Tokyo Women's Medical University, Tokyo, Japan.

STUDY DESIGN: Cross sectional and prospective observational study in Japanese postmenopausal women. OBJECTIVE: The aim of the study was 2-fold. The first was to investigate what kind of comorbidities could be found in conjunction with back pain in Japanese postmenopausal women. The second was to investigate whether significant relationship between baseline back pain and future fracture exists or not. SUMMARY OF BACKGROUND DATA: Back pain has been reported to be associated with vertebral degeneration or vertebral fracture. However, there has been no available data that indicates the relationship between back pain and future fracture risks. METHODS: The subjects who visited their practitioner were examined for their prevalent back pain or pains in other site. Bone mineral density, body height, body weight, and serum parameter were measured at baseline, and comorbidities were investigated by interview. Fragility fractures were also assessed at baseline and then followed up with 1- to 2-year intervals. The correlation between back pain and baseline characteristics was investigated by logistic regression analysis. The hazard ratio of back pain to future vertebral fracture was estimated by multivariate Cox regression analysis. RESULTS: A total of 899 postmenopausal ambulatory women (62.5 +/- 10.3 years old) were enrolled and 81 subjects were dropped out from the study within 1 year. The remaining 818 postmenopausal women (62.1 +/- 10.3 years) were followed-up for 5.7 +/- 3.5 years. Compared to the group without pain, the group with back pain had significantly higher age, lower bone mineral densities at lumbar spine and hip, and higher number of prevalent vertebral fractures. The back pain was significantly associated with rheumatic arthritis (odds ratio [OR]: 2.01, P < 0.05), prevalent vertebral fracture (OR: 4.60, P < 0.001) and osteoporosis (OR: 2.14, P < 0.001). A total of 189 future fractures were observed, of which the most frequent was vertebral fractures (78.3%). The fact that baseline back pain was a significant risk factor for time-dependent vertebral fractures (hazard ratio: 1.62, 95% confidence interval: 1.16-2.27, P = 0.005) was demonstrated by the Cox hazards model after adjusting for traditional risk factors, such as age, bone mineral density, and prevalence of vertebral fractures. CONCLUSION: The data obtained in this study indicated that the back pain is significantly associated with osteoporosis and rheumatoid arthritis and that it can be useful predictor for future vertebral fracture risk in Japanese postmenopausal women in clinical settings.

 

 

Obesity (Silver Spring). 2009 Aug 20. [Epub ahead of print]

Testosterone and Visceral Fat in Midlife Women: The Study of Women's Health Across the Nation (SWAN) Fat Patterning Study.

Janssen I, Powell LH, Kazlauskaite R, Dugan SA.

Department of Preventive Medicine, Rush University Medical Center, Chicago, Illinois, USA.

Visceral fat (VF) increases with the menopause and is an independent predictor of the metabolic syndrome, diabetes, and cardiovascular disease (CVD) in women. Little is known about how hormonal changes during the menopausal transition are related to the increase in VF. We aimed to determine the relationship between bioavailable testosterone and VF in middle-aged women at various stages of the menopausal transition and whether this relationship is independent of age and other CVD risk factors. The Study of Women's Health Across the Nation (SWAN) is a longitudinal, community-based study. This report uses baseline data from a population-based longitudinal ancillary study at the Chicago site to examine the cross-sectional relationship between testosterone and computed tomography (CT)-assessed VF in women at different stages of the menopausal transition. Included are 359 women (47.2% black), aged 42-60 years, who were randomly selected from a complete community census in which a 72% participation rate was achieved. In multivariate models, bioavailable testosterone was associated with VF independent of age, race, percent total body fat, and other cardiovascular risk factors. Bioavailable testosterone was a stronger predictor than estradiol and was interchangeable in its strength of association with sex hormone-binding globulin (SHBG). As bioavailable testosterone was associated with VF even after adjusting for insulin resistance, this suggests that it plays an important role in regional fat distribution. Our findings may have direct implications in explaining the effect of menopause-related testosterone predominance on VF accumulation and subsequent cardiovascular risk.

 

Stroke. 2009 Aug 20. [Epub ahead of print]

Body Mass Index and Stroke Mortality by Smoking and Age at Menopause Among Korean Postmenopausal Women.

Yi SW, Odongua N, Nam CM, Sull JW, Ohrr H.

From the Department of Preventive Medicine and Public Health, Kwandong University College of Medicine, Gangneung, Korea; the Department of Preventive Medicine, College of Medicine, and Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea; the Department of Public Health, Graduate School of Yonsei University, Seoul, Korea; and Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.

BACKGROUND AND PURPOSE: The association between body mass index and mortality caused by subtypes of stroke among postmenopausal women in terms of smoking status and age at menopause remains controversial. METHODS: The data were derived from a cohort study of 3321 with 17.8 years of follow-up (1985 to 2002). Hazard ratios (HRs) and 95% CIs for strokes as related to body mass index were estimated by Cox proportional hazard models adjusted for age, hypertension, smoking, drinking, occupation, education, self-reported health, and age at menopause. A stratified analysis was conducted by age at menopause and smoking status. RESULTS: The obese group (body mass index >/=27.5 kg/m(2)) had higher risks of total stroke mortality (HR, 1.59; 95% CI, 1.05 to 2.42) and hemorrhagic stroke mortality (HR, 2.91; 95% CI, 1.37 to 6.19) than the normal weight group (18.5</= body mass index <23.0). Among ever smokers, the obese group showed significantly increased risks of total stroke mortality (HR, 2.33; 95% CI, 1.00 to 5.43) and ischemic stroke mortality (HR, 7.21; 95% CI, 1.18 to 44.3). Obesity had more effect on stroke mortality among women who experienced menopause at age <50 than women with age >/=50. For the obese group of the former, the HR of total stroke was 2.04 (95% CI, 1.25 to 3.34) and that of hemorrhagic stroke 6.46 (95% CI, 2.42 to 17.25). CONCLUSIONS: In this prospective study, obesity raised the risks of total stroke mortality and hemorrhagic stroke mortality among Korean menopausal women. It was more evident with women who experienced menopause at age <50. The obese group of ever smokers was at an increased risk of ischemic stroke mortality.

 

 

 Semana del 26 de Agosto al 1 de Septiembre de 2009

 

 Ir J Med Sci. 2009 Aug 28. [Epub ahead of print]

The effect of intramuscular vitamin D (cholecalciferol) on serum 25OH vitamin D levels in older female acute hospital admissions.

Nugent C, Roche K, Wilson S, Fitzgibbon M, Griffin D, Nichaidhin N, Mulkerrin E.

Department of Medicine for the Elderly, University College Hospital Galway, Galway, Ireland, cathalnugent@gmail.com.

INTRODUCTION: Many studies have demonstrated the prevalence of vitamin D insufficiency in the older population. OBJECTIVE: This study sought to determine whether supplementation with intramuscular vitamin D improved 25OH vitamin D levels significantly. SUBJECTS: Ninety female inpatients aged over 65 years were assigned to receive 300,000 IU of intramuscular vitamin D3 (cholecalciferol) or no intervention. METHODS: Baseline 25OH vitamin D and intact parathyroid hormone (iPTH) levels were taken and repeated 3 months after supplementation. RESULTS: Patients who received treatment showed a significant improvement in 25OH vitamin D levels, from 25.5 to 81 nmol/L with 11% remaining deficient. No patient became hypercalcaemic after treatment. CONCLUSIONS: Vitamin D deficiency is common throughout all age groups in the Irish population and particularly the older female population who have increased risk of osteoporosis and fractures. Intramuscular vitamin D significantly improves 25OH vitamin D levels compared to no treatment and may combat non-compliance with oral medication.

 

Menopause. 2009 Aug 26. [Epub ahead of print]

"Persistence" improves the 60-day amenorrhea marker of entry to late-stage menopausal transition for women aged 40 to 44 years.

Taffe JR, Cain KC, Mitchell ES, Woods NF, Crawford SL, Harlow SD.

From the 1Monash University Melbourne, Australia; 2University of Washington, Seattle, WA; 3University of Massachusetts, Boston, MA; and 4University of Michigan, Ann Arbor, MI.

OBJECTIVE:: The ReSTAGE collaboration evaluated four menstrual markers of entry to late-stage menopausal transition. The aim of this study was to assess the additional usefulness of "persistence" in relation to a clinically accessible menstrual marker of late menopausal transition, taking age into account. METHODS:: In this study, a secondary analysis of menstrual calendar data in two ReSTAGE-collaborating studies with comparatively low age at beginning of menstrual calendar observation was performed. RESULTS:: Sixty days of amenorrhea is as useful for predicting time to the final menstrual period as the currently accepted 90-day marker for women older than 45 years. For those aged between 40 and 44 years, recurrence of the 60-day marker within the next 10 cycles is a better indicator than a single occurrence of the 60-day marker or the 90-day marker. CONCLUSIONS:: Sixty-day amenorrhea is as reliable a marker of late menopausal transition as the traditional 90-day marker for women older than 45 years. For those aged 40 to 44 years, keeping menstrual records to check for a recurrence of the 60-day marker will be useful.

 

Menopause. 2009 Aug 26. [Epub ahead of print]

Quality of life and psychosocial health in postmenopausal women achieving public health guidelines for physical activity.

Vallance JK, Murray TC, Johnson ST, Elavsky S.

From the 1Centre for Nursing and Health Studies, Athabasca University, Athabasca; 2Faculty of Physical Activity and Recreation, University of Alberta, Edmonton, Alberta, Canada; and 3Department of Kinesiology, Pennsylvania State University, University Park, PA.

OBJECTIVE:: The aim of this study was to determine if there are differences in health-related quality of life (HRQoL) and psychosocial health between postmenopausal women who meet public health physical activity (PA) guidelines versus those who do not (ie, self-report) and those women who achieve at least 7,500 steps . day versus those who do not (ie, via objective monitor). METHODS:: Postmenopausal women (n = 297) residing in Southern Alberta, Canada, completed a mailed questionnaire that assessed self-reported PA, HRQoL, and psychosocial health outcomes. Total daily steps were assessed with a pedometer via a 3-day step monitoring period. RESULTS:: Of the postmenopausal women, 43.1% were meeting public health PA guidelines. A significant multivariate model (Wilks lambda = 0.968, F2,294 = 4.918, P = 0.008) indicated that women achieving public health PA guidelines reported higher HRQoL on both the physical (mean difference [Mdiff] = 2.4, P = 0.008, d [effect size] = 0.31) and mental (Mdiff = 2.3, P = 0.011, d = 0.30) component scales of the RAND-12 compared with women not achieving PA guidelines. Furthermore, women achieving at least 7,500 steps . day indicated significantly higher scores on the physical component scale (Mdiff = 4.33, P < 0.001, d = 0.56) than did women achieving fewer than 7,500 pedometer steps . day. CONCLUSIONS:: These findings lend support for the health benefits of achieving public health PA guidelines in postmenopause and further the rationale for developing, evaluating, and implementing strategically designed PA behavior change programs for postmenopausal women.

 

Maturitas. 2009 Aug 24. [Epub ahead of print]

Hormone therapy, mammographic density, and breast cancer risk.

Martin LJ, Minkin S, Boyd NF.

Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada.

Percent mammographic density (PMD) is a strong independent risk factor for breast cancer. The effects of age, parity and menopause on PMD are consistent with it being a marker of susceptibility to breast cancer. In this review, we describe the association of PMD with breast cancer, the biological plausibility of this association, and discuss the extent to which PMD meets the criteria for a surrogate marker for the effects of exogenous hormones on risk of breast cancer. Combined hormone therapy is associated with a small increase in both PMD and the risk of breast cancer. However there is evidence that the associations of blood estradiol levels and HRT with breast cancer risk are independent of the association of PMD with risk, suggesting that different biological pathways may be involved. Tamoxifen, an anti-estrogenic drug, reduces both the risk of breast cancer and PMD, but the potential mediation of the effects of anti-estrogens on breast cancer risk by their effects on PMD has not yet been examined. Given the evidence that estradiol and PMD are independently associated with breast cancer risk, it seems unlikely that an effect of these agents on PMD mediates their effects on risk. We thus find that the available evidence is insufficient to conclude that PMD can be used as a surrogate marker for the effect of exogenous hormones on breast cancer. Further research to examine the potential role of PMD as a mediator of the effects of other risk factors is required.

 

Maturitas. 2009 Aug 24. [Epub ahead of print]

Risks of osteoporosis associated with breast cancer treatment: The need to access to preventive treatment.

Rozenberg S, Carly B, Liebens F, Antoine C.

Department of Ob-Gyn, CHU ST PIERRE, Université Libre de Bruxelles, Rue Haute 290, Brussels 1000, Belgium.

The results of available clinical studies suggest that breast cancer treatment significantly affect bone turnover, BMD and fracture risk. This is for instance the case for all third-generation aromatase inhibitors. For these reasons it is recommended that breast cancer patients exercise regularly and take daily calcium (1500mg) and vitamin D (800UI) supplements. Most experts recommend that all women starting medical castration or aromatase inhibitor therapy should be assessed for their risk of osteoporosis and undergo bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DEXA). Patients with pre-existing osteopenia and osteoporosis should be evaluated for conditions which worsen skeletal health, such as vitamin D deficiency, hyperparathyroidism, hyperthyroidism and hypercalcuria. If these patients have a BMD score of -2.5 or lower, a low BMD (T-score between -1 and -2.5) and additional risk factors for osteoporosis or fragility fractures, bisphosphonate therapy should be considered. The optimal duration of bisphosphonate therapy is unknown. It should probably be given for as long as aromatase inhibitor therapy is continued. In addition, bisphosphonate therapy may also reduce the risk of bone metastases. This approach seems to be cost effective based on an economic evaluation model.

 

Metabolism. 2009 Aug 24. [Epub ahead of print]

Metabolically healthy but obese individuals: relationship with hepatic enzymes.

Messier V, Karelis AD, Robillard ME, Bellefeuille P, Brochu M, Lavoie JM, Rabasa-Lhoret R.

Department of Nutrition, Université de Montréal, Montreal, Canada H3T 1A8; Institut de recherches cliniques de Montréal (IRCM), Montreal, Canada H2W 1R7.

The purpose of this study was to investigate the level of plasma hepatic enzymes in obese women displaying the metabolically healthy but obese (MHO) phenotype. We studied 104 obese, sedentary, postmenopausal women. Subjects were classified as MHO or at risk based on insulin sensitivity as assessed with the oral glucose tolerance test-derived Matsuda index. Subjects were divided into quartiles according to insulin sensitivity values. Subjects in the upper quartile were categorized as MHO, whereas subjects in the lower 3 quartiles represented at-risk subjects. Outcome measures were hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, and gamma-glutamyltransferase [GGT]], high-density lipoprotein cholesterol, triglycerides, triglycerides to high-density lipoprotein cholesterol ratio, apolipoprotein B, fatty liver index, body composition (dual-energy x-ray absorptiometry), and visceral adipose tissue (computed tomography). The MHO individuals had significantly lower concentrations of ALT, AST, and GGT as well as a lower fatty liver index compared with at-risk subjects (P < .05). In addition, lean body mass index and visceral adipose tissue were significantly lower in MHO individuals (P < .05). Moreover, stepwise regression analysis showed that ALT explained 17.9% of the variation in insulin sensitivity in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that postmenopausal women displaying the MHO phenotype present favorable levels of ALT, AST, and GGT. Lower concentrations of hepatic enzymes, in particular, lower circulating ALT levels, in MHO individuals may reflect lower hepatic insulin resistance and lower liver fat content; and this could be involved, at least in part, in the protective profile of MHO individuals.

 

Metabolism. 2009 Aug 25. [Epub ahead of print]

Changes in C-reactive protein from low-fat diet and/or physical activity in men and women with and without metabolic syndrome.

Camhi SM, Stefanick ML, Ridker PM, Young DR.

Population Science, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.

Change in high-sensitivity C-reactive protein (CRP) from low-fat diet (diet) and physical activity (PA) interventions is relatively unknown for adults with metabolic syndrome. The objective of the study was to assess CRP change (DeltaCRP) with diet and/or PA in men and women with and without metabolic syndrome. Men (n = 149) and postmenopausal women (n = 125) with elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol were recruited into a 1-year randomized controlled trial. Treatment groups were as follows: control, diet (reduced total fat, saturated fat, and cholesterol intake), PA (45-60 minutes at 60%-85% maximum heart rate), or diet + PA. Weight loss was not an intervention focus. Metabolic syndrome was defined using the American Heart Association/National Heart, Lung, and Blood Institute criteria. Stored plasma samples were analyzed for CRP. Change in CRP was compared between treatments, within sex and metabolic syndrome status, using analysis of covariance, including covariates for baseline CRP and body fat change. For women with metabolic syndrome (n = 39), DeltaCRP was greater in diet vs control (-1.2 +/- 0.4, P = .009), diet + PA vs control (-1.3 +/- 0.4, P = .006), and diet + PA vs PA (-1.1 +/- 0.4, P = .02). Women with metabolic syndrome receiving the diet component (diet or diet + PA) had greater DeltaCRP compared with those who did not (control or PA) (P = .001). Change in CRP was not significantly different between intervention groups in men overall, women overall, men with (n = 47) or without metabolic syndrome (n = 102), or women without metabolic syndrome (n = 86). Low-fat diet may be the most effective treatment for reducing CRP in women with metabolic syndrome.

 

PLoS Med. 2009 Aug;6(8):e1000135. Epub 2009 Aug 25.

Decreased bone mineral density in adults born with very low birth weight: a cohort study.

Hovi P, Andersson S, Järvenpää AL, Eriksson JG, Strang-Karlsson S, Kajantie E, Mäkitie O.

Hospital for Children and Adolescents, Institute of Clinical Medicine, University of Helsinki, Helsinki,

BACKGROUND: Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood. METHODS AND FINDINGS: The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28-0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34-0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults' shorter height and lower self-reported exercise intensity. CONCLUSIONS: Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention.

 

J Clin Oncol. 2009 Aug 24. [Epub ahead of print]

Use of Hormone Replacement Therapy and the Risk of Colorectal Cancer.

Rennert G, Rennert HS, Pinchev M, Lavie O, Gruber SB.

Department of Community Medicine and Epidemiology, Carmel Medical Center; Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology; Clalit Health Services National Cancer Control Center; Gyneco-oncology Unit, Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel.

PURPOSE: Estrogen/progestin replacement therapy is prescribed to women in menopause for purposes of postmenopausal symptom control or prevention of hormone deficiency-related diseases such as osteoporosis. Such treatments have formerly been shown to be associated with lower colorectal cancer risk in an as yet unknown mechanism. PATIENTS AND METHODS: The Molecular Epidemiology of Colorectal Cancer study was a population-based case-control study in northern Israel of patients with colorectal cancer who were diagnosed between 1998 and 2006, and age-, sex-, clinic-, and ethnicity-matched population controls. Use of hormone replacement therapy (HRT) was assessed using a structured interview and validated by studying prescription records in a subset of patients for whom they were available. RESULTS: Two thousand four hundred sixty peri/postmenopausal women were studied from among 2,648 patients with colorectal cancer and 2,566 controls. The self-reported use of HRT was associated with a significantly reduced relative risk of colorectal cancer (odds ratio [OR], 0.67; 95% CI, 0.51 to 0.89). This association remained significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of colorectal cancer, ethnic group, and level of vegetable consumption (OR, 0.37; 95% CI, 0.22 to 0.62). Statistically significant interactions were seen between use of HRT and use of aspirin and involvement in sports activity. Using pharmacy data, only users of combined oral preparations demonstrated a significant negative association with colorectal cancer. CONCLUSION: The use of oral HRT was associated with a 63% relative reduction in the risk of colorectal cancer in postmenopausal women after adjustment for other known risk factors. This effect was not found in aspirin users and women with intensive sports participation.