Selección de Resúmenes de Menopausia

Enero de 2009

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

Semana del 31 de Diciembre de 2008 al 6 de Enero de 2009

 

Maturitas. 2008 Dec 30. [Epub ahead of print]

Progestogen use in women approaching the menopause and breast cancer risk.

Campagnoli C, Ambroggio S, Lotano MR, Peris C.

S.C. Ginecologia Endocrinologica Ospedale Ostetrico Ginecologico, ASO OIRM-S.Anna, Torino, Corso Spezia 60, Italy.

OBJECTIVE: Progestogens, particularly synthetic progestins, are widely used to contrast the clinical consequences of the relative hyperestrogenism that characterizes the years preceding the menopause. As a large body of data on postmenopausal hormone therapy (HT) demonstrates that the addition of synthetic progestins to estrogen increases the breast cancer risk compared to estrogen alone, it is important to evaluate if the use of progestogens in premenopausal years is associated with the risk of breast cancer. METHODS: Main literature data on the association with breast cancer risk of progestogens, either used alone in premenopausal years or added to estrogen in postmenopausal HT, were reviewed. RESULTS: Available data suggest that long-term current use of progestogens in premenopausal women after the age of 40 years can increase the risk of breast cancer. Consistently with the data on postmenopausal HT, the risk increase is higher for lobular cancer than for ductal cancer. CONCLUSIONS: The most important and widely accepted indications to the use of progestogens in the years preceding the menopause are anovulatory menstrual disorders, for which a limited period of treatment is generally sufficient. Awaiting for further data, when using progestogens for longer periods to treat other problems (endometriosis, cyclical mastalgia, etc.), the possibility of increased breast cancer risk and clinical benefits have to be weighed. Anyway, as micronized progesterone and dydrogesterone, at least when they were used in postmenopausal HT, seem to have, according to a large observational study, a safer risk profile on the breast, the preferential use of these preparations could be suggested.

 

Pharmacotherapy. 2009 Jan;29(1):74-81

Use of gabapentin in patients experiencing hot flashes.

Brown JN, Wright BR.

1 Pharmacy Service, Durham Veterans Affairs Medical Center, Durham, North Carolina.

Abstract Hot flashes occur frequently in menopausal women and in women with breast cancer, diminishing their quality of life. A report from the Women's Health Initiative published in 2002 raised concerns about the long-term safety of estrogen therapy. As a result, nonhormonal alternatives have emerged as preferred treatments. Gabapentin is an anticonvulsant that the United States Food and Drug Administration approved as an adjunct therapy for partial seizures and postherpetic neuralgia. Somnolence, dizziness, ataxia, fatigue, nystagmus, and peripheral edema are adverse effects commonly associated with gabapentin in the treatment of epilepsy and postherpetic neuralgia. The North American Menopause Society and the American College of Obstetricians and Gynecologists recommend the use of gabapentin as an option for managing hot flashes in women who are unwilling to take estrogen-containing supplements. To evaluate the efficacy and safety of gabapentin for the treatment of hot flashes in women with menopause and/or breast cancer, we performed a search of the MEDLINE database (1966-March 2008) and International Pharmaceutical Abstracts, as well as manually searching reference articles for relevant articles and abstracts; 10 clinical studies were identified. Although the studies were few, all showed gabapentin to be safe and effective in the treatment of hot flashes. At doses used to control hot flashes, gabapentin was well tolerated, with drowsiness as its most reported adverse effect. Gabapentin can be considered effective in the treatment of hot flashes and should be considered a reasonable alternative when estrogen therapy is not desired.

 

Climacteric. 2008 Dec 31:1-9. [Epub ahead of print]

Assessment of sexuality among middle-aged women using the Female Sexual Function Index.

Chedraui P, Perez-Lopez FR, San Miguel G, Avila C.

Collaborative Group for Research of the Climacteric in Latin America (REDLINC).

Objective The purpose of the present investigation was to assess sexual function among middle-aged women and determine related risk factors (personal and partner) for sexual dysfunction. Methods In this cross-sectional study, women aged 40-59 years were requested to fill out the Female Sexual Function Index (FSFI) and a general demographic questionnaire containing personal and partner data. Results A total of 409 women with a mean age of 47 +/- 5.3 years were surveyed. Of these, 42.1% were premenopausal, 24.4% perimenopausal and 33.5% postmenopausal. At the time of survey, 10.5% of women were hysterectomized, 1.5% used psychotropic drugs, and 9.8% were on hormone therapy (HT) for the menopause; 28.1% had less than 12 years of schooling and 80.4% had only one partner at the moment of survey. Among their male partners, 7.3% abused alcohol, 10.3% had erectile dysfunction, 11.2% premature ejaculation and 63.83% were faithful partners. Mean (+/- standard deviation) scores for the FSFI domains were: desire (3.7 +/- 1.2), arousal (3.1 +/- 2.5), lubrication (3.3 +/- 2.6), orgasm (2.6 +/- 2.3), satisfaction (4 +/- 1.7), and pain/dyspareunia (3.2 +/- 2.6). The mean total FSFI score was 20.1 +/- 12.4 (median 24.7). In this series, the prevalence of female sexual dysfunction (FSFI score </=26.55) was 55.7%, with women presenting difficulties across all domains of female sexual function but mostly in the dyspareunia and lubrication domains. Logistic regression analysis determined that female age (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.6-6.8), p = 0.001), postmenopausal status (OR 2.8, 95% CI 1.3-6.1, p = 0.007), partner's age (OR 2.0, 95% CI 1-4, p = 0.03), educational level (OR 2.7, 95% CI 1.5-5, p = 0.001), and the presence of erectile dysfunction (OR 3.8, 95% CI 1.3-10.9, p = 0.01) and premature ejaculation (OR 4.1, 95% CI 1.4-11.7, p = 0.0001) significantly increased the risk for female sexual dysfunction. Partner faithfulness (OR 0.2, 95% CI 0.1-0.4, p = 0.001) and menopausal HT use (OR 0.4, 95% CI 0.1-1, p = 0.04) decreased this risk. Conclusions In this series, male sexual health and demographic profile and female HT use were relevant determinants for sexual functioning among middle-aged women.

 

Int J Cancer. 2008 Nov 7. [Epub ahead of print]

Does the increase of endogenous steroid hormone levels also affect breast cancer risk in Chinese women? A case-control study in Chongqing, China.

Wang B, Mi M, Wang J, Wei N, Zhang Q, Zhu J, Yang S, Guo B, Xu J, Yang X.

Department of Nutrition and Food Hygiene, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, People's Republic of China.

Accumulating epidemiological evidence suggests that sex steroid hormones are positively associated with the development of breast cancer. However, most of these studies were conducted among Caucasian women and few have been carried out in China. To determine whether the associations of sex steroid hormone levels with breast cancer risk observed by and large in Caucasian populations are also evident in Chinese women, we conducted a case-control study in Chongqing, China. The study included 367 incident breast cancer patients and 367 healthy controls matched on menstrual status, age and periods of blood collection in the menstrual cycle. Plasma concentrations of estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were determined by electrochemiluminescene immunoassay (ECLIA). Conditional logistic regression analysis was performed to examine their associations with breast cancer risk. From comparisons of upper and lower tertiles, we observed statistically significant positive associations with breast cancer risk for plasma estradiol levels in follicular phase (adjusted odds ratio [OR] = 5.48, 95% confidence interval [CI] = 1.58-18.97), luteal phase (OR = 4.23, CI = 1.65-10.87) and postmenopausal (OR = 2.67, CI = 1.20-5.93); for progesterone levels in luteal phase (OR = 3.11, CI = 1.28-7.56), and for testosterone levels in postmenopausal (OR = 2.83, CI = 1.26-6.35). No significant association was found with DHEAS or SHBG. Our study suggests that high circulating levels of estradiol and testosterone are positively associated with increased breast cancer risk in Chinese women, which are generally consistent with the observations in Caucasian populations.

 

Med Sci Monit. 2009 Jan;15(1):CR5-9.

Decreased bone mineral density in men with metabolic syndrome alone and with type 2 diabetes.

Yaturu S, Humphrey S, Landry C, Jain SK.

Department of Endocrinology, Overton Brooks VA Medical Center, Shreveport, LA 71101-4295, U.S.A.

BACKGROUND: Metabolic syndrome is associated with decreased physical activity and increased incidence of diabetes. Bone Mineral density (BMD) is positively associated with physical activity. Lower BMD is a risk factor for bone fractures. Whether subjects with metabolic syndrome alone show early signs of lower BMD and osteoporosis similar to those present in diabetic is not known. MATERIAL/METHODS: This cross-sectional study in male veterans examined the BMD in 3458 non-diabetic men and 735 men with type 2 diabetes. In addition, the BMD changes in non-diabetic men without any metabolic syndrome were compared with non-diabetic men with metabolic syndrome as established by the criteria of the Adult Treatment Panel III. RESULTS: BMD of hip was significantly lower and incidence of osteoporosis higher in diabetic subjects compared with age and body mass index (BMI) matched non-diabetic subjects. BMD of AP spine was significantly higher in diabetic subjects compared with non-diabetics but similar when subjects were matched for BMI. Men with metabolic syndrome alone had higher osteoporosis and lower BMD of hip compared with those without metabolic syndrome. CONCLUSIONS: The BMD of hip is lower in diabetics compared with age and BMI-matched non-diabetic men, and its level is similar in age and BMI-matched diabetics and non-diabetic men with metabolic syndrome. This suggests that both diabetes and metabolic syndrome are associated independently with higher osteoporosis and lower BMD of hip and are risk factors for increased incidence of hip fractures in men

 

J Bone Miner Res. 2008 Dec 29. [Epub ahead of print]

Dietary Calcium and Serum 25-hydroxyvitamin D Status in Relation to Bone Mineral Density Among U.S. Adults.

Bischoff-Ferrari HA, Kiel DP, Dawson-Hughes B, Orav JE, Li R, Spiegelman D, Dietrich T, Willett WC.

Abstract A higher calcium intake is still the primary recommendation for the prevention of osteoporosis, while vitamin D deficiency is often not addressed. To study the relative importance of dietary calcium intake and serum 25-hydroxyvitamin D (25(OH)D) status in regard to hip bone mineral density (BMD) in 4958 community-dwelling women and 5003 men age 20 years + from the US NHANES III population-based survey. Calcium supplement users and individuals with a prior radius or hip fracture were excluded. We calculated standardized means for BMD by quartiles of gender-specific calcium intake for three 25(OH)D categories (< 50, 50-74, 75+ nmol/l) among men and women separately controlling for other important predictors of BMD . Only for women with 25(OH)D status below 50 nmol/l , a higher calcium intake was significantly associated with higher BMD (p-value for trend: p = 0.005), whereas calcium intake beyond the upper end of the lowest quartile ( > 566 mg/d) was not significantly associated with BMD at 25(OH)D concentrations above 50 nmol/l. Among men, there was no significant association between a higher calcium intake beyond the upper end of the lowest quartile (626 mg/d) and BMD within all 25(OH)D categories. Among both genders, BMD increased stepwise and significantly with higher 25(OH)D concentrations(< 50, 50-74, 75+ nmol/l; p-value for trend: women < 0.0001; men = 0.0001). Among men and women, 25(OH)D status appears to be the dominant predictor of BMD relative to calcium intake. Only women with 25(OH)D concentrations below 50 nmol/l appear to benefit from a higher calcium intake.

 

Atherosclerosis. 2008 Nov 18. [Epub ahead of print]

Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population.

Hansen T, Ahlström H, Söderberg S, Hulthe J, Wikström J, Lind L, Johansson L.

Dept. of Radiology, Uppsala University Hospital, Sweden.

OBJECTIVE: The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS: Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS: VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

 

 

Semana del 7 al 13 de Enero de 2009

 

Maturitas. 2009 Jan 2. [Epub ahead of print]

Hysteroscopy for asymptomatic postmenopausal women with sonographically thickened endometrium.

Schmidt T, Breidenbach M, Nawroth F, Mallmann P, Beyer IM, Fleisch MC, Rein DT.

Department of Gynecology and Obstetrics, University of Cologne Medical Center, Cologne, Germany.

Endometrial carcinoma is the most common genital cancer in women. While patients usually present with vaginal bleeding, in 10-20% this characteristic symptom is absent. Endometrial thickness (double layer) is measured by transvaginal sonography and thickening indicates an increased risk of malignancy or other pathology (hyperplasia or polyps). Objective: We sought to correlate hysteroscopic and pathological findings in asymptomatic postmenopausal women with sonographically thickened endometrium (>6mm). Study design: A prospective observational study in a university hospital of 304 postmenopausal women referred between 1996 and 2006 because of a sonographically thickened endometrium in the absence of abnormal bleeding, who underwent continuous flow hysteroscopy (4.5mm Storz hysteroscope) and fractionated curettage of the uterine cervix and corpus (D & C) in addition to vaginal sonography (5MHz probe). Results: The mean age of the women was 64.8 (range 57.7-71.9) years. Average endometrial thickness measured by ultrasound was 12mm+/-6.7mm. Hysteroscopy suggested the presence of endometrial polyps in 226 women (74.3%), simple endometrial hyperplasia in 34 (11.2%), atrophic endometrium in 18 (5.9%), complex endometrial hyperplasia in 2 (0.7%), atypical hyperplasia in 3 (1%) and leiomyoma in 9 (3.0%). In 12 women (3.9%), the hysteroscopic appearance suggested malignancy and histology revealed endometrial adenocarcinoma. All hysteroscopic results were confirmed by histological examination. Conclusion: Hysteroscopy represents an easy, safe and effective method for the investigation of asymptomatic women with a thickened endometrium found with transvaginal ultrasound. The commonest pathology was endometrial polyps.

 

Bone. 2008 Dec 16. [Epub ahead of print]

Efficacy and safety of pharmacological agents in managing osteoporosis in the old old: Review of the evidence.

Inderjeeth CA, Foo AC, Lai MM, Glendenning P.

University of Western Australia, Australia; North Metropolitan Area Health Service, Australia.

INTRODUCTION: Osteoporosis and fracture risk increase exponentially in postmenopausal females. This places a significant burden in terms of morbidity, mortality and costs that are likely to increase with an ageing population. Despite this there is very limited data on pharmacological management of osteoporosis in this high risk group. OBJECTIVES OF THIS REVIEW: To review the published literature on the clinical efficacy and safety of specific anti osteoporosis treatments in the reduction in fracture risk in females >75 years of age. The following major endpoints were used in this review: SEARCH METHODS FOR IDENTIFICATION OF STUDIES: We performed an electronic search of Medline (1970 to June 2007) and the Cochrane Library (1996 to June 2007). Our search strategy included MeSH terms for osteoporosis and treatments. We reviewed the reference list of identified articles for additional relevant published trials. RESULTS: Two hundred and fifty-two potentially relevant abstracts were identified. Only six publications were deemed to meet full eligibility criteria and one met most criteria. There is evidence for significant vertebral fracture relative risk reduction(RR) at 1 year for Risedronate (RR 81%; p<0.001), Teriparatide (RR 65%; p<0.05) and Strontium Ranelate (RR 59%; p=0.002) and 3 years for Risedronate (RR 44%; p=0.003), Alendronate (RR 38%; p<0.05) and Strontium Ranelate (RR 32%; p=0.013). There is evidence for significant non-vertebral fracture relative risk reduction at 1 year for Strontium Ranelate (RR 41%; p=0.027) but not Teriparatide (p=0.66) and 3 years for Strontium Ranelate (RR 31%; p=0.011) but not Risedronate (p=0.66). The only study to report a reduction in hip fracture at 3 years is the TROPOS study with Strontium Ranelate (RR 36%; p=0.046). DISCUSSION: This review reinforces the irony that the least evidence is available for fragility fracture reduction in the group at greatest risk; the old old and those with non vertebral and hip fracture. Although there is good evidence for the benefit of the bisphosphonates (Alendronate and Risedronate), Teriparatide and Strontium Ranelate in vertebral fracture reduction, there are very limited data for non vertebral and hip fracture reduction. Strontium Ranelate is the only agent to date that has demonstrated a reduction in non vertebral and hip fracture events in this high risk elderly female population. Perhaps we need to adopt different strategies in managing older patients with osteoporosis as their fracture risks and treatment strategies may be quite different from younger populations.

 

J Womens Health (Larchmt). 2009 Jan-Feb;18(1):105-13

Dose-Response Relationship between Moderate-Intensity Exercise Duration and Coronary Heart Disease Risk Factors in Postmenopausal Women.

Dalleck LC, Allen BA, Hanson BA, Borresen EC, Erickson ME, De Lap SL.

University of Wisconsin-Eau Claire, Eau Claire, Wisconsin.

PURPOSE: This study was designed to investigate whether, in a dose-response manner, there would be greater health benefits in a group of postmenopausal women completing 45 minute- vs. 30 minutes of moderate intensity (50% maximal oxygen uptake reserve, VO2R) exercise 5 days . wk(-1). METHODS: Apparently healthy but sedentary postmenopausal women (n = 33) were randomized to a nonexercise control group, a 30-minute exercise duration group, or a 45-minute exercise duration group. Exercise training was performed 5 days . wk(-1) for 12 weeks at 50% VO2R. Participants were instructed to not change their usual diet throughout the study. RESULTS: Twenty-six women completed the study. After 12 weeks, VO2max increased significantly (p < 0.05) in both 30-minute (0.20 +/- 0.21 L . min(-1)) and 45-minute (0.41 +/- 0.10 L . min(-1)) groups. Repeated measures ANOVA identified a significant interaction between exercise duration and VO2max values (F = 4.72, p < 0.05), indicating that VO2max responded differently to 30-minute and 45-minute exercise durations. Trend analysis showed that body mass, body composition, waist circumference, and high-density lipoprotein cholesterol (HDL-C) changed favorably (p < 0.05) across control, 30-minute, and 45-minute groups. CONCLUSIONS: Although most health organizations agree that 150 min . wk(-1) of physical activity will reduce the risk of all-cause and cardiovascular mortality, few randomized, controlled studies have examined whether completing more physical activity than the recommended amount will yield additional benefits. Findings from the present study suggest that there is a dose-response relationship between exercise duration and numerous health outcomes in postmenopausal women, including cardiorespiratory fitness, body mass, body composition, waist circumference, and HDL-C.

 

Menopause. 2009 Jan-Feb;16(1):104-9

Vascular effects of estrone and diethylstilbestrol in porcine coronary arteries.

Teoh H, Quan A, Leung SW, Man RY.

From the Department of Pharmacology, University of Hong Kong, Hong Kong, China.

OBJECTIVE:: To explore the effects of different estrogens on vascular function, we compared the vasorelaxant effects of 17beta-estradiol, 17alpha-estradiol, estrone, and the synthetic estrogen diethylstilbestrol (DES) on porcine coronary arterial segments. DESIGN:: Porcine coronary arterial rings were contracted with the stable thromboxane A2 analogue U46619 (3 x 10 M), and direct relaxation was examined by the addition of increasing concentrations of 17beta-estradiol, 17alpha-estradiol, estrone, or DES (10 to 10 M). Modulation of agonist-induced contraction and relaxation was studied in coronary arterial rings incubated for 20 minutes with DES or estrone (10-10 M) with 17beta-estradiol (10 M) as comparison. RESULTS:: Direct relaxation of arterial rings potentiated by these estrogens was recorded with a rank order potency of DES > 17beta-estradiol > estrone > 17alpha-estradiol. 17beta-Estradiol potentiated relaxation responses to sodium nitroprusside and levcromakalim but not bradykinin or A23187 while reducing contractions to 5-hydroxytryptamine and U46619. DES and estrone, both at 10 M, mimicked the 17beta-estradiol-potentiated sodium nitroprusside and levcromakalim relaxation responses. Additionally, the inhibitory effects of 17beta-estradiol (10 M) on 5-hydroxytryptamine- and U46619-induced contractions were partially reproducible by DES (10 M) and estrone (10 M). CONCLUSIONS:: Although DES is the most potent among the tested estrogenic compounds in eliciting relaxation, 17beta-estradiol is more effective than estrone and DES at enhancing endothelium-independent relaxation and reducing vascular contraction in porcine coronary arteries.

 

Cancer. 2009 Jan 6. [Epub ahead of print]

Body mass index and risk of ovarian cancer.

Leitzmann MF, Koebnick C, Danforth KN, Brinton LA, Moore SC, Hollenbeck AR, Schatzkin A, Lacey JV Jr.

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.

BACKGROUND:: Convincing epidemiologic evidence links excess body mass to increased risks of endometrial and postmenopausal breast cancers, but the relation between body mass index (BMI) and ovarian cancer risk remains inconclusive. Potential similarities regarding a hormonal mechanism in the etiology of female cancers highlight the importance of investigating associations according to menopausal hormone therapy (MHT) use. However, to the authors' knowledge, data addressing whether the relation between BMI and ovarian cancer differs by MHT use are very sparse. METHODS:: The authors prospectively investigated the association between BMI and ovarian cancer among 94,525 US women who were followed between 1996 through 1997 to December 31, 2003. During 7 years of follow-up, 303 epithelial ovarian cancer cases were documented. RESULTS:: Compared with normal weight women (BMI of 18.5-24.9 kg/m(2)), the multivariate relative risk (MVRR) of ovarian cancer for obese women (BMI of >/=30 kg/m(2)) in the cohort as a whole was 1.26 (95% confidence interval [95% CI], 0.94-1.68). Among women who never used MHT, the MVRR for obese versus normal weight women was 1.83 (95% CI, 1.18-2.84). In contrast, no relation between BMI and ovarian cancer was apparent among women who ever used MHT (MVRR = 0.96; 95% CI, 0.65-1.43; P interaction = 0.02). Exploratory analyses also suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer (MVRR comparing obese vs normal weight women = 1.36; 95% CI, 1.00-1.86), but no relation with BMI was apparent among women with a positive family history of ovarian cancer (MVRR = 0.74; 95% CI, 0.34-1.62 [P interaction = .02]). CONCLUSIONS:: Based on the results of the current study, the authors suspect that obesity is associated with enhanced ovarian cancer risk through a hormonal mechanism.

 

J Clin Endocrinol Metab. 2009 Jan 6. [Epub ahead of print

Adipokines, Inflammation, and Visceral Adiposity Across The Menopausal Transition: A Prospective Study.

Lee CG, Carr MC, Murdoch SJ, Mitchell E, Woods NF, Wener MH, Chandler WL, Boyko EJ, Brunzell JD.

University of Washington Medical Center, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, 1959 NE Pacific St., Box 356426, Seattle, WA 98195; University of Washington, Family and Child Nursing, WA 98195; University of Washington, Department of Laboratory Medicine, 1959 NE Pacific St., Box 357110, Seattle, WA 98195; VA Puget Sound Health Care System (S-152E), 1660 S. Columbian Way, Seattle, WA 98108.

Context: Postmenopausal women have greater visceral adiposity compared to premenopausal women. Adipokines are associated with increased adiposity, insulin-resistance and atherosclerosis. Objective: To assess changes in adipokines and inflammatory markers through the menopausal transition and to correlate them with changes in visceral adiposity. Design and Setting: This is a prospective cohort study of women through the menopausal transition conducted at the University of Washington. Participants: 69 healthy women were followed longitudinally from premenopausal (ages 45-55) to postmenopausal status (ages 49-60). Outcome: On premenopausal and postmenopausal visits, fasting blood was drawn for adiponectin, leptin, serum amyloid A (SAA), C-reactive protein (CRP), monocyte-chemotactic protein-1 (MCP-1), tissue plasminogen activator antigen (tPA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Body composition measures were assessed by body mass index (BMI), whole body dual x-ray absorptiometry (DEXA) scan, and computed tomography (CT) scan of the abdomen at the lumbar 4-5 level. Results: Women had a statistically significant increase in SAA, tPA, MCP-1, and adiponectin between the two measurement occasions (p=0.04, p=0.02, p=0.001, and p<0.001, respectively). The increase in intra-abdominal fat was correlated positively with the change in SAA (r=0.31, p=0.02), CRP (r=0.56, p<0.001), tPA (r=0.40, p=0.002) leptin (r=0.41, p=0.002), and negatively correlated with the change in adiponectin (r=-0.37, p=0.005). After adjustment for change in subcutaneous abdominal fat, the correlation between change in CRP, tPA, leptin and adiponectin remained significantly associated with change in intra-abdominal fat. Conclusions: Women going through the menopausal transition have deleterious changes in inflammatory markers and adipokines that correlate with increased visceral adiposity.

 

 

Semana del 20 al 27 de Enero de 2009

 

Cochrane Database Syst Rev. 2009 Jan 21;(1):CD005997.

Hormone therapy for endometriosis and surgical menopause.

Al Kadri H, Hassan S, Al-Fozan HM, Hajeer A.

Obstetrics & Gynaecology, KFNGH, PO Box 57374, Riyadh, Saudi Arabia, 11574.

BACKGROUND: Endometriosis is characterized by the presence of ectopic endometrial tissue that might lead to many distressing and debilitating symptoms. Despite available studies supporting standard hormone therapy for women with endometriosis and post-surgical menopause, there is still a concern that estrogens may induce a recurrence of the disease and its symptoms. OBJECTIVES: This review aimed to look at pain and disease recurrence in women with endometriosis who used hormone therapy for post-surgical menopause. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialized Register (March 2008), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), and references lists of articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomized controlled trials studying hormone therapy for women with endometriosis in post-surgical menopause. DATA COLLECTION AND ANALYSIS: Review authors assessed the eligibility of trials and their quality. MAIN RESULTS: Two studies fulfilled our inclusion criteria. One trial compared the nonstop transdermal application of 17beta-estradiol (0.05 mg/day) combined with cyclic medroxy progesterone acetate (10 mg per day) for 12 days per month in women with a conserved uterus with nonstop tibolone (2.5 mg/day). The second trial used sequential administration of estrogens and progesterone with two 22 cm(2) patches applied weekly to produce a controlled release of 0.05 mg/day. Micronized progesterone was administered orally (200 mg/day) for 14 days with a 16-day interval free of treatment. Pain and dyspareunia The first trial reported recurrence of pain in the estrogen and progesterone arm in 4/10 of women compared with 1/11 in the tibilone arm. In the latter, 4/115 women reported recurrence of pain in the treatment group compared with 0/57 patients in the no-treatment arm. Neither finding was statistically different.Confirmed recurrence or exacerbation of endometriosis This outcome was not reported in the first trial. The second found that 2/115 of the treatment group developed recurrence of endometriosis with no recurrence reported in the no-treatment group. This was not statistically significant. No woman was re-operated on in the no-treatment group compared with 2/115 in the treatment group. AUTHORS' CONCLUSIONS: Hormone replacement therapy for women with endometriosis in post-surgical menopause could result in pain and disease recurrence. However, the evidence in the literature is not strong enough to suggest depriving severely symptomatic patients from this treatment. There is a need for more randomised controlled studies.

 

Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003799

Hormone replacement therapy to maintain cognitive function in women with dementia.

Hogervorst E, Yaffe K, Richards M, Huppert FA.

Department of Human Sciences, Loughborough University, Loughborough, Leicestershire, UK, LE11 3TU.

BACKGROUND: As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline in women with Alzheimer's disease (AD) or other dementia syndromes. OBJECTIVES: To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group Specialized Register, which contains records from many medical databases, The Cochrane Library, EMBASE, MEDLINE, CINAHL, PsycINFO and LILACS were searched on 7 November 2007 using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen* and progesterone*. SELECTION CRITERIA: All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane. MAIN RESULTS: A total of seven trials including 351 women with AD were analysed. Because different drugs were used at different studies it was not possible to combine more than two studies in any analysis.On a clinical global rating, clinicians scored patients taking CEE as significantly worse compared with the placebo group on the Clinical Dementia Rating scale after 12 months (overall WMD = 0.35, 95% CI = 0.01 to 0.69, z = 1.99, P < 0.05).Patients taking CEE had a worse performance on the delayed recall of the Paragraph Test (overall WMD = -0.45, 95% CI = -0.79 to -0.11, z = 2.60, P < 0.01) after one month than those taking placebo. They had a worse performance on Finger Tapping after 12 months (WMD = -3.90, 95% CI = -7.85 to 0.05, z = 1.93, P < 0.05).Limited positive effects were found for the lower dosage of CEE (0.625 mg/day) which showed a significant improvement in MMSE score only when assessed at two months, and disappeared after correction for multiple testing. No significant effects for MMSE were found at longer end points (3, 6 and 12 months of treatment). With a dosage of 1.25 mg/d CEE, short-term significant effects were found for Trial-Making test B at one month and Digit Span backward at four months. After two months of transdermal diestradiol (E2) treatment, a highly significant effect was observed for the word recall test (WMD = 6.50, 95% CI = 4.04 to 8.96, z = 5.19, P < 0.0001). No other significant effects were found for other outcomes measured. AUTHORS' CONCLUSIONS: Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD.

 

Maturitas. 2009 Jan 19. [Epub ahead of print

Influence of menopause on biochemical markers of endothelial dysfunction-A case-control pilot study in North Indian population.

Salhotra S, Arora S, Anubhuti, Trivedi SS, Bhattacharjee J.

Department of Biochemistry, Lady Hardinge Medical College & Smt. Sucheta Kriplani Hospital, New Delhi, India.

OBJECTIVE: Menopause, an estrogen deficient state, is known to increase the cardiovascular risk. Lipid changes accompanying menopause account for only few cases of coronary artery disease (CAD). Endothelium-dependent nitric oxide-mediated vasodilatory mechanisms are also known to play a role in development of coronary artery disease, but studies in menopausal women are very few. This study was hence undertaken to see if nitric oxide (NO)-cyclic guanidine monophosphate (c-GMP) pathway is influenced by menopause. DESIGN: This study was a hospital-based case-control study involving 100 women in age group 40-55 years. Of these, 50 women were postmenopausal and 50 were premenopausal. Women with known risk factors for CAD were excluded. Fasting blood samples from these women were collected and analyzed for estradiol levels, lipid profile, apolipoprotein B, plasma nitric oxide, c-GMP and platelet nitric oxide using standard kits and reagents. Statistical analysis was done on SPSS and two-tailed p-value <0.05 was considered significant. RESULT: Postmenopausal women had significantly lower estradiol, plasma NO, and c-GMP levels as compared to premenopausal women (p<0.05). Cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) levels were higher and HDL levels were lower in postmenopausal as compared to premenopausal women (p<0.05). Plasma NO showed a significant positive correlation with estradiol, HDL levels and negative correlation with apo-B levels. CONCLUSION: Menopause tends to downregulate NO-c-GMP pathway resulting in endothelial dysfunction. The mechanism may be directly through estrogen receptors or indirectly through potentiation of dyslipidemia.

 

Climacteric. 2009 Jan 15:1-8. [Epub ahead of print

Food groups and risk of forearm fractures in postmenopausal women in Chengdu, China.

Xu L, Dibley M, D'Este C, Phillips M, Porteous J, Attia J.

West China Second University Hospital, Sichuan University, Chengdu, China.

Background Forearm fractures are a major cause of disability in postmenopausal women. However, no prior report on the relationship of dietary patterns and forearm fracture in mainland China is available and the results from Western studies may not be applicable to the Chinese population. Objective To determine whether food groups are associated with the risk of forearm fracture among postmenopausal women in China. Design Case-control study. Methods Cases were 209 postmenopausal women aged 50-70 years with new forearm fractures, identified in hospitals in Chengdu. Controls were age- and district-matched subjects randomly selected from the community of Chengdu. Dietary habits and food group intake were measured by a structured food frequency questionnaire. Results The dietary pattern in Chinese postmenopausal women was of high intakes of cereals, vegetables, fruits, beans or bean products, but lower intakes of meat and milk. The estimated odds ratios (95% confidence intervals) for forearm fracture were 0.53 (0.42-0.67) for each quintile increase in vegetable intake, 0.73 (0.59-0.92) for each quintile increase in cereal intake, and 0.26 (0.14-0.48) in subjects who met World Health Organization (WHO) dietary recommendations for vegetables and fruits. Conclusions This is the first report indicating that the levels of vegetable and cereal intake, and that meeting WHO recommendations for vegetable and fruit intake, are associated with a decrease in the risk of forearm fractures in Chinese postmenopausal women.

 

Acta Obstet Gynecol Scand. 2009 Jan 22:1-6. [Epub ahead of print]

Physical training decreases waist circumference in postmenopausal borderline overweight women.

Bergstrom I, Lumbardo C, Brinck J.

Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm.

Objective. To examine if healthy borderline overweight postmenopausal women with osteoporosis can improve their waist circumference and lipid profile with a moderate physical training program. Design. Randomized controlled trial. Setting. One hundred and twelve postmenopausal women were randomized to normal sedentary life or one year of physical training consisting of three brisk walks and 1-2 aerobic exercises/week. Main Outcome Measures. Waist circumference reduction, waist circumference reduction in relation to observed level of participation in physical intervention and changes in cholesterol, triglycerides, apolipoproteins B and A1 and high-sensitivity C-reactive protein (hs-CRP). Results. At start the mean (SD) waist circumference was 83.6 (7.7) and 81.8 (7.5) cm in the control and training groups, respectively. In relation to baseline, the 12 months intervention led to a waist reduction of 0.3 cm (2.7) (p=0.36) and 1.6 cm (4.7) (p=0.02) in the respective groups but the inter-group comparison was not significant in an intention-to-treat analysis (p=0.09). The ninety-two women completing the study intervention were analyzed per protocol. A tendency for better waist reduction in relation to the women's observed physical intensity level was observed (p=0.07, ANOVA for linear trend across training intensity levels). Training women improved their waist circumference 1.7 cm (p=0.01) compared to baseline and was borderline significantly better than controls (p=0.059). No significant changes in response to the intervention were observed for blood pressure, cholesterol, triglycerides, apolipoproteins and hs-CRP. Conclusions. A moderate physical exercise program for healthy postmenopausal women during one year reduced the waist circumference in a training intensity dependent manner.

 

Biochim Biophys Acta. 2008 Dec 29. [Epub ahead of print

An attempt to prevent senescence: A mitochondrial approach.

Skulachev VP, Anisimov VN, Antonenko YN, Bakeeva LE, Chernyak BV, Erichev VP, et al.

Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.

Antioxidants specifically addressed to mitochondria have been studied to determine if they can decelerate senescence of organisms. For this purpose, a project has been established with participation of several research groups from Russia and some other countries. This paper summarizes the first results of the project. A new type of compounds (SkQs) comprising plastoquinone (an antioxidant moiety), a penetrating cation, and a decane or pentane linker has been synthesized. Using planar bilayer phospholipid membrane (BLM), we selected SkQ derivatives with the highest permeability, namely plastoquinonyl-decyl-triphenylphosphonium (SkQ1), plastoquinonyl-decyl-rhodamine 19 (SkQR1), and methylplastoquinonyldecyltriphenylphosphonium (SkQ3). Anti- and prooxidant properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested in aqueous solution, detergent micelles, liposomes, BLM, isolated mitochondria, and cell cultures. In mitochondria, micromolar cationic quinone derivatives were found to be prooxidants, but at lower (sub-micromolar) concentrations they displayed antioxidant activity that decreases in the series SkQ1=SkQR1>SkQ3>MitoQ. SkQ1 was reduced by mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Nanomolar SkQ1 specifically prevented oxidation of mitochondrial cardiolipin. In cell cultures, SkQR1, a fluorescent SkQ derivative, stained only one type of organelles, namely mitochondria. Extremely low concentrations of SkQ1 or SkQR1 arrested H(2)O(2)-induced apoptosis in human fibroblasts and HeLa cells. Higher concentrations of SkQ are required to block necrosis initiated by reactive oxygen species (ROS). In the fungus Podospora anserina, the crustacean Ceriodaphnia affinis, Drosophila, and mice, SkQ1 prolonged lifespan, being especially effective at early and middle stages of aging. In mammals, the effect of SkQs on aging was accompanied by inhibition of development of such age-related diseases and traits as cataract, retinopathy, glaucoma, balding, canities, osteoporosis, involution of the thymus, hypothermia, torpor, peroxidation of lipids and proteins, etc. SkQ1 manifested a strong therapeutic action on some already pronounced retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision was restored to 67 of 89 animals (dogs, cats, and horses) that became blind because of a retinopathy. Instillation of SkQ1-containing drops prevented the loss of sight in rabbits with experimental uveitis and restored vision to animals that had already become blind. A favorable effect of the same drops was also achieved in experimental glaucoma in rabbits. Moreover, the SkQ1 pretreatment of rats significantly decreased the H(2)O(2) or ischemia-induced arrhythmia of the isolated heart. SkQs strongly reduced the damaged area in myocardial infarction or stroke and prevented the death of animals from kidney ischemia. In p53(-/-) mice, 5 nmol/kgxday SkQ1 decreased the ROS level in the spleen and inhibited appearance of lymphomas to the same degree as million-fold higher concentration of conventional antioxidant NAC. Thus, SkQs look promising as potential tools for treatment of senescence and age-related diseases.

 

Geriatr Gerontol Int. 2008 Dec;8(4):259-64

Effects of long-term transdermal hormone replacement therapy on the renin-angiotensin- aldosterone system, plasma bradykinin levels and blood pressure in normotensive postmenopausal women.

Ichikawa A, Sumino H, Ogawa T, Ichikawa S, Nitta K.

Department of Internal Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo.

AIM: This study was designed to investigate the effects of 24-month long-term transdermal hormone replacement therapy (HRT) on the circulating levels of components of the renin-angiotensin-aldosterone system (RAAS) and bradykinin, blood pressure (BP) and lipid profile in normotensive postmenopausal women (PMW). METHODS: Twenty-two normotensive PMW were randomized to receive transdermal HRT (continuous 17-beta estradiol patch at 36 microg/day plus cyclic oral medroxyprogesterone acetate 2.5 mg/day for 12 days/month) (n = 12) or control (n = 10). The plasma renin activity (PRA), serum angiotensin-converting enzyme (ACE) activity, plasma angiotensin (Ang) I, Ang II, aldosterone, bradykinin, and BP were measured before, and 12 and 24 months after, the start of the HRT. RESULTS: In the HRT group, the diastolic BP and mean BP were significantly decreased at 12 and 24 months (both P < 0.05) after the start of therapy, however, no significant change of the systolic BP was noted during the study period. No changes in the RAAS components or lipid profile were noted in either group. The plasma bradykinin levels were significantly reduced at 12 (P < 0.05) and 24 months (P < 0.01), while no changes were observed in the control group. CONCLUSION: More than 12 months of long-term transdermal HRT kept diastolic BP, mean BP and plasma bradykinin levels decreased in normotensive PMW, without influencing any of the components of the RAAS. This therapy may allow optimal blood pressure control and prevent elevation of the cardiovascular risk.

 

Ann Endocrinol (Paris). 2009 Jan 20. [Epub ahead of print

Etiologic discussion and clinical relevance of thyroid ultrasonography in subclinical hypothyroidism. A retrospective study in 1845 patients.

Nys P, Cordray JP, Merceron RE.

Groupe de recherches cliniques en endocrinologie, 5, rue Dupin, 75006 Paris, France.

BACKGROUND: Acquired subclinical hypothyroidism in adulthood is mainly due to autoimmune thyroiditis. In the absence of a goiter or a palpable firm thyroid, measurement of thyroid antibodies can improve the diagnosis. Whether thyroid antibodies are detected or not, what might be the clinical relevance of ultrasonography in this setting? METHODS: We studied 1845 cases of subclinical hypothyroidism in adults recruited for symptoms indicative of hypothyroidism or thyroid pathology. All patients were screened for thyroid antibodies and underwent an ultrasonographic thyroid examination. LOCALISATION: Multicentric retrospective study. RESULTS: Chronic autoimmune thyroiditis was confirmed in 70% of patients. Thyroid antibodies were undetectable in 30% of patients. In all patients, thyroid ultrasound facilitated measurement of the thyroid volume and detection of non-palpable nodules and therefore allowed biopsy. In patients negative for thyroid antibodies, ultrasonography suggested autoimmune thyroiditis in 31% of cases. Ultrasonography did not contribute to diagnosis in a large number of patients without nodules and in case of normal echostructure. The strategy of thyroid hormone replacement therapy was not influenced by ultrasonographic data. Thyroid biopsies detected smears suspected to be cancerous in 10 patients (4%). Cancer was confirmed in nine patients after surgery. Ultrasonography displayed suspicious aspects in six patients. CONCLUSION: In subclinical hypothyroidism, thyroid ultrasonography is not required for the diagnosis of autoimmune thyroiditis but is useful for patients with abnormal thyroid palpation and allows detection of non-palpable thyroid nodules. For patients that were negative for thyroid antibodies, thyroid ultrasonography can improve diagnosis for some patients, allowing detection of autoimmune thyroiditis.

 

Cancer. 2009 Jan 20. [Epub ahead of print

Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype.

Calle EE, Feigelson HS, Hildebrand JS, Teras LR, Thun MJ, Rodriguez C.

Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia.

BACKGROUND:: Data from large prospective studies are needed to fully characterize the impact of exogenous hormones on breast cancer incidence by type of hormone preparation and histology of the cancer. METHODS:: In a prospective cohort of 67,754 postmenopausal women in the US, 1821 cases of invasive ductal cancer and 471 cases of invasive lobular or mixed lobular cancer occurred during 13 years of follow-up. The authors computed age-adjusted rates, as well as age-adjusted and multivariate-adjusted rate ratios (RR) for ductal and lobular breast cancer and for the use of estrogen only (E-only) and estrogen and progesterone (E + P) for current and former hormone users by duration of use and years since last use. RESULTS:: Current use of E + P was associated with an increased risk of both ductal (RR of 1.75; 95% confidence interval [95% CI], 1.53-2.01) and lobular (RR of 2.12; 95% CI, 1.62-2.77) breast cancer. Risk increased within the first 2 to 3 years of use and attenuated 2 years after cessation. In contrast, current use of E-only was not associated with an overall increased risk of invasive ductal cancer. The only exceptions to this finding were in lean (body mass index <25) women and for ductal cancers diagnosed at the regional/distant stage, where in both cases the use of E-only was associated with an increased risk. E-only use was associated with a 50% increased risk of invasive lobular cancer after >/=10 years of use. CONCLUSIONS:: Use of E + P is more detrimental to the breast than E-only use, in terms of both ductal and lobular cancer. The findings from the current study suggest a window of 2 to 3 years for the risks of E + P both to become apparent after initial use and to attenuate after cessation. Cancer 2009. (c) 2009 American Cancer Society.

 

Nat Clin Pract Endocrinol Metab. 2009 Feb;5(2):113-121

Testosterone and ill-health in aging men.

Yeap BB.

Department of Endocrinology and Diabetes, Fremantle Hospital, WA, Australia.

As men age, testosterone levels decline, and decreased testosterone levels are associated with increased risks of osteoporosis, metabolic syndrome, type 2 diabetes mellitus and mortality. Nevertheless, it is still uncertain whether reduced testosterone level is a cause of ill-health or a marker of pre-existing disease, as systemic illness lowers testosterone levels. Most circulating testosterone is bound to sex-hormone-binding globulin (SHBG) and albumin, whereas a small proportion circulates as free testosterone. Decreased SHBG level is associated with increased risks for insulin resistance and metabolic syndrome, although it would also be expected to be associated with increased free testosterone level. During male aging, total and free testosterone levels fall while SHBG level rises. Thus, associations between decreasing androgens and negative health outcomes might differ across men of various ages. Trials of testosterone therapy report benefits for body composition and BMD, but there are limited data on the effect of testosterone supplementation on cardiovascular risk. Whereas men who have androgen deficiency should be considered for testosterone therapy, the role of testosterone supplementation in older men who are not clearly hypogonadal requires further clarification. Further studies are also needed to establish whether the age-related decline in circulating testosterone level in men can be modified or prevented.

 

 

Semana del 28 de Enero al 3 de Febrero de 2009

 

Postgrad Med. 2009 Jan;121(1):73-85.

The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?

Holtorf K.

Holtorf Medical Group, Inc., Torrance, CA, 90505, USA. kholtorf@cox.net.

Background: The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administration and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective. Objective: This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the commonly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease. Methods: Published papers were identified from PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords associated with bioidentical hormones, synthetic hormones, and HRT. Papers that compared the effects of bioidentical and synthetic hormones, including clinical outcomes and in vitro results, were selected. Results: Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized controlled trials have been documented. Synthetic progestins have a variety of negative cardiovascular effects, which may be avoided with progesterone. Conclusion: Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animalderived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly.

 

Gynecol Endocrinol. 2008 Dec;24(12):718-23.

Effects of two estroprogestins containing ethynilestradiol 30 microg and drospirenone 3 mg and ethynilestradiol 30 microg and chlormadinone 2 mg on skin and hormonal hyperandrogenic manifestations.

Lello S, Primavera G, Colonna L, Vittori G, Guardianelli F, Sorge R, Raskovic D.

Endocrinological Gynecology and Pathophysiology of Menopause Unit, IRCCS-Istituto Dermopatico dell'Immacolata, Rome, Italy. lellostefano@libero.it

Hyperandrogenic manifestation in women, such as seborrhea, acne and increased hair growth are common reasons of psychological distress. Skin appearance is very important for young women. This study evaluated the hormonal and skin effects of two estroprogestins (EPs) containing ethinyl-estradiol (EE) 30 microg associated with drospirenone (DRSP) 3 mg or chlormadinone acetate (CMA) 2 mg, respectively. Fifty-five women with signs and symptoms of hyperandrogenism (seborrhea, acne and increased hair growth) were enrolled in the study; randomly, 30 women were treated with EE 30 microg + DRSP 3 mg and 25 with EE 30 microg + CMA 2 mg. Follicle-stimulating hormone (FSH), luteinising hormone (LH), 17-hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG) and free androgen index (T x 100/SHBG, FAI) were assessed at baseline, and after 3 and 6 months of treatment with EPs. Effects on seborrhea, acne and increased hair growth (as Ferriman-Gallwey score) were also evaluated at the same time points. Finally, skin hydration, transepidermal water loss (TEWL) and skin homogeneity were studied with non-invasive technique during the study. Treatment for 6 months with both EPs decreased significantly the circulating androgen levels (A, T, DHEAS) and FAI, and increased SHBG levels; also skin pattern was improved. EP containing EE and DRSP was better than EP containing EE and CMA as for skin changes, as seborrhea, acne, increased hair, hydration, homogeneity and overall quality of the skin; moreover, hormonal changes (as FAI) under therapy were more pronounced with EE/DRSP than EE/CMA. These effects may be considered in EP choice and could be important in improving patient's compliance and quality of life in hyperandrogenic women.

 

Gynecol Endocrinol. 2008 Dec;24(12):696-700

Coronary heart disease and HRT in France: MISSION study prospective phase results.

Mares P, Chevallier T, Micheletti MC, Daures JP, Postruznik D, De Reilhac P.

Service de Gynecologie Obstetrique, CHU Hopital Caremeau, Nimes, France.

OBJECTIVE: To determine the morbidity incidence associated with Hormone Replacement Therapy (HRTs) in postmenopausal women. This paper presents the results concerning the incidence of coronary heart disease (CHD). DESIGN: MISSION study started on 5 January 2004, the cutoff for data collection was June 2006 (follow-up no. 1). 'Exposed group': postmenopausal women currently on HRT, commonly prescribed in France or stopped < or =5 years previously. 'Unexposed group': never received HRT or stopped >5 years previously. RESULTS: Data were available for 4949 patients (without CHD at the beginning of the follow-up): 2693 Exposed group and 2256 Unexposed group. The incidence during follow-up no. 1 of postmenopausal CHD was not significantly different in the Exposed group (0.11%) compared with the Unexposed group (0.13%). In the Exposed group the time between start of HRT and menopause was 2.93 +/- 4.46 years in those who experienced CHD and 1.53 +/- 3.20 years in those who had no incidence of CHD (p = 0.3). CONCLUSION: In the MISSION cohort, no increased risk of CHD was found in the Exposed group compared with the Unexposed group.

 

Gynecol Endocrinol. 2008 Dec;24(12):691-5

Effect of androgens combined with hormone therapy on quality of life in post-menopausal women with sexual dysfunction.

Blümel JE, Del Pino M, Aprikian D, Vallejo S, Sarrá S, Castelo-Branco C.

Facultad Medicina, Departamento Medicina Sur, Universidad de Chile, Santiago de Chile, Chile.

AIM: To evaluate with validated instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy (AHT). DESIGN: Randomised, double-blind, double-dummy study with two parallel treatment arms. PATIENTS AND METHODS: Forty-seven healthy post-menopausal women, aged 45-64 years, were evaluated using the Female Sexual Function Index (FSFI) and the menopause-specific quality of life questionnaire (MENQOL). Of them, 40 diagnosed with sexual dysfunction were randomised (1:1) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo. After 3 months follow-up, FSFI and MENQOL questionnaires were administered for a second time. RESULTS: Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor, psychological, physical and sexual symptoms. As expected, FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly. In addition, at the end of the study, 68.7% of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI (p < 0.0001). CONCLUSIONS: Adding methyl-testosterone to hormone therapy improves quality of life and sexuality in post-menopausal women with sexual dysfunction.

 

Arch Intern Med. 2009 Jan 26;169(2):132-40.

Loop diuretic use and fracture in postmenopausal women: findings from the Women's Health Initiative.

Carbone LD, Johnson KC, Bush AJ, Robbins J, Larson JC, Thomas A, LaCroix AZ.

Department of Veterans Affairs Medical Center, Memphis, TN, USA. LCarbone@utmem.edu

BACKGROUND: The relationship of loop diuretics to bone mineral density (BMD), falls, and fractures in postmenopausal women has not been established. METHODS: We examined whether loop diuretics are associated with changes in BMD, falls, and fractures in women enrolled in the Women's Health Initiative. We included the 133,855 women (3411 users and 130,444 nonusers of loop diuretics) who were enrolled in the WHI from October 29, 1993 to December 31, 1998 and determined incident falls and fractures for a mean of 7.7 years. Women who had BMD measurements at baseline and at year 3 (300 users and 9124 nonusers of loop diuretics) were also examined. RESULTS: After adjustment for covariates, no significant association was found between ever use of loop diuretics and total (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.00-1.19), hip (HR, 1.21; 95% CI, 0.91-1.60), and clinical vertebral fractures (HR, 1.17; 95% CI, 0.92-1.48) and falls (1.02; 0.96-1.08). An increased risk was found for other clinical fractures (1.16; 1.01-133) and total fractures (1.16; 1.03-1.31) with more than 3 years' use of loop diuretics. The BMD changes were not associated with loop diuretic use. CONCLUSIONS: After adjustment for confounding variables, no significant association was found between ever use of loop diuretics and changes in BMD, falls, and fractures. Loop diuretics were used by women in poor health who were already at risk for fractures. However, prolonged use of loop diuretics was associated with higher fracture risk in postmenopausal women.

 

Appl Nurs Res. 2009 Feb;22(1):35-41.

Incidence of bone loss, falls, and fractures after Roux-en-Y gastric bypass for morbid obesity.

Berarducci A, Haines K, Murr MM.

University of South Florida Colleges of Medicine and Nursing, Tampa, FL 33612, USA. aberardu@health.usf.edu

The objectives of this study were to determine the incidence of and associated risks for falls and fractures after gastric bypass surgery for morbid obesity and to determine the clinical signs of bone loss. The sample consisted of 167 individuals at a mean age of 47 years (SD = 10). Ten participants (6%) reported a decrease in height since surgery, and 33 (20%) reported a decrease in height since they were 20 years old. Eight participants (5%) reported postoperative fractures. Twenty-three participants (13.8%) reported falling once since surgery, and 34 (20.4%) reported falling two or more times since surgery. Twelve participants reported a new diagnosis of osteoporosis postoperatively, and 1 participant reported a new diagnosis of osteopenia. Sixty-seven percent (n = 112) of the participants were never advised to undergo a bone density test postoperatively. The findings from this study suggest that bone loss is a critical issue in this patient population, with 25% (n = 42) reporting a decrease in height, 8% (n = 13) reporting a new diagnosis of osteoporosis or osteopenia, and 5% (n = 8) reporting fractures during a mean postoperative interval of 2.4 years. In addition, risk for skeletal fragility is profound in this cohort of individuals, with 34% (n = 57) indicating a history of one or more falls postoperatively. The results from this study clearly indicate a need for early recognition of bone loss in this population so that timely interventions can be initiated to prevent further loss and subsequent fractures.

 

J Sex Med. 2009 Jan;6(1):175-83

Clinically relevant changes in sexual desire, satisfying sexual activity and personal distress as measured by the profile of female sexual function, sexual activity log, and personal distress scale in postmenopausal women with hypoactive sexual desire disorder.

DeRogatis LR, Graziottin A, Bitzer J, Schmitt S, Koochaki PE, Rodenberg C.

Johns Hopkins University School of Medicine and Center for Sexual Medicine at Sheppard Pratt-Department of Psychiatry, Baltimore, MD, USA. DeRogatis@sheppardpratt.org

INTRODUCTION: Transdermal testosterone patch (TTP) treatment produced statistically significant improvements in a satisfying sexual activity (SSA), sexual desire, and personal distress in postmenopausal women suffering from hypoactive sexual desire disorder (HSDD), but clinical significance of these changes was not determined. AIM: To quantify the magnitude of change in three principal outcomes measures determined by HSDD patients as associated with the perception of meaningful benefit with TTP therapy. METHODS: The criteria for defining responders were determined using anchoring methodology and receiver operating characteristics analysis to establish minimum important differences (MIDs) in a representative subsample of 132 patients in two randomized, controlled trials in surgically menopausal women with HSDD (N = 1,094). Perceived benefit was established based upon the question "Overall, would you say that you experienced a meaningful benefit from the study patches?". These data defined responders and established MIDs for changes in sexual desire, SSA, and personal distress. The MIDs were applied to the two trials to establish responder rates in each treatment group. MAIN OUTCOME MEASURES: Changes in score that correspond to the MID for sexual desire, SSA, and personal distress, and responder rates in each treatment group based upon these values. RESULTS: Increases in frequency of SSA of greater than 1 activity/4 weeks, increases in sexual desire score of > or = 8.9, and decreases in the personal distress score of > or = 20.0 were identified as threshold improvements best able to differentiate responders and nonresponders. The responder rate was significantly higher (P < 0.001) in the testosterone group vs. placebo for all three outcomes measures (sexual desire, 50% vs. 34%; SSA, 44% vs. 30%; personal distress, 51% vs. 39%). CONCLUSIONS: Changes in sexual desire, SSA, and personal distress observed with TTP treatment in surgically menopausal women with HSDD were clinically significant and were associated with a meaningful treatment benefit.

 

J Sex Med. 2009 Jan;6(1):30-9

The effects of hypoestrogenism on the vaginal wall: interference with the normal sexual response.

Lara LA, Useche B, Ferriani RA, Reis RM, de Sá MF, de Freitas MM, Rosa e Silva JC, Rosa e Silva AC.

Ribeirão Preto School of Medicine, University of São Paulo-Department of Gynaecology and Obstetrics, Ribeirão Preto, Brazil. luciaalvess@yahoo.com.br

INTRODUCTION: The sexual response depends on the adequate function of all systems related to the genital and extra-genital organs. Physiological conditions such as menopause can interfere with sexual expression because of central and peripheral changes. Genital effects of estrogen include vaginal trophism, lubrication, and local pleasure sensation in the sexual arousal phase. Hypoestrogenism causes changes in the four layers of the vaginal wall that may result in dyspareunia and a loss in the quality of the genital arousal response. AIM: The purpose of this review is to highlight the changes in the vaginal wall caused by hypoestrogenism, its possible relationship with dyspareunia, and its repercussions for genital arousal. Treatments for hypoestrogenism are also discussed. METHODS: We evaluated the data available in PubMed (1982-2008) and surveyed the reference list for relevant studies. Two reviewers analyzed the data independently. A study was considered to be of high quality if it had all three of the following characteristics: (i) prospective design; (ii) valid data; and (iii) adequate sample size. Reviews and experimental animal studies were also considered. MAIN OUTCOME MEASURES: Normal genital morphology, hypoestrogenism and hormone replacement therapy were the focus of the studies reviewed in this paper. RESULTS: Atrophy of the vaginal wall may be associated with dyspareunia and genital sexual arousal disorder, but psychological and sociocultural aspects must also be considered. Regardless, however, local estrogen therapy is useful in improving vaginal wall trophism and, thus, in improving the sexual response. CONCLUSIONS: There are many possible alterations in the structure of the vaginal wall that are related to estrogen deficiency that may require medical intervention beyond the usual strategies used to attain adequate sexual function. Physicians should attempt to treat these alterations, and more research is needed to elucidate the physiopathology of dyspareunia and genital sexual arousal physiology.

 

J Sex Med. 2009 Jan;6(1):8-18; quiz 19-20

Testosterone replacement therapy in naturally and surgically menopausal women.

Panzer C, Guay A.

Rose Medical Center-Department of Endocrinology, Denver, Colorado, USA.

INTRODUCTION: Testosterone replacement therapy in naturally and surgically menopausal women is a complex and currently highly debated topic. Opposing guidelines for the use of testosterone exist, which create a therapeutic dilemma for clinicians confronted by severely distressed women who experience a decrease in sexual desire after surgical or natural menopause. AIM: In this review, we will address the current knowledge on androgen physiology, conditions associated with a low androgen state, and risks and benefits of androgen therapy. METHODS: An English-language Medline review was performed. MAIN OUTCOME MEASURE: Review of available literature. RESULTS: A review of normal androgen physiology in women is summarized and a brief review of prior use of androgens over the last six decades is included. The data on the use of androgen replacement in pre- and postmenopausal women is evaluated, especially its relationship to sexual functioning. Special concerns about the effect of androgens on cardiovascular disease, breast, and endometrial tissue are discussed. The balance of evidence seems to show that androgens have more of a positive effect than a negative effect in women if used properly. CONCLUSIONS: Testosterone replacement therapy for surgically and naturally menopausal women with low sexual desire can be accomplished physiologically and effectively after ruling out other medical conditions leading to low sexual desire and after proper information of the patient that testosterone therapy is not an FDA-approved medication in the United States. The majority of available data suggests that testosterone replacement in women can be used safely without increased risk of endometrial or breast cancer.

 

BMC Public Health. 2009 Jan 26;9(1):37. [Epub ahead of print

Age-specific symptom prevalence in women 35-64 years old . A population-based study.

Bardel A, Wallander MA, Wedel H, Svardsudd K.

ABSTRACT: BACKGROUND: Symptom prevalence is generally believed to increase with age. The aim of this study was to evaluate the age specific prevalence of 30 general symptoms among Swedish middle-aged women. METHODS: A cross-sectional postal questionnaire study in seven Swedish counties in a random sample of 4,200 women 35-64 years old, with 2,991 responders. Thirty general symptoms included in the Complaint Score subscale of the Gothenburg Quality of Life Instrument were used. RESULTS: Four groups of age specific prevalence patterns were identified after adjustment for the influence of educational level, perceived health and mood, body mass index, smoking habits, use of hormone replacement therapy, and use of other symptom relieving therapy. Only five symptoms (insomnia, leg pain, joint pain, eye problems and impaired hearing) increased significantly with age. Eleven symptoms (general fatigue, headache, irritability, melancholy, backache, exhaustion, feels cold, cries easily, abdominal pain, dizziness, and nausea) decreased significantly with age. Two symptoms (sweating and impaired concentration) had a biphasic course with a significant increase followed by a significant decrease. The remaining twelve symptoms (difficulty in relaxing, restlessness, overweight, coughing, breathlessness, diarrhoea, chest pain, constipation, nervousness, poor appetite, weight loss, and difficulty in urinating) had stable prevalence with age. CONCLUSIONS: Symptoms did not necessarily increase with age instead symptoms related to stress-tension-depression decreased.

 

Menopause. 2009 Jan 23. [Epub ahead of print]

Additive effect of depressed mood and vasomotor symptoms on postmenopausal insomnia.

Zervas IM, Lambrinoudaki I, Spyropoulou AC, Koundi KL, Voussoura E, Tzavara C, Verdeli H, Aravantinos L, Creatsa M, Paparrigopoulos T.

From the 1Women's Mental Health Clinic; 2IPT Unit, First Department of Psychiatry, Eginition Hospital; and 3Menopause Clinic, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Athens University Medical School, Athens, Greece; 4Department of Counseling and Clinical Psychology, Teachers College; and 5College of Physicians and Surgeons, Columbia University, New York, NY; and 6Sleep Research Unit, First Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece.

OBJECTIVE:: The aim of this study was to investigate the role of vasomotor and mood symptoms on insomnia in postmenopausal women. METHODS:: One hundred sixty-three postmenopausal women, not receiving hormone therapy, attending a menopause clinic at the University of Athens, Greece, were included in this cross-sectional study. Climacteric symptoms were assessed by Greene's scale, whereas psychological morbidity was measured by Zung Self-Assessment Depression Scale, Symptom Checklist-90-R, and Athens Insomnia Scale. RESULTS:: Vasomotor symptoms were significantly associated with insomnia (P = 0.001). When depressive symptomatology was added to the logistic regression analysis, the predictive ability of the model was significantly improved as defined by the increase in the log likelihood (P < 0.001) and the increase in the area under the receiver operating characteristic curve. CONCLUSIONS:: Insomnia in postmenopausal women attending a menopause clinic is related both to the effects of vasomotor symptoms and depressive symptomatology. Mood symptoms seem to affect sleep independently of vasomotor symptoms, suggesting that depression should be carefully assessed and treated in postmenopausal women with insomnia.

 

Menopause. 2009 Jan 21. [Epub ahead of print

A prospective study of the association between endogenous hormones and depressive symptoms in postmenopausal women.

Ryan J, Burger HG, Szoeke C, Lehert P, Ancelin ML, Dennerstein L.

From 1The University of Melbourne, Parkville, Victoria, Australia; 2Inserm U888, Montpellier, F-34093 France; 3University of Montpellier, Montpellier, F-34000 France; 4Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; and 5University of Mons, Belgium.

OBJECTIVE:: Across a woman's lifetime, variations in hormone levels are known to influence mood and well-being. Whether absolute or changes in hormone levels over time are associated with depression among postmenopausal women remains unclear. METHODS:: The Melbourne Women's Midlife Health Project is a longitudinal population-based study of women who were followed through the menopausal transition. This analysis is based on data collected from 138 postmenopausal women in years 11 and 13 of the study, who were assessed for the presence of depressive symptoms using the Center for Epidemiological Studies Depression Scale. Logistic regression models were developed to determine whether absolute or changes in hormone levels were associated with depression. RESULTS:: No significant associations were found between depressive symptoms and the absolute levels of sex hormone-binding globulin, testosterone, free androgen index, estradiol, free estradiol, or follicle-stimulating hormone (FSH). On the other hand, women with a decline in total serum estradiol over the 2-year period had a more than threefold increased risk of depressive symptoms (odds ratio, 3.5; 95% CI, 1.2-9.9). A large increase in FSH levels over this period was also associated with depressive symptoms (odds ratio, 2.6; 95% CI, 1.0-6.7). These associations remained even after adjustment for initial depression score, as well as a range of potential confounding factors. CONCLUSIONS:: Changes in estradiol and, to a lesser extent, in FSH levels are associated with an increased risk of depressive symptoms in postmenopausal women. These results further support a role for fluctuating rather than absolute hormone levels in depression in later life.