Selección de Resúmenes de Menopausia

Mayo de 2009

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

Semana del 28 de Abril al 5 de Mayo de 2009

 

Horm Metab Res. 2009 Apr 30. [Epub ahead of print

Plasma CRP Levels in Premenopausal Women with Major Depression: A 12-Month Controlled Study.

Cizza G, Eskandari F, Coyle M, Krishnamurthy P, Wright EC, Mistry S, Csako G.

1Clinical Endocrine Section, Clinical Endocrinology Branch, NIDDK, NIH, DHHS, Bethesda, MD, USA.

C-reactive protein (CRP), an inflammatory marker of cardiovascular risk, is often elevated in major depressive disorder (MDD). The magnitude and consistency of this elevation have not been previously characterized in premenopausal women with MDD. The aim of the study was to prospectively assess plasma CRP levels, body composition, endocrine and metabolic parameters, and depressive status in premenopausal women with MDD (n=77) and controls (n=41), aged 21 to 45. Women were enrolled in a 12-month, controlled study of bone turnover, the P.O.W.E.R. ( Premenopausal, Osteoporosis, Women, Al Endronate, Dep Ression) Study. Blood samples were taken at Baseline, Month 6, and Month 12. Most subjects with MDD were in clinical remission. These women tended to have consistently higher CRP levels than controls over 12 months (p=0.077). BMI was positively related to log[CRP] in women with MDD only. Nine women with MDD had CRP levels greater than 10 mg/l, a value associated with a very high cardiovascular risk. This subset was obese and had significantly higher triglycerides, total cholesterol, LDL-cholesterol, fasting insulin, and HOMA-IR than the rest of women with MDD. The variations in CRP levels over time were high (intra- and inter-individual coefficients of variations of approximately 30-50% and approximately 70-140%, respectively). No control had CRP levels greater than 10 mg/l. Depression was associated with increased plasma CRP in women with MDD. The clinical significance of abnormal plasma CRP for cardiovascular risk needs to be assessed in large prospective studies of women with depression

 

Ann Clin Biochem. 2009 May;46(Pt 3):218-21

The mean and the biological variation of insulin resistance does not differ between polycystic ovary syndrome and type 2 diabetes.

Cho LW, Jayagopal V, Kilpatrick ES, Atkin SL.

Department of Medicine University of Hull.

BACKGROUND: There is an assumption that the mean and biological variation of insulin resistance (IR) is less in polycystic ovary syndrome (PCOS), and intuitively higher in type 2 diabetes (T2DM). To test this hypothesis we compared the mean and biological variation in IR in PCOS to that of T2DM and to age- and weight-matched controls. METHODS: Twelve PCOS, 11 matched healthy women; 12 postmenopausal diet-controlled T2DM and 11 matched healthy postmenopausal women were recruited. Blood samples were collected at 4-d intervals on 10 consecutive occasions. The biological variability of IR was derived on duplicate samples. RESULTS: Mean and biological variability of HOMA-IR for PCOS did not differ from T2DM. Both measures were higher than the matched controls. There was no difference in insulin or IR measures between the body mass index matched pre- and postmenopausal women. Percentage beta cell function were 208.8%, 62.3%, 106.5% and 111.9%, respectively, in PCOS, postmenopausal women with T2DM, healthy premenopausal and healthy postmenopausal women. CONCLUSIONS: The progression from PCOS to the development of T2DM is unlikely to be due to a further increase in IR (or variability), but rather the progressive failure of pancreatic beta cells with a decrease in insulin production.

 

Menopause. 2009 Jan 16. [Epub ahead of print

An open-label randomized trial to determine the most effective regimen of vaginal estrogen to reduce the prevalence of atrophic changes reported in postmenopausal cervical smears.

Bateson DJ, Weisberg E.

From Family Planning NSW, Sydney Centre for Reproductive Health Research, Ashfield, NSW, Australia.

OBJECTIVE:: Atrophic Papanicolaou (Pap) smears from postmenopausal women may be unsatisfactory for assessment or result in a false-positive diagnosis of a cytological abnormality. We investigated the effect of vaginal estrogen treatment before the Pap test on the odds of an atrophic smear. METHODS:: An open-label randomized controlled trial was conducted to compare the proportion of atrophic Pap smears from postmenopausal women assigned to either (1) a regimen of one 25-mug vaginal estradiol tablet inserted nightly for five nights before their Pap test, (2) a single 25-mug vaginal estradiol tablet before the test, or (3) a control group with no previous estrogen administration. All smears were reread and classified as atrophic or nonatrophic at the conclusion of the study by a single cytopathologist who was blinded to the study arms. RESULTS:: One hundred fifty-four (94%) of the 164 postmenopausal women who consented to the study were included in the final analysis. Fifty-one women had received the five-night course of tablets, 50 had received one tablet, and 53 were assigned to the group with no previous estrogen use. The odds of an atrophic smear were significantly lower in women who used the five-night estrogen regimen than in women who did not use estrogen. The estimated odds ratio of an atrophic smear in the five-night regimen was 0.01 (95% CI, 0.03-0.26) compared with the no-estrogen control group. Moreover, using one tablet of estrogen had no significant effect on the likelihood of an atrophic smear compared with using none. The odds ratio of an atrophic smear in the single estrogen tablet group was 1.05 (95% CI, 0.48-2.29) compared with the no-estrogen group. CONCLUSIONS:: The odds of an atrophic smear are significantly reduced for postmenopausal women who use a five-night regimen of vaginal estrogen before their Pap test.

 

J Clin Endocrinol Metab. 2009 Apr 28. [Epub ahead of print

Low Serum Testosterone and Estradiol Predict Mortality in Elderly Men.

Tivesten A, Vandenput L, Labrie F, Karlsson MK, Ljunggren O, Mellström D, Ohlsson C.

University of Uppsala, Uppsala, Sweden.

Context: Age-related reduction of serum testosterone may contribute to the signs and symptoms of aging, but previous studies report conflicting evidence about testosterone levels and male mortality. No large prospective cohort study has determined a possible association between serum estradiol and mortality in men. Objective: The main objective was to examine the association between serum testosterone and estradiol and all-cause mortality in elderly men. Design, setting and participants: We used specific gas chromatography-mass spectrometry to analyze serum sex steroids at baseline in older men who participated in the prospective population-based MrOS Sweden cohort (n=3,014, mean 75 years of age, range 69-80). Main outcome measure: All-cause mortality by serum testosterone and estradiol levels. Results: During a mean follow-up period of 4.5 years, 383 deaths occurred. In multivariate hazards regression models, low levels (within quartile 1; versus quartiles 2-4) of both testosterone (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.29-2.12) and estradiol (HR 1.54, 95% CI 1.22-1.95) associated with mortality. A model including both hormones showed that both low testosterone (HR 1.46, 95% CI 1.11-1.92) and estradiol (HR 1.33, 95% CI 1.02-1.73) predicted mortality. Risk of death nearly doubled (HR 1.96, 95% CI 1.46-2.62) in subjects with low levels of both testosterone and estradiol compared with subjects within quartiles 2-4 of both hormones. Conclusions: Elderly men with low serum testosterone and estradiol have increased risk of mortality, and subjects with low values of both testosterone and estradiol have the highest risk of mortality.

 

Menopause. 2009 Apr 22. [Epub ahead of print]

Efficacy and safety of vaginal estriol and progesterone in postmenopausal women with atrophic vaginitis.

Chollet JA, Carter G, Meyn LA, Mermelstein F, Balk JL.

From the 1Beth Israel Deaconess Medical Center, Boston, MA; 2University of Pittsburgh Medical Center, Pittsburgh, PA; and 3Peartree Women's Healthcare, Cambridge, MA.

OBJECTIVE:: The aim of this study was to assess the efficacy and safety of intravaginal estriol and progesterone on atrophic vaginitis in postmenopausal women. METHODS:: Under a physician-sponsored Investigational New Drug application, 19 healthy postmenopausal women with atrophic vaginitis received vaginal suppositories containing estriol (1 mg) and progesterone (30 mg). The participants were instructed to insert one suppository intravaginally once daily for 2 weeks and thrice weekly for a total of 6 months. Vaginal pH, Vaginal Maturation Index, urinalysis, self-reported vaginal dryness, menopausal quality of life, and serum estriol and progesterone levels were measured at enrollment and after 3 and 6 months of suppository use. Endometrial biopsies were obtained at enrollment and at 6 months. After 2 weeks of therapy, six participants had serum estriol and progesterone measured. RESULTS:: The Vaginal Maturation Index, vaginal pH, and vaginal dryness rating improved significantly at 3 and 6 months compared with baseline. Menopausal quality of life scores improved significantly in all domains, with the sexual subscale showing the most improvement. There were no cases of endometrial hyperplasia after 6 months of suppository use. Serum preinsertion estriol at week 2 and months 3 and 6 were similar to baseline levels. Serum preinsertion progesterone increased but returned to baseline preinsertion levels at month 6, and preinsertion levels were significantly less at month 6 compared with month 3. CONCLUSIONS:: Intravaginal administration of a combination estriol and progesterone agent to women with atrophic vaginitis may represent a safe and effective alternative to systemic hormone replacement, although this study was not adequate to provide proof of efficacy given that it was uncontrolled.

 

Int J Gynaecol Obstet. 2009 Apr 24. [Epub ahead of print

Compared effects of surgical and natural menopause on climacteric symptoms, osteoporosis, and metabolic syndrome.

Ozdemir S, Celik C, Görkemli H, Kıyıcı A, Kaya B.

Department of Gynecology and Obstetric, Meram Medical Faculty, Selçuk University, Konya, Turkey.

OBJECTIVE: To compare the effects of surgical (ie, earlier) and natural (ie, later) menopause on climacteric symptoms, osteoporosis, and metabolic syndrome. METHOD: The study was conducted with 94 women who underwent hysterectomy and bilateral oophorectomy and 95 women who were older than 40 years and in natural menopause. None had received hormone theraphy or osteoporosis treatment. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III. RESULTS: The rates of hot flushes (P=0.001), sweating (P=0.001), poor memory (P=0.04), change in sexual desire (P=0.04), and osteoprosis (diagnosed in the hip bone, P=0.005) were significantly higher among the women in surgical menopause, but the rate of metabolic syndrome was similar in the 2 groups (47.8% and 40%; P=0.28). CONCLUSION: Compared with natural menopause, surgical menopause was found to be associated with highter rates of climacteric symptoms and osteoporosis but not of of metabolic syndrome.

 

Brain Res. 2009 Jan 19. [Epub ahead of print

Effects of Two Years of Conjugated Equine Estrogens on Cholinergic Neurons in Young and Middle-Aged Ovariectomized Monkeys.

Browne C, Tobin JR, Voytko ML.

Department of Biology, Wake Forest University, Winston-Salem, North Carolina, ZIP, United States.

The effect of estrogen on the number and size of cholinergic neurons in the basal forebrain was examined in surgically menopausal young and middle-aged cynomolgus monkeys. Young and middle-aged female monkeys were ovariectomized and treated with conjugated equine estrogens (Premarin) at doses that are equivalent to those currently prescribed to postmenopausal women. In the medial septum/diagonal band (MS/DB), no effect of treatment with Premarin was observed in the cholinergic neurons in either ovariectomized young or middle-aged monkeys. However, the number and size of cholinergic neurons in the MS/DB of middle-aged monkeys was greater than that in the young monkeys. In the nucleus basalis of Meynert (NBM) of middle-aged monkeys, the number of cholinergic neurons in the intermediate region (Ch4i) was greater in Premarin-treated monkeys as compared to controls and numbers of neurons in this region were greater at higher levels of estrogen. No effects of estrogen were observed in other NBM regions in the middle-aged monkeys and the size of cholinergic neurons was unaffected by Premarin. These findings suggest that treatment with Premarin has selective beneficial effects on cholinergic neurons in the basal forebrain but that these effects are both age and region specific.

 

Maturitas. 2009 Apr 23. [Epub ahead of print]

Use of calcium supplements and the risk of coronary heart disease in 52-62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study.

Pentti K, Tuppurainen MT, Honkanen R, Sandini L, Kröger H, Alhava E, Saarikoski S.

Kuopio University Hospital, Department of Obstetrics and Gynecology, FIN-70211, Kuopio, Finland.

BACKGROUND: To analyse prospectively the effect of calcium or calcium+D supplementation on coronary heart disease (CHD) in 52-62-year-old women. METHODS AND RESULTS: 10,555 52-62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994-2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Cox's proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium+D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium+D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02-1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium+D supplements was 1.26 (95% CI 1.01-1.57). CONCLUSIONS: Calcium or calcium+D supplementation appears to increase the risk of CHD among women before old age.

 

Semana del 6 al 12 de Mayo de 2009

 

Horm Metab Res. 2009 Apr 30. [Epub ahead of print

Plasma

Menopause. 2009 May 6. [Epub ahead of print]

Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women.

Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, et al.

Laval University Hospital Research Center and Laval University, Quebec, Canada

OBJECTIVE:: The objective of this study was to provide evidence that the transformation of DHEA into both androgens and/or estrogens locally in cells of the three layers of the vagina (epithelium, lamina propria, and muscularis) would have effects of greater impact, including effects on sexual function, than only effects on superficial epithelial cells as achieved with estrogens. METHODS:: This prospective, randomized, double-blind, and placebo-controlled phase III clinical trial has evaluated the effect of daily local intravaginal application of Prasterone (dehydroepiandrosterone; DHEA) for 12 weeks on the domains of sexual dysfunction, namely, desire/interest, arousal, orgasm, and pain at sexual activity, in 216 postmenopausal women with moderate to severe symptoms of vaginal atrophy. RESULTS:: A time- and dose-dependent improvement of the four domains of sexual function was observed. At the 12-week time interval, the 1.0% DHEA dose led, compared with placebo, to 49% (P = 0.0061) and 23% (P = 0.0257) improvements of the desire domains in the Menopause Specific Quality of Life and Abbreviated Sex Function questionnaires, respectively. Compared with placebo, the Abbreviated Sex Function arousal/sensation domain was improved by 68% (P = 0.006), the arousal/lubrication domain by 39% (P = 0.0014), orgasm by 75% (P = 0.047), and dryness during intercourse by 57% (P = 0.0001). CONCLUSIONS:: By a local action in the vagina, DHEA applied daily at doses at which serum steroids remain well within normal postmenopausal values exerts relatively potent beneficial effects on all four aspects of sexual dysfunction. Such data indicate that combined androgenic/estrogenic stimulation in the three layers of the vagina exerts important beneficial effects on sexual function in women without systemic action on the brain and other extravaginal tissues.

 

Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1531-7

Colorectal Cancer in Relation to Postmenopausal Estrogen and Estrogen Plus Progestin in the Women's Health Initiative Clinical Trial and Observational Study.

Prentice RL, Pettinger M, Beresford SA, Wactawski-Wende J, Hubbell FA, Stefanick ML, Chlebowski RT.

Director, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

BACKGROUND: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women's Health Initiative (WHI) estrogen plus progestin-randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast, the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants and METHODS: Postmenopausal women ages 50 to 79 years at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial, respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review. RESULTS: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53-1.20) for estrogen and 1.15 (0.74-1.79) for estrogen plus progestin, with, respectively, 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period. CONCLUSION: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up.

 

Menopause. 2009 May 6. [Epub ahead of print]

Acupuncture for vasomotor menopausal symptoms: a systematic review.

Cho SH, Whang WW.

From the Hospital of Korean Medicine, Kyung Hee University Medical Center, Seoul, Korea.

OBJECTIVE:: The aim of this study was to critically assess whether acupuncture therapy reduces vasomotor menopausal symptoms and to evaluate the adverse effects of acupuncture therapy on the basis of the results of randomized controlled trials (RCTs). METHODS:: Nineteen electronic databases, including English, Korean, Japanese, and Chinese databases, were systematically searched for RCTs in which acupuncture was used to reduce vasomotor menopausal symptoms before July 2008. There were no language restrictions. The methodological quality of the eligible studies was assessed using the categories provided by the Menstrual Disorders and Subfertility Review Group. RESULTS:: Eleven studies, which included a total of 764 individual cases, were systematically reviewed. The methodological quality of the trials varied substantially. Six trials compared acupuncture treatment to sham or placebo acupuncture. Only one study using a nonpenetrating placebo needle found a significant difference in the severity outcomes of hot flashes between groups (mean difference, 0.48; 95% CI, 0.05-0.91). Five studies reported a reduced frequency of hot flashes within groups; however, none found a significant difference between groups. An analysis of the outcomes of the trials that compared acupuncture with hormone therapy or oryzanol for reducing vasomotor symptoms showed that acupuncture was superior. Three RCTs reported minimal acupuncture-related adverse events. CONCLUSIONS:: There is no evidence from RCTs that acupuncture is an effective treatment in comparison to sham acupuncture for reducing menopausal hot flashes. Some studies have shown that acupuncture therapies are better than hormone therapy for reducing vasomotor symptoms. However, the number of RCTs compared with a nonpenetrating placebo control needle or hormone therapy was too small, and the methodological quality of some of the RCTs was poor. Further evaluation of the effects of acupuncture on vasomotor menopausal symptoms based on a well-controlled placebo trial is therefore warranted.

 

Curr Opin Rheumatol. 2009 May 6. [Epub ahead of print]

Denosumab update.

Lewiecki EM.

New Mexico Clinical Research & Osteoporosis Center, Albuquerque, New Mexico, USA.

PURPOSE OF REVIEW: Denosumab is an investigational fully human monoclonal antibody to receptor activator of nuclear factor kappaB ligand, an essential mediator of osteoclastic bone resorption. Receptor activator of nuclear factor kappaB ligand plays a major role in the pathogenesis of postmenopausal osteoporosis, structural damage in rheumatoid arthritis, and bone loss associated with other skeletal disorders. This is a review of recent clinical data on the efficacy and safety of denosumab for the treatment of postmenopausal osteoporosis and rheumatoid arthritis. RECENT FINDINGS: Denosumab reduces bone turnover markers and increases bone mineral density in postmenopausal women with low bone mineral density, reduces fracture risk in women with postmenopausal osteoporosis, and inhibits structural damage in patients with rheumatoid arthritis when added to ongoing methotrexate treatment. In postmenopausal women with low bone mineral density, denosumab is associated with a greater increase in bone mineral density and greater reduction in bone turnover markers compared with alendronate; when women treated with alendronate are switched to denosumab, there is an increase in bone mineral density that is greater than in those continuing alendronate. Adverse events and serious adverse events, including infections and malignancy, are generally similar in patients treated with denosumab compared with those receiving placebo or alendronate. SUMMARY: Denosumab is a promising therapeutic agent for the management of postmenopausal osteoporosis and rheumatoid arthritis.

 

Menopause. 2009 May-Jun;16(3):559-65

Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.

Schaefers M, Muysers C, Alexandersen P, Christiansen C.

Bayer Schering Pharma AG, Berlin, Germany; and Center for Clinical and Basic Research, Byvej, Denmark.

OBJECTIVE:: Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis. METHODS:: This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters. RESULTS:: In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years. CONCLUSIONS:: Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.

 

Prescrire Int. 2008 Dec;17(98):243

Progestagen-only treatment before menopause: increased risk of breast cancer.

[No authors listed]

(1) A prospective cohort study (E3N) conducted in France included approximately 100 000 women aged 40 to 64 years who were regularly questioned about their use of hormone and other treatments. More than 70 000 of the 100 000 women responded to the questionnaire. The study showed an increase in breast cancer among women using an oral progestagen alone for more than 4.5 years before menopause (low-dose progestagens were excluded from the study); (2) The risk of developing breast cancer was approximately 1.5 times higher than among women who had not taken progestagen. After progestagen discontinuation, regardless of treatment duration, the risk of breast cancer dropped to levels similar to those of non-users; (3) There is widespread use of progestagen-only products before menopause in spite of the lack of robust evidence concerning their risk-benefit balance, particularly with long-term treatment. It is advisable to evaluate drugs before their use provokes adverse reactions in patients.

 

Menopause. 2009 May 5. [Epub ahead of print]

Vasomotor symptoms and mortality: the Rancho Bernardo Study.

Svartberg J, von Mühlen D, Kritz-Silverstein D, Barrett-Connor E.

Department of Medicine, University Hospital of North Norway, Tromsø, Norwayla; Rancho Bernardo, CA.

OBJECTIVE:: The purpose of this study was to examine the associations of vasomotor symptoms with risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in community-dwelling older women, with a mean age of 69 years. METHODS:: This prospective population-based study included 867 postmenopausal women who provided lifestyle and menopause-related history at the 1984 to 1987 visit of the Rancho Bernardo Study and answered a 1989 mailed questionnaire on menopause and vasomotor symptoms. Ninety-eight percent were followed for vital status through July 2004. RESULTS:: Overall, 73% reported hot flashes, of whom 39% also reported night sweats. During the 11.5-year average follow-up, there were 405 deaths, of which 194 were attributed to CVD and 71 to CHD. Hot flashes alone were not associated with all-cause mortality, but women who, in addition to hot flashes, also had night sweats had an almost 30% (hazard ratio [HR], 0.72; 95% CI, 0.55-0.94) lower all-cause mortality risk compared with women without this symptom, independent of body mass index, past or current use of estrogen or progestin, physical exercise, and smoking habit. There was a similar lower risk of CVD and CHD mortality in women with night sweats when adjusted for past or current use of estrogen or progestin (HR, 0.62; 95% CI, 0.42-0.92 and HR, 0.51; 95% CI, 0.26-0.99, respectively). These associations were independent of hormone use but were no longer significant after adjusting for body mass index, physical exercise, and smoking. CONCLUSIONS:: Reported night sweats at menopause are associated with reduced risk of death over the following 20 years, independent of multiple risk factors including past or current use of postmenopausal estrogen therapy.

 

J Bone Miner Res. 2009 May 6. [Epub ahead of print]

A 5-Year Cohort Study of the Effects of High Protein Intake on Lean Mass and Bone Mineral Content in Elderly Postmenopausal Women.

Meng X, Zhu K, Devine A, Kerr DA, Binns CW, Prince RL.

Abstract Long term effects of high dietary protein intake on muscle and bone structure in the elderly are not clear. The aim of this study was to investigate the relationship between baseline protein intake and lean mass and bone mineral content (BMC) five years later in a cohort of elderly postmenopausal women. A total of 862 community-dwelling women aged 75 +/- 3 years provided baseline data including nutrient intake assessed by a food frequency questionnaire. At five years upper arm muscle area (UAMA) and body composition using dual-energy X-ray absorptiometry were measured. Baseline protein intake was 81 +/- 28 g/d (1.2 +/- 0.4 g/kg/d) contributing 19 +/- 3 % of the total energy intake. There were positive correlations between baseline protein intake and whole body and appendicular bone-free lean mass and BMC (r = 0.14-0.18, P < 0.001) and UAMA (r = 0.08, P < 0.05). Compared to those in the lowest tertile of protein intake (< 66 g/d), women in the top tertile (> 87 g/d) had 5.4-6.0 % higher whole body and appendicular lean mass and UAMA and 5.3-6.0 % higher whole body and appendicular BMC. These effects remained after adjusted for potential confounders. However, the effect on BMC disappeared after further adjustment for lean mass. This study demonstrates that a high protein intake is associated with long term beneficial effects on muscle mass and size and bone mass in elderly women. The protein effect on bone may be partly mediated via its effects on muscle.

 

Climacteric. 2009 May 2:1-9. [Epub ahead of print

Effects of estrogen therapy on age-related differences in gray matter concentration.

Robertson D, Craig M, van Amelsvoort T, Daly E, Moore C, Simmons A, Whitehead M, Morris R.

Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK.

Objective Previous studies suggest that estrogen therapy (ET) either improves or has a neutral effect on the structural integrity of neural tissue in postmenopausal women. The inconsistency in the findings of previous studies is likely to be due to a variety of methodological factors. In this study, we attempted to overcome many of these factors. Method We used magnetic resonance imaging and voxel-based morphometry to study the long-term effects of ET commenced immediately postmenopause on age-related differences in (1) normalized lobar brain volumes and (2) regional gray and white matter concentrations. We included 61 healthy women: 23 young, 19 postmenopausal long-term ET users (who had started ET around the time of menopause) and 19 postmenopausal ET never-users. Results We report that ET users did not differ significantly from never-users in age, duration of menopause, general intelligence, mnemonic function or apolipoprotein E allele frequency. Compared to young women, both ET users and never-users had significantly smaller normalized volumes of whole brain and left and right frontal lobes, but ET users did not differ significantly from never-users in bulk brain volumes. Compared to young women and ET users, never-users had significantly lower gray matter concentration bilaterally in orbitofrontal cortices and cerebellum, right inferior frontal and precentral cortices, and left paracentral cortex. Conclusion These findings suggest that initiation of ET around the time of menopause may modulate age-related differences in regional gray matter concentration. The functional significance of our findings remains unknown.

 

Eur J Obstet Gynecol Reprod Biol. 2009 May 2. [Epub ahead of print

Sleep in post-menopausal women: Differences between early and late post-menopause.

Hachul H, Bittencourt LR, Soares JM Jr, Tufik S, Baracat EC.

Department of Gynaecology, Universidade Federal de São Paulo, Brazil; Department of Psychobiology, Center for Sleep Medicine, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.

OBJECTIVE: The aim of this study was to evaluate the differences in sleep between women of early and late post-menopause. STUDY DESIGN: Thirty post-menopausal women who came to the climacteric service of their own volition were selected. Fourteen were in early post-menopause (less than 5 years after menopause), and sixteen were in late post-menopause (more than 5 years since menopause). None of the women were suffering from any other clinical diseases. Participants had no previous history of hormone therapy or hypnotic drug use. These patients were not previously selected with regard to any sleep complaints. All participants answered a sleep questionnaire and underwent a polysomnography recording. RESULTS: Subjective complaints included body pain, bruxism, anxiety, depression, lack of concentration, and sleepiness (measured by the Epworth Sleepiness Scale). These complaints were more frequent in the late post-menopause group. In contrast, complaints of memory impairment were more frequent in the early post-menopause group (p</=0.05). Polysomnographic findings revealed no differences between the early and late post-menopause groups. CONCLUSIONS: Although early menopause is associated with several symptoms, complaints related to sleep were higher in the late post-menopausal group.

 

Semana del 13 al 26 de Mayo de 2009

 

Osteoporos Int. 2009 May 21. [Epub ahead of print

The effect of calcium supplementation on bone loss in 32 controlled trials in postmenopausal women.

Nordin BE.

Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia,

christopher.nordin@imvs.sa.gov.au.

In 32 controlled trials of calcium supplementation (700-2000 mg) in 3,169 postmenopausal women, mean bone loss in the controls was -1.07% p.a. and in the treated subjects -0.27% p.a. (P for difference <0.001). The effect was similar at all measured sites and at all doses of 700 mg or more but became weaker after 4 years. INTRODUCTION: We have reviewed 32 trials of calcium supplementation in 3,169 postmenopausal women. METHODS: We found 24 publications reporting 32 controlled trials lasting at least 1 year, which provided annual percentage changes in bone mass or density at one or more sites in the calcium-treated and control subjects. RESULTS: The median calcium supplement was 1,000 mg, median duration of the trials 2 years and total number of sites measured 79. The average of the mean rates of change in bone mass or density was -1.07% p.a. (P < 0.001) in the controls and -0.27% p.a. (ns) in the treated subjects (P for difference < 0.001). The effect of calcium was much the same at all measured sites (forearm/hand, proximal femur, spine, and total body and others). Supplements of less than 700 mg were not effective, but there was no significant beneficial effect of higher doses. There was significantly faster bone loss at total calcium intakes below 1,150 mg than on intakes over 1,350 mg. The effect of calcium appeared to be lost after 4 years of treatment. CONCLUSION: Calcium supplementation of about 1,000 mg daily has a significant preventive effect on bone loss in postmenopausal women for at least 4 years.

 

Osteoporos Int. 2009 May 21. [Epub ahead of print]

Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis.

Cotté FE, Fardellone P, Mercier F, Gaudin AF, Roux C.

CERMES, IFR69, INSERM U750, National Institute of Health and Medical Research, Villejuif, France.

This primary care database survey evaluated whether osteoporotic women treated with bisphosphonates were more adherent to monthly than to weekly treatment. Both compliance (medication possession ratio [MPR]) and persistence (time to discontinuation) were superior in the monthly ibandronate treatment group. Better control of fracture risk may thus be achieved using monthly treatment regimens. INTRODUCTION: Treatment adherence in osteoporosis is poor. The objective of this study was to evaluate whether monthly bisphosphonate treatment provided superior adherence than weekly treatment. METHODS: We analysed medical claims from a national prescription database (Thales). All women aged >45 years receiving a first prescription of monthly ibandronate or weekly bisphosphonates in 2007 were included. Treatment adherence was monitored from initial prescription until January 2008. Compliance was measured by the MPR and persistence by the time from treatment initiation to discontinuation. Multivariate analysis was used to identify variables independently associated with adherence. RESULTS: Twelve-month persistence rates were 47.5% for monthly ibandronate and 30.4% for weekly bisphosphonates. Compliance was significantly higher in the monthly cohort (MPR = 84.5%) than in the weekly cohort (MPR = 79.4%). After adjustment for potential confounding variables, women with monthly regimens were 37% less likely to be non-persistent (HR = 0.63 [0.56-0.72]) and presented a 5% higher mean MPR (84.5% versus 79.3%, p < 0.001) than women with weekly regimens. Other major factors associated with improved adherence were previous densitometry and calcium or vitamin D supplementation (p < 0.01). CONCLUSIONS: Adherence to bisphosphonates may be superior for monthly treatment than for weekly treatment and may thus provide improved fracture protection.

 

Menopause. 2009 May 19. [Epub ahead of print

Sexual dysfunction in middle-aged women: a multicenter Latin American study using the Female Sexual Function Index.

Blümel JE, Chedraui P, Baron G, Belzares E, Bencosme A, Calle A, Espinoza MT, Flores D, Izaguirre H, Leon-Leon P, Lima S, Mezones-Holguin E, Monterrosa A, Mostajo D, Navarro D, Ojeda E, Onatra W, Royer M, Soto E, Vallejo S, Tserotas K; for the Collaborative Group for Research of the Climacteric in Latin America (REDLINC). From the Collaborative Group for Research for the Climacteric in Latin America (REDLINC). OBJECTIVE:: The purpose of this study was to assess the prevalence of sexual dysfunction (SD) and associated risk factors among middle-aged Latin American women using one validated instrument. METHODS:: The Female Sexual Function Index (FSFI) was applied to 7,243 healthy women aged 40 to 59 years who were users of 19 healthcare systems from 11 Latin American countries. An itemized questionnaire containing personal and partner sociodemographic data was also filled out. RESULTS:: Mean +/- SD age of surveyed women was 49.0 +/- 5.7 years, with 11.6 years of schooling on average. There were 55.1% of women who were married, 46.8% who were postmenopausal, 14.1% who used hormonal therapy (HT), and 25.6% who were sexually inactive. Among those who were active (n = 5,391), the mean +/- SD total FSFI score was 25.2 +/- 5.9 and 56.8% of them presented SD (FSFI total score </=26.55), with a prevalence varying from 21.0% to 98.5% depending on the center. Centers were grouped in terciles (according to mean +/- SD prevalence). The tercile with higher SD prevalence (86.4%) compared with that with lower SD prevalence (32.2%) had significantly older women (49.5 +/- 5.3 vs 48.0 +/- 5.6 y) with a higher rate of vaginal dryness (60.4% vs 40.8%) and older partners (53.0 +/- 6.9 vs 50.2 +/- 7.5 y). Similarly, there was a significantly higher rate of married (68.5% vs 63.1%), postmenopausal (49.7% vs 39.3%), and HT-using women (23% vs 9.2%). There were no differences in regard to their health perception, history of oophorectomy, rape, and partner SD rate (27% vs 26.2%). The total FSFI score was significantly lower in the tercile with higher SD prevalence (22.0 +/- 5.0 vs 27.5 +/- 5.4). Logistic regression analysis was used to determine the odds ratios (95% CIs) for the main risk factors associated with SD among those who were sexually active: bad lubrication, 3.86 (3.37-4.43); use of alternative menopausal therapies, 2.13 (1.60-2.84); partner SD, 1.89 (1.63-2.20); older women (>48 y), 1.84 (1.61-2.09); bladder problems, 1.47 (1.28-1.69); HT use, 1.39 (1.15-1.68); negative perception of female health status, 1.31 (1.05-1.64); and being married, 1.22 (1.07-1.40). Protective factors were higher educational level (women), partner faithfulness, and access to private healthcare. CONCLUSIONS:: The prevalence of SD in this middle-aged Latin American series was found to be high, varying widely in different populations. A decrease in vaginal lubrication was the most important associated risk factor. Differences in the prevalence of risk factors among the studied groups, several of which are modifiable, could explain the variation of SD prevalence observed in this study.

 

Menopause. 2009 May 19. [Epub ahead of print]

Body mass index, urinary incontinence, and female sexual dysfunction: how they affect female postmenopausal health.

Pace G, Silvestri V, Gualá L, Vicentini C.

From the Departments of 1Surgical Sciences and 2Health Sciences, University of L'Aquila, L'Aquila; and 3Department of Urology, Mazzini Hospital, Teramo, Italy.

OBJECTIVE:: The aim of this study was to evaluate the relationship between body mass index (BMI) and female sexual dysfunction (FSD) among perimenopausal and postmenopausal women with urinary incontinence (UI). METHODS:: From 2005 to 2008, we enrolled 208 consecutive women affected by UI; all underwent a comprehensive history including two validated questionnaires, physical examination, and urodynamic evaluation. Based on BMI, participants were grouped into normal weight, overweight, and obese. RESULTS:: A total of 158 participants completed both questionnaires (76% response rate); 41 (26%) were normal weight, 73 (46%) were overweight, and 44 (28%) were obese. The increasing Urogenital Distress Inventory score had a direct correlation with age (P < 0.01), year of menopause onset (P < 0.05), and BMI (P < 0.01). FSD was diagnosed in 97 women (61%): 31 (32%) with hypoactive sexual desire, 20 (21%) with sexual arousal disorder, 7 (7%) with orgasmic deficiency, and 39 (40%) with sexual pain disorder. BMI greater than 30 kg/m was independently associated with an increased risk of FSD (odds ratio [OR], 2.02) and UI (OR, 2.03). With adjustment for BMI, the OR for FSD was 1.22 for overweight women and 1.56 for obese women, with respect to healthy participants. The total Female Sexual Function Index score correlated with BMI (r = -0.82, P = 0.0001); in particular, arousal (r = -0.82), orgasm (r = -0.72), lubrication (r = -0.61), and satisfaction (r = -0.63, all P < 0.001) showed an inverse correlation with BMI, whereas desire and pain did not. CONCLUSIONS:: Increased BMI early in menopause represents a risk both for UI and for sexual dysfunction. Weight control has an essential role in postmenopause and should be considered early in perimenopause to safeguard female quality of life as well as to prevent or improve UI and female sexual dysfunction symptoms.

 

Hum Reprod Update. 2009 May 20. [Epub ahead of print]

Female contraception over 40.

The ESHRE Capri Workshop Group.

BACKGROUND The majority of women 40-49 years of age need an effective method of contraception because the decline in fertility with age is an insufficient protection against unwanted pregnancy. Although pregnancy is less likely after the age of 40 years, the clinical and social consequences of an unexpected pregnancy are potentially detrimental. No contraceptive method is contraindicated by advanced reproductive age alone; thus there is a need to discuss the effectiveness, risks and non-contraceptive benefits of all family planning methods for women in this age group. METHODS MEDLINE searches were done by topic (epidemiology, age and reproduction, sexual function, delayed childbearing and specific contraceptive methods). The topic summaries were presented to the Workshop Group and omissions or disagreements were resolved by discussion. RESULTS The decline in fecundity in the fifth decade is insufficient for contraceptive purposes. Thus a family planning method is needed. Sterilization is by far the most common method in several countries. Copper intrauterine devices and hormone intrauterine systems have similar effectiveness, with fewer than 1% failures in the first year of typical use. Special considerations in this age group include the frequency of menstrual irregularity, sexual problems and the possibility of menopausal symptoms, all of which may respond to hormonal methods of contraception. CONCLUSIONS Women should be advised to continue with a contraceptive method until they have reached the menopause with its natural state of sterility.

 

J Womens Health (Larchmt). 2009 May 20. [Epub ahead of print]

Association of Oxidative Stress, Iron, and Centralized Fat Mass in Healthy Postmenopausal Women.

Crist BL, Alekel DL, Ritland LM, Hanson LN, Genschel U, Reddy MB.

1 Department of Food Science and Human Nutrition, Iowa State University , Ames, Iowa.

Abstract Objective: Centralized adiposity, insulin resistance, excess iron, and elevated oxidative stress place postmenopausal women at risk for atherosclerotic cardiovascular disease (CVD). The objective of this study was to determine the relationship among excess iron, oxidative stress, and centralized fat mass in healthy postmenopausal women. Methods: The parent project recruited healthy women for a randomized, double-blind, clinical trial designed to examine the effect of soy isoflavones on bone. At baseline (n = 122), we measured three antioxidant enzymes, iron status indices (serum ferritin among others), oxidative stress indices (oxidized low-density lipoprotein [oxLDL], urinary isoprostanes [PGF(2alpha)], protein carbonyls, DNA damage), and waist, hip, and thigh fat mass using dual-energy x-ray absorptiometry (DXA). We calculated insulin resistance using the homeostasis model assessment (HOMA). Multiple regression analysis was used to determine the CVD risk factors that contributed to oxidative stress and centralized fat mass (waist + hip/thigh = AndGynFM ratio). Results: Almost 14% (p < 0.0005) of the variability in oxLDL was accounted for by AndGynFM ratio (6.1%, p < 0.0005), age (4.0%, p = 0.012), and serum iron (2.8%, p = 0.053). Similarly, 16% (p < 0.0001) of the variability in PGF(2alpha) was accounted for by the AndGynFM ratio (4.8%, p = 0.011), HOMA (3.9%, p = 0.021), and serum iron (2.7%, p = 0.054). We accounted for 33% (p </= 0.0001) of the variability in AndGynFM ratio by high-density lipoprotein cholesterol (HDL-C) (4.3%, p = 0.008), ferritin (4.9%, p = 0.005), HOMA (4.5%, p = 0.006), oxLDL (2.6%, p = 0.04), and PGF(2alpha) (3.0%, p = 0.025). Conclusions: Our study suggests that reducing centralized fat mass and maintaining a favorable lipid profile, antioxidant status, and iron status all may be important in protecting postmenopausal women from atherosclerotic CVD.

 

Menopause. 2009 May 15. [Epub ahead of print]

Vasomotor symptoms usually reappear after cessation of postmenopausal hormone therapy: a Swedish population-based study.

Lindh-Åstrand L, Brynhildsen J, Hoffman M, Hammar M.

From the 1Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine; and 2Division of Drug Research, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

OBJECTIVE:: The purpose of this study was to investigate the extent of reappearance of vasomotor symptoms after cessation of postmenopausal hormone therapy (HT) in women who started HT because of hot flashes. METHODS:: A cross-sectional postal survey was conducted. A validated questionnaire was sent to all women 53 to 54 years old living in Linköping, Sweden (n = 1,733), including questions about menopause, HT, and vasomotor symptoms. Pearson's chi test and logistic regression were used for statistical analyses. RESULTS:: Response rate after one reminder was 77.3%. After omitting incomplete answers, 72.9% remained for analysis. In all women, 319 (25.3%) were current users of HT, 242 (19.2%) were previous users, and 702 (55.6%) were never-users. Of the 242 previous users, 165 (69%) women stated that they had vasomotor symptoms before starting HT. Vasomotor symptoms recurred after cessation of HT in 143 (87%) of these 165 women. We found no significant difference in symptom recurrence in comparisons of the three groups based on usage of HT for 0 to 1, 2 to 4, or 5 years or more. CONCLUSIONS:: Most women who had vasomotor symptoms when they initiated HT reported recurrence of symptoms after cessation of HT (87%), although the flashes were usually reported to be less frequent and bothersome than they were before HT. Effective and safe treatment approaches for women with recurrence of vasomotor symptoms are needed.

 

Eur J Endocrinol. 2009 May 15. [Epub ahead of print]

Long term hormone replacement therapy preserves bone mineral density in Turner syndrome.

Cleeman L, Hjerrild B, Lauridsen A, Heickendorff L, Christiansen J, Mosekilde L, Gravholt CH.

L Cleeman, Pediatric Unit, Hilleroed Hospital, Hilleroed, Denmark.

Context: Reduced bone mineral density (BMD) and increased risk of fractures are present in many women with TS. Objective: Examine longitudinal changes in BMD in TS and relate changes to biochemical parameters. Design: Prospective, pragmatic, observational study. Examinations at baseline and follow-up (5.9 +/- 0.7 years). Setting: Tertiary hospital. Participants: 54 women with TS (43.0 +/- 9.95 yr). Interventions: Hormone replacement therapy and calcium and vitamin D supplementation. Main Outcome Measures: Bone mineral density (BMD; grams/ square centimetre) measured at lumbar spine, hip and the non-dominant forearm. Bone formation and resorption markers, sex hormones, IGF-I and maximal oxygen uptake. Results: At follow-up forearm BMD, radius ultradistal BMD and hip BMD remained unchanged, radius 1/3 BMD declined (0.601+/-0.059 vs. 0.592+/-0.059, p= 0.03), while spine BMD increased (0.972+/-0.139 vs. 1.010+/-0.144, p<0.0005). Bone formation markers did not change over time in TS. Bone resorption markers decreased over time in TS. Testosterone, IGF-I and maximal oxygen uptake was significantly reduced in TS. Conclusion: Longitudinal changes in BMD in TS were slight. BMD can be maintained at most sites in well-informed women with TS, being encouraged to maintain a healthy life-style including HRT and intake of calcium and vitamin D.

 

Ann Clin Psychiatry. 2009 Apr-Jun;21(2):70-6

Escitalopram reduces hot flashes in nondepressed menopausal women: A pilot study.

Defronzo Dobkin R, Menza M, Allen LA, Marin H, Bienfait KL, Tiu J, Howarth J.

Department of Psychiatry, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA. dobkinro@umdnj.edu

BACKGROUND: Hot flashes are one of the most troubling manifestations of menopause, affecting about 80% of women. Due to recent controversies about hormone replacement therapy, many women seek alternative treatments. The use of antidepressants to treat hot flashes and other menopausal symptoms has been an active area of investigation. However, the majority of past research in this area has included women with significant medical or psychiatric histories that may influence treatment response. This was the first study to examine the impact of escitalopram on hot flashes, mood, sleep, and quality of life in a sample of healthy nondepressed menopausal women. METHODS: This study enrolled 25 menopausal women who had no significant psychiatric or medical history. All women were treated with escitalopram (10 to 20 mg flexibly dosed) for 8 weeks. The active treatment phase was preceded by a single-blind placebo lead-in period. RESULTS: Over the course of the study, women reported significant decreases in both hot flash frequency and severity as well as improvements in dysphoria, anxiety, quality of life, and sleep. CONCLUSION: These preliminary findings suggest that escitalopram may be a feasible and effective option for treating hot flashes and other menopausal symptoms in healthy women who might not ordinarily consider antidepressant treatment.

 

Menopause. 2009 May 19. [Epub ahead of print]

Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women.

Bachmann GA, Schaefers M, Uddin A, Utian WH.

From the 1Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ; 2Bayer Schering Pharma AG, Berlin, Germany; 3Bayer HealthCare Pharmaceuticals, Inc., Montville, NJ; and 4Rapid Medical Research, Cleveland, OH.

OBJECTIVE:: The aim of this study was to investigate the effectiveness of microdose transdermal 17beta-estradiol (E2) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms. METHODS:: This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline, from a previous randomized, double-blind, placebo-controlled, multicenter study of 425 healthy, symptomatic, postmenopausal women. Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week. Effects on coprimary efficacy variables have been reported previously. Participants received low-dose transdermal E2 plus levonorgestrel (n = 43; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel), microdose E2 (n = 42; nominal delivery 0.014 mg/d), or placebo (n = 36) for 12 weeks. Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index, the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12, and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy. RESULTS:: Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy. There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index. CONCLUSIONS:: Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome.

 

 

Semana del 27 de Mayo al 2 de Junio de 2009

 

Climacteric. 2009 May 25:1-8. [Epub ahead of print]

Micro-dose transdermal estradiol for relief of hot flushes in postmenopausal Asian women: a randomized controlled trial.

Haines C, Yu SL, Hiemeyer F, Schaefers M.

Prince of Wales Hospital, The Chinese University of Hong Kong, New Territories, Hong Kong.

Objectives To compare the effect of micro-dose transdermal estradiol and placebo on the incidence and severity of menopausal symptoms and well-being in postmenopausal Asian women with vasomotor symptoms. Design Multicenter, double-blind, randomized, placebo-controlled study. Results Of 165 subjects randomized to estradiol 0.014 mg/day or placebo for 12 weeks, 80 per group were included in the analysis. Groups were comparable at baseline, although time since menopause was slightly shorter in the estradiol group. There was a greater reduction in mean weekly hot flushes at week 12 in the estradiol group (55%) than the placebo group (40%; p < 0.01), which was evident by week 4. A similar pattern was seen for moderate and severe hot flushes (-58% vs. -39%, respectively). Reductions were statistically significant at weeks 4, 8, and 12. Vaginal pH fell significantly in the estradiol group by week 4 and then remained stable throughout the treatment period, but there were no significant changes in the placebo group. Vaginal maturation value increased more in the estradiol than the placebo group (p < 0.001). Few subjects had vaginal bleeding or spotting. Quality of life improved similarly in both groups. Urogenital symptoms improved considerably from baseline in both treatment groups, with no significant differences. Eight subjects experienced treatment-related adverse events (seven in the estradiol group). Conclusions In Asian women, micro-dose estradiol was significantly superior to placebo in improving vasomotor symptoms. The bleeding profile was comparable with that of placebo. Micro-dose estradiol was safe and well tolerated in Asian women.

 

Am J Primatol. 2009 May 27. [Epub ahead of print]

Neuroprotective effects of estrogen therapy for cognitive and neurobiological profiles of monkey models of menopause.

Voytko ML, Tinkler GP, Browne C, Tobin JR.

Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Many postmenopausal women question whether to start or continue hormone therapy because of recent clinical trial negative results. However, evidence from other studies of postmenopausal women, and from studies in menopausal monkeys, indicate that estrogen has neurocognitive protective effects, particularly when therapy is initiated close to the time of menopause before neural systems become increasingly compromised with age. In this review, we present studies of menopausal women and female monkeys that support the concept that estrogen therapies protect both cognitive function and neurobiological processes.

 

Am J Clin Nutr. 2009 May 27. [Epub ahead of print]

Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial.

Kenny AM, Mangano KM, Abourizk RH, Bruno RS, Anamani DE, Kleppinger A, Walsh SJ, Prestwood KM, Kerstetter JE.

BACKGROUND: Soy foods contain several components (isoflavones and amino acids) that potentially affect bone. Few long-term, large clinical trials of soy as a means of improving bone mineral density (BMD) in late postmenopausal women have been conducted. OBJECTIVE: Our goal was to evaluate the long-term effect of dietary soy protein and/or soy isoflavone consumption on skeletal health in late postmenopausal women. DESIGN: We conducted a randomized, double-blind, placebo-controlled clinical trial in 131 healthy ambulatory women aged >60 y. Ninety-seven women completed the trial. After a 1-mo baseline period, subjects were randomly assigned into 1 of 4 intervention groups: soy protein (18 g) + isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein + placebo tablets, control protein + isoflavone tablets, and control protein + placebo tablets. RESULTS: Consumption of protein powder and isoflavone pills did not differ between groups, and compliance with the study powder and pills was 80-90%. No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers. However, there were significant negative correlations between total dietary protein (per kg) and markers of bone turnover (P < 0.05). CONCLUSIONS: Because soy protein and isoflavones (either alone or together) did not affect BMD, they should not be considered as effective interventions for preserving skeletal health in older women. The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover.

 

Clin Endocrinol (Oxf). 2009 May 16. [Epub ahead of print]

Distribution of plasma levels of adiponectin and leptin in an adult Caucasian population.

Marques-Vidal P, Bochud M, Paccaud F, Mooser V, Waeber G, Vollenweider P.

Centre for Cardiovascular and Metabolic Research, University of Lausanne, Lausanne, Switzerland.

Objective Little is known regarding the distribution and the determinants of leptin and adiponectin levels in the general population. Design Cross-sectional study. Patients:ensp; 3,004 women and 2,552 men aged 35-74 living in Lausanne, Switzerland. Measurements:ensp; Plasma levels of leptin and adiponectin (ELISA measurement). Results Women had higher leptin and adiponectin levels than men. In both genders, leptin and adiponectin levels increased with age. After adjusting for fat mass, leptin levels were significantly and negatively associated with age in women: 18.1+/-0.3, 17.1+/-0.3, 16.7+/-0.3 and 15.5+/-0.4 ng/mL (adjusted mean+/-standard error) for age groups [35-44], [45-54], [55-64] and [65-75], respectively, p<0.001. A similar but non-significant trend was also found in men. Conversely, the age-related increase of adiponectin was unrelated to body fat in both genders. Post-menopausal women had higher leptin and adiponectin levels than pre-menopausal women, independently of hormone replacement therapy. Although body fat mass was associated with leptin and adiponectin, the associations were stronger with BMI, waist and hip in both genders. Finally, after adjusting for age and anthropometry, no relationships were found between leptin or adiponectin levels with alcohol, caffeine consumption and physical activity, whereas smoking and diabetes decreased leptin and adiponectin levels in women only. Conclusions The age-related increase in leptin levels is attributable to changes in fat mass in women and probably also in men. Leptin and adiponectin levels are more related to BMI than to body fat mass. The effects of smoking and diabetes appear to be gender-specific.

 

Neurology. 2009 May 26;72(21):1850-7.

Effects of the menopause transition and hormone use on cognitive performance in midlife women.

Greendale GA, Huang MH, Wight RG, Seeman T, Luetters C, Avis NE, Johnston J, Karlamangla AS.

Division of Geriatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA

BACKGROUND: There is almost no longitudinal information about measured cognitive performance during the menopause transition (MT). METHODS: We studied 2,362 participants from the Study of Women's Health Across the Nation for 4 years. Major exposures were time spent in MT stages, hormone use prior to the final menstrual period, and postmenopausal current hormone use. Outcomes were longitudinal performance in three domains: processing speed (Symbol Digit Modalities Test [SDMT]), verbal memory (East Boston Memory Test [EBMT]), and working memory (Digit Span Backward). RESULTS: Premenopausal, early perimenopausal, and postmenopausal women scored higher with repeated SDMT administration (p < or = 0.0008), but scores of late perimenopausal women did not improve over time (p = 0.2). EBMT delayed recall scores climbed during premenopause and postmenopause (p < or = 0.01), but did not increase during early or late perimenopause (p > or = 0.14). Initial SDMT, EBMT-immediate, and EBMT-delayed tests were 4%-6% higher among prior hormone users (p < or = 0.001). On the SDMT and EBMT, compared to the premenopausal referent, postmenopausal current hormone users demonstrated poorer cognitive performance (p < or = 0.05) but performance of postmenopausal nonhormone users was indistinguishable from that of premenopausal women. CONCLUSIONS: Consistent with transitioning women's perceived memory difficulties, perimenopause was associated with a decrement in cognitive performance, characterized by women not being able to learn as well as they had during premenopause. Improvement rebounded to premenopausal levels in postmenopause, suggesting that menopause transition-related cognitive difficulties may be time-limited. Hormone initiation prior to the final menstrual period had a beneficial effect whereas initiation after the final menstrual period had a detrimental effect on cognitive performance.

 

Cancer Prev Res (Phila Pa). 2009 May 26. [Epub ahead of print]

Association between Plasma 25-Hydroxyvitamin D and Breast Cancer Risk.

Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E, Shane E, Terry MB, Desai M, Teitelbaum SL, Neugut AI, Santella RM.

Department of Medicine, Division of Hematology/Oncology, College of Physicians and Surgeons, Arnold School of Public Health, Columbia, South Carolina.

Vitamin D has been associated with decreased risk of several cancers. In experimental studies, vitamin D has been shown to inhibit cell proliferation and induce differentiation and apoptosis in normal and malignant breast cells. Using a population-based case-control study on Long Island, New York, we examined the association of breast cancer with plasma 25-hydroxyvitamin D (25-OHD) levels, a measure of vitamin D body stores. In-person interviews and blood specimens were obtained from 1,026 incident breast cancer cases diagnosed in 1996 to 1997 and 1,075 population-based controls. Plasma 25-OHD was measured in batched, archived specimens by Diasorin RIA. The mean (SD) plasma 25-OHD concentration was 27.1 (13.0) and 29.7 (15.1) ng/mL in the cases and controls, respectively (P < 0.0001). Plasma 25-OHD was inversely associated with breast cancer risk in a concentration-dependent fashion (P(trend) = 0.002). Compared with women with vitamin D deficiency (25-OHD, <20 ng/mL), levels above 40 ng/mL were associated with decreased breast cancer risk (odds ratio, 0.56; 95% confidence interval, 0.41-0.78). The reduction in risk was greater among postmenopausal women (odds ratio, 0.46; 95% confidence interval, 0.09-0.83), and the effect did not vary according to tumor hormone receptor status. In summary, these results add to a growing body of evidence that adequate vitamin D stores may prevent breast cancer development. Whereas circulating 25-OHD levels of >32 ng/mL are associated with normal bone mineral metabolism, our data suggest that the optimal level for breast cancer prevention is >/=40 ng/mL. Well-designed clinical trials are urgently needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention.

 

Menopause Int. 2009 Jun;15(2):82-6.

Hormonal management of migraine at menopause.

Nappi RE, Sances G, Detaddei S, Ornati A, Chiovato L, Polatti F.

Research Center of Reproductive Medicine, Unit of Gynecological Endocrinology and Menopause, IRCCS Maugeri Foundation, University of Pavia, Via Ferrata 8, 27100 Pavia, Italy. renappi@tin.it.

In this review, we underline the importance of linking migraine to reproductive stages for optimal management of such a common disease across the lifespan of women. Menopause has a variable effect on migraine depending on individual vulnerability to neuroendocrine changes induced by estrogen fluctuations and on the length of menopausal transition. Indeed, an association between estrogen 'milieu' and attacks of migraine is strongly supported by several lines of evidence. During the perimenopause, it is likely to observe a worsening of migraine, and a tailored hormonal replacement therapy (HRT) to minimize estrogen/progesterone imbalance may be effective. In the natural menopause, women experience a more favourable course of migraine in comparison with those who have surgical menopause. When severe climacteric symptoms are present, postmenopausal women may be treated with continuous HRT. Even tibolone may be useful when analgesic overuse is documented. However, the transdermal route of oestradiol administration in the lowest effective dose should be preferred to avoid potential vascular risk.

 

Menopause Int. 2009 Jun;15(2):76-81

Depression and the menopause: why antidepressants are not enough?

Graziottin A, Serafini A.

Via Enrico Panzacchi 6, 20123 Milano, Italy. a.graziottin@studiograziottin.it.

BACKGROUND: Gender differences, related to varying sexual hormone levels and hormone secretion patterns across the lifespan, contribute to women's vulnerability to mood disorders and major depression. Women are more prone than men to depression, from puberty onwards, with a specific exposure across the menopausal transition. However, controversy still exists in considering fluctuation/loss of estrogen as a specific aetiologic factor contributing to depression in perimenopause and beyond. AIMS: To briefly review the interaction between changes in menopausal hormone levels, mood disorders, associated neuropsychological co-morbidities and ageing, and to evaluate the currently available therapeutic options for perimenopausal mood disorders: (a) treatment of light to moderate mood disorders with hormonal therapy (HT); (b) treatment of major depression with antidepressants; (c) the synergistic effect between HT and antidepressants in treating menopausal depression. RESULTS: Depression across the menopause has a multifactorial aetiology. Predictive factors include: previous depressive episodes such as premenstrual syndrome and/or postpartum depression; co-morbidity with major menopausal symptoms, especially hot flashes, nocturnal sweating, insomnia; menopause not treated with HT; major existential stress; elevated body mass index; low socioeconomic level and ethnicity. Postmenopausal depression is more severe, has a more insidious course, is more resistant to conventional antidepressants in comparison with premenopausal women and has better outcomes when antidepressants are combined with HT. CONCLUSION: The current evidence contributes to a re-reading of the relationship between menopause and depression. The combination of the antidepressant with HT seems to offer the best therapeutic potential in terms of efficacy, rapidity of improvement and consistency of remission in the follow-up.

 

Menopause Int. 2009 Jun;15(2):55-7

Hormone replacement therapy and cardiovascular disease revisited.

Stevenson JC.

Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. j.stevenson@imperial.ac.uk.

Controversy still rages about whether hormone replacement therapy (HRT) confers cardiovascular benefit or harm. There is a wealth of biological evidence that estrogen has a beneficial effect, supporting a large body of epidemiological evidence demonstrating reduction in coronary events with HRT. A large randomized placebo-controlled clinical trial of preventive strategies for coronary heart disease (CHD) in postmenopausal women, the Women's Health Initiative (WHI), included HRT arms. The published preliminary findings of this trial showed a significant increase in coronary events, stroke, venous thromboembolism and breast cancer with estrogen-progestogen, leading to the conclusion that HRT was unsafe to use other than for short-term relief of menopausal symptoms. But subsequent publications of the more complete data from WHI have shown no significant increase in CHD, and a tendency to a reduction in those initiating HRT below age 60 years. This is important because other therapeutic strategies for the primary prevention of CHD, such as aspirin and statins, are not of proven benefit in women, in contrast to men. Subsequent WHI findings have not shown a clear increase in breast cancer, and any potential increase from HRT is similar to that seen with many lifestyle factors and other commonly used medications. The preliminary WHI results do not reflect accurately true benefits and risks, and HRT should remain a potential preventive treatment for CHD.

 

Menopause Int. 2009 Jun;15(2):52-4.

Why are physicians reluctant to use estrogens for anything - or do they prefer 'PROFOX'?

Studd J.

London PMS & Menopause Clinic, 46 Wimpole Street, London W1G8SD, UK. harley@studd.co.uk.

The reluctance of physicians to use estrogens in women with hormone responsive disorders is a tragic result of the 2002 WHI study. Although their hostility to estrogen therapy antedated these studies, the flawed data is now used as justification for the denial of estrogens for treatment of low bone density and various types of hormone responsive depression in women. Estrogens should be first choice therapy for osteoporosis in women under the age of 60 years, but in practice bisphosphonates, with its increasing number of long-term side-effects, has become first-line therapy for physicians. These side-effects include osteonecrosis of the jaw, mid-shaft femoral fractures and the need for proton pump inhibitors, which further reduce bone density and add to the fracture risk. Pyschiatrists fail to use transdermal estradiol for postnatal depression, premenstrual depression and perimenopausal depression in spite of randomized trials demonstrating their efficacy. Selective serotonin reuptake inhibitor therapy for depression independently decreases bone density and is also responsible for loss of libido, loss of mental acuity and dependence. Thus postmenopausal women with vasomotor symptoms, depression, loss of libido, vaginal dryness or low bone density are frequently denied effective estrogen therapy and given a combination of low-cost generic prozac and fosamax, which is in danger of becoming a post-WHI nightmare drug PROFOX (PROzacFOsamaX). This can only be avoided if advisory bodies review the reassuring evidence concerning estrogen therapy in women under the age of 60 years and advise accordingly.

 

Joint Bone Spine. 2009 May 20. [Epub ahead of print]

Antioxidant status in patients with osteoporosis: A controlled study.

Sendur OF, Turan Y, Tastaban E, Serter M.

Physical Medicine Rehabilitation, Adnan Menderes University School of Medicine, Aydin, Turkey.

OBJECTIVE: We aimed to investigate serum antioxidant enzymes and nitric oxide (NO) levels in postmenopausal women with osteoporosis (OP) and in healthy controls; and to determine the relationship between these enzymes, NO and clinical parameters in this present study. METHODS: Forty-five postmenopausal women fulfilling OP diagnostic criteria of World Health Organization (WHO) and 42 postmenopausal healthy women without OP were enrolled. Patients in the study population were selected among individuals that were not pre-diagnosed or pre-treated for OP. Patients with metabolic bone diseases, fracture history, which were smokers, alcohol users and taking antioxidant drug treatment, were excluded from the study. Dual Energy X-ray Absorptiometry (DXA) results, body mass indices and demographic data were recorded. Erythrocyte catalases (CAT), glutathione reductase (GR) enzyme activities and erythrocyte glutathione (GSH) levels, plasma malondialdehyde (MDA) levels were measured by spectrophotometer whereas plasma nitrite+nitrate (NOx) levels were measured by ELISA microplate-reader. RESULTS: Patients had significantly lower GR (P<0.01) enzyme activity and higher levels of MDA (P<0.01) and NO (P<0.01) than non osteoporotic healthy controls. There was no significant difference between both groups in erythrocyte GSH levels and CAT activities. Total femoral BMD measurements significantly correlated with MDA levels (P=0.001). There was no significant relationship between other antioxidants and lumbar or femoral BMD. CONCLUSION: Oxidative stress may play an important role in postmenopausal bone loss and therefore it might be considered when pathogenesis of postmenopausal OP has been investigated.

 

Maturitas. 2009 May 20. [Epub ahead of print]

Menopause and sexuality: Prevalence of symptoms and impact on quality of life.

Nappi RE, Lachowsky M.

Research Center for Reproductive Medicine, Dept of Morphological, Eidological and Clinical Sciences, Italy; Unit of Gynecological Endocrinology and Menopause, Dept of Internal Medicine and Endocrinology, IRCCS "S Maugeri Foundation", University of Pavia, Pavia, Italy.

OBJECTIVE: This article aims to summarise the available knowledge on the prevalence of sexual symptoms at the menopause and their impact on quality of life in elderly women. Sexual changes are analysed in the context of the menopause transition and beyond. METHODS: The medical literature was searched (1990-2008) with regard to menopause and sexuality using several related terms. RESULTS: The prevalence of sexual symptoms at the menopause differs across studies depending on several factors such as sample size, design, hormonal status and country. The most common sexual complaints are reduced sexual desire, vaginal dryness and dyspareunia, poor arousal and orgasm and impaired sexual satisfaction. Age and declining oestradiol levels have significant detrimental effects on sexual functioning, desire and responsiveness (arousal, sexual pleasure and orgasm) across the normal menopause transition, while reduced androgens levels played a role in hypoactive sexual desire disorder (HSDD), a symptom frequently diagnosed in surgically menopausal women. CONCLUSIONS: Women attending menopause clinics are vulnerable to female sexual dysfunction (FSD) because of a complex interplay of individual factors variably affecting well-being. Surgically menopausal women may be more distressed by sexual symptoms. Giving women the opportunity to talk about sexual problems is a fundamental part of health care and may improve their quality of life.