Recent Menopause Research Articles

The Current Strategy in Hormonal and Non-Hormonal Therapies in Menopause—A Comprehensive Review

Menopause is a natural stage of hormonal aging in women, accompanied by a series of symptoms that reduce the quality of life of a fully active person. As no therapy is entirely satisfactory, the race for a better option is in full swing. Our study objective is to investigate the most recent menopause studies on pharmacological resources, emerging therapies, and the particularities of hormonal replacement therapy (HRT). For this purpose, a comprehensive search was conducted in two main databases (PubMed and Web of Science) guided by the specific keywords "menopause" and "therapy" or "estrogen" or "progesterone" or "hormone replacement" during the last ten years period. Studies were eligible if they met certain criteria: randomized controlled trials (RCT) in adult women with menopause and hormonal or non-hormonal therapies. We selected 62 RCTs, which are focused on four main topics: (a) epidemiology of menopause-related symptoms, (b) hormonal replacement therapy (HRT) selective estrogen receptor modulators, (c) emerging therapies, and (d) menopause. HRT has proven a real health benefit for menopausal women; besides, complementary interventions must be considered. Further studies are needed on menopause and menopause-related therapies. The continuous updating of clinical experience will strengthen the therapeutic benefit and the decision to treat patients safely. This goal will fully access all therapeutic resources to address an unresolved health issue of active adult women.

RF06 | PSAT152 Associations between Bone Mass, Hormone Levels and Body Composition in Postmenopausal Women

Abstract Emerging evidence suggests an association between FSH and bone mass in peri- and postmenopausal women. The aim of the present study was to assess body composition parameters and hormone levels as risk factors for low bone mass in women with recent menopause. In this cross-sectional study, we analyzed biorepository samples from 139 postmenopausal women aged 42 to 68 years with no evidence of clinical CVD. Inclusion criteria were as follows: menopause, defined as last menstrual period at least 12 months of amenorrhea and/or 6 months or more of amenorrhea plus FSH levels ≥35 mIU/mL occurring after 40 years of age, and no use of hormone therapy (HT) in the past 3 month. BMD and body composition were assessed by dual-energy X-ray absorptiometry (DXA), SHBG and FSH levels were measured in all patients. Serum estradiol levels were measured by gas chromatography/tandem mass spectrometry assay (GC/MS/MS) in a subset of 57 participants and free estrogen index (FEI) was estimated by dividing estradiol by SHBG × 100. Low bone mass was considered osteoporosis and osteopenia. The mean age was 54.33±5.30 years and median time since menopause was 4 (2 - 9) years. The mean BMI was 26.73±4.38 kg/m2 and 66% of participants were classified as overweight or obese. BMI, BMD and T-sc, lean mass index (LMI) and fat mass index (FMI) were lower, and SHBG was higher in women with FSH levels above the median values (83.6mUI/mL). FSH was inversely correlated with FEI (rho=-0.283, p=0.033) as well as with FMI (rho=-0.288, p=0.001) and LMI (rho=-0.186, p=0.029), but significance was lost after adjustment for estradiol levels (p=0.651). In the univariate linear regression analysis, FSH, FEI, time since menopause, SHBG, FMI and LMI were significant predictors to total femur bone mass, explaining 3.8%, 11.9%, 7.4%, 14.7%, 19.7% and 8.4% of variance in BMD at this site, respectively. In the multivariate model, the association of FSH, time since menopause and FMI with hip bone mass was no longer significant after inclusion of FEI in the respective model. The present results indicate that the negative association between FSH levels and femoral BMD in postmenopausal women are influenced by endogenous estradiol levels, time since menopause and fat mass. Additional studies are needed in order to further analyze whether some direct effect of FSH on bone mass may be additive to the presence of low bone mass in this population. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

OR19-6 Functional Hypothalamic Amenorrhea and Preclinical Cardiovascular Disease

Abstract Background Functional Hypothalamic Amenorrhea (FHA) is characterized by suppression of central GnRH drive with secondary anovulation and hypoestrogenemia, hypercortisolism, and low leptin that results from a combination of psychosocial stress and metabolic imbalance due to excess physical activity and/or weight loss. Cardiovascular disease (CVD) is the leading killer of women at all ages and CVD mortality rates are unchanged or increasing in young women aged 35-44 years. We investigated relations between FHA and preclinical CVD measured by endothelial dysfunction in premenopausal women with and without FHA, and recently menopausal women not on hormone therapy. Methods We studied 31 women with FHA, 29 eumenorrheic controls, and 30 recently menopausal women not on hormone therapy. FHA was defined as amenorrhea ≥3 consecutive months, estradiol <50 pg/mL, FSH <10 mIU/L, and LH <10 mIU/L, and exclusion of other etiologies including polycystic ovary syndrome, prolactinoma, thyroid dysfunction, and pregnancy. Eumenorrheic controls had self-reported monthly menstrual cycles, were not on hormones, with a day 22-24 progesterone level >3 ng/ml to confirm ovulation. Preclinical CVD testing for eumenorrheic controls took place days 3-5 of menses. Recently menopausal women had natural menopause within 3 years, FSH >30, and not on hormone therapy. Preclinical CVD was measured using Endo PAT 2000 (Itamar® Medical Ltd) to calculate reactive hyperemic index (RHI) stress to rest pulse amplitude. RHI ≤1.67 indicates endothelial dysfunction. Statistical analysis included analysis of variance for normal distributed variables and Kruskal Wallis test for non-parametric variables. Results The mean age, BMI and estradiol of FHA, no FHA and recent menopause was 26.4 ± 6.2 y, 30.3 ± 3.7 and 53.3 ± 2.6, respectively (p<0.0001); BMI 21.6 ± 6.2 kg/m2, 21.8 ± 2.0, and 23.5 ± 4.2 (p=0.06); and estradiol 29.7±18.2, 46.4 ± 15.7, and 10.9 ± 14.4 pg/ml (p<0.0001), respectively. The median months of FHA amenorrhea was 10.8 months. There were no differences in testosterone (p=0.48), however FHA women had lower leptin (p=0.012) and higher cortisol (p=0.0005) compared to both no FHA and recently menopausal women. Preclinical CVD measured by RHI was significantly lower in FHA compared to no FHA and recently menopausal women (1.8 + 0.5 vs 2.2 + 0.5 vs 2.2 +0.6;p=0.007, respectively). Further 35% of FHA women had RHI ≤1.67 indicating endothelial dysfunction. Conclusion Our results demonstrate endothelial dysfunction in young women with FHA women as compared to eumenorrheic women and older recently menopausal women not on hormone therapy. Our findings suggest that FHA may be an important contributor to CVD mortality in younger women and that preclinical CVD in FHA is not likely due to hypoestrogenemia alone. Future studies will focus on identifying potential treatment targets for CVD prevention. Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.

Balance and functional mobility predict low bone mineral density among postmenopausal women undergoing recent menopause with osteoporosis, osteopenia, and normal bone mineral density: A cross-sectional study

The purpose of this study was to determine whether balance and functional mobility independently predict bone mineral density (BMD) in postmenopausal women. BMD at the hip and spine was measured with dual-energy x-ray absorptiometry (DEXA). Participants were assigned into groups (i.e., osteoporosis: n=20; osteopenia: n=20; normal BMD: n=20) according to DEXA T-scores. Participants performed the single leg stance test (SLS), timed-up-and-go (TUG), and 6-meter walking test. An ordinal logistic regression was performed to determine whether the SLS, TUG, 6MWT independently predict BMD, while accounting for age, age at menopause, and body mass index. Three factors predicted low BMD: (1) less time to hold the SLS (odds ratio (OR): 0.50); (2) longer TUG time (OR: 2.85); and (3) older Age (OR: 1.31). Women with recent menopause diagnosed with osteoporosis are at a high-risk for fracture; incorporating the SLS and TUG into risk assessments may enable prompt and targeted intervention.

Determinants of attained estradiol levels in response to oral estradiol plus progesterone therapy

Objectives Among postmenopausal women taking hormone therapy (HT), the estradiol (E2) dose and E2 levels were differentially associated with change in metabolic measures. We evaluated determinants of attained E2 levels in response to HT. Methods Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models assessed characteristics associated with E2 levels among women with ≥80% HT compliance, adjusted for E2 dose and baseline E2 level. Results Among 1173 postmenopausal women with mean (standard deviation) age 55 (4.3) years and 5.2 (4.8) years since menopause, higher treated E2 levels were significantly related to younger age, more recent menopause, and current alcohol use, while lower E2 levels were related to current smoking. Both age and time since menopause were significantly inversely associated with E2 levels; time since menopause had a stronger association with E2 levels. In the final multivariable model, E2 levels were positively associated with current alcohol use, and inversely associated with time since menopause and current smoking. Conclusion Adjusting for E2 dose and baseline E2 level, on-trial E2 levels were significantly associated with time since menopause, current smoking, and current alcohol use. Practitioners should consider these factors in individual women to achieve a desirable E2 level during HT.

Association of hot flushes with ghrelin and adipokines in early versus late postmenopausal women.

Vasomotor flushing (hot flushes) is a common menopausal symptom experienced by most women going through the menopausal transition; flushing continues for a variable period in postmenopause. Primarily due to lack of ovarian estrogen, other biomarkers of hot flushes have not been clearly identified. We examined the relationship of hot flushes with ghrelin and adipokines. Baseline data from two clinical trials, the Women's Isoflavone Soy Health (WISH) trial and Early versus Late Intervention Trial of Estrogen (ELITE), were used in this post hoc cross-sectional study. Both WISH and ELITE had similar study designs, inclusion criteria, and data collection processes. Study participants were healthy postmenopausal women not taking estrogen-based hormone therapy, free of cardiovascular disease, or any other chronic diseases. Both trials used the same hot flush diary in which participants recorded the number of daily hot flushes by severity over a month on average. Serum concentrations of ghrelin, leptin, adiponectin, and resistin were assessed in stored fasting blood samples using highly specific radioimmunoassay. In this analysis, self-reported flushing experience was tested for an association with leptin, adiponectin, resistin, and ghrelin concentrations using logistic regression and mean comparisons. A total of 898 postmenopausal women from the ELITE and WISH trials contributed to this analysis. Mean (SD) age was 60.4 (7.0) years, body mass index (BMI) 27 (5.3) kg/m, 67% were white, and 47% were within 10 years of menopause. Reported flushing was significantly associated with younger age, lower education, lower BMI, being married, and more recent menopause. Adjusted for these factors other than BMI, women in the highest quartile of ghrelin had significantly greater likelihood of experiencing hot flushes (OR [95% CI] = 1.84 [1.21-2.85]) compared to women in the lowest quartile. The association was more pronounced among overweight or obese women (OR [95% CI] = 2.36 [1.28-4.35]) compared to those with normal BMI (1.24 [0.54, 2.86]; interaction P value = 0.46). The association between ghrelin and hot flushes was similar among early (within 10 y) and late (over 10 y) postmenopausal women. Blood levels of adiponectin and resistin were not associated with hot flushes. Higher concentrations of ghrelin were associated with greater likelihood of hot flushes in both early- and late-postmenopausal women. Leptin, adiponectin, and resistin levels were not associated with hot flushes in postmenopausal women.

Cardiac perfusion and function after high-intensity exercise training in late premenopausal and recent postmenopausal women: an MRI study.

We examined the influence of recent menopause and aerobic exercise training in women on myocardial perfusion, left ventricular (LV) dimension, and function. Two groups (n = 14 each) of healthy late premenopausal (50.2 ± 2.1 yr) and recent postmenopausal (54.2 ± 2.8 yr) women underwent cardiac magnetic resonance imaging (cMRI) at baseline and after 12 wk of high-intensity aerobic training. Measurements included LV morphology, systolic function, and myocardial perfusion at rest and during an adenosine stress test. At baseline, resting myocardial perfusion was lower in the postmenopausal than the premenopausal group (77 ± 3 vs. 89 ± 3 ml·100 g-1·min-1; P = 0.01), while adenosine-induced myocardial perfusion was not different (P = 0.81). After exercise training, resting myocardial perfusion was lower in both groups (66 ± 2; P = 0.002 vs. 81 ± 3 ml·100 g-1·min-1; P = 0.03). The adenosine-induced change in myocardial perfusion was lower in the groups combined (by 402 ± 17 ml·100 g-1·min-1; P = 0.02), and the adenosine-induced increase in heart rate was 10 ± 2 beats/min lower (P < 0.0001) in both groups after training. Normalization of myocardial perfusion using an estimate of cardiac work eliminated the differences in perfusion between the premenopausal and postmenopausal groups and the effect of training. Left ventricle mass was higher in both groups (P = 0.03; P = 0.006), whereas LV end-diastolic (P = 0.02) and stroke (P = 0.045) volumes were higher in the postmenopausal group after training. Twelve weeks of exercise training increased left ventricle mass and lowered resting and adenosine-induced myocardial perfusion, an effect that was likely related to cardiac work. The current data also suggest that the early menopausal transition has limited impact on cardiac function and structure. NEW & NOTEWORTHY This study provides for the first time estimates of myocardial perfusion in late premenopausal and recent postmenopausal women before and after a period of intense aerobic training. Resting myocardial perfusion was lower in postmenopausal than premenopausal women. Training lowered myocardial resting and stress perfusion in both groups, an effect that was likely influenced by the lower heart rate.

Short-term effects of low-dose estradiol on endothelial function and blood viscosity in nondiabetic postmenopausal overweight women: a double-blind, placebo-controlled study.

The beneficial effects of estrogen on endothelial function depend on its integrity. This study evaluates the short-term effects of low-dose transdermal estradiol on endothelial function, insulin sensitivity, and blood viscosity in nondiabetic overweight/obese women. Forty-four nondiabetic overweight/obese women with a history of recent menopause were randomly allocated, in a double-blind fashion, to receive transdermal estradiol (1 mg/d, n = 22) or placebo (n = 22). The following parameters were assessed: endothelial reactivity (venous occlusion plethysmography and nailfold videocapillaroscopy), plasma levels of soluble adhesion molecules, insulin sensitivity (homeostasis model assessment of insulin resistance and areas under the curve of insulin and glucose during an oral glucose tolerance test), and blood and plasma viscosity. Data were expressed as means ± SD or medians [first to third quartiles]. Participants were aged 51.8 ± 2.3 years with a body mass index of 31.5 ± 2.5 kg/m and time since menopause was 3 [2-5] years. At baseline, no differences between the groups were observed; however, after 3 months of treatment, the following changes were observed in the estradiol group compared with the placebo group: a decrease in the forearm vascular resistance at baseline (36.37 [24.9-51.27] vs 51.3 [40.88-70.03] mm Hg/mL per min 100 mL tissue, P < 0.01) and during the postocclusive reactive hyperemia response (15.93 [11.32-22.29] vs 22.13 [16.46-29.7] mm Hg/mL per min 100 mL tissue, P < 0.01), and an increase in red blood cell velocity at rest (0.316 [0.309-0.326] vs 0.303 [0.293-0.308] mm/s, P < 0.001) and during postocclusive reactive hyperemia response (0.374 [0.353-0.376] vs 0.341 [0.333-0.355] mm/s, P < 0.001). Furthermore, blood viscosity was lower in the estradiol group than in the placebo group (3.57 ± 0.12 vs 3.76 ± 0.22 mPa.s; P < 0.01). Short-term use of low-dose transdermal estradiol in nondiabetic overweight/obese women with a history of recent menopause improved endothelial function and decreased blood viscosity compared with placebo.

Abstract P3-12-09: Factors influencing aromatase inhibitor induced musculoskeletal syndrome: Roles of menopause timing and osteoporosis therapy

Abstract Background: Aromatase Inhibitor (AI) therapy is the most effective hormonal treatment in post-menopausal estrogen receptor (ER) positive breast cancer. Side effects such as arthralgias - termed aromatase inhibitor induced musculoskeletal syndrome (AIMSS) - limit their use in some patients. We evaluated factors associated with AIMSS and explored possible therapeutic options in a large cohort of patients. Methods: We performed an IRB-approved retrospective review of breast cancer patients seen in the Norris Cotton Cancer Center clinics from April 2011 to January 2013. 378 patients were included in our chart review on the basis of taking an AI for breast cancer with follow up documented in the electronic health record. Statistical analysis was performed by chi squared test for dichotomous variables and students t-test for continuous variables. Results: In our cohort 91% of patients were taking an AI as adjuvant therapy (9% for metastatic disease) with 41% (n=153) reporting new or worsening arthralgias after initiation of an AI. AIMSS was 42.5%(95%CI: 0.375 to 0.478) in the adjuvant and 22.7%(95%CI: 0.101 to 0.434) in the metastatic groups. The median time to symptom onset was 120 days. 2.1% (n=8) discontinued AI therapy due to AIMSS. There was no association with prior chemotherapy, baseline arthralgia, BMI, or statin use. We found an increased risk of developing AIMSS with more recent menopause (p=0.055), and therapy in the adjuvant setting (p=0.067). We also note a potential association of baseline osteoporosis and osteoporosis therapies with lower rates of AIMSS. Treatments included temporary discontinuation of AI, switching between AI, and non-steroidal anti-inflammatory therapy (NSAIDs). Of those attempting such treatment, all had improvement with temporary discontinuation, 25% improved after AI switch, and 85% had symptomatic benefit on NSAIDs. Conclusions: The incidence of AIMSS in our review was 41%. Patients treated in the metastatic setting may have a lower rate of AIMSS. Our cohort revealed that more recent menopause did seem to be a risk factor. Baseline osteoporosis and osteoporosis treatments have a potential association to be explored. Management options included switching between AIs, temporary discontinuation, and NSAID treatment. Updated analysis will be presented. Potential risk factors for the development of AIMSSCharacteristicN(-)Arthralgia N(%)(+)Arthralgia N(%)p-valueType of AI UsedAnastrozole204112(55.9)92(45.1)0.19Letrozole13183(63.4)48(36.6)Exemestane3623(64.9)13(36.1)Menopause timingLMP &amp;lt; 5 years prior to AI start15179(52.3)72(47.7)0.055LMP 5-10 years prior to AI start4023(57.5)17(42.5)LMP &amp;gt; 10 years prior to AI start155102(65.8)53(34.2)Type of therapyAdjuvant348200(57.5)148(42.5)0.067Metastatic2217(77.3)5(22.7)Baseline T-score by DEXA ScanNormal (T-score 0 to -1.49)11255(49.1)57(50.9)0.049Osteopenia (T-score -1.5 to -2.49)17196(56.1)75(43.9)Osteoporosis(T-score &amp;lt; -2.5)4029(72.5)11(27.5)On active osteoporosis therapy†(-) Therapy218118(54.1)100(45.9)0.03(+) Therapy12781(63.8)41(32.3)† Bisphosphonate/denosumab; LMP=Last menstrual period, AI=Aromatase Inhibitor, DEXA=Dual-energy x-ray absorptiomotry Citation Format: Clinton R Morgan, Zsolt Kulcsar, Jonathan D Jones, William F Rigby, Peter A Kaufman. Factors influencing aromatase inhibitor induced musculoskeletal syndrome: Roles of menopause timing and osteoporosis therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-09.

ANALIZA CZYNNIKÓW ETIOLOGICZNYCH ZESPOŁU CIEŚNI NADGARSTKA W POPULACJI OSÓB PRACUJĄCYCH ZAWODOWO Z UŻYCIEM KOMPUTERA

Carpal tunnel syndrome (CTS) is the most frequent mononeuropathy of upper extremities. From the early 1990's it has been suggested that intensive work with computers can result in CTS development, however, this relationship has not as yet been proved. The aim of the study was to evaluate occupational and non-occupational risk factors for developing CTS in the population of computer-users. The study group comprised 60 patients (58 women and 2 men; mean age: 53.8 +/- 6.35 years) working with computers and suspected of occupational CTS. A survey as well as both median and ulnar nerve conduction examination (NCS) were performed in all the subjects. The patients worked with use of computer for 6.43 +/- 1.71 h per day. The mean latency between the beginning of employment and the occurrence of first CTS symptoms was 12.09 +/- 5.94 years. All patients met the clinical and electrophysiological diagnostic criteria of CTS. In the majority of patients etiological factors for developing CTS were non-occupational: obesity, hypothyroidism, oophorectomy, past hysterectomy, hormonal replacement therapy or oral contraceptives, recent menopause, diabetes, tendovaginitis. In 7 computer-users etiological factors were not identified. The results of our study show that CTS is usually generated by different causes not related with using computers at work.

Abstract A8: Estrogen metabolism and mammographic density in postmenopausal women

Abstract Estrogens play important roles in the pathophysiology of breast tumors and are recognized causal factors in the etiology of breast cancer. Parent estrogens (estrone and estradiol) can be hydroxylated at the 2, 4, or 16 position of the steroid ring, resulting in metabolites with different biological activity and availability. Estrogen metabolism shows great inter-individual variation, is modifiable, and may contribute to differences among women at risk of breast cancer. We conducted a cross-sectional study to investigate whether urinary estrogens and estrogen metabolites (jointly referred to as EM) are associated with mammographic density (MD), the strongest predictor of sporadic breast cancer risk among women apart from age. Methods: Postmenopausal women without breast cancer, aged 48–82 y, and reporting no current use of exogenous hormones were recruited and interviewed at a mammography clinic in Western NY in 2005. Concentrations of 15 EM were measured in first morning urine samples from 195 participants using liquid chromatography-tandem mass spectrometry. MD (%) was measured using computer-assisted analyses of digitized films. Linear models were used to assess associations of log-transformed EM concentrations and ratios with MD while adjusting for age, body mass index (BMI, kg/m2), and history of combination menopausal hormone therapy. We assessed effect modification by these factors and by years since menopause. Results: The median age of participants was 58, and median time since menopause was 8 years; 35% of participants were obese (BMI ≥30), and 33% had previously used combination menopausal hormones. Among all participants, urinary concentrations of parent estrogens were not associated with MD while some individual 2-pathway and 4-pathway EM had significant inverse associations with MD. Associations between EM profiles and MD were modified by years since menopause (≤8 or &amp;gt;8 y) and by obesity. Among women with a recent menopause, MD was positively associated with parent estrogens (p=0.02), and inversely associated with 2- and 4-hydroxylation pathway EM (p=0.03 and 0.02); these associations were not observed in women with a more distant menopause (pinteraction=0.02, 0.18, 0.16, respectively). Similarly, parent estrogens were directly associated with MD (p=0.003) among women who were obese but not among thinner counterparts (pinteraction=0.08). Conclusion: This is the first study to examine the relations between 15 EM and MD in postmenopausal women. EM profiles were most strongly associated with MD in subgroups with higher estrogen levels including obese women and those with a more recent menopause. In these groups, more extensive 2- and 4-hydroxylation of parent estrogens was associated with reduced MD. This pattern of metabolism may influence MD by facilitating clearance of estrogens from breast tissues. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A8.

Local Estriol Treatment

All women with urinary incontinence should be provided with the opportunity for individualized treatment. In women with an overactive bladder, this includes local vaginal administration of estriol (0.5 mg/day). This metabolite of estradiol, which does not affect the endometrium, does not require addition of gestagen because it binds to the estrogen receptor for 1–4 hours only, compared with 6–24 hours for estradiol. This difference, by a factor of 6, means that local estriol treatment does not incur any risk of thromboembolism or increased diagnoses of breast cancer, according to studies from Scandinavia To treat urge incontinence that develops after the menopause as a result of tissue atrophy subsequent to estrogen deficiency, estriol has been successful for 30 years. In urinary urge in women of perimenopausal age, progesterone deficiency should be borne in mind. Substitution treatment (locally-vaginally, without any relevant risks) reduces detrusor overactivity. This applies to women with a fairly recent menopause. Estriol has a proliferative effect in the vaginal, urethral, and bladder epithelium via beta-receptors. Estriol binds by a factor of 7 less often to the alpha-receptor than estradiol (dominant in the endometrium and glandular breast tissue). Estriol improves perfusion in the urethral area including closure mechanisms via beta-receptors in the endothelia. Local estriol 0.5 mg/day for 2–3 weeks is then reduced to 3-day intervals and later 1-week intervals. Optimum therapy is reached after 3 months. A prospective, multicenter study (1) showed for 80% of 600 postmenopausal women with symptoms of incontinence a subjective improvement after 6 weeks (even for grade 3 incontinence). High frequency of micturition halved. These findings were confirmed by a smaller study (2) and a placebo controlled study (3): local estriol significantly improved incontinence as a result of urogenital atrophy in 7 out of 10 women; in the placebo group, only 1 in 7 women experienced an improvement.

Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates

Aromatase inhibitors have demonstrated their superiority to tamoxifen as adjuvant therapy for early breast cancer in postmenopausal women, but are associated with an increased risk of fractures. The aim of our study was to analyze bone loss, bone turnover and their determinants in postmenopausal women treated with anastrozole.We investigated bone loss and bone turnover markers (BTM) in a prospective open cohort study of 118 postmenopausal women treated with anastrozole for an early hormone-dependent breast cancer. Women without osteoporosis were not treated and compared with an age-matched control group of 114 healthy women. Osteoporotic patients (T-score≤−2.5 S.D.) received weekly risedronate. Bone mineral density (BMD), and the BTM serum osteocalcin and serum C-terminal cross linking telopeptide of type I collagen (CTX) and 17β-estradiol were measured at baseline and 1 year later.In the surveillance group, anastrozole induced after 1 year of treatment a marked bone loss at the spine (mean±S.E.M., [95% confidence interval]) −3.3±0.4% [−4.1 to −2.5]), and hip (2.8±0.4% [−3.6 to −2]) that was significantly greater than in controls (p<0.0001). Anastrozole induced an increase in bone remodelling: osteocalcin (+36.6%, p<0.0001) and CTX (+34%, p<0.0001). In univariate models, a recent menopause, a low body mass index, a complete chemotherapy (≥6 courses) and a marked antiestrogenic response – defined by a level of 17β-estradiol ≤2 pg/ml at 1 year or a decrease >50% between baseline and 1 year – were associated with greater bone loss. In multivariate model, women in the highest quartile of bone loss at the spine (>5.6% at 1 year) and hip (>4.9%) had a marked antiestrogenic response with OR of 10.4 [95% C.I. 1.9–57.2] (p=0.007) and 5.7 [1.3–25] (p=0.024) respectively. Among patients in the surveillance group, those with a normal T-score at both sites (n=46) had also a significant bone loss at spine −3.3±0.5% [−4.3 to −2.3], p<0.0001 and at the hip −2.9±0.6% [−4.1 to −1.7] p<0.0001. In osteoporotic women treated simultaneously with anastrozole and risedronate, bone loss was prevented at hip, and increased at the spine (+4.1±0.9% [2.3 to 5.9], p=0.008), and BTM decreased (−24%, −39% for CTX, p=0.003 and 0.001 vs. changes in the untreated group).Anastrozole increases bone turnover and induces an accelerated bone loss that is significantly related to the suppression of 17β-estradiol production induced by aromatase inhibitor. The bisphosphonate risedronate prevents anastrozole induced bone loss.

Life prevalence and determinants of hormone replacement therapy in women living in Porto, Portugal

Objective To survey the life prevalence and determinants of hormone replacement therapy (HRT) in Portugal. Methods We evaluated 908 women with mean age (standard deviation) 62.3 (9.6) years, as part of the assembling of a cohort of adults, representative of Porto inhabitants. Extensive data collection was conducted and included socio-demographic, lifestyle and clinical characterisation. The latter comprised gynecologic and obstetric history, as well as lifetime use and duration of HRT. Results Life prevalence of hormone replacement therapy was 26.8% (95% confidence interval: 23.9–29.8). Prevalence of lifetime HRT was higher in younger (born after 1949: 37.1%) and more educated women (over 12 schooling years: 48.7%), as in white-collar workers (36.8%), and women using private healthcare (39.4%). HRT use was also more frequent among ever smokers (43.1%), and in women reporting regular sports practice (35.6%). Ever users of oral contraceptives underwent HRT more frequently (33.3%) and women who experienced menopause more recently were more likely to use HRT (after 1994: 40.5%). No differences were found in the prevalence of HRT according to whether women had been hysterectomised or oophorectomised. Education, regular sports practice and menopause year were independent determinants of HRT. Median duration of therapy was 2 years. Short-term HRT users were more educated, and had more recent menopause. Long-term HRT users were more educated, engaged in sports more frequently, and were more frequently oophorectomised. Conclusions Prevalence of hormone replacement therapy increased until 2001 and was mainly determined by high socioeconomic status, regardless of important therapeutic indications, such as oophorectomy and hysterectomy.

Estrogen therapy effects on different vasoactive factors in recent postmenopausal healthy women

Background To evaluate whether the route of estrogen therapy (ET) may affect the levels of different vasoactive factors in healthy recent post-menopausal women. Methods We conducted a cross-over study in 20 healthy nonsmoking women in recent postmenopause (1.8 ± 0.1 years). Women received either 1-month oral-ET (O-ET, 2 mg oral micronized 17β estradiol daily) or transdermal-ET regimen (T-ET, 17β estradiol 1.5 mg gel daily) with a 1-month wash-out interval. Blood pressure, plasma levels of endothelin-1 (ET), 6-ketoPGF1a (6-ketoPG, prostacyclin metabolite), nitrite/nitrate (NOx), epinephrine (E) and norepinephrine (NE) and lipid profile were measured at baseline and after each treatment. Results Both regimens significantly reduced E ( p < 0.01) and NE levels ( p < 0.05). O-ET reduced low-density lipoproteins (LDL) levels ( p < 0.05) and increased NOx values ( p < 0.01). Neither regimen caused significant changes of ET or 6-ketoPG. Conclusions Our results, obtained in healthy women in recent menopause, indicate that the ratio between vasodilator (NOx and prostacyclin) and vasoconstrictor (ET) bioavailability shifted towards the previous ones after O-ET, while it remained unchanged after T-ET; moreover, catecholamines levels were reduced by both treatments already from 1 month of therapy. These changes might represent very early beneficial effects evoked by ET on the cardiovascular system.

Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease.

Risedronate is a novel orally administered pyridinyl bisphosphonate indicated for the prevention or treatment of postmenopausal and glucocorticoid-induced osteoporosis and Paget's disease. The drug reduces bone turnover and decreases resorption chiefly through osteoclastic effects, with no undesirable effects on cortical porosity or thickness or on cancellous bone volume. Four randomised, double-blind trials have been carried out in 4873 patients with postmenopausal osteoporosis. In 2 of these studies, the primary end-point of vertebral fracture incidence was reduced by risedronate 5mg once daily by up to 65 and 49% relative to placebo after 1 and 3 years, respectively. Across all 4 trials, risedronate improved lumbar spine, femoral neck and femoral trochanter bone mineral density (BMD) statistically significantly relative to placebo. The drug also prevented bone loss in a study in 383 women with recent menopause, and reduced the risk of hip fracture in elderly women with confirmed osteoporosis in a trial involving a total of 9331 patients. Risedronate 5 mg/day plus estrogen has been shown to be superior to estrogen alone in a 12-month double-blind study in 524 women with at least 1-year's history of menopause. Two randomised, double-blind and placebo-controlled 12-month studies in a total of 518 patients have shown risedronate 5 mg/day to prevent or reverse bone loss in patients receiving glucocorticoid therapy. Risedronate 30 mg/day was associated with statistically significant reductions in mean serum levels of alkaline phosphatase (ALP) in noncomparative studies in patients with Paget's disease. ALP normalisation rates ranged from 53.8 to 65% across two 84-day treatment cycles in 2 of these trials in 180 patients. In a randomised, double-blind study in 123 patients, risedronate 30 mg/day for 2 months evoked significantly greater serum ALP responses than etidronate 400 mg/day for 6 months. The overall tolerability profile of risedronate was similar to that of placebo in clinical studies, with no evidence of acute-phase reactions or mineralisation defects, or excess incidence of upper GI lesions, in patients receiving the drug. Risedronate is an effective and well tolerated novel bisphosphonate that is suitable for first-line therapy in Paget's disease. The rapid and sustained reductions in vertebral fracture incidence and BMD changes seen in patients with postmenopausal and glucocorticoid-induced osteoporosis indicate the drug to be a valuable treatment option with first-line potential, particularly in patients for whom hormonal therapy is inappropriate. The effects of the drug on hip fracture incidence in elderly women with confirmed osteoporosis point to a particular role in older patients, or those with more advanced disease.

Menopause and the transmission of women's knowledge: African American and white women's perspectives.

Recent menopause literature does not sufficiently explore women's attitudes on the transmission of knowledge about menopause from sources other than biomedical providers. Analysis of 70 interviews with African American and Euro-American women shows that their perceptions of the intergenerational transfer of knowledge about menopause from their mothers shaped their attitudes toward menopause and the health-care technologies surrounding it. African American women who grew up in the segregated South frequently expressed that their mothers provided them with the knowledge and power to negotiate difficulties during the menopausal process, while many middle-class Euro-American women expressed that their mothers did not. Drawing on literature that examines the effects of race, class, and kinship on mother/daughter relationships, this article explores the reasons for this divergence.

Coping style and climacteric symptoms in a clinical sample of postmenopausal women

Hormonal changes as well as sociocultural and personal factors account for climacteric symptoms. The aim of this study is to investigate in a clinical population the correlation between the severity of hot flashes and vaginal dryness and the ‘coping—ineffectiveness of coping’ construct. Out of 120 women consecutively referring to the University Menopause Clinic, 85 subjects were evaluated for their climacteric complaints including anxiety and depression and for their coping style assessed with the Italian version of the Utrechtse Coping Lijst. Daily hot flashes and severe vaginal dryness were reported by almost half of the studied population, regression analyses were performed in order to investigate how much of the variance in such symptoms was explained by the psychosocial variables and by the coping mechanisms. A more recent menopause, a lower educational level and an active coping predict a higher severity of hot flashes; a longer time since last menstrual period and a coping of avoidance predict a higher severity of vaginal dryness. The present study suggests that the severity of hot flashes and vaginal dryness among a clinical sample of postmenopausal women is not only determined by biological and social variables, but personal resources also explain part of the variance of such climacteric complaints.

The use of bone histomorphometry in osteoporosis research. How many patients do we need?

The purpose of this study was to determine whether balance and functional mobility independently predict bone mineral density (BMD) in postmenopausal women. BMD at the hip and spine was measured with dual-energy x-ray absorptiometry (DEXA). Participants were assigned into groups (i.e., osteoporosis: n=20; osteopenia: n=20; normal BMD: n=20) according to DEXA T-scores. Participants performed the single leg stance test (SLS), timed-up-and-go (TUG), and 6-meter walking test. An ordinal logistic regression was performed to determine whether the SLS, TUG, 6MWT independently predict BMD, while accounting for age, age at menopause, and body mass index. Three factors predicted low BMD: (1) less time to hold the SLS (odds ratio (OR): 0.50); (2) longer TUG time (OR: 2.85); and (3) older Age (OR: 1.31). Women with recent menopause diagnosed with osteoporosis are at a high-risk for fracture; incorporating the SLS and TUG into risk assessments may enable prompt and targeted intervention.

Blood Lead Levels in Relation to Menopause, Smoking, and Pregnancy History

Postmenopausal bone loss may result in the release of lead stored in bone. This study examined Mexican-American women aged 20 years and older who participated in the Hispanic Health and Nutrition Examination Survey (1982-1984) to assess the influence of menopause, pregnancy history, and smoking on blood lead levels. After adjustment for factors likely to influence blood lead levels and for design effects, the authors confirmed associations with age, income level, education, degree of urbanization, and body mass. Blood lead concentrations were markedly higher among current smokers and postmenopausal women, with these two factors showing separate, roughly additive effects. Gravidity had little impact on blood lead level among premenopausal women. However, among postmenopausal women, never-pregnant women had higher blood lead levels than did those who had ever been pregnant. The largest increase (4.4 micrograms/dl, 95 percent confidence interval 0.95, 7.8) was observed among smokers. In a separate analysis of postmenopausal women, women with recent menopause (4 years or less) had blood lead concentrations 1.4 micrograms/dl higher (95 percent confidence interval 0.20, 2.7) than did those whose menopause occurred more than 4 years previously. This finding, along with an overall slow decline in blood lead levels with each year after menopause, suggests that lead is being mobilized at rates consistent with the patterns of bone loss, placing women with recent menopause at increased risk for higher blood lead levels.