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IMS Menopause Live

Commentaries from the IMS on recently published scientific papers that may be of interest. The latest articles from September 2018 onward are available to Members only when logged in. Selected articles are open to public.

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Measuring vulvovaginal symptoms in postmenopausal women

8 July, 2013

Erekson and colleagues recently published in the journal Menopause on their development of a Vulvovaginal Symptoms Questionnaire (VSQ) to determine the symptoms, emotions, life impact, and sexual impact of vulvovaginal symptoms on postmenopausal women [1]. They performed a number of validation tests which confirmed the utility of the questionnaire. Postmenopausal vulvovaginal symptoms include dryness, burning, pruritus, and dyspareunia. Vulvovaginal symptoms are common and have been reported by 9.6–44.4% of postmenopausal women. The authors found the VSQ to be a reliable and internally consistent instrument for measuring vulvovaginal symptoms in postmenopausal women. The authors demonstrated a reasonable validity of the VSQ, particularly in the absence of a gold standard for measuring vulvovaginal symptoms.

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Sugary foods and gynecological cancer risk

17 June, 2013

Once in 5 years, the American Cancer Society publishes its updated guidelines on nutrition and physical activity in the context of cancer prevention [1]. Among the detailed advice is the following quote: 'Limit consumption of sugar-sweetened beverages such as soft drinks, sports drinks, and fruit-flavored drinks.' How this general phrasing relates to specific cancer types is discussed below, and a recent study serves as a good starting point [2]. The investigators evaluated the impact of dietary intake of sugary foods and beverages, as well as added sugar and total sugar on endometrial cancer risk in a population-based, case-control study, including 424 cases and 398 controls. Participants completed an interview and food frequency questionnaire and provided self-recorded waist and hip measurements. Women in the highest quartile of added sugar intake had significantly increased endometrial cancer risk (OR 1.84, 95% CI 1.16–2.92). Among women with waist-to-hip ratio ≥ 0.85, risk was significantly higher for the highest versus lowest tertile of added sugar intakes (OR 2.50, 95% CI 1.38–4.52). The association with added sugar also became stronger when analyses were restricted to never users of hormone replacement therapy (OR 2.03, 95% CI 1.27–3.26, for highest versus lowest tertile). There was little evidence of effect modification by body mass index or physical activity.

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Vitamins and bone health in women

27 May, 2013

Have you heard of a potential interaction between vitamin E and bone health? A recent study from Spain evaluated the relationship between vitamin E status and osteoporosis in early postmenopausal women [1]. Anthropometric data, osteoporosis risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum parameters that may influence bone mineral density in postmenopausal women were analyzed in a cross-sectional study. The associations between osteoporosis and age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin E (measured as 25-hydroxyvitamin D and as the α-tocopherol : lipid ratio, respectively), bone alkaline phosphatase, smoking status, leisure physical activity and alcohol intake were modeled by a multivariate logistic regression and multi-linear regression analysis in 232 early postmenopausal women. A lower vitamin E : lipid ratio was associated with osteoporosis in multivariate logistic regression. In a multivariate linear model with BMD of the lumbar spine as a dependent variable, the vitamin E : lipid ratio was clearly related with BMD of the lumbar spine (Fratio = 6.30,p= 0.002). BMD of the lumbar spine was significantly higher in the highest tertile of the vitamin E : lipid ratio than in the lowest tertile. The mean vitamin E : lipid ratio was significantly lower in osteoporotic postmenopausal women (Tscore ≤ -2.5) (3.0 ± 0.6 μmol/mmol) than normal postmenopausal women (Tscore > -1) (3.5 ± 0.7 μmol/mmol) using multivariable-adjusted BMD. These findings highlight that vitamin E may increase BMD in healthy postmenopausal women.

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Menopausal women with symptoms do cost more

20 May, 2013:

Kleinman and colleagues have attempted to quantify the economic burden of employees who are diagnosed with menopause symptoms [1]. Their regression-based study analyzed the 2001–2010 medical, pharmacy, sick leave, disability, workers' compensation, and productivity data of large US employers. A cohort of employed women with diagnosed menopause symptoms (DMS), aged more than 40 years, was identified using medical claims. Control employees were propensity-matched on age, employer, plan enrollment length, and enrollment end date. The study included 17,322 women in each cohort. Employees with DMS had significantly higher medical costs ($4315 vs. $2972, p< 0.001), pharmacy costs ($1366 vs. $908, p < 0.001), sick leave costs ($647 vs. $599, p < 0.001), and sick leave days (3.57 vs. 3.30, p < 0.001). Employees with DMS had 12.2% (p = 0.007) lower hourly productivity and 10.9% (p = 0.014) lower annual productivity than controls.

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Endogenous androgen and body fat in the menopause

13 May 2013

Menopause is associated with dramatic changes in a woman's hormonal and metabolic profile. Whereas menopause per se does not seem to affect body weight, the estrogen decline around menopause is associated with a body fat redistribution favoring an android pattern [1]. Furthermore, although incapable of producing estrogens, the postmenopausal ovary remains an active endocrine organ, contributing substantially to the circulating androgen pool [2]. Cao and colleagues [3] in their recent paper conducted a cross-sectional study in early (≤ 5 years) and late (≥ 10 years) postmenopausal women to investigate the association of these two parameters, namely body fat distribution and circulating serum androgens. Late postmenopausal women had a higher percentage of body fat, compared to their younger counterparts, although body mass index (BMI) did not differ between groups. Both early and late obese postmenopausal women had higher androgen levels and more abdominal fat compared to women with normal weight. Serum androgens (free testosterone in early and DHEAS in late postmenopausal women) showed an independent and significant positive association with abdominal adiposity.

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Peripheral arterial disease and menopause

29 April, 2013: 

Looking at the cardiovascular system, it is clear that the heart has been extensively investigated and discussed in regard to the effects of menopause on the one hand, and hormone therapy (HT) on the other hand. But the area of peripheral arterial disease (PAD) in this respect has received much less attention. In a new cross-sectional study on 887 women aged 52–81 years, reproductive parameters were obtained by standardized interviews, and PAD was assessed by measuring non-invasively the ankle-brachial index (using a cut-off value of 0.9) and by assessing the presence of claudication using the Edinburgh questionnaire [1]. The only significant associations with the presence of PAD were later age at menarche (> 15 years) compared to age at menarche between 12 and 15 years (odds ratio (OR) 0.48; 95% confidence interval (CI) 0.24–0.98), and the presence of hot flushes (OR 2.09; 95% CI 1.11–3.92). Other reproductive parameters, such as parity, age at menopause, time since menopause, duration of fertility, ever use or current use of HT, ever use of oral contraceptives, history of hysterectomy, bilateral oophorectomy and depressive mood in relation to menopausal transition showed no significant association with PAD.

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WHI and breast cancer risk: the same old story

15 April, 2013:

WHI investigators keep hammering the issue of hormone therapy (HT) and related increased risk of breast cancer. Their 'money' is actually on what they call the estrogen + progestin (E+P) users, since they cannot claim a real risk in the estrogen-alone users. So now they bring new data from the WHI observational study [1]. Here is the Abstract:

In the WHI randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis for breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied. We identified 41,449 postmenopausal women with no prior hysterectomy and mammogram-negative within 2 years who were either not hormone users (n = 25,328) or estrogen and progestin users (n = 16,121). After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in non-users (0.60% vs. 0.42%, annualized rate, respectively; hazard ratio (HR) 1.55, 95% confidence interval (CI) 1.41–1.70, p < 0.001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (p < 0.001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and non-users (HR 1.03, 95% CI 0.79–1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR 1.32, 95% CI 0.90–1.93, p = 0.15), and more all-cause deaths after breast cancer (HR 1.65, 95% CI 1.29–2.12, p < 0.001) in estrogen plus progestin users than in non-users.

Thus the investigators concluded that, consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of non-users, increased breast cancer mortality can be expected.

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Lupus erythematosus, rheumatoid arthritis and menopause

8 April, 2013:

Understanding the impact of menopause and age-related androgen decline on the onset and course of autoimmune diseases, as well as the potential for hormonal interventions, is critically important [1]. In women, the course of systemic lupus erythematosis (SLE) and rheumatoid arthritis (RA) with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk and, after menopause, disease course changes in SLE and RA. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation.

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Genetic profiling of fracture risk

25 March, 2013:

A few decades ago, this might have been considered science fiction. But the ability to screen the entire human genome has become an important aid in the individualization of management of severe diseases. So far, gene profiling is mainly used in the hemato-oncology field and, to a lesser extent, in the area of chronic inflammatory diseases. A new review has shed light on both the research and clinical implications of genetic profiling as a means to identify individuals with high fracture risk [1]. To note, the tools already available in the market focus on people already afflicted with some serious disease, in which case gene profiling helps to decide on the best therapeutic approach. However, in regard to osteoporotic fractures, the idea is to detect future risk early and to implement primary prevention strategies accordingly. At the moment, bone mineral density (BMD) is the best predictor of fracture risk, and the initiation of anti-fracture therapies is based primarily on BMD results. However, several additional parameters (clinical, laboratory, personal and family history) should be part of decision-making as well. The FRAX score, adapted for each country, represents an approach better to identify individuals at higher risk for fractures. Early intervention according to predictive models has proved to have a beneficial effect in this respect [2]: in a fairly large study using the FRAX model, women lying at the 75th percentile of fracture probability (10-year probability, 24% at baseline) demonstrated a 27% reduction in fracture risk as a result of bisphosphonate therapy, whereas, in those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38%.

Nevertheless, the existing predictive models have not considered genetic variants in the prediction. Genome-wide association studies conducted in the past decade have identified several genetic variants relevant to fracture risk. These genetic variants are common in frequency but have very modest effect sizes. All genetic variants identified so far when considered in a multivariate model explain < 5% of variance in BMD and fracture susceptibility. It is thus assumed that additional genes should be sought, and perhaps some of these will demonstrate a higher impact on risk prediction. Empirical and simulation studies have shown that the usefulness of a single genetic variant for fracture risk assessment is very limited, but a profile of 50 genetic variants, each with an odds ratio ranging from 1.02 to 1.15, could improve the accuracy of fracture prediction beyond that obtained by use of existing clinical risk factors.

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SERMs, vulvovaginal atrophy and breast cancer

18 February, 2013:

A recent review [1] was intriguing, since it brought again to our attention the search for a desired molecule which should have optimal dual characteristics: inducing estrogen-like effects on menopause-related symptoms on the one hand, but avoiding the potentially serious adverse effects of postmenopausal hormone therapy on the other hand. Here is an Abstract of this review:

Vulvovaginal atrophy (VVA) in postmenopausal breast cancer patients has a significant impact on quality of life. While the etiology of VVA is primarily related to low estrogen levels seen in menopause, women with breast cancer have an added risk of VVA induced by a combination of chemotherapy, hormonal therapy, and menopause. Ospemifene is a new, non-hormonal selective estrogen receptor modulator (SERM) triphenylethylene derivative that is effective in treating VVA in postmenopausal women. Although other SERMs have antagonistic effects on the vagina, ospemifene exerts an estrogen-like effect on the vaginal epithelium. The review focuses on data demonstrating the antiestrogenic activity of ospemifene in several unique breast cancer animal models, and the implications for utilizing ospemifene in patients with breast cancer suffering from VVA.

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