IMS Menopause Live

Commentaries from the IMS on recently published scientific papers that may be of interest. The latest articles from July 2015 onward are available to Members only when logged in. Selected articles are open to public.

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Migraine and cardiovascular risk in the menopause

8 August, 2016

Long ago it was perceived that migraineurs have a higher risk for ischemic stroke, mainly because of short-term pro-thrombotic alterations during attacks [1, 2]. Migraine with aura confers a lifelong 2–2.5-fold elevated risk of stroke. Frequency of migraine directly correlates with higher stroke risk, but only minimal evidence supports reducing migraine frequency with medications to reduce stroke risk. Women suffering from migraine with aura who smoke have a 9-fold increased risk of stroke. There are several potential mechanisms for the increased risk of ischemic stroke in migraineurs. Migraine may increase ischemic stroke risk via vasospasm-induced cerebrovascular hypoperfusion, platelet activation, increased platelet aggregation, and increased concentrations and activity of various vascular pro-coagulant factors. Still, the absolute risk of migraine-associated stroke in women is relatively low.

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Sorry folks, we were wrong at the time

18 April 2016

Despite the availability of effective hormonal and non-hormonal treatments for menopausal symptoms, few women with these symptoms are evaluated or treated  

Whoever can download from The New England Journal of Medicine and read the paper by Manson and Kunitz entitled 'Menopause management: getting clinical care back on track', or from the relevant commentary in Medscape must do so at their earliest convenience [1,2]. As a reminder, the authors were among the WHI study investigators, and Manson was also a Steering Committee member. Needless to detail again the consequences of the misinterpretation of the initial WHI study results, which reduced the use of postmenopausal hormone therapy (HT) by 80% or even more, just because of misunderstanding of its safety profile in recently menopausal women. Many later studies discussed the adverse outcomes of banning HT, mainly related to quality of life issues and bone health. The best would be just to bring some quotes from the article (in italics).

Despite the availability of effective hormonal and non-hormonal treatments for menopausal symptoms, few women with these symptoms are evaluated or treated. Leading medical societies devoted to the care of menopausal women agree that systemic hormone therapy is the most effective treatment currently available for these symptoms and should be recommended for women with moderate-to-severe vasomotor symptoms, in the absence of contraindications. Such criteria apply to approximately 20% of women in early menopause, most of whom remain untreated despite having symptoms that adversely affect their daily activities, sleep, and quality of life. Women's decisions regarding such therapy are now surrounded by anxiety and confusion. The WHI trial was designed to address the risks and benefits of long-term use of hormone therapy for the prevention of chronic disease in postmenopausal women who were on average 63 years of age at initiation of therapy. But the results are now being used inappropriately in making decisions about treatment for women in their 40s and 50s who have distressing vasomotor symptoms. The new generation of medical graduates and primary-care providers often lacks training and core competencies in management of menopausal symptoms and prescribing of hormonal treatments. Most primary-care residency programs in the United States don't provide adequate education in women's health in general or in menopause management in particular. Reluctance to treat menopausal symptoms has derailed and fragmented the clinical care of midlife women, creating a large and unnecessary burden of suffering.

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Midlife ADHD in women: any relevance to menopause?

12 October, 2015

Some cognitive decline, particularly in the domains of executive functions, is common among menopausal women. A new study has examined the effect of the psychostimulant lisdexamfetamine (LDX) on subjective and objective cognitive function among menopausal women who report new-onset executive function complaints [1]. LDX is a very popular medication indicated for the treatment of attention deficit hyperactive disorder (ADHD). Thirty-two healthy perimenopausal and early postmenopausal women experiencing mid-life-onset executive function difficulties, as measured using the Brown Attention Deficit Disorder Scale (BADDS), were administered LDX 40–60 mg/day for 4 weeks in this double-blind, placebo-controlled, cross-over study. Diagnosis of lifetime ADHD was exclusionary. BADDS total and subscale scores and performance on verbal memory and working memory tasks were outcomes of interest. Analyses revealed a significant effect of LDX treatment over placebo for total BADDS scores (p= 0.0001) and for four out of the five BADDS subscales (allp< 0.004). LDX treatment also resulted in significant improvement in delayed paragraph recall (p= 0.018), but there was no significant effect of treatment on other cognitive measures. Systolic blood pressure (p= 0.017) and heart rate increased significantly (p= 0.006) when women were on LDX but remained, on average, within the normal range. Treatment was well tolerated and improved the subjective measures of executive function as well as objective measures of delayed verbal recall in this sample of healthy menopausal women. The above study results raise several questions: (1) could some of the classical adult ADHD symptoms be related to reciprocal menopausal complaints? (2) Should we use psychostimulants as a therapeutic mode for certain menopausal ill outcomes, especially within the cognitive domains?

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Late peri/postmenopausal women have greater cardiovascular fat

28 September, 2015: 

Growing evidence suggests a role of cardiovascular fat (epicardial + paracardial + aortic) in the pathogenesis of coronary heart disease. In order to study the relationship between deposits of cardiovascular fat and the menopause, El Khoudary and colleagues studied 456 women with an average age of 50 years from the SWAN heart cohort. Sex hormone levels were measured and cardiovascular fat volume was quantified by computerized tomographic scan. Late peri/postmenopausal women had greater volume of cardiovascular fat as compared with pre/early perimenopausal women independent of age and obesity. Lower estradiol concentrations were associated with greater cardiovascular fat volumes. The authors concluded that cardiovascular fat perhaps plays a role in the higher risk of coronary heart disease reported in women after the menopause [1].

Comment

The relationship between the menopause and increased weight is not completely clear; what is clear is that the cessation of ovarian function is associated with redistribution of body fat, increased abdominal fat and waist circumference, all known cardiovascular risk factors [2]. Accumulation of abdominal fat is greatest in postmenopausal women and may play a role in the increased prevalence of cardiovascular risk observed after menopause onset. Adipose tissue is not merely a silent organ for energy storage, but rather an active source of multiple bioactive factors called adipokines, peptides that signal the functional status of adipose tissue to targets in the brain, liver, pancreas, immune system, vasculature, muscle, and other tissues. Secretion of adipokines (adiponectin, fibroblast growth factor 21, vaspin, apelin, progranulin, etc.) is altered in adipose tissue dysfunction and may contribute to a spectrum of obesity-associated conditions such as cardiovascular and metabolic, chronic inflammatory, and several malignant diseases [3].

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Older women sleep differently to older men

21 September, 2015: 

Sleep disturbances increase with advancing age in both women and men although inherent gender differences are apparent. Older women take longer to fall asleep, have greater difficulty in staying asleep, have more daytime sleepiness, less stage 1 and stage 2 NREM sleep. Older women are also more likely to develop insomnia, the restless sleep syndrome and its accompanying sleep disturbances and have more obstructive sleep apneic symptoms compared to older men [1].

Comment

Human and animal studies have shown that gender and gonadal hormones do influence the circadian and homeostatic processes, although it remains unknown whether the gender-associated differences in the sleep/wake cycle are mediated by either, or both, of these processes. The studies addressing the subject are still speculative, but there is evidence that both the sex chromosomes and gonadal hormones are very likely to contribute to these differences at cellular, organic and systemic levels, whilst environmental, social and cultural influences are also likely to further impact on these differences in sleep [2].

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Pooled analysis of interventions for menopausal vasomotor symptoms

14 September, 2015

The aim of a recently published study by Guthrie and colleagues was to describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women [1]. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health (FLASH) network tested several interventions for menopausal vasomotor symptoms in three randomized clinical trials. Participants were 899 perimenopausal and postmenopausal women with at least 14 bothersome vasomotor symptoms per week. Interventions included 10–20 mg escitalopram per day, non-aerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose oral 17β-estradiol (E2) per day, and 75 mg low-dose venlafaxine XR per day. The main outcome measures were changes from baseline in mean daily vasomotor symptom frequency and bother during 8–12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and the corresponding control group adjusted for baseline characteristics. The 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at -1.4 per day (95% CI -2.7 to -0.2), low-dose E2 at -2.4 (95% CI -3.4 to -1.3), and venlafaxine at -1.8 (95% CI -2.8 to -0.8); vasomotor symptom bother reduction was minimal and did not vary across these three pharmacologic interventions (mean -0.2 to -0.3 relative to placebo). No effects on vasomotor symptom frequency or bother were seen with aerobic exercise, yoga, or omega-3 supplements. These analyses suggest that escitalopram, low-dose E2, and venlafaxine provide comparable, modest reductions in vasomotor symptom frequency and bother among women with moderate hot flushes.

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