desirable levels of vitamin D and supplementation

21 December, 2015: 

In a recent article in JAMA, Hansen and colleagues presented a randomized clinical trial of treatment of vitamin D insufficiency in postmenopausal women [1]. The trial compared the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density (BMD), timed-up-and-go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency. This randomized, double-blind, placebo-controlled trial studied a total of 230 postmenopausal women 75 years or younger with baseline levels of 25-hydroxyvitamin D or 25(OH)D of 14–27 ng/ml and no osteoporosis. Outcome measures were 1-year change in total fractional calcium absorption using two stable isotopes, BMD and muscle mass, using dual-energy X-ray absorptiometry. After baseline absorption was controlled for, calcium absorption increased by 1% (10 mg/day) in the high-dose arm but decreased by 2% in the low-dose arm (p = 0.005 vs. high-dose arm) and 1.3% in the placebo arm (p = 0.03 vs. high-dose arm). We found no between-arm changes in spine, mean total hip, mean femoral neck, or total body BMD, trabecular bone score, muscle mass, and timed-up-and-go or five sit-to-stand test scores. Likewise, we found no between-arm differences for number of falls, number of fallers, physical activity, or functional status.

High-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on BMD, muscle function, muscle mass, or falls. We found no data to support experts’ recommendations to maintain serum 25(OH)D levels of 30 ng/ml or higher in postmenopausal women. Instead, we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/ml.

Comment

In the US National Library of Medicine [2], we can read that vitamin D includes both cholecalciferol and ergocalciferol. Vitamin D is a hormone since it is formed in the skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone (PTH). But, because in our times, exposure to sunlight is so difficult, vitamin D is really a vitamin, as we need take vitamin D with meals; however, we have another problem: a diet does not usually contain a sufficient amount of vitamin D, as it is present in very few foods.

14 December, 2015: 

Obesity is a well-known major risk factor for many disease situations as well as for mortality. This risk is easily identified by a simple measurement of weight or of body mass index (BMI). However, there are several additional related parameters, namely lean body mass, total body fat, visceral fat, body composition and distribution of body fat, which have been investigated in light of their potential prognostic values. A recent study presented data from the Women's Health Initiative on associations between BMI, body composition, and incident mortality [1]. About 10,500 postmenopausal women, who underwent dual-energy X-ray absorptiometry scans (DXA) for estimation of total body fat and lean body mass, were followed for 13.6 (± 4.6) years. Their baseline characteristics were: age 63 (± 7) years; age at menopause 47 (± 7) years; weight 74 kg (± 16) kg; BMI 28 (± 6) kg/m2; total lean body mass 53% (± 7%); total fat body mass 44% (± 7%). Overall, BMI 35 kg/m2 was associated with increased mortality (adjusted HR 1.45, 95% CI 1.16–1.82), while total body fat and lean body fat were not. Among women aged 50–59 years, higher % total body fat increased risk of death (HR 2.44, 95% CI 1.38–4.34) and higher % lean body mass decreased risk of death (HR 0.41, 95% CI 0.23–0.74), despite broad-ranging BMIs. However, the relationships were reversed among women aged 70–79 years (p < 0.05). When the results were stratified by waist circumference, the protective association of higher lean body mass in younger women (age < 60 years) was seen only among those with low waist circumference (< 88 cm) and not those with larger waists (≥ 88 cm). Furthermore, the increased mortality risk among older women (ages 60–69 and ≥ 70 years) with higher lean body mass was seen only among those with a high waist circumference.

Comment

Body weight and BMI give pretty good correlations with many metabolic, cardiovascular and neoplastic diseases.

30 November, 2015: 

Climacteric symptoms including hot flushes, night sweats, pain during sexual intercourse, hair loss, forgetfulness, depression and sleeping disturbances are common complaints among breast cancer patients. Some of them are receiving anti-hormonal treatment and others develop ovarian failure as a consequence of cancer treatment. Among these patients, many therapies for alleviating such symptoms have been tested but the results are conflicting. Recently, Münstedt and colleagues have published an study assessing the role of bee pollen and honey in relieving menopausal symptoms in patients receiving tamoxifen and aromatase inhibitors/inactivators [1]. The authors compared a pollen honey mixture with pure honey (placebo) in a prospective, randomized, cross-over trial. Of the 46 patients recruited; 68.3% reported an improvement in their symptoms while taking honey, compared with 70.9% (22/31) who reported an improvement with pollen (the difference was non-significant). This study provided evidence that honey and bee pollen may improve menopausal symptoms in breast cancer patients on anti-hormonal treatment.

Comment

This study highlights that both honey and the pollen–honey mixture improved menopausal complaints in breast cancer patients. Honey was found to be very effective in patients receiving aromatase inhibitors; nevertheless, an increase in estradiol levels was detected among these subjects and this may raise some concerns regarding the safety of honey in such patients. Previous studies have suggested the possible role of bee products for symptoms in menopausal women [2,3]; however, this study is the first suggesting that the pollen–honey mixture improves menopausal symptoms even in breast cancer patients undergoing anti-hormonal treatment. Anecdotally, certain patients also reported additional favorable effects, including reduced hair loss, improvement in bowel movement and normalized blood pressure.

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?

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].

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].

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.

31 August, 2015:

Vulvovaginal atrophy (VVA) is a major consequence of menopause and related loss of the estrogenic effect on the vaginal epithelium. For many decades, the ideal therapeutic approach was to use systemic estrogen, which was very effective. Local treatment with vaginal estrogen (creams, tablets, and rings) is effective to the same extent. But, on the other hand, the downside of systemic hormone therapy (risks for breast cancer, cardiovascular and thromboembolic events, perhaps some cognitive decline) became a major issue after the first release of data from the Women's Health Initiative (WHI) trial in 2002, and changed both patients' preferences and prescription habits. The uncertainty about estrogen resulted in two changes concerning the treatment of VVA. The first has been to lower the dosage of local estrogen preparations, still maintaining a good clinical response and symptom relief, but keeping serum estrogen levels well below premenopausal levels. The other was to promote non-estrogenic and non-hormonal therapies, either by using marketed products, or by developing new drug formulations. Among the recently approved medications is prasterone – an intravaginal DHEA preparation [1,2]. In a 52-week-long study which showed a significant improvement in vaginal dryness and irritation/itching, and in pain during sexual activity, the authors commented that 'The treatments currently used against VVA are essentially intravaginal and oral estrogen; however, as indicated by the black box on the estrogen information leaflets, there are risks. In fact, even at the lowest dose and dosing regimen, all intravaginal estrogen preparations increase serum estrogens above the normal postmenopausal range or above the threshold of no biological activity with the accompanying risk of systemic effects' [2]. Is this statement supported by hard clinical data?

24 August, 2015

Breast cancer can occur in women below 50 years old and represents 25% of the total number of cases. Risk factors and histological characteristics of breast cancer are different in young women compared with older women. There are many publications on the risk of breast cancer and hormone treatment (MHT) in postmenopausal women. However, less is known about use of MHT in young women and especially looking separately at the impact of estrogen-only treatment (ET) and combined estrogen–progestin treatment (EPT). A recent study aimed to investigate whether the use of MHT is a risk factor for young-onset breast cancer [1]. The authors used the Two Sister Study for this purpose. It is a sister-matched case–control study of young-onset breast cancer from the Sister Study, a prospective cohort study of 50,884 women without breast cancer who had a full or half sister who had been diagnosed with breast cancer; 1422 cases and 1689 controls were included. Because 10% of control sisters and no case sisters had reached the age of 50 years before 2002 when the WHI study was published and because MHT prescriptions decreased drastically thereafter, a propensity score was used to decrease the impact of this bias. Results show that a low percentage of women used MHT. The most frequent was ET (7% of controls and 4% of cases), then EPT (3% and 2%, respectively) and progestin alone (PT) (1% and 1%). Crude odds ratios (OR) for breast cancer were less than 1 for every MHT category except PT. ET use was inversely associated with young-onset breast cancer (propensity score, adjusted OR =0.58; 95% CI 0.34–0.99); the adjusted OR for EPT use was 0.80 (95% CI 0.41–1.59) and for PT was 1.51 (95% CI 0.76–3.00). Adjustment for duration of use, age at first use, menopausal status at first use, and recency of use did not appear to modify the association. There was no interaction by oophorectomy status but women using ET were more often hysterectomized and oophorectomized. The authors concluded that neither ET nor EPT increase the risk of young-onset breast cancer and that ET might be associated with a reduced risk.

17 August, 2015

In contrast to the large body of literature on psychological symptoms during the menopause transition, relatively little is known about positive well-being including happiness, satisfaction with life and self-actualization at this time. Our recent review article 'Positive well-being during the menopausal transition' [1] responded to this issue though synthesizing quantitative work on positive functioning across the menopause transition. Nineteen relevant studies were identified, and the vast majority found that both menopausal stage and the presence/frequency of vasomotor symptoms were independent of positive well-being. Four studies using aggregate scales of menopausal symptoms such as the Greene Climacteric Scale (GCS), however, demonstrated that symptoms were strong predictors of diminished well-being. These findings demonstrate the importance of delineating menopausal factors in order to clearly determine which aspects of menopause are most likely to have an impact on positive well-being.