Sleep problems are common in the menopause for a number of physiological reasons. Ingredients in Drift such as tryptophan, folic acid, saffron, melissa, hops, magnesium and vitamin D, can not only deliver improvements in sleep quality and duration, but also help relieve problematic issues such as hot flashes, low mood and anxiety and generally contribute to wellbeing during this period in a woman’s life. This makes Drift the ideal supplement to recommend to pre, peri and post menopausal women-all due to synology.

Melatonin supplements appear to be ineffective for insomnia in the menopause    

Melatonin levels decrease with aging after the age of 50 (1). Melatonin age-related decline is correlated with a decreased melatonin biosynthesis and release by the pineal gland, which is considered to be due to decreased retinal light perception and the changing nature of the vitreous body, which transmits less light (2). Thus, the reduction of melatonin levels usually occurs contemporarily to menopause age (3). It appears, serum melatonin levels decrease with age, attaining minimum levels in menopause. Indeed, in a prospective study, Toffo et al. showed that the duration of secretion and concentration of melatonin tended to be lower in postmenopausal women (aged 58–71 years) than in perimenopausal (4). Hence, the decline of melatonin secretion which physiologically occurs with age could be a further player that could contribute to sleep disturbances in menopause

However, in a systematic review and meta-analysis of randomized controlled trials examining the effects of exogenous melatonin on sleep quality and menopausal symptoms in menopausal women, the general menopausal symptoms, sleep quality, mood state, oestradiol levels, and BMI did not improve under the intervention (5).

Drift and sleep disturbances during the menopause

In contrast in menopausal women mean sleep hours and insomnia have been shown to be significantly correlated with platelet tryptophan concentrations with differences observed in evaluations of insomnia and hot flashes (6)

Low Serum Tryptophan Levels appear to be an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age. In menopausal women a negative correlation between age and tryptophan levels has been demonstrated, and that likewise depression scores correlated negatively with serum tryptophan (7). 

In a case control study, Bravo et al. showed an increase in total sleep time and sleep efficiency after a week of consumption of 60mg tryptophan daily in mainly female volunteers of menopausal age who suffered from sleep disorders (8). The consumption of tryptophan showed an increased sleep efficiency (sleep percentage while the volunteer is in bed), actual sleep time (assumed sleep minus awake time) and decreased total nocturnal activity and sleep latency. In a randomised, placebo controlled, parallel trial, Mohajeri et al. investigated the effects of a tryptophan-rich supplement on cognitive and sleep quality, in fifty-nine mentally and physically healthy women aged 45–65 years (9). The authors concluded daily consumption of the tryptophan supplement appears to have beneficial effects on emotional and sleep quality. The quality of sleep tended to improve over the duration of the treatment compared with controls. Thus, the consumption of a tryptophan supplement appears to be suitable in menopausal women with sleep disorders.

Beneficial effects of ingredients in Drift on menopausal sleep disturbances and hot flashes

Tryptophan and hot flashes

In patients going through medically induced menopause such as women treated for breast cancer, experiencing symptoms such as hot flushes, asthenia, and insomnia, the administration of tryptophan as a nutritional supplement has been demonstrated to be well tolerated, improve quality of life, and is associated with improvement in the scale scores of the symptoms of interest such as insomnia and hot flashes (10).

A study treated menopausal women with folic acid or placebo once a day during four weeks. The mean hot flash frequency was significantly different in third and fourth weeks. The results indicated that folic acid was effective in reducing the severity, duration, and frequency of hot flashes during menopause (11). 

Magnesium and hot flashes

Findings suggest that oral magnesium supplementation is effective in reducing the severity and frequency of hot flashes in women after treatment of breast cancer (12). Magnesium appears to be a safe and inexpensive therapy for those with bothersome hot flashes. The greater than 50% reduction in symptoms suggests that oral magnesium is likely more effective than placebo and meets pre-established criteria of sufficient success to test in a randomized, placebo-controlled trial. Symptoms associated with hot flashes, such as fatigue, abnormal sweating, and perceived distress from the hot flashes were significantly reduced.

Vitamin D and bone health

During menopause, the decline of ooestrogens results in increased bone turnover, a decrease in bone mineral density and elevated fracture risk. Musculoskeletal discomfort might impair quality of life, mood disturbances do frequently occur and the risk of metabolic and cardiovascular disease increases. Moreover, body composition changes including increased fat mass and decreased lean mass, which results in an increased risk of vitamin D (VD) deficiency. There are precise recommendations regarding a sufficient VD intake in order to prevent bone loss in peri- and postmenopausal women (13). Considering the fact that VD deficiency and menopause share risk factors beyond bone health such as cardiovascular, metabolic, cognitive and affective disorders, a sufficient VD status should be attained in all peri- and postmenopausal women. This might be beneficial not only considering bone health but also regarding cognitive, affective, metabolic and cardiovascular health of women.

Saffron in anxiety and depression in the menopause

The aim of a recent study was to examine the tolerability and efficacy of saffron extract on menopausal symptoms over a 12 week period. Results from the Greene Climacteric Scale (GCS), revealed a significantly greater reduction in the GCS psychological score (P = 0.032), characterised by a 33% reduction in anxiety and a 32% reduction in depression scores from baseline to week 12. There was also a significantly greater reduction in the Psychological Negative Affect Schedule (PANAS), negative affect score (P = 0.043) compared to the placebo (14). 

In a meta-analysis comprising 23 studies, saffron administration had a large positive treatment effect when compared with the placebo on depressive and anxiety symptoms (15). These studies have been conducted on adults of varying ages, with no trial specifically examining its mood enhancing effects during perimenopause. However, in a study on post-menopausal women with hot flushes, improvements in depressive symptoms were identified after the 6-week administration of a saffron extract (16). 

Melissa in the menopause

Melissa officinalis is rich in caffeic acid and this herb is used to treat nerve stimulation and sleep problems especially in menopause. There is no report on dangerous side effects induced by the intake of therapeutic doses of this herb (17,18).

Chamomile in the menopause

A 2019 study investigated the outcome of the use of chamomile extract on sleep disorders occurring after the menopause (19). After 4 weeks of treatment, significant improvement was observed in sleep latency, time of waking after sleep onset, number of awakenings and total sleep time in the Chamomile group compared with placebo group.

In a separate study investigated the use of Chamomile extract twice a day for one month (20). There was significant difference between the mean of sleep quality score in the intervention group before and after the intervention (P=0.001). Also, there was significant difference between mean score of sleep quality in intervention and control groups after the intervention (P=0.001). The authors concluded using Chamomile extract is effective in reducing sleep disorder of menopausal women.

Hops and hot flashes

Results of a 2015 study showed that consumption of a hops supplement dramatically reduced the mean score of the early symptoms of menopause (21). This decrement was evident according to the follow-up of the subjects for 12 weeks and comparison of the total score of the Greene Scale and its dimensions, as well as the number of hot flashes in the intervention group compared with the control group. The results of a randomized, double-blind study in Belgium (22) also showed that Hop extract significantly decreased the mean score of menopausal indicators and the number of hot flashes in comparison with placebo in postmenopausal women after 6 and 12 weeks (22). Another trial in Finland (23) of hops extract, over 16 weeks identified a reduction of vasomotor symptoms. 

Sleep problems during the menopausal transition: prevalence, impact, and management challenges

Menopause, defined by cessation of menses, marks an important transition in reproductive states in women. The menopausal transition, which begins 4–6 years before cessation of menses (occurring at a median age of 51 years), is associated with fluctuating hormone levels and emergence of physiological and psychological symptoms such as hot flashes (HFs), sleep disturbances, mood changes, and vaginal dryness. Symptoms vary between women in frequency, severity, and duration, persisting for several years after menopause in some women. Sleep disturbances are a major complaint of women transitioning menopause (1–5)and have a far-reaching impact on the quality of life, mood, productivity, and physical health, especially in women in whom sleep disturbances are severe and associated with functional impairment.

The incidence of insomnia in the menopause

Sleep difficulties, particularly night-time awakenings, are a major complaint in the approach to menopause, being present in 40–60% of women (6) and are one of the top health issues in peri- and postmenopausal women (7). Together with hot flashes/night sweats, feeling tired and weight gain, sleep problems are the most common symptoms women discuss with their healthcare providers (8). In 26% of perimenopausal women (a prevalence that is higher than in premenopausal or postmenopausal women), sleep disturbances cause significant distress and impact women’s daytime functioning qualifying them for a diagnosis of insomnia disorder (9).

The consequences of insomnia in the menopause

Untreated insomnia is associated with several adverse physical (e.g. hypertension, diabetes) and psychological (e.g. depression) consequences (10), yet it is under-appreciated and under-treated, possibly due to its subjective diagnostic nature and multifactorial etiology making it difficult to recognize and treat. The economic burden of insomnia is substantial, with decreased productivity and increased healthcare utilization (11). The impact of insomnia is particularly relevant in midlife women; in the United States, an estimated 2 million women reach menopause every year (The North American Menopause Society, 2010) and by 2030 more than 1.2 billion women worldwide will be 50 years or older. Hence there is overwhelming evidence of an increase in perceived sleep difficulties as women approach menopause from several large longitudinal studies like the Study of Women’s Health Across the Nation (SWAN) (12), the Australian Longitudinal Study on Women’s Health (13), and the Seattle Midlife Women’s Health study (14).

Insomnia in different phases of the menopause

A recent meta-analysis from 24 studies found women in perimenopause are 60% more likely to experience sleep disturbances relative to pre-menopause, 67% more likely in the postmenopausal stage and be 217% more likely to be affected if the menopause is surgically induced (15). 

In order to further quantify the problem of poor sleep in menopause a new study investigated Polysomnography (PSG), including electroencephalographic (EEG) sleep measures within a group of women all in the menopause transition, comparing those who had or had not developed insomnia in association with their transition. The sleep deficit in the insomniacs was substantial; PSG data indicated that they slept, on average, 6 hours and 4 minutes, with 47.4% of them sleeping less than 6 hours. The shorter sleep duration in insomniacs compared with controls was evident in subjective sleep ratings and was not specific to the laboratory environment, being apparent across several days of monitoring with sleep diaries (16). The National Sleep Foundation recommends 7–9 hours of sleep in healthy adults; less than 6 hours is not recommended (17) and is associated with increased risk for poor health outcomes (18). Insomnia also is an independent risk factor for poor health (Irwin, 2015) and the most dramatic consequences arise when insomnia and short sleep duration coexist. Individuals with combined insomnia and PSG-defined short sleep duration (<6 hours) have an increased risk of hypertension (19) and Type-2 Diabetes, and deficits in executive attention (20). The presence of PSG-defined short sleep duration (<6 hours) in insomnia is a strong predictor of persistent insomnia years later (21).  

Insomnia and menopause: pathophysiologic links

Mechanisms causing insomnia in menopausal women are multifactorial and involve hormonal changes, transition-stage symptoms (e.g. hot flashes [HFs], night sweats), and mood disorders as well as some factors coincident with midlife and being older, such as stress, obesity, poor health, and increased incidence of other sleep disorders (22,23)

Hormonal changes

Many studies reported an effect of sexual hormones on sleep (24-28). Progesterone exerts anxiolytic and sedative properties, stimulating benzodiazepine receptors favouring nonrapid eye movement sleep. Ooestrogens seem to decrease sleep latency and the number of awakenings (28). Indeed, low ooestrogen levels have been found to be associated with a greater severity of awakenings (29). Moreover, they regulate the time of lowest body temperature during the night, as demonstrated by the evidence that stopping oestrogen therapy leads to a shift forward of the aforementioned time and changes the depth of the temperature drop (30).  Other findings on the relationship between steroid hormone levels and sleep difficulties in menopause showed an association between follicle stimulating hormone, estradiol changes, and estradiol to total testosterone ratio and poor sleep quality across the transition and in the late reproductive stage (31).

Hot flashes

HFs are common symptoms of impending menopause (reported by up to 80% of women (32) and are considered an important source of sleep disturbance (33,34). The presence of HFs has been consistently associated with poorer self reported sleep quality, suggesting a possible link between HFs and nocturnal awakenings (35). Campbell and Murphy (36) found that high body core temperature prior to and during sleep was significantly correlated with poorer sleep efficiency and higher luteinizing hormone levels even in women without vasomotor symptoms (VMS). More recently, it has been found that almost 80% of HFs interfered with sleep (37). Longitudinal data have shown that women with moderate-to-severe HFs present a higher risk of frequent nocturnal awakenings in comparison to women without HFs. Bothersome HFs, but not HFs alone, seem to be associated with sleep difficulties. A recent protocol demonstrated that an objective increase of HFs is most common during early sleep and wake, typically preceding or occurring simultaneously with wake episodes, and that the number of HFs reported at night correlates with worsening of sleep disturbance indices (38). Finally, treatment of HFs using menopausal hormone therapy (MHT) seems to improve sleep quality (39).

Mood disorders

The association between menopause, mood disorders, and insomnia is widely reported. Depression represents a risk factor for poor sleep (40) and menopausal women are at increased risk of developing a major depressive episode, especially when HFs are present. In accordance with the ‘domino effect theory’, sleep is disturbed by HFs or other menopause related factors, and multiple arousals permit the development of intrusive anxious thoughts several times during the night (also exacerbated by pre-existing anxiety or depression). In turn, waking up repeatedly offers plenty of opportunities for presenting anxiety throughout the night. Finally, sleep fragmentation may contribute to daytime mood symptoms. In this context, insomnia follows sleep disruption and depression follows insomnia within a vicious circle (41).

Circadian modifications

The sleep/wake alternation is regulated by two biological mechanisms, the circadian and the homeostatic processes (42). While the homeostatic system regulates sleep intensity, the circadian clock controls sleep timing. This latter process is driven by an endogenous pacemaker located in the hypothalamic suprachiasmatic nuclei. 

Aging is typically associated with both alteration of the circadian system and a decrease in melatonin secretion, which are two strongly connected conditions. Limited data suggest that differences in circadian regulation (advanced circadian phase) in postmenopausal women could contribute to sleep difficulties, particularly a more fragmented sleep or early morning awakening (42). Animal models also suggest that alterations of reproductive hormone secretion may alter circadian rhythmicity (44), although many knowledge gaps remain. Circadian processes are critical to both sleep/wake and mood regulation. Consistent with findings in general populations, sleep/wake rhythms alterations are correlated with both higher anxiety and the presence of depression in menopausal women (45,46).

Together with the sharp decrease of oestrogen levels during menopause, even the gradual reduction of melatonin levels seems to play a role in developing insomnia. Indeed, these hormonal changes can eventually bring sleep disturbances and decreased quality of life in menopausal women. Toffol et al. demonstrated that postmenopausal women had lower night-time serum melatonin concentrations than perimenopausal women (45). Interestingly, a transient peak was observed at the time of full-blown menopause, where women can feel a transient improvement in sleep quality in spite of low oestrogen levels (47). Following this time period, melatonin secretion continues to decrease, sometimes to the extent that the woman experiences an advanced sleep phase syndrome. The loss of ovarian hormones during menopause could act on cognitive reserve both directly and indirectly through an increase of sleep disorders, accelerating cognitive decline (48).

Model of insomnia in the perimenopause

Conclusion

Sleep difficulties increase in prevalence as women transition menopause. For some women, sleep problems are severe and impact daytime functioning and quality of life and may have long-term consequences for mental and physical health. HFs are a unique aspect of insomnia in the menopausal transition and are strongly associated with reports of disrupted sleep, and HF-associated wakefulness makes a significant contribution to the amount of PSG-measured wakefulness during the night. In addition, given the co-occurrence of HFs and awakenings, women attribute those awakenings as specifically caused by HFs. Since some women may have sleep problems independent of HFs, other factors directly related to the menopausal transition (eg, instability/changes in the hormone environment with progressive decreases in estradiol and increases in FSH) and/or coincident with the transition (eg, movement disorders, mood disturbance, presence of a medical condition, and life stressors) also need to be considered. It, therefore, is critical to assess insomnia symptoms in the context of menopause as well as considering physical and mental health and presence of stressful life events. Given the presence of unique sleep disruptive factors (eg, HFs) and the multifactorial nature of sleep difficulties in women approaching menopause, with multiple factors often interacting, treatment needs to be tailored for women.

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Written by

Mike Wakeman, Pharmacist MSc, MSc, MSc, MA, BSc, MRPharmS

A pharmacist and healthcare specialist with 30 years’ experience in the natural products industry. Mike holds a Masters’s Degree in Pharmaceutical Analysis, Nutritional Medicine and Clinical Oncology.