Menopause

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Chapter 25 Menopause

Introduction

The definition of menopause is when there is no menstruation over a 12-month period. That is, when menstrual periods permanantly stop. Women undergo significant reproductive transitional and physiological changes which are accompanied by the additional effects of ageing and social adjustment. This phase known as the climacteric or perimenopause describes the time leading up to a woman’s final menstruation, along with the endocrinological, biological, and clinical features of the approaching menopause. The length of this transition is usually about 4 years, but is shorter in smokers than non-smokers.1 Ten percent of women may not experience this phase and menses may stop abruptly. The median age for menopause is 51 years, over an age range of 39–59 years.1, 2

This transitional phase is associated with a number of vasomotor, urinary symptoms and psychological tribulations (Table 25.1). There is a variation in symptoms experienced.

Table 25.1 Physical, vasomotor and urogenital symptoms, and psychological problems encountered by women approaching and during menopause

Physical/vasomotor symptoms Urogenital symptoms Psychological problems
Hot flushes

Loss of confidence Night sweats Depressed mood Palpitations Lack of libido Irritability/anxiety Headaches   Forgetfulness Amenorrhoea   Difficulty in concentrating Dry skin   Panic attacks Hair loss   Insomnia Joint pains   Fatigue Breast tenderness        

The severity of symptoms that women may experience range from mild to severe. Approximately 40–65% of women experience hot flushes or night sweats, 30–60% disturbed sleep, and 25–35% vaginal dryness which leads women to consult health professionals.3 The duration of these symptoms may vary from 2–20 years.4

The most effective treatments for hot flushes include oestrogens and progestagens.2 Current evidence supports short-term use of hormone replacement therapy (HRT) as the standard therapy for hot flushes.5, 6 Since the Women’s Health Initiative and Millenium study findings with long-term use of HRT in menopausal women, demonstrated increased risk of breast cancer7 more women are turning to non-pharmacological and various complementary medicines (CMs) for the relief of menopausal symptoms. Many women are reluctant to accept hormonal treatments, except when symptoms are severe, as they see this stage of their lives as a natural event, and not a disease. Menopause is an opportunity for lifestyle changes and it is worthwhile exploring prevention strategies, as women who commence HRT for hot flushes are likely to re-experience them after stopping HRT, even after 5 years.8

This chapter explores the scientific evidence base and safety concerns for lifestyle, non-pharmacological approaches to the management of menopausal symptoms.

Lifestyle changes

Reduced physical activity, low socioeconomic status and cigarette smoking (past and current) are contributors documented to increase the relative risk of hot flushes in menopausal women.9 A recent review has reported that lifestyle and diet adjustment interventions have the potential to significantly improve menopausal symptoms.10, 11 Hence, lifestyle behaviours are important determinants of menopausal symptoms. The available literature suggests that smoking and greater body weight are risk factors for vasomotor symptoms; women with vasomotor symptoms who smoke may benefit from smoking cessation, and women who are heavier than ideal body weight may benefit from weight reduction.12

Cigarette smoking

A case-control study of 611 middle-aged women (45–54 years) demonstrated that past and current smokers have higher odds of experiencing hot flushes compared with never smokers.14 Past and current smoking and duration of smoking influenced frequency and the severity of hot flushes. The longer the women smoked, the more severe the symptoms. Smoking did not influence blood levels of estradiol and estrone and the risk persisted even when women were treated with hormones. Cigarette smoking is therefore a strong predictor of experiencing hot flushes, including the severity of hot flushes.

Cultural differences

There are many cultures where the prevalence of menopausal symptoms is reported as low. Prevalence rates for vasomotor symptoms in surveys of women (on average 2-week recall of symptoms) conducted between 2000–2005 include:15 of interest, the lowest reported symptoms are found in peasant Greek women and Mayan women from Mexico.15, 16

Under-reporting of symptoms by women in surveys may also contribute to low prevalences. It is not clear why the incidence of menopausal symptoms vary in different geographical areas. A recent review has reported that the prevalence variation of these symptoms may be influenced by a range of factors, including climate, diet, lifestyle, women’s roles, and attitudes regarding the end of reproductive life and ageing.17 Women’s attitude and expectations that can influence the experience of the perimenopause are determined by a number of factors including cultural attitudes and expectations, medicalisation (menopause viewed as an illness), their reproductive history, general health, mother’s experience, marital status, relationships with and attitude by their husbands/partners, extended family, social support, career and religious belief. In general, a healthy lifestyle, namely diet (e.g. foods high in phytoestrogens and isoflavones), exercise and avoiding smoking, and strong support from friends and family can positively impact on menopausal symptoms.15

negligible

15.1% 17.6% 23% 22–46.6% 36.6–37.8% 46.5% 26.2–44.7% 49% 55% 61%

Health practitioners and other caregivers should recognise that variations exist and ask patients specific questions about symptoms and their impact on usual functioning.1720

Mind–body medicine

Psychological support

In a study of 78 menopausal women suffering hot flushes and breast cancer, the women were randomised to education and psychosocial support groups or a control group.25 A significant improvement in symptoms was found with the active treatment.25 A recent pilot trial demonstrated a possible effectiveness of cognitive behavioural interventions for the treatment of climacteric syndrome.26 A further pilot investigating cognitive behavioural group therapy (CBGT) supported the notion that CBGT interventions aimed at reducing vasomotor symptoms may be of value for menopausal hot flushes when administered in a small-group format.27 A recent systematic review has concluded that psycho-educational interventions seem to alleviate hot flushes in menopausal women and breast cancer survivors.28

Relaxation therapies

Nervous tension may cause instability of the thermoregulatory centre leading to sudden, transient, and erratic peripheral vasodilation in the skin blood vessels causing the sensation of flushing.29 Interestingly, even excitement, such as laughter, can stimulate the nervous system and bring on more hot flushes. Relaxation can alleviate menopausal symptoms.28

Three randomised control trials (RCTs) identified by the North American Menopausal Society,30 demonstrated paced respiration (slow, controlled, diaphragmatic breathing) reduced hot flushes by 50%, particularly if performed at the onset of a hot flush when compared with controls. A pilot study of mindfulness-based stress reduction for hot flushes has shown a positive result in improving both quality of life and reducing severity of hot flushes in 15 women experiencing severe hot flushes over the course of treatment.31

Physical activity/exercise

Aerobic exercise and customised exercise programs

Physical activity may ameliorate hot flushes and insomnia by influencing opioid levels.32 It is known that opioid levels are lowered in menopause and that exercise can increase opioid levels such as endorphins and activity.33 Although data supporting physical activity are still preliminary recent studies suggest that women who exercise regularly are less likely to experience severe hot flushes.34 A customised exercise program is valuable for improving the health related quality of life of menopausal women compared to those who do not perform any form of physical activity.35

A Cochrane review of RCTs identified 1 small trial that compared exercise with HRT and found both interventions were effective in reducing vasomotor symptoms, although HRT was more effective than exercise.36

A recent systematic review of the literature of RCTs found aerobic exercise improves psychological health and quality of life in vasomotor symptomatic women.37 The review also identified several RCTs of middle-aged menopausal women and found aerobic exercise can invoke significant improvements in this age group of menopause-related symptoms such as mood, health-related quality of life and insomnia compared with middle-aged women who did not exercise.37

Yoga

Yoga can play an important role in the management of menopausal symptoms. A number of trials support the recommendation of specific yoga exercises as an evidence-based prescription for menopausal symptoms.38, 39, 40

A recent randomised control study of 180 perimenopausal women comparing yoga comprised of breathing practises, sun salutation and meditation was found to be significantly beneficial for reducing hot flushes and night sweats and improving cognitive functions such as memory, mental balance, attention, concentration and recall when compared with control group; a set of simple physical exercises, under supervision.41

A trial of 120 women (aged 40–55 years) with menopausal symptoms randomised women into 2 study arms: yoga and an exercise (control) group.42 In the yoga therapy group, women were instructed to practise various yoga postures such as sun salutation that consists of 12 postures, pranayama (breathing practices) and avartan dhyan (cyclic meditation). Women in the control group were instructed a set of simple physical exercises (supervision by trained teachers). Women in both groups practised either yoga or physical exercises 1 hour daily, 5 days per week over the 8-week study period.

The perimenopausal women in the yoga therapy group demonstrated significantly reduced perceived stress, climacteric symptoms, and neuroticism traits compared with controls.42

A systematic review that explored the role of meditation and yoga for treating diseases concluded the strongest evidence for efficacy was found for epilepsy, symptoms of the premenstrual syndrome and menopausal symptoms.43

However, a recent systematic review of 7 studies reported mixed results and the evidence at present is insufficient to suggest that yoga is effective in menopause.44

Some studies did not demonstrate any benefit of yoga on menopausal symptoms, sleep or self-esteem in menopausal women.44, 45, 46

More rigorous studies are required to assess the role of specific yoga and breathing practises for the management of menopausal symptoms.

Nutritional influences

It is essential that women consume a healthy well-balanced diet and are aware of the importance of exercise (weight-bearing) and sunshine for vitamin D synthesis well before menopause to prevent health problems accelerated after the menopause, such as cardiovascular disease and osteoporosis. Women presenting with menopausal symptoms provide an opportunity to discuss and educate them about the importance preventative advice, the importance of lifestyle changes, and a healthy diet (see clinical tips at the end of this chapter).

Calcium and vitamin D for menopausal women

There is a role for the recommendation of calcium and vitamin D (cholecalciferol) supplementation by menopausal women with demonstrated vitamin D deficiency for the prevention of osteoporosis. Routine use, however, is questionable. (See Chapter 30 for osteoporosis.)

A Cochrane review of 45 trials, found vitamin D alone is not effective in preventing hip fracture, vertebral fracture or any new fracture.47 Vitamin D with calcium reduced hip fractures especially in people in institutional care, but not significantly in the community-dwelling subgroup.47

The World Health Initiative for the calcium/vitamin D RCT of 36 282 post-menopausal women (aged 51–82 years) from 40 US clinical centres assigned to 1000mg of elemental calcium carbonate and 400IU of vitamin D(3) daily or placebo with average follow-up of 7 years, found that supplementation did not have a statistically significant effect on mortality rates but may reduce mortality rates in post-menopausal women.48

Furthermore, findings from the Women’s Health Initiative study also found adherence to calcium and vitamin D supplements over 4 years did not produce any favourable effects compared to placebo on physical functioning or physical performance in the older women.49

Despite these findings, there is strong overwhelming evidence that vitamin D deficiency is associated with an increased risk of osteomalacia, fractures, falls and osteoporosis. Hence, when serum vitamin D levels are below normal range, women should be supplemented with combined calcium and cholecalciferol vitamin D3 supplements, and be encouraged to increase appropriate sun exposure.

Phytoestrogens and isoflavones in diet

Phytoestrogens are oestrogenic compounds found in plants and consist of isoflavones, lignans and coumestans (Table 25.2).50 Isoflavones have a similar structure to oestrogen and have the capacity to exert both mild oestrogenic effects in menopausal women and anti-oestrogenic effects in pre-menopausal women.50 Comparative surveys of Japanese women and parallel groups of women from Canada and North America determined significant differences in the incidence of hot flushes and nocturnal sweating during premenopausal, perimenopausal and post-menopausal phases.51

Table 25.2 Foods rich in phytoestrogen content

Phytoestrogen food sources Phytoestrogen content (μg/100g)
Flax seed 379380
Soy beans 103920
Tofu 27150.1
Soy yoghurt 10275
Sesame seed 8008.1
Flax bread 7540
Black bean sauce 5330.3
Multigrain bread 4798.7
Soy milk 2957.2
Hummus 993
Soy bean sprouts 789.6
Garlic 603.6
Mung bean sprouts 495.1
Dried apricots 444.5
Alfalfa sprouts 441.4
Pistachio nuts 382.5
Dried dates 329.5
Sunflower seed 216
Chestnuts 210.2
Dried prunes 183.5
Olive oil 180.7
Walnuts 139.5
Almonds 131.1
Green beans 105.8
Broccoli 94.1
Cabbage 80
Peaches 64.5
Strawberry 51.6
Peanuts 34.5
Onion 32
Blueberry 17.5
Corn 9
Coffee with cow’s milk 6.3
Watermelon 2.9
Milk, cow 1.2

(Source: adapted and modified from Thompson LU, Boucher BA, Lui Z, et al. Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans and coumestan. Nutrition and Cancer 2006; 54:184–201.)

However, a diet high in phytoestrogens alone is probably less successful in addressing menopausal symptoms without a change in lifestyle and more physical activity as well as the awareness of a low-calorie diet and stress management. This notion was evident in a cross-cultural comparison of health-related quality of life in Australian and Japanese midlife women.52 It was reported that if the women had a lowered body mass index, undertook physical activity, consumed dietary phytoestrogens, and consumed some alcohol (any regular use of alcohol) their physical functioning seemed to be better.52

Asians and Japanese ingest on average 25–45mgs isoflavones per day over long periods of time. Just 40mg of isoflavones alone is sufficient to reduce menopausal symptoms which are up to 50 000 times higher than levels of endogenous estradiol.15

High phytoestrogen consumption in Asian women is thought to contribute to the low incidence of menopausal symptoms such as hot flushes, and exert protective effects on the cardiovascular system, reduce reproductive-related cancer risk, cardiovascular risk, reduce total cholesterol lipid levels and the risk of osteoporosis.

Furthermore, a high-phytoestrogen diet especially if initiated before puberty is associated with reduced risk of breast, colon and prostate cancer.53, 54

Middle-aged Japanese women are generally healthier than North American women, have lower rates of heart disease, breast cancer and osteoporosis, and have one of the longest life expectancy in the world (mean 85.33 yrs).51

The incidence of breast cancer is one-third compared with North American women, for osteoporosis less than half of Caucasian women in North America, even though Asian women have lower bone density, and 28% suffer a chronic health problem such as diabetes, allergies, asthma, arthritis and hypertension compared with 45% of Canadian (Manitoban) women and 53% of US (Massachusetts) women.15

The authors attribute these results to exercise, including weight-bearing exercise, no smoking, minimal consumption of alcohol and coffee, and a low-fat diet high in soybeans, vegetables and herbal teas (phytoestrogen-rich).15

Comparative studies of Japanese-oriental women, US and Finnish women proved that the Japanese women had a 60 to 110 times higher amount of isoflavones excreted in the urine while the concentration of oestrone and oestradiol was nearly identical and the amount of oestradiol was slightly less.55 The average age in both groups (Japan and Finland) was 50.4 years. Both groups came from rural regions, therefore the socio–psychological differences were less than assumed. The measured higher concentrations of isoflavones in Japanese women were attributed to high consumption of soy products such as tofu, miso, aburage, atuage, koridofu as well as cooked soy beans. It was concluded that this dietary factor was responsible for less climacteric complaints and protective effect against cancer. (See Table 25.3.)

More research on the use of foods rich in phytoestrogens for menopausal symptoms with lifestyle modifications is required. Other food groups such as high fish, vegetable, fruit, nut intake and calcium rich foods also play a role and contribute to health benefits, reducing the risk of cardiovascular disease and osteoporosis (see chapters on cardiovascular disease and osteoporosis).

Nutritional supplements

Soy (Glycine max L.) isoflavone extracts

Soy supplementation may play a role in the management of menopause and cholesterol, although diet plays a bigger role here.

A randomised double-blind, placebo-controlled trial has demonstrated that supplementation of soy isoflavones up to 100mgs/day for 4 months in post-menopausal women reduced cholesterol and menopausal symptoms by 21%.60

In another RCT, 25g of soy protein alone was able to reduce total cholesterol and LDL-cholesterol (-29.0 and -24.0mg/dL, p<0.001 and p<0.006) after 16 weeks compared with placebo and resistance exercise.61

Other studies have demonstrated its effectiveness only when the diet involved increasing phytoestrogen intake. Murkies et al.62 demonstrated that after 3 months, the soy flour supplementation evidenced a 40% reduction in hot flushes compared with controls fed wheat flour resulting in only 25% reduction. Advising patients to add 2 tablespoons of soy grits to their diet, such as cereal, may be comparable.

A double-blind, randomised, placebo-controlled study of 80 post-menopausal women (mean age = 55.1 years), who reported 5 or more hot flush episodes per day, were randomised to receive either 250mg of standardised soy extract (Glycine max AT) a total of 100mg/day of isoflavone or placebo.63

After 10 months, there was a significant reduction in severity and frequency of hot flushes among isoflavone users when compared to those on placebo. Endometrial thickness, mammography, vaginal cytology, lipids and hormonal profile did not change in both groups.

A 12-week randomised placebo-controlled trial of 84 post-menopausal women randomised to 20g of soy protein containing 160mg of total isoflavones or taste-matched placebo (20g whole milk protein) demonstrated a significant improvement in all 4 quality-of-life subscales (vasomotor, psychosexual, physical, and sexual) among the women taking isoflavones compared with no changes observed in the placebo group.64

However, total testosterone and HDL levels were significantly lower in the isoflavone group compared to placebo group.

Another study has also demonstrated efficacy and safety of a soy isoflavone extract in post-menopausal women.65 The soy isoflavone extract exerted favourable effects on vasomotor symptoms and compliance was good, providing a safe and effective alternative therapy for post-menopausal women.

However, RCTs have yielded mixed results for the effectiveness of soy isoflavones for menopausal symptoms due to various factors such as small sample sizes, short-term treatment and variation in dosage used. In addition, there is sub-population and individual variation in the metabolisation of daidzein which converts to the more bioactive estrogenic product equol by the gut bacteria. Western women are only 30% equol producers compared with 50–60% of Japanese women.15

A recent Cochrane review66 concluded that there was no evidence of effectiveness in the alleviation of menopausal symptoms with the use of phytoestrogen treatments.

Most trials were small, of short duration and poor quality. Some trials found a slight reduction in hot flushes and night sweats, but overall no benefit compared with no treatment. There was no evidence of harm with short-term use.

Yet another systematic review and meta-analysis of multiple RCTs using a non-random effects model, demonstrated that isoflavone therapy had a significant 30% reduction in frequency hot flushes, especially in women with frequent hot flushes.67

Interestingly it has also been reported that the quality of soy phytoestrogens is almost certainly likely to influence efficacy.68