Menopause

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Chapter 21 Menopause

Jon Wardle, ND, MPH

OVERVIEW

Menopause represents the natural transition from fertility to age-related non-fertility. The term ‘menopause’ specifically means the cessation of menstruation, and most often occurs between the ages of 45 and 55 years, with the average age for the last period being 51 years.

All healthy women will transition from a reproductive (premenopausal) period—marked by regular ovulation and cyclic menstrual bleeding—to a postmenopausal period marked by amenorrhoea. The onset of the menopausal transition is marked by changes in the menstrual cycle and in the duration or amount of menstrual flow (see Table 21.1). Subsequently, cycles are missed, but the pattern is often erratic early in the menopausal transition. Therefore the menopause is defined retrospectively after 12 months of continued amenorrhoea.

Table 21.1 The stages of menopause

The term ‘perimenopause’ is most often used to describe the time leading up to and directly following menopause.² During perimenopause, hormone levels fluctuate and women may experience a variety of symptoms including vasomotor symptoms (hot flushes and night sweats), vulvovaginal atrophy, emotional fluctuations and cognitive decline (memory problems). Some women experience very little in the way of these symptoms; for others this time is particularly debilitating. Low oestrogen levels postmenopause also increase the risk of a number of other physical conditions including osteoporosis and cardiovascular disease. The various symptoms of the menopausal transition are associated with a variety of physiological changes and the responses to these changes. Figure 21.1 shows the symptoms associated with changes in hormone levels.

Figure 21.1 Menopausal symptom and hormone changes over time ³

In the postmenopausal phase FSH rise to levels 10–15 times the level that can be expected during the follicular phase of a reproductive cycle, while LH levels increase to around three times that experienced during menstruation. The ovaries do continue to excrete minimal amounts of oestrogens, and continue to excrete significant amounts of androgens.²

It should also be noted that individual women will experience the menopausal transition differently. The prevalence rates of the main symptoms can vary greatly across the different stages of menopause (see Figure 21.2).⁴

Figure 21.2 Prevalence rates of the main symptoms of menopause ⁴

CONVENTIONAL TREATMENT

Conventional practitioners tend to underestimate the effects of perimenopausal symptoms on their patients.⁵ However, fewer than 25% of women experience a (relatively) symptom-free menopause and over 25% of women experience debilitating symptoms.⁶ Many women turn to conventional practitioners for explanation and reassurance rather than treatment.³

Much controversy has raged during recent years over what is termed the ‘medicalisation’ of naturally occurring life stages, of which the most publicised is menopause. Conventional practice has often viewed menopause as a condition of oestrogen deficiency, and treatment is based on the use of supplemental hormones, commonly referred to as hormone therapy (HT).

There is much conjecture and controversy surrounding the use of HT in menopause. There are definite benefits to using HT. HT is effective for vasomotor symptoms, vulvovaginal atrophy symptoms, osteoporosis-related fracture prevention, and benefits cardiovascular and central nervous systems.⁷ However, continued use of HT can increase the risk for venous thromboembolism and increases the risk of developing breast cancer.⁷

BIOIDENTICAL HORMONE THERAPY: SAFER, MORE EFFECTIVE?

Most of the data suggesting risks associated with hormone therapy have been conducted using equine or synthetic hormones, and there is little evidence of the safety or efficacy of bioidentical or natural hormones. Theoretically they are suggested to proffer advantage in that they are more closely aligned with the innate hormones seen in the body and can be individually tailored (when compounded), but they should not automatically be considered the safer option. Both the Therapeutic Goods Administration of Australia and The Federal Drug Administration in the United States of America consider the adverse effects of HT as reported to be a ‘class effect’—that is, that bioidentical hormones can be considered to have the same risks and benefits as conventional HT. In fact most conventional HT used in Australia already uses oestradiol and other forms considered to be bioidentical. However, progestin is known to have very different, often contradictory, physiological actions to natural progesterone in many women. Regardless, focusing solely on direct hormone replacement does not address the underlying causes of the symptoms experienced by perimenopausal women and therefore when used alone may not be reflective of naturopathic or holistic best practice. While HT use is ultimately a matter for discussion between physician and patient, it should form only part of the treatment strategy in the naturopathic management of menopause.

HT may be recommended in certain circumstances—specifically, distressing symptoms or significant osteoporosis.⁷ Longer-term use of HT is generally considered a matter for discussion between the physician and the patient, with risks taken into account in addition to potential benefit to bone health and quality of life. Generally, long-term use is discouraged and physicians are encouraged to use lower therapeutic doses.

Various forms of oestrogen have been used for many years as a hormonal supplement to treat menopausal symptoms and are generally thought to be the most effective treatment for vasomotor symptoms. Oestrogen is therefore no longer recommended for prevention of chronic conditions, although it is effective and approved for osteoporosis prevention.⁴ Women with an intact uterus are usually prescribed the ‘opposed’ regimen (when oestrogen is combined with a progestin to avoid the development of endometrial hyperplasia and endometrial cancer). Testosterone may also be given to women. Examples of commonly used HT in Australia are listed in Tables 21.2 and 21.3.

Table 21.2 Oestrogens often used in menopause ³

Table 21.3 Progestogens often used in menopause

GENERIC NAME	DAILY DOSE RANGE	USUAL DAILY PROTECTIVE DOSE
Dydrogesterone	10–20 mg	10 mg
Medroxyprogesterone acetate	2.5–20 mg	10 mg
Norethisterone	1.25–5 mg	2.5 mg

However, much conventional medical treatment of menopause is comprised of educational and lifestyle management of symptoms. Several other classes of prescription medications are also used in the treatment of menopausal symptoms, including antihypertensive medications such as clonidine for hot flushes and various antidepressants or anxiolytics for psychological symptoms. Much of this research has come from the treatment of menopausal women with breast cancer, in whom hormone therapy is contraindicated.

RISK FACTORS

Although much focus tends to be drawn towards the effect that HT can have on increasing breast cancer risk, other modifiable lifestyle factors such as little exercise, smoking, postmenopausal weight gain and high alcohol consumption may increase the risk of not only breast cancer but other menopausal symptoms as well.⁸

Risk factors for severity of symptoms during perimenopause include genetics (symptoms experienced by the mother may give a guide), body mass index (BMI)—women with a higher BMI may experience a lower level of perimenopause symptoms due to the production of oestrogen by aromatase in adipose tissue (see Chapter 19 on endometriosis).

The duration of symptoms appears independent of HT but is less in those groups with higher physical activity.⁹ Other lifestyle factors, such as increased alcohol and caffeine use and smoking, are also associated with worsened menopausal symptoms.¹⁰

KEY TREATMENT PROTOCOLS

Perimenopause is a natural stage of life and not a disease or a disorder. Therefore it does not automatically require any kind of medical intervention or treatment. However, this natural transition is not always a smooth one and in certain cases the physical, mental and emotional effects associated with perimenopause can be quite severe and may significantly disrupt the lives of women experiencing them. Naturopathic treatment therefore focuses on reducing these effects and ensuring quality of life throughout this transition. Various lifestyle and dietary habits can have significant effects on the severity of menopausal symptoms, so treatment should otherwise focus on ensuring optimal health.

NATUROPATHIC TREATMENT AIMS

• Improve quality of life.

• Reduce symptoms (hot flushes, psychological symptoms and fatigue).

• Maintain ideal weight and health parameters (for cardiovascular and bone health).

• Manage stress.

• Address sexual health.

• Modify diet to improve symptoms and to reduce osteoporosis and cardiovascular risk.

Naturopathic treatment focuses on general improvement in physiology as opposed to correction or counteracting the effects of menopause with oestrogen supplementation. Many clinicians make the assumption that only climacteric symptoms are of concern in menopausal patients. As naturopathic treatment of a perimenopausal patient is focused on supportive care throughout the process, rather than correction of an aetiological or pathological condition, a broader clinical enquiry that extends beyond symptoms relating to oestrogen deficiency needs to be undertaken. Enquiries need to be made about mental state—anger and irritability, depression, moodiness, loss of self-esteem and sleeping difficulties. Sexual function and urinary function also need to be explored in depth.

Women undergoing the menopause transition turn to complementary medicines not only to seek effective treatment but also to gain greater control over their symptoms.¹⁷ It is therefore essential that a strong participatory relationship is encouraged during treatment and that the naturopath does not fall into the habit of product-prescribing only.

When looking at the literature there seems to be little relation to gross product sales (the most commonly sold complementary therapies for menopause) and specific clinical effectiveness. However, these therapies may be working on broader improvements or act on a psychosomatic level by offering the patients the opportunity to take control of their condition. For example, while acupuncture does not seem to have specific effects on menopausal symptoms such as hot flushes ¹⁸ it does seem to offer improvements to quality of life scores in perimenopausal women overall.¹⁹

For example, treatment with a combination Hypericum perforatum and Cimicifuga racemosa product for 16 weeks resulted in a 50% reduction in Menopause Rating Scale (MRS) scores, with a 41.8% reduction in the Hamilton Depression Rating Scale.²⁰

OESTROGEN-LIKE COMPOUNDS AND OESTROGEN RECEPTOR ACTIVITY

Many compounds—both natural and synthetic—may mimic endogenous sex hormones.¹¹^–¹³ Phytoestrogens may bind to and activate these oestrogen receptor sites. Given the use of hormone replacement therapy in conventional treatment, these compounds are gaining popularity amongst both the public and practitioners for relieving menopausal symptoms.

For example, the phytoestrogenic isoflavones found in Trifolium pratense and soy are thought to have beneficial effects on cognitive abilities, bone mineral density and plasma lipid concentrations in menopausal women.¹⁴ Phytoestrogenic activity may also be utilised in traditional Chinese medicine. Astragalus membranaceus and Scutellaria baicalensis are traditionally used in the treatment of menopausal symptoms in traditional Chinese medicine and exert oestrogenic activity in vivo.¹⁵

Dietary intake of phytoestrogens and an increased consumption of whole-grain foods may also be associated with a reduction in vasomotor symptoms.¹⁶

Many compounds exerting oestrogenic activity will be discussed in relation to symptoms. Many have not actually been studied extensively for menopausal symptoms, but phytoestrogens are discussed in more detail in Chapter 19 on endometriosis.

Although C. racemosa was effective in treating neurovegetative symptoms of depression in menopausal women, combination treatment was more effective than C. racemosa treatment alone.²¹ These changes seem more significant than the effects on vasomotor symptoms alone. And while H. perforatum does not seem to exert a significant effect on hot flush symptoms, it does proffer significant improvement on quality of life scales due to its effect on other symptoms associated with menopause and should therefore also be considered.²² C. racemosa also has positive effects on overall quality of life scales and other broader menopause rating scales when used alone in addition to its effects on individual symptoms.²³ Several relaxation therapies have also proven to be effective in alleviating or reducing a number of perimenopausal symptoms, rather than having specific outcomes.

Because exercise has demonstrated effects on sex steroids, it may moderate at least the severity, if not the frequency, of hot flushes.^9,²⁴^–²⁶ One epidemiological study found that women who belonged to a gymnasium club reported lower incidence of hot flushes than those who were not, although their individual exercise regimens were unreported.²⁷ However, studies on exercise, while generally demonstrating reduced severity and incidence of hot flushes, suggest it has had the greatest effect on quality of life scores.

Herbal medicine

A 2007 systematic review of 17 trials of which 11 could be included showed a demonstrated effect of Trifolium pratense in reducing hot flush symptoms in menopause.³⁴ A 2005 review of trials found 12 clinical trials of C. racemosa in vasomotor symptoms,

BLACK COHOSH SAFETY

Although concerns relating to the hepatotoxicity of Cimicifuga racemosa have been raised, systematic reviews have suggested it can be generally thought to be a safe medicine, with the main side effects being mild and reversible, and no direct causal link to Cimicifuga was found in cases of severe hepatotoxicity.²⁸^–³¹ In the most recent trial, long-term supplementation of Cimicifuga for a period of 1 year was found to have no effects on hepatic blood flow or liver function.³² However, an association does exist as hepatotoxicity has occurred in several people taking supplements containing Cimicifuga. This is thought to be related to issues of product quality, concomitant medications or individual genetic susceptibility. Although the specific mechanism relating to hepatotoxicity associated with Cimicifuga use is unknown, one theory gaining credence is an immunologic reaction to triterpene glycosides in the plant in susceptible individuals, rather than the direct result of inherent toxicity.³³ Therefore these issues should be considered when advising or treating patients using these therapies, as they should for any other pharmacological intervention.

all but one of which demonstrated benefit,³⁵ and a later non-specific review found significant benefit also.³⁶

C. racemosa may act through a number of pathways independent of its activity as a phytoestrogen. Recent evidence suggests that it may have an effect on opiate receptors.³⁷ Cimicifuga extract has also been demonstrated to exert dopaminergic activity in vitro.³⁸ This may in part also explain the effects of Cimicifuga in menopause as dopaminergic drugs are often used to treat menopausal symptoms such as hot flushes. Some studies have suggested that Cimicifuga has an equipotent effect to oestrogen³⁹ although this does not seem reflective of the entirety of the data.^40,⁴¹ It should be noted, however, that significant heterogeneity exists in the results for differing formulations, suggesting that quality issues need to be considered before prescribing.

Angelica sinensis and Matricaria recutita in combination has been demonstrated to reduce hot flushes and improve sleep in menopausal women,⁴² but other trials have failed to demonstrate these results when Angelica sinensis was used alone.^43,⁴⁴

Humulus lupulus supplementation over 12 weeks was found to reduce discomforting symptoms of menopause, particularly hot flushes, even at low doses.⁴⁵ This is thought to be due to the oestrogenic nature of H. lupulus.⁴⁶ Salvia officinalis was also demonstrated to improve symptoms of hot flushes and nights sweats in perimenopausal women.⁴⁷