What exactly is the menopause?

Menopause by definition is the time of cessation of menstruation. Women are said to be postmenopausal after 1 year of amenorrhoea. This occurs on average at 51.4 years¹; in smokers, those with a hysterectomy and chronic disease, however, it occurs earlier.² The perimenopause refers to those years leading up to and including the menopause. Premature menopause (that which occurs before the age of 40) occurs in up to 2.5% of women.³ It is usually iatrogenic, coming about as a result of bilateral oophorectomy, radiation or chemotherapy.

The current nomenclature used to describe stages of reproductive aging⁴ is described in Box 14.1 and shown in Figure 14.1.

FIGURE 14.1 Nomenclature used to describe stages of reproductive aging

(From Soules et al⁴)

From just after menarche (stage –5) cycles can be irregular for several years, but should then occur every 21 to 35 days for a number of years (stages –4 and –3). In the early menopausal transition (stage 2), the menstrual cycle remains regular but the length changes by 7 days or more (regular cycles are now every 24 instead of 31 days). The late menopausal transition (stage +1) is characterised by two or more skipped menstrual cycles and at least one intermenstrual interval of 60 days or more.⁴

Follicle-stimulating hormone (FSH) levels gradually increase throughout the menopausal transition, but the variability is high and an FSH level of 40 IU/L or more is not necessarily as predictive of the late menopausal transition as amenorrhoea of 60 days or more.⁵

Why does the menopause come about?

The menopause commences when there are only a few thousand primordial follicles remaining in the ovary, an insufficient number to stimulate cyclical activity. Oestrogen levels fall in the course of about 5 years and this has a positive feedback on the pituitary, increasing the production of FSH and luteinising hormone (LH). Eventually the ovary produces only androstenedione (also produced by the adrenal glands), which is converted by peripheral fat into the weak oestrogen, oestrone.

How can women tell if the menopause is imminent?

The dominant feature of the early menopausal transition is cycle length variability of 7 days or more, with cycle irregularity marking for most women the approach of their final menstrual period. The time when a woman is most likely to experience menopausal symptoms is during the late menopausal transition when there is amenorrhoea of 60 days or more. An indicator of the approach of menopause (less than 20 cycles remaining) is a rise in cycle length to 42 days or greater.⁶ Bleeding patterns are most indicative sign of menopausal stage, not necessarily hot flushes.⁵

Are there any investigations that can be used to determine whether menopause has occurred?

In women still experiencing menstrual bleeding, FSH levels measured on day 2 or day 3 after the onset of bleeding are considered increased when they exceed 10–12 IU/L, which is an indication of diminished ovarian response.⁷ FSH levels over 40 IU/L are indicative of the late menopausal transition.⁵ However, studies show that a single FSH determination alone poorly predicts menopausal status and cannot be used to predict final menstrual period.⁸ It has been common practice to consider ovarian failure highly likely when two measurements of FSH >30 IU/L are obtained at least 1 or 2 months apart. FSH should be measured when the woman is not taking either HT or hormonal contraception.

What are the true signs and symptoms of the menopause?

Despite the fact that all women pass through the menopause if they live long enough, the symptoms directly attributable to the menopausal transition are difficult to quantify because of confounding factors such as age, social class and education. One study⁹ found that vasomotor symptoms (hot flushes and night sweats), difficulty falling asleep, decreased sexual interest and vaginal dryness are all associated with menopause after controlling for the effects of age. Sexual satisfaction, however, was not related to menopausal status and symptoms often associated with menopause, such as cognitive difficulties, depression and irritability, were more strongly associated with social class and employment. Dennerstein et al¹⁰ found that from early to late perimenopause increasing numbers of women reported five or more symptoms (+14%), hot flushes (+27%), night sweats (+17%) and vaginal dryness (+17%). Breast soreness/tenderness decreased with the menopausal transition (–21%). Figure 14.2 (p 258) illustrates the association between hormone status and symptoms in the women they studied. A list of the common signs and symptoms associated with menopause is given in Box 14.2 (p 259).

FIGURE 14.2 Geometric means (± 95% confidence interval) of hormone levels by menopausal status

(From Dennerstein et al¹⁰)

Another important point to note about menopausal symptoms is that, while a large proportion of women may experience menopausal symptoms, the proportion of women who experience the symptom as a problem is much less. For example, a British study¹¹ found that 57% of women experienced hot flushes but only 22% said they were a problem, 66% reported sleep problems but only 33% said this was a problem. Interestingly, only 10% of women seek help from healthcare providers.¹²

How long do menopausal symptoms usually last?

For most women, symptoms are transient, with 30–50% of women improving within several months. Hot flushes usually last for 4–5 years and in some women may take longer to resolve. A recent meta-analysis has shown peak vasomotor symptom prevalence at 1 year after the final menstrual period, with 50% of women reporting symptoms after 4 years and 10% reporting symptoms as long as 12 years later¹³ (Fig 14.3).

FIGURE 14.3 Pooled estimates of proportion of vasomotor symptoms by years to/from final menstrual period

(From Politi et al¹³)

What are the long-term health implications of the menopause?

Osteoporosis, urogenital atrophy, cardiovascular disease and stroke all increase in incidence in women after menopause. While twice as many women as men suffer from Alzheimer’s disease (the most common cause of dementia among the elderly), this may in part be due to longer life expectancy.¹⁴ Interestingly, limited clinical trial evidence suggests that HT does not improve symptoms or slow disease progression in Alzheimer’s disease and that it may actually increase dementia risk when initiated after age 64 years.^15,16,17 Observational studies suggest that HT used by younger women around the time of menopause is associated with lower risk of Alzheimer’s disease. However, further research is needed to determine whether there might exist an early window during which HT effects on Alzheimer’s disease risk are beneficial rather than harmful.

What can a GP do for women with atrophic vaginitis?

First, it is important always to examine these patients, as their symptoms may in fact be due to a condition other than atrophic vaginitis. Treatment of atrophic vaginitis involves oestrogen replacement, either systemically or locally. An alternative if symptoms are not severe is the use of lubricant to assist sexual activity.

Oestrogen can be delivered transvaginally either through the use of creams, pessaries or a hormone-releasing ring. Initially, creams and pessaries should be used daily for about 2 weeks, but once symptoms improve the dosage can be reduced to once or twice a week. The advantages of creams and pessaries are that they are effective in treating symptoms and have fewer systemic effects, thereby lessening the risk of endometrial carcinoma. However, they involve vaginal manipulation and the twice-weekly dosage may lead to decrease of patient compliance. The transvaginal ring offers an alternative, as the ring can remain in the vagina and deliver a constant low dose of hormones. It can be easily removed and reinserted and can still be worn during sex.

What has been the uptake and usage of HT by women in recent times?

The use of HT by menopausal and postmenopausal women has been controversial since first suggested. The medical profession has been subject to intense pressure

by pharmaceutical companies to prescribe HT as both a therapeutic and preventive agent, as the potential market for HT is enormous (all women over 45).

Despite this, it is interesting to note that less than 20% of population samples of postmenopausal women in the USA have ever had HT prescribed. In addition, less than 40% of women who commence HT are still using it 1 year later,²⁰ and after 3 years that percentage drops further to 25%.²¹ The reasons for this poor compliance may be related to the side effects that women experience when they use HT, such as bloating, breast tenderness and withdrawal bleeds, or to the perceived risks, especially breast cancer.

Up until 2002, when the Women’s Health Initiative (WHI) study results were publicised,²² use of HT in postmenopausal women varied from <10% in the UK, to 30–40% in the US. Australia was slightly less than the US with 28% of postmenopausal women taking HT and 12–22% throughout Europe.²³ In Australia, prescriptions for oestrogen/medroxyprogesterone acetate fixed-dose preparations dropped by 55.4% in the following 12 months; uptake of HT preparations decreased by about 30% in the same period and continued to fall at a lower rate following publication of the oestrogen-only (9%) and memory arms of the WHI (4%).²⁴

What advice should general practitioners give patients seeking information about the pros and cons of HT?

In recent years, controversy has raged over the indications for HT and the risks and benefits of using HT in peri- and postmenopausal women. Much of this controversy stems from the undue fears and confusion that have resulted from the misinterpretation of clinical studies and the overrepresentation of risks arising from these studies,²⁵ in particular:

In counselling women about HT, it is essential that GPs are skilled in representing risk accurately (Box 14.3). Common non-cancer risks and benefits are outlined in Table 14.1.

TABLE 14.1 The benefits and harms of using HT for 1 year in 10,000 women aged 65–74 years

(From Nelson et al⁸²)