The Menopause

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Chapter 18 The Menopause

The menopause

The word menopause means the cessation of menstruation, but it is commonly also used to describe events leading up to, and following, the final menstrual period. For about 10% of women, menses cease suddenly, but for a majority of women, the final period is preceded by several years of erratic periods. This phase is known as the perimenopause.

Oestrogen levels fall over the 5 years preceding ovarian failure, which occurs usually between 45 and 55 years of age, with an average of around 50 years. The fall in oestradiol has a positive feedback effect on the pituitary, increasing the production of follicle stimulating hormone (FSH) and luteinising hormone (LH). Once menopause has occurred, the FSH level is usually above 30 iu/l. FSH levels increase in the perimenopause but levels can fluctuate. The anti-Müllerian hormone (AMH) is a better marker of ovarian reserve. The ovary eventually produces only androstenedione, also produced by the adrenals, which is converted in the peripheral fat to the weak oestrogen, oestrone.

Cause of Menopause

Ovarian failure occurs when only a few thousand primordial follicles remain – an insufficient number to stimulate cyclical activity. Now that women in developed countries have a life expectancy of around 80 years, at least one-third of a woman’s life is spent in the post-reproductive, ‘menopausal’ phase.

Premature menopause may occur due to surgical removal of the ovaries, radiotherapy or chemotherapy; however, for most women, the cause is less clear. Premature ovarian failure is associated with auto-immune conditions, but in some women there may be a genetic element.

There is a slightly higher chance that conserved ovaries may fail following a hysterectomy. Menopause occurs 6–18 months earlier in smokers.

Differential Diagnosis

Before the days of immunological pregnancy tests and effective contraception, pregnancy and menopause were easily confused. Other causes of amenorrhoea, for example, polycystic ovarian syndrome or a prolactinoma should also be considered (see Chapter 6).

Signs and symptoms

Common menopausal symptoms

The greene climacteric scale

Please indicate the extent to which you are troubled at the moment by any of these symptoms by placing a tick in the appropriate box.

This scale may be used to measure climacteric symptoms and their response to treatment or to compare different treatment regimes.

An Anxiety score of 10 or more indicates severe, and possibly clinical, anxiety. A Depression score of 10 or more indicates severe, and possibly clinical, depression.

Changes in the genital tract

These changes are of atrophic type and affect the external genitalia as well as the internal organs. These changes occur over a number of years.

Not only are the main pelvic structures reduced in size but, more importantly, the fascial framework and the intrapelvic ligaments supporting the bladder and genitalia are weakened; this may lead to vaginal prolapse and urinary incontinence.

Vulva: There is flattening of the labia majora, the minor labia become more evident. Sexual hair becomes grey and sparse. The clitoris shrinks.

Uterus: The uterus becomes small with a relatively large cervix – a return to infantile proportions.

Tubes and ovaries: These show great shrinkage, the tubes becoming thin while the ovaries are reduced to small white wrinkled bodies, about 2–3 cm in length.

In addition to shrinkage of the vaginal introitus, the vagina diminishes in length and its secretions are limited, leading to vaginal dryness and dyspareunia. Changes in the vaginal epithelium are also seen. There is loss of rugosity and the epithelium becomes atrophic, with petechial haemorrhages in some cases and loss of glycogen.

Normal premenopausal vaginal epithelium. Note the thick cornified layer.

Smear of premenopausal vaginal epithelium. The cells are large with small nuclei and characteristic folded edges. Polymorphs are few in number.

Osteoporosis

Osteoporosis is the most common metabolic bone disease. Postmenopausal osteoporosis results from an excess of bone resorption over bone formation, and is associated with the loss of oestrogen. Women have 20% less bone than men at peak skeletal development, and hence they have less bone to lose before reaching the fragility threshold. More than 50% of Caucasian women suffer one or more osteoporotic fractures by the age of 70. Osteoporotic fractures, particularly of the neck of the femur and vertebrae, have significant impact on the lives of the affected women, and for society as a whole.

Risk factors for osteoporosis are:

1. Female sex.

2. White or oriental race.

3. Family history of osteoporosis.

4. Early menopause (natural or oophorectomy).

5. Sedentary life-style.

6. Low weight for height.

7. Tobacco and alcohol.

8. Low calcium intake.

Incidence of classical osteoporotic fractures by decades of life (stipple). Note the loss of height and the development of dorsal kyphosis with age.

DEXA (dual X-ray densitometry) is currently the favoured technique for measuring the lumbar spine and femoral neck densities, even though loss of height or the radiological demonstration of vertebral crush fractures also give clear evidence of osteoporosis. Bone mineral density (BMD) above minus 1 SD below the young adult mean is normal, osteopenia lies between −1 and −2.5 SD and osteoporosis below −2.5 SD of the young adult mean.

Ultrasonic densitometry of the calcaneum is of some value, but is not at present a substitute for DEXA scanning.

Bone Densitometry

L2–L4 BMD (g/cm²)	0.809 ± 0.01
L2–L4% young adult	67 ± 3
L2–L4% age matched	79 ± 3

At –3.26 SD of young adult, there is definite osteoporosis of lumbar spine

Neck BMD (g/cm²)	0.614 ± 0.02
Neck % young adult	63 ± 3
Neck % age matched	75 ± 3

Osteoporosis at all three sites in this hip

Comparative cortical bone thicknesses:

Normal vertebral body. Notethe thick trabeculae of bone.

Vertebrae from postmenopausal woman showing extreme rarefaction of the trabeculae.

Oestrogens have an antiresorptive effect on the bone, and there is good evidence that hormone replacement therapy (HRT) use is associated with a decreased risk of fractures. HRT is not recommended as a first line treatment for osteoporosis; however, HRT should be considered for women who have experienced a premature menopause, whether natural or surgical.

First line treatment for osteoporosis is the administration of bisphosphonates, a non-hormonal preparation. Other options include raloxifene, a selective oestrogen receptor modulator that has an antioestrogen effect on the breast and endometrium.

Bone loss recommences on stopping therapy, so withdrawal of HRT at age 65 results in bone density at ages 75 or 80 being no better than that of untreated women.

Cardiovascular disease and the menopause

In European countries, 40 to 45% of deaths are due to cardiovascular causes, with a relative increase in risk in females after the menopause. (The actual risk is greater in males even after 75 years.)

Mortality rate for selected causes per 100,000 population in Scotland, 1988.

The risk of coronary heart disease is increased sevenfold by bilateral oophorectomy before 35 years of age and by premature menopause at 35 years. The rates of coronary heart disease are lower for women when compared to men, but there is an increase which occurs in the years after the menopause. Endogenous female hormones have a number of protective effects on the cardiovascular system and HRT has been shown to replicate some of these features.

Lipid metabolismoestrogen increases high density lipoprotein (HDL) cholesterol and lowers low density lipoprotein (HDL) cholesterol.

Carbohydrate metabolismoestrogen reduced insulin resistance.

Blood flowoestrogen increases arterial blood flow.

They also have multiple effects on coagulation and fibrinolysis, with evidence for activation of coagulation. This is particularly the case with oral HRT. There is also evidence of an inflammatory effect as CRP increases with oral HRT.

Risks and benefits of HRT

Early observational studies had suggested a number of health benefits associated with HRT use, specifically a significantly lower risk of cardiovascular disease and osteoporosis. It had also been shown that HRT use was associated with a small increase in the risk of breast cancer and that this was higher with long-term use. It had also been shown that HRT use was associated with an increased risk of venous thromboembolic disease.

Several large randomised placebo-controlled trials were published in the late 1990s and the subsequent years. These demonstrated no evidence of HRT having a protective effect against heart disease. The largest of these studies, The Women’s Health Initiative, was stopped before completion as there was an overall small increase in the risks, when compared to the benefits of HRT use. A higher risk of breast cancer, venous thromboembolic disease, heart disease and stroke, but a lower risk of osteoporosis and colon cancer, was demonstrated. There is, however, some evidence that HRT, started in the early postmenopausal years, has a cardioprotective effect, presumably before vascular disease has become established.

The results of these studies have significantly reduced HRT prescription and uptake. However, the women recruited were older than the typical HRT seeking population, for symptom control. The current recommendation is that women should be prescribed HRT for menopausal symptoms and not for health benefits such as prevention of osteoporosis. The lowest effective dose should be used for the shortest time possible. This will vary from woman to woman.

HRT and the breast

Fear of an increased risk of breast cancer is the main cause of concern about HRT, in both patients and doctors.

Breast cancer is increasing in incidence and may affect one woman out of nine in a lifetime.

Alcohol use in young women may increase the risk, and obesity, high socioeconomic status and delayed first pregnancy are other risk factors. Early menarche, late menopause and nulliparity are also risk factors. Only 20% of the subjects have a positive family history. A woman’s risk of developing breast cancer is significantly increased when her mother, sister or daughter have developed the disease before the age of 50 years. A number of genetic mutations have been identified, with the commonest being the BRCA gene, and women with a strong family history of breast and ovarian cancer should be referred for genetic counselling.

Early menopause decreases breast cancer risk (70% reduction with menopause before 35 years).

Between the ages of 50 and 70 years, when most HRT is prescribed, 45 women per thousand not taking HRT, will develop breast cancer. Using HRT for 5 years between the ages 50 and 70 increases this by only 2 per thousand, 10 years use adds 6 per thousand and 15 years use adds 12 per thousand.

Hormone replacement therapy

Oestrogen replacement remains the most effective treatment for menopausal symptoms. The doses required are much lower than those used for oral contraception. For women with an intact uterus progesterone is also required as oestrogen alone (unopposed oestrogen) is associated with endometrial hyperplasia and an increased risk of endometrial cancer.

Factors influencing prescription of HRT

HRT prescription should be considered carefully for any woman, but a number of factors need to be taken into account and the risks and benefits discussed on an individual basis.

Severity of symptoms and quality of life

Women who have minimal symptoms may require no treatment. Clearly, women who experience symptoms that affect their quality of life will be more likely to opt for HRT.

Contraindications	Relative contraindications
Pregnancy	Cerebrovascular accident
Uninvestigated abnormal vaginal bleeding	Severe migraine
Breast cancer or other oestrogen-dependent tumour	Thrombophilia
Venous thromboembolic disease
Myocardial infarction or unstable angina
Severe liver disease