The menopause

The menopause, or cessation of periods, naturally occurs about the age of 45-55 years. During the late forties, FSH initially, and then LH concentrations begin to rise, probably as follicle supply diminishes. Oestrogen levels fall and the cycle becomes disrupted. Most women notice irregular scanty periods coming on over a variable period, though in some sudden amenorrhoea or menorrhagia occur. Eventually the menopausal pattern of low estradiol levels with grossly elevated LH and FSH levels (usually > 50 and > 25 U/L, respectively) is established. Menopause may also occur surgically, with radiotherapy to the ovaries and with ovarian disease (e.g. premature menopause).

Clinical features and treatment

Features of oestrogen deficiency are hot flushes (which occur in most women and can be disabling), vaginal dryness and atrophy of the breasts. There may also be vague symptoms of loss of libido, loss of self-esteem, non-specific aches and pains, irritability, depression, loss of concentration and weight gain.

Women show a rapid loss of bone density in the 10 years following the menopause and the premenopausal protection from ischaemic heart disease disappears.

Symptomatic patients should usually be treated but the previous widespread use of hormone replacement therapy (HRT) has been thrown into doubt by a number of large prospective studies which have reported in recent years. Although there is no universal agreement, the overall benefits and risks may be summarized as follows (percentages are from the Women's Health Initiative (WHI) study of 16600 women):

• Symptomatic improvement in most menopausal symptoms for the majority of women. Oestrogen-deficient symptoms respond well to oestrogen replacement, the vaguer symptoms generally, but not always, less well. Vaginal symptoms respond to local oestrogen preparations.

• Protection against fractures of wrist, spine and hip, secondary to osteoporosis (∼24-33%), owing to protection of predominantly trabecular bone.

• A significant reduction in the risk of large bowel cancer (∼33%).

• A significant increase in the risk of breast cancer (+26%) - but no change in breast cancer mortality, and some studies suggest breast cancers diagnosed on HRT are easier to treat effectively. This increased risk has been disputed.

• A significant increase in the risk of endometrial cancer when unopposed oestrogens are given to women with a uterus.

• A significant increase in the risk of ischaemic heart disease (+29%) and stroke (+41%).

• The inconvenience of withdrawal bleeds, unless a hysterectomy has been performed or regimens which include continuous oestrogen and progesterone are used.

• Other disputed effects include possible reductions in the incidence of Alzheimer's disease and increase in general well-being.

Absolute risks and benefits for individual women clearly depend on their background risk of that disease, and there is as yet no evidence on the relative risks of different hormone preparations or routes of administration (oral, transdermal or implant). Overall, the WHI study estimated that, over 5 years of treatment, an extra 1 woman in every 100 would develop an illness that would not have occurred had she not been taking HRT. However, the decision about whether or not a woman takes HRT is now very much an individual decision based on the severity of that woman's menopausal symptoms, her personal risk of conditions which may be prevented or made more likely by HRT, and ultimately individual patient choice. For example, the decision is likely to be very different for a non-smoking 50-year-old with severe menopausal symptoms and a family history of osteoporosis, compared to a 60-year-old hypertensive smoker with mild symptoms and a family history of breast cancer. HRT is no longer recommended purely for prevention of postmenopausal osteoporosis in the absence of menopausal symptoms. Where symptomatic treatment is given, use of the lowest effective dose is now advocated, usually for short-term rather than long-term treatment. However, its exact place in therapy is still unclear.

Selective oestrogen receptor modulators, SERMs (e.g. raloxifene), offer a potentially attractive combination of positive oestrogen effects on bone and cardiovascular system with no effects on oestrogen receptors of uterus and breast and possible reduction in breast cancer incidence; long-term outcome studies, however, are still awaited.

Premature menopause

The most common cause of premature menopause in women (before age 40) is ovarian failure, which may be autoimmune or of unknown aetiology. Bilateral oophorectomy causes the same oestrogen-deficiency state. HRT should almost always be given, as the risk of osteoporosis and other conditions related to oestrogen deficiency almost always outweigh the risks at this younger age. HRT may still also be actively recommended when normal menopause occurs relatively early (e.g. before age 50).