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 oestradiollevels with grossly elevated LH and FSH (usually >50 and >25 Ulitre-I, respectively) is established. Menopause may also occur surgically, with radiotherapy to the ovaries and with ovarian disease (e.g. premature menopause). 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 loss of bone density (osteoporosis, see p.426) and the premenopausal protection from ischaemic heart disease disappears.
Some of the usual hazards of oestrogens apply (see below)but most physicians are now treating symptomatic patients much more widely and some recommend the widespread use of HRT, though still much less widely than in the USA. Current evidence suggests that, when given with a progestogen, the benefits of HRT far outweigh the small risks, unless there are clear contraindications. The overall benefits may be summarized as follows:
SYMPTOMATIC IMPROVEMENT in many, but not all, 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.
REDUCTION IN ISCHAEMIC HEART DISEASE and cerebrovascular disease mortality-blood pressure falls in the majority.
PROTECTION AGAINST FRACTURES OF WRIST, SPINE AND HIP, secondary to osteoporosis, at least where HR T is used before the age of 60 years when loss of bone mass is maximal. This is due to predominant protection of trabecular rather than cancellous bone. In HR T oestrogen should be given cyclically with a progestogen (if the uterus is present) to prevent endometrial carcinoma from unopposed oestrogen action. Apart from individual risks from oestrogen therapy (e.g. migraine, thrombosis) -and even with these the effect of HR T may not parallel those of the ‘pill’: the oestrogen dose is much smaller and does not guarantee contraception- the main concerns have been induction of cancer of the uterus or breast. Given with a progestogen, the risk of uterine cancer is not significantly increased, while the data on breast carcinoma are conflicting. There is of course the inconvenience of withdrawal bleeds, unless a hysterectomy has been performed. The preferred route of administration has been oral, but oestrogen implants and skin patches are now also widely used. The length of treatment with HR T is controversial.
The commonest cause of early menopause in the twenties and thirties is ovarian failure which is usually autoimmune in nature. HR T should be given, as the risk of osteoporosis and premature ischaemic heart disease far outweigh the risks.
The ageing male In the male there is no sudden ‘change of life’. However, there is a progressive loss in sexual function with reduction in morning erections and frequency of intercourse. The age of onset varies widely but overall testicular volume diminishes and gonadotrophin levels gradually rise. If premature hypogonadism is present for any reason, replacement testosterone therapy should be given to prevent osteoporosis. A new agent, finasteride, which is an inhibitor of Sa-reductase, is now used in benign prostatic hypertrophy. It prevents the conversion of testosterone to dihydrotestosterone which causes local prostatic hyperplasia.
Physiology of prolactin secretion
The hypothalamic-pituitary control of prolactin secretion is illustrated. It is under tonic dopamine inhibition, while other factors
known to increase prolactin secretion (e.g. TRH) are probably of less importance. Prolactin stimulates milk secretion but also reduces gonadal activity. It decreases LHRH pulsatility at hypothalamic level and, to a lesser extent, blocks the action of LH on the ovary or testis, producing hypogonadism. These actions may be clinically important.
Frequency of intercourse
Menstruation-relation of symptoms to cycle
Breasts (? galactorrhoea)
Evidence of systemic disease
Secondary sexual characteristics
Genital size (testes. ovaries. uterus)
Breast development. gynaecomastia
Extent/distribution of hair