Post Reproductive Health

In all multicellular animals the female germ cells are dependent on somatic organs for successful propagation, and it is the ageing of these organs, especially the uterus in viviparous animals, which limits reproductive output. Studies on laboratory rodents have shown that females cease producing litters well before the end of life, due to failure of the uterus to carry offspring to term. At this time and at death the ovary still has a store of oocytes. The major exception to this is women, in whom the ovary is depleted of oocytes during middle age; this gives rise to the menopause. It appears that the menopause is a non-adaptive consequence of two evolutionary developments. The first, which is common to all mammals and birds, is the entry of all female gametogonia into meiosis before birth, giving a finite store of oocytes in the ovary. The second, which is common to both male and female humans, is their very greatly increased longevity compared to other mammals of equivalent size. This results in the ovary using up its store of oocytes whilst ageing processes in somatic organs are at an early stage. In view of the dual origin of the human menopause and the fact that other mammals have an equivalent period of reproductive quiescence, it is unlikely that the menopause would have evolved in response to adaptive pressure.

A number of agents are now available which are effective in the prevention and treatment of postmenopausal osteoporosis. The management strategy of this condition will be influenced by factors including the age, clinical presentation, bone mineral density and treatment preferences of the individual woman. Assessment of fracture risk and intervention thresholds will be discussed. The available therapeutic agents and how to target treatment appropriately at different ages will be examined.

A number of studies have determined a major role for genetic factors in the development of early onset familial Alzheimer's Disease (AD). These include the findings of rare, largely highly penetrant, autosomal dominant mutations in the genes coding for amyloid precursor protein, presenilin-1 and presenilin-2. In contrast, late onset AD, defined as age of onset at or after 65 years, is a complex disorder with a multi-factorial aetiology of variable genetic penetrance. To date, although a number of other candidates have been proposed, the clearest genetic risk factor associated with late onset AD remains the common ε4 polymorphism of apolipoprotein E (ApoE). The identification of new genetic risk factors for late onset AD is likely to depend upon a combination of both linkage and association studies.

Only a small proportion of all female breast cancer can be accounted for by the inheritance of a germline mutation in a cancer predisposition gene. However, for the individuals affected the risk of developing cancer can be very high. It is likely that the development of cancer may be modulated by other factors such as endogenous or exogenous hormonal exposure and research is continuing in this area to try to find preventative agents. Testing for mutations in these genes is possible, although currently a live affected family member is necessary for the identification of the specific familial mutation before predictive testing of unaffected family members is possible. Specialist genetic counselling of these families is necessary to provide information about cancer risks, advice about screening and cancer prevention and the implications for other family members.

Hot flushes are experienced by the majority of menopausal women especially in the perimenopause. They are the most characteristic menopausal symptom. Hypogonadal men also suffer from hot flushes. Enough evidence exists to suggest that oestrogen withdrawal is probably the main cause of hot flushes. They are mainly experienced when circulating oestrogen levels are low and are successfully treated by replacing this steroid. However, it is clear that other non-hormonal mechanisms play an important role in the pathophysiology of hot flushes. The neurotransmitter serotonin seems to be especially involved. This review examines the involvement of serotonin in hot flushes and especially the role of the 5-HT_2A receptor subtype. It is concluded that non-hormonal treatment with either 5-HT_2A receptor antagonists or 5-HT_2C receptor agonists may have several advantages over hormonal therapy.