Post Reproductive Health

Endocrine disruptors are substances which can potentially modify the normal hormonal functions of the body, and include both naturally occurring compounds (such as plant phytoestogens) and anthropogenically derived environmental contaminants. This article reviews the evidence for possible links between exposure to anthropogenic chemicals and a number of common conditions in women, including breast cancer, cardiovascular disease and atherosclerosis, osteoporosis, endometrial disease, autoimmunity and menopausal symptoms. The question whether phytoestrogens might exert some beneficial effects during the postmenopausal period is also addressed. In addition, the possible consequences of early life exposure to potential endocrine disruptors or phytoestrogens are discussed.

Oestrogen is thought to have a role in cognitive function, specifically verbal memory. Despite the growing evidence that memory function may be preserved in older women and surgically menopausal women through the administration of oestrogen replacement therapy, the implications for perimenopausal women remain unclear. This paper overviews the literature in this area and suggests that there are insufficient grounds at present to conclude that memory is impaired during the menopausal transition. However, given the lack of information about cognitive function in the climacteric, a number of issues are presented which may be helpful to consider in assessing women during this period who may be experiencing memory difficulties. Some directions for future research are also considered.

Increasing life expectancy has led to an increasingly elderly population and it is now common for women to spend a third of their lives in the oestrogen-deficient postmenopausal state. Oestrogen is known to have an important physiological impact on the female lower urinary tract and the loss of endogenous oestrogen is associated with the development of urogenital atrophy and lower urinary tract dysfunction, offering a rationale for prevention and treatment. Whilst the role of systemic hormone replacement therapy and the use of topical oestrogens in the management of urogenital atrophy has been firmly established, the use of oestrogens in urinary incontinence remains more controversial. Oestrogen therapy alone has been shown to have little effect in management of genuine stress incontinence, although it may have a synergistic role when used with an α-adrenergic agonist. When considering the irritative urinary symptoms associated with urinary urgency and urge incontinence, oestrogen may be beneficialalthough this may simply reflect a reversal of urogenital atrophy rather than a direct effect on the lower urinary tract. Finally, oestrogens would appear to be efficacious in the management of recurrent lower urinary tract infections, with the most convincing evidence being in support of local vaginal administration.

Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate, but contain a P-C-P bond in the middle of the molecule instead of a P-O-P bond. The addition of different side chains allows many structural variations, producing bisphosphonates with a range of potencies and properties. Bisphosphonates are poorly absorbed from the bowel, but once absorbed they localise to the skeleton, where they inhibit the recruitment and function of osteoclasts. This provides a rationale for their use in the management of patients with bone diseases. Osteoporosis is characterised by a reduction in bone density, associated with skeletal fragility and an increased risk of fracture after minimal trauma. Bisphosphonates decrease bone resorption and formation, but because of the transient uncoupling of these processes, there is an increase in bone density of 5-10%. Cyclical etidronate, alendronate and risedronate decrease the incidence of further vertebral fractures, but only alendronate and risedronate have been shown to reduce the risk of hip and other non-vertebral fractures. Paget's disease is a focal disorder of bone remodelling, associated with bone pain, skeletal deformity and increased risk of fracture. Specific treatment is directed at suppressing the overactivity of osteoclasts, thereby decreasing bone turnover. Tiludronate, risedronate and iv pamidronate reduce the activity of Paget's more effectively than etidronate. Although bisphosphonates decrease bone pain and reduce the activity of Paget's disease, there is currently no evidence that any treatment will prevent skeletal deformity, fractures or other complications of the condition. The choice of bisphosphonate for the treatment of osteoporosis and Paget's disease will depend on the potential advantages and disadvantages in the individual patient.

Osteoporosis is a systemic skeletal disease characterised by low bone mass and micro-architectual deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Bone mineral density is a major component of bone strength and is predictive of future fracture risk. It is possible to measure BMD non-invasively at various skeletal sites using dual energy absorptiometry. Techniques such as quantitative ultrasound and magnetic resonance imaging also provide additional information on other facets of skeletal strength, although at present further research is required before they are incorporated into routine clinical practice. There is currently much interest in identifying factors involved in the determination of BMD and bone strength. Based on this knowledge, it may be possible to identify subjects who will have low BMD and will therefore be at risk of future fracture. Lifestyle interventions and drug treatments could therefore be targeted to "high risk" subjects to reduce the burden of osteoporotic fractures.

Objective. The effect of hormone replacement therapy (HRT) on the sexual functioning and quality of life of breast cancer patients has not received significant attention.

Study design. One hundred postmenopausal women with early stage breast cancer who were experiencing vasomotor symptoms and/or vaginal dryness participated in a randomised trial of HRT.

Main outcome measures. Women completed questionnaires at three and six months to determine changes in their quality of life, vaginal dryness and sexual activity.

Results. At baseline, 52% (49/94) of patients were sexually active. Lack of a partner was the main reason for sexual inactivity (38% (17/45)). HRT had no significant effect on the proportion of women complaining of vaginal dryness or the severity of this symptom. HRT did not increase the proportion of women who were sexually active (53%(43/81)) but was associated with non-significant trends for improvements in pleasure and reduction of discomfort during intercourse. Non-significant trends towards improvements in physical functioning, sleep disturbance and fatigue were observed with HRT. Patient numbers were too small to determine whether the concomitant use of tamoxifen influenced any of these outcomes.

Conclusions. Lack of a significant improvement in quality of life with HRT may reflect the possibility that patient concern about HRT negated its symptomatic benefits. Failure of HRT to improve vaginal dryness may partly account for a lack of improvement in sexual functioning. There is a need for evaluation of interventions to improve sexual functioning in breast cancer patients but the use of hormonal therapy should be restricted to controlled trials.