Post Reproductive Health

Objective: The aim of this study was to evaluate the long-term endometrial safety of long-cycle sequential oestrogenprogestogen hormone replacement therapy (HRT).

Study design: A prospective, longitudinal, single group study was undertaken in postmenopausal women, aged 45-66 years, treated with up to 21 3-month cycles (five years) of sequential oestrogen-progestogen HRT. Treatment consisted of 70 days of 2 mg/day oestradiol valerate (E₂V), followed by 14 days of E₂V combined with 20 mg/day medroxyprogesterone acetate (MPA), followed by seven days placebo.

Endometrial biopsies were assessed at baseline, at 12 months in women with an endometrial thickness >6 mm and in all participants at 24, 36, 48 and 60 months. Mammography was performed at baseline and at 24-month intervals thereafter. Adverse events were assessed throughout the study.

Results: Of 132 women enrolled, 94 completed five years of treatment (540 women years). Endometrial changes (oestrogen effect II) were apparent in most women from 24-60 months (95, 83.3% women at 24 months). One case of simple hyperplasia was found (at 60 months), and none of complex hyperplasia or endometrial cancer. The pattern and frequency of adverse events were consistent with other sequential oestrogen-progestogen HRT regimens.

Conclusions: The incidence of hyperplasia over five years (0.19%, upper 95% CI 0.88) was well within the acceptable rates defined by the European Union Committee for Proprietary Medicinal Products (CPMP).

Undernutrition and other adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology and metabolism. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the GH/IGF-1 and HPA axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have suggested that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Finally, childhood growth rates have been directly linked to the risk of hip fracture many decades later. Further work is needed to use this approach to develop novel therapeutic and preventative strategies to reduce the burden of osteoporotic fractures in the population.

Metastatic breast cancer (MBC) may present de novo but more commonly develops in women initially presenting with early breast cancer despite the widespread use of adjuvant hormonal and cytotoxic chemotherapy. MBC is incurable. Hormone sensitive MBC eventually becomes resistant to endocrine therapy in most women. Anthracyclines are the agents of choice in the treatment of endocrine resistant MBC. With the widespread use of anthracyclines in the adjuvant setting, taxanes have become the agents of choice for many patients. Recently capecitabine has become established as a standard of care for patients pretreated with anthracyclines and taxanes. However, a range of agents have activity as third line treatment. These include gemcitabine, vinorelbine and platinum analogues. The sequential use of non-cross resistant single agents rather than combination therapy is preferable in most women with MBC. Even though combination therapy can improve response rates and increase progression free interval, there is no robust evidence to indicate an advantage in terms of overall survival. Moreover, combination therapy is associated with a higher toxicity rate and poor quality of life. There is no role for dose-intense therapy, high dose therapy or maintenance chemotherapy outside the context of a clinical trial. The introduction of trastuzumab, monoclonal antibody targeting growth factor receptors, has improved the therapeutic options for women with tumours overexpressing HER2/neu. DNA micro-array profiles of tumours can potentially help to individualise therapy in future. Molecular targeted therapy has the potential to revolutionise the management of MBC.

Mammographic screening for breast cancer commenced in the UK in 1988 following the recommendations of the Forrest Committee and is now well established. This article reviews the evidence for efficacy of mammographic screening, the mode of delivery of the service including the assessment of mammographic abnormalities and the role of needle biopsy in diagnosis. Despite the established position of breast screening in the UK there are continuing challenges, not least workforce issues and the recent extension of the programme. There is increasing interest in the use of digital mammography and research continues into the possibility of computer-assisted detection (CAD) of mammographic abnormalities.

Lower urinary tract symptoms are a common, distressing and embarrassing problem for women of all ages, but become increasingly more common with advancing age. Oestrogen preparations have been used for many years to manage urinary symptoms, but there is still controversy over the efficacy of these preparations. The purpose of this review is to provide a critical overview of the epidemiological evidence when considering hormone replacement therapy for treatment of urinary symptoms in women.

Various studies have demonstrated that oestrogen replacement can improve, or even cure, urinary stress and urge incontinence. High dose oestrogen can reduce the total number of voids in 24 hours, including nocturnal voids. Vaginal oestriol significantly reduces the risk of recurrent infections in postmenopausal women with a history of recurrent urinary tract infections. Data on combining oestrogen with a progestogen are limited, but suggest it may negate the benefit and more research is still required in this area to clarify their role.

The British Menopause Society Council aims to help health professionals to inform and advise women about the menopause. The oestrogen plus progestogen arm of the Women's Health Initiative was stopped in July 2002. This guidance regarding hormone replacement therapy (HRT) use responds to the results and analysis that have been published since then, as well as the Million Women Study published in August 2003. Because there are few effective alternatives to HRT for vasomotor and urogenital symptoms, oestrogen-based treatments still have a major role. HRT is also most effective for the prevention of osteoporosis. Unopposed oestrogens are contraindicated in women with an intact uterus, and hence a range of oestrogen and progestogen combinations, with differing routes of delivery, now exists under the title of "HRT". Treatment choice should be based on up to date information and targeted to individual women's needs. Hormone replacement still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.