News Forum

GPs with an interest in women's health review the latest papers of significance from research teams across the world.

Key areas of concern and health priorities for women
Health risks and benefits after oestrogen and progestogen
Risk of recurrence after HRT in breast cancer survivors
The risk of invasive cancer in women with CIN 3
Intergenerational recurrence of breech delivery
Missed diagnosis in women with postnatal depression
Basis for new weight loss drug

Key areas of concern and health priorities for women
Ribeiro PS, Jacobsen KH, Mathers CD, Garcia-Moreno C. Int J Gynaecol Obstet 2008 Apr 1; doi:10.1016/j.ijgo.2008.01.025

Women's health is increasingly recognised as a global health priority, with considerable attention focused on sexual and reproductive health.

However, it is now becoming apparent that common health conditions, such as cardiovascular disease, cancer, injuries and mental health disorders must also be addressed.

This paper identifies key areas of concern for women by age group and WHO region, using the 2005 estimates of mortality and disease burden from the WHO Global Burden of Disease study. The leading causes of death in women aged 15-44 years include infectious diseases, such as HIV/AIDS, tuberculosis, maternal health conditions and injuries.

The leading causes of death in women aged 45 years or more include cardiovascular diseases, COPD and other non-communicable conditions. Neuropsychiatric and sensory disorders are a major cause of disability for both age groups.

Furthermore, infectious and parasitic diseases are the most common causes of death in sub-Saharan Africa, whereas the most common causes of death in Europe and the former Soviet republics are non-communicable conditions.

The mortality rate from infectious and parasitic diseases in sub-Saharan Africa is 71.3 per 10,000 but only 4.6-16.6 per 10,000 in other regions. Mortality from non-communicable conditions is 110.5 per 10,000 in Europe and the former Soviet republics and only 52.6-66.9 per 10,000 in other regions.
This study of the key regional and age-specific priorities for women's health will facilitate the development of appropriate interventions and policies to reduce disease burden worldwide.

- Miss Margaret Rees is reader in reproductive medicine, University of Oxford, honorary consultant in medical gynaecology and visiting professor, faculty of medicine, University of Glasgow

Health risks and benefits after oestrogen and progestogen
Heiss G, Wallace R, Anderson GL et al. JAMA 2008; 299: 1036-45

Health outcomes at three years (mean 2.4 years of follow-up) after stopping the oestrogen plus progestogen (E+P) arm of the Women's Health Initiative (WHI) are reported.

The risk of cardiovascular events and fractures was no different between the intervention and placebo groups. A greater risk of all malignancies occurred in the E+P than in the placebo group, although this incidence rate was not statistically different from the incidence rate seen during the trial.

There was no significant difference between the groups in terms of breast, endometrial and colorectal cancer incidence. Thus the only difference between the groups was in the 'other cancers' category, which included lung cancer.

No analysis according to age has been made, although previous WHI papers have shown differences. For example, women who initiated HRT closer to menopause tended to have reduced CHD risk compared with the increase in risk among women more distant from the menopause. This paper has not increased the body of knowledge about the risks and benefits of HRT and further analyses should be undertaken. MR

Risk of recurrence after HRT in breast cancer survivors
Holmberg L, Iversen O-E, Rudenstam CM et al; HABITS Study Group. J Natl Cancer Inst 2008; 100: 475-82

Survival rates are increasing and it has been estimated that about 172,000 women are alive in the UK having had a diagnosis of breast cancer. Breast cancer survivors with menopausal symptoms pose a management problem, because traditional advice is to avoid the use of exogenous systemic oestrogens.

Early interim analysis of two randomised trials in Scandinavia (HABITS and Stockholm studies) have shown contradictory results. The former showed an increased risk of recurrence, but the latter did not.
The increased risk of recurrence reported in HABITS might be explained by the fact that most women randomised to HRT did not use tamoxifen and most used continuous combined HRT, whereas in the Stockholm study, most took tamoxifen and had long-cycle combined HRT. There was also a higher proportion of women with node-positive breast cancer in the HABITS trial than in the Stockholm trial.
This paper examines follow-up data in 442 women after a median of four years in the HABITS study.

Thirty-nine of the 221 women in the HRT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR 2.4, 95 per cent CI 1.3-4.2). Cumulative incidences at five years were 22.2 per cent in the HRT arm and 8.0 per cent in the control arm.

By the end of follow-up, six women in the HRT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = 0.51, log-rank test).

Although there appears to be an increased risk of breast cancer in the HRT arm of the research, the numbers of women included in the study are small and the original methodological problems still pertain. MR

The risk of invasive cancer in women with CIN 3
McCredie MR, Sharples KJ, Paul C et al Lancet Oncology 2008; 9: 425-34

What is the risk of developing invasive cervical cancer from CIN 3, also termed stage 0 carcinoma?
It is one of those odd quirks of medicine that sometimes the most value comes from research which would no longer be allowed. At the National Women's Hospital, Auckland, New Zealand, treatment of a large cohort of women with CIN 3 was withheld from 1965 to 1974 as part of a clinical study, which would now be considered unethical.

In 1988, a judicial inquiry referred all of the surviving women for independent clinical review, which has allowed them to be, in effect, a 'control' arm of non-treatment. Adequacy of treatment by type of procedure, presence of CIN 3 at the excision margin and subsequent cytology were analysed in 1,229 women. The primary outcome was cumulative incidence of invasive cancer of the cervix or vaginal vault.
In 143 women managed only by punch or wedge biopsy, cumulative incidence of invasive cancer of the cervix or vaginal vault was 31.3 per cent (95 per cent CI 22.7-42.3) at 30 years, rising to 50.3 per cent (37.3-64.9) in the subset of 92 such women who had persistent disease within 24 months.

However, cancer risk at 30 years was only 0.7 per cent (0.3-1.9) in 593 women whose initial treatment was deemed adequate or probably adequate, and whose treatment for recurrent disease was conventional.
This retrospective analysis shows that women who have untreated CIN 3 have an almost one in two risk of progressing to cervical cancer, whereas the risk is very low in those women who are treated conventionally.

- Dr Sally Hope is a GP in Woodstock, Oxfordshire, and honorary research fellow in women's health, department of primary healthcare, University of Oxford

Intergenerational recurrence of breech delivery
Nordtveit TI, Melve KK, Albrechtsen S, Skjaerven R BMJ 2008; 336: 872-6

This paper uses as a database the medical birth registry of Norway, based on all births in Norway 1967-2004 (2.2 million births). Generational data were provided through linkage by national identification numbers, to look for breech delivery in the second generation.

Men and women who were themselves delivered in breech presentation had more than twice the risk of breech delivery in their own first pregnancies, compared with men and women who had been cephalic presentations (OR 2.2, 95 per cent CI 1.8-2.7 for men and OR 2.2, 95 per cent CI 1.9-2.5 for women).

The strongest risks of recurrence were found for vaginally delivered offspring and were equally strong for men and women. Increased risk of recurrence of breech delivery in offspring was present only for parents delivered at term.

In the past, I have never asked any of my antenatal patients how their partners were delivered. I had always assumed that a breech delivery was an interaction between the fetus and the mother's pelvic brim, which, of course, it still is. This paper attributing the observed pattern of familial predisposition to term breech delivery to genetic inheritance, predominantly through the fetus, shows that if we asked about the father's delivery, we would be more aware of the possible risk of a breech delivery for the baby. SH

Missed diagnosis in women with postnatal depression
Pawlby S, Sharp D, Hayc D, O'Keane V J Affect Disord 2008; 107: 241-5

GPs should diagnose postnatal depression using face-to-face interviews instead of the Edinburgh Postnatal Depression Scale (EPDS), UK research suggests.

The study found that the EPDS method, recommended by NICE in its guidance on postnatal mental health from 2007, missed 65 per cent of cases of postnatal depression.

These findings add to the growing concern that cases of postnatal depression are being missed. A UK study found that changes to maternity care in England have reduced contact time between GP and patient, which is vital for diagnosing depression. The average prevalence rate of postnatal depression in the UK is currently estimated at 12 per cent.

For this latest study, the researchers randomly selected 147 antenatal women from two general practices in south London.The women were assessed for depression three months after the birth of their baby, completing the EPDS, a 10-item self-report questionnaire and face-to-face interviews.

A total of 34 women were diagnosed with postnatal depression using the interview method. But the EPDS method identified just 12 women with postnatal depression, giving the method a sensitivity of only 35 per cent.

The researchers, from the Institute of Psychiatry in London, concluded that 'the majority of women with a clinical diagnosis of depression were not identified by the EPDS'. They added that 'a brief semi-structured face-to-face clinical interview may be a more accurate way of detecting those women who are depressed following childbirth'. PH

Basis for new weight loss drug
King BF, Townsend-Nicholson A J Pharmacol Exper Ther 2008; 324: 1055-63

Two proteins that control how much the stomach expands could form the basis of a new weight loss drug, according to this paper by UK researchers. The proteins help to relax the gut, meaning that it can expand to a volume of two litres.

By blocking these proteins, patients' food intake could be better regulated, add the researchers, who suggest the technique could one day replace gastric banding. PH.

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