News forum

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

Abdominal aortic aneurysm in postmenopausal women
Intrauterine contraception immediately after abortion
Borrowing and sharing of prescription drugs in women
Diminished ovarian reserve and reproductive concerns
The effect of hormone therapy regimen on the risk of MI
HRT and risk of breast cancer in BRCA1 mutation carriers
Size at birth and the risk of developing breast cancer

Abdominal aortic aneurysm in postmenopausal women
Lederle FA, Larson JC, Margolis KL et al. Women's Health Initiative Cohort Study. BMJ 2008; 337: a1724. doi: 10.1136/bmj.a1724

This is a spin-off paper from the Women's Health Initiative study, which was designed to look at cardiovascular and cancer outcomes with and without HRT. It has followed a substantial cohort of women in the US over nearly eight years and is now working through its collected data.
Abdominal aortic aneurysm (AAA) kills 15,000 people a year in the US and 40 per cent of these are women. Although AAA is more common in men, women who have AAA have a higher mortality because they rupture at a smaller diameter and the intervention rate is lower.
Women who smoke are eight times more likely to have an AAA than never-smokers and four times more likely than ex-smokers. Increasing height, hypertension and cholesterol, and coronary and peripheral artery disease, were also associated with an increased risk of aneurysm events.
This study has proven that HRT provided protection from AAA events, despite previous smaller studies reporting that estrogen therapy alone may increase the risk. This will reopen the debate about HRT and cardiovascular risks, because many people criticised the WHI study at the time for putting older, obese postmenopausal women on higher doses of HRT than have ever been used in that age group in the UK.
They also found that women with diabetes were at reduced risk of aneurysm events; a similar association has been reported in men, which is also hard to explain. I think the message from this paper is that we ought at least to think more about AAA as a possibility in the differential diagnosis of abdominal or back pain in older women who smoke.
- Dr Sally Hope is a GP in Woodstock, Oxfordshire, and honorary research fellow in women's health, department of primary care, University of Oxford

Intrauterine contraception immediately after abortion
Goodman S, Hendlish SK, Reeves MF, Foster-Rosales A. Contraception 2008; 78(2): 143-8

In the US, 1.3 million abortions are performed annually, which is clearly a failure of education and access to family planning resources on a catastrophic scale. Furthermore, about 50 per cent of these abortions are repeat procedures, which indicates the education missed by these women, even when they are being seen by the abortion services.
A trial of immediate post-abortion IUD insertion has been completed in California. A cohort of 'controls' had the abortion but chose other, non-IUD contraception. Women who received an immediate post-abortion IUD had a lower rate of repeat abortions than controls (p <.001). Women who received a post-abortion IUD had 34.6 abortions per 1,000 woman-years of follow-up, compared to 91.3 for the control group.
With typical use, moderately effective hormonal methods, such as the combined oral contraceptive pill, the patch and the vaginal ring, have approximately 8 per cent annual failure rates in the general population. However, in the post-abortion population, even much more effective methods, such as depot medroxyprogesterone acetate, have been shown to have failure rates as high as 16 per cent because of discontinuation.
Given that up to 83 per cent of abortion patients ovulate within the first cycle after the procedure, the risk of repeat pregnancy is high without good contraception. Delayed post-abortion IUD insertion may not be adequate because 40 per cent of patients never return for the insertion.
There were no reported pregnancies with an IUD in place. Of the 41 women (6.1 per cent) in the IUD cohort who had repeat abortions, 12 followed voluntary removals. Another five women became pregnant following complete or partial expulsion and one woman had her IUD removed because of infection.
It is unclear whether women who opt for the IUD at the time of abortion may be more determined to avoid pregnancy than those who choose other methods. Even without an IUD option, a subset of 'determined' women might be good users of other methods and avoid pregnancy more effectively than a typical contraceptive user. The short-term contraceptive methods appear to be rapidly discontinued after a brief period for the typical woman who chooses those methods.
Screening protocols have also presented barriers to immediate post-abortion IUD access. Conventional practice has suggested that STI screening results must be confirmed as negative before proceeding with IUD insertion. But such requirements involve extra visits and a waiting period, during which IUD candidates may miss the opportunity for immediate post-abortion insertion.
Following updated WHO medical eligibility criteria, it is becoming more acceptable to allow IUD insertion on the same day as STI screening among low-risk women with no clinical evidence of infection. In some UK regions, all TOP patients are given antibiotics against chlamydia routinely at screening.
Recent studies have shown that more intensive contraceptive counselling and service provision did not improve contraceptive use or adherence at four to six months after an abortion. Providers should emphasise the advantages of an IUD, which is less subject to user error and does not need repeat prescriptions. To assist women in avoiding unintended pregnancy, more effective, convenient and long-acting contraception would be advantageous in those with a history of induced abortion. SH

Borrowing and sharing of prescription drugs in women
Petersen EE, Rasmussen SA, Daniel KL et al. Women's Health (Larchmt). 2008; 17(7): 1073-80

A patient at my practice who had very bad asthma often needed short courses of oral steroids. She had also had a gastric ulcer many years ago, so was on long-term PPIs. I thought that she understood she should never take aspirin or any other NSAID. Three years ago she died and the postmortem revealed a perforated, bleeding gastric ulcer.
She had taken her husband's prescribed 'back tablets' (diclofenac sodium), a stark example of how one person's medication can be lethal to another in the same household. We know patients take all sorts of OTC medications - I also found a patient who shared his medication with his dog.
In a US survey of health behaviour in more than 26,000 people, 28.8 per cent of women and 26.5 per cent of men reported borrowing or sharing prescription medications. Women of reproductive age were more likely to report prescription medication borrowing or sharing (36.5 per cent) than women of non-reproductive age (over 45 years) (19.5 per cent) (RR 1.87, 95% CI 1.77-1.99).
Of reproductive-age women who borrowed or shared prescription medication, the most commonly borrowed or shared medications were for allergy (43.8 per cent) and pain (42.6 per cent). Prescription medication borrowing and sharing is a common behaviour among adults and is more common among reproductive-age women than women in other age groups. Perhaps we need to take greater account of the fact that patients may be taking other people's medication. SH

Diminished ovarian reserve and reproductive concerns
Pal L, Bevilacqua K, Zeitlian G et al. Menopause 2008 Sep 10. doi 10.1097/gme.0b013e3181728467

Premature ovarian failure affects about 1 per cent of women aged less than 40 years. The authors investigated whether a diagnosis of diminished ovarian reserve (DOR) in 89 women aged less than 42 years attending an academic infertility practice has adverse implications for skeletal health and quality of life.
Women younger than 41 years with DOR were significantly more likely to manifest disturbed sleep (p = 0.049) and sexual problems (p = 0.004) compared with those with infertility and normal ovarian reserve. A diagnosis of DOR was significantly associated with low bone mass density. This study emphasises that management of women with early ovarian failure extends beyond that of infertility and gynaecology and requires a multidisciplinary team.
- 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

The effect of hormone therapy regimen on the risk of MI
Lokkegaard E, Andreasen AH, Jacobsen RK et al. Eur Heart J 2008 Sep 30. doi:10.1093/eurheartj/ehn408

'HRT' is often used as a generic global term and some consider that all types are the same, in terms of risks and benefits. This study of 698,098 healthy women in Denmark, aged 51-69 years, who were followed from 1995 to 2001, assessed the risk of MI and different regimens of HRT (sequential, continuous combined, oral, transdermal). Overall, no increased risk (RR 1.03 95% CI 0.95-1.11) of MI was found in current HRT users compared with never-users. An increasing risk with longer duration of use was found for younger women, which was not observed with older age groups.
In all age groups, the highest risk of MI was found with continuous combined HRT. No increased risk was found with unopposed estrogen, sequential combined therapy, or tibolone. Significantly lower risk was found with the transdermal route than oral unopposed estrogens (p = 0.04), probably reflecting the reduced effects on coagulation with the former. No associations were found with either progestogen type or estrogen dose.
It must be noted that the risk of MI for women in their fifties is low. Progestogens are given to non-hysterectomised women to reduce the risk of endometrial cancer that would occur if they took unopposed estrogen. Furthermore, continuous addition confers a greater endometrial benefit than sequential addition. This study confirms that different regimens and delivery systems have different effects.MR

HRT and risk of breast cancer in BRCA1 mutation carriers
Eisen A, Lubinski J, Gronwald J et al; the Hereditary Breast Cancer Clinical Study Group. J Natl Cancer Inst 2008; 100: 1361-7

There is concern that HRT might increase the risk of breast cancer, especially in women who are BRCA1 carriers.
These women may have prophylactic surgical oophorectomy at a young age, resulting not only in menopausal symptoms, but also in increased risk of osteoporosis, cardiovascular disease, dementia, cognitive decline and parkinsonism.
The authors undertook a matched case-control study of 472 postmenopausal women with a BRCA1 mutation to examine whether HRT is associated with an increased subsequent risk of breast cancer. In this group of BRCA1 mutation carriers, the adjusted OR for breast cancer associated with ever use of HRT compared with never use was 0.58 (95% CI 0.35-0.96, p =.03).
In analyses by type of HRT, an inverse association with breast cancer risk was observed with use of estrogen only (OR 0.51, 95% CI 0.27-0.98, p =.04); the association with use of estrogen plus progestogen was not statistically significant (OR 0.66, 95% CI 0.34-1.27, p =.21). Thus HRT use was not associated with increased risk of breast cancer in women with BRCA1 mutation. MR

Size at birth and the risk of developing breast cancer
Silva IdS, Stavola BD, McCormack V; Collaborative Group on Pre-Natal Risk Factors and Subsequent Risk of Breast Cancer. PLoS Medicine 2008; 5(9): e193 doi:10.1371/journal.pmed.0050193

This study examined whether size at birth affects breast cancer risk. Data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Birthweight was positively associated with breast cancer risk in studies based on birth records. Relative to women who weighed 3.000-3.499kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed <2.5kg and 1.12 (95% CI 1.00-1.25) in those who weighed ≥4.0kg. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment 1.06 (95% CI 1.03-1.10) and 1.09 (95% CI 1.03-1.15) respectively).
The cumulative incidence of breast cancer per 100 women by age 80 was estimated to be 10.0, 10.0, 10.4 and 11.5 in those who were, respectively, in the bottom, second, third and top fourths of the birth length distribution. However, one needs to query the accuracy of length measurements in wriggling babies. MR


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