Abstract
A team of European researchers claim that women are seriously under-represented in trials of heart disease medication and call for gender-specific effects to be given more attention.
Women are under-represented in heart drug trials, claim a team of German researchers in a recent issue of the European Heart Journal. Dr Verena Stangl and co-authors from the Charité Hospital, Humboldt-University Berlin, conducted an extensive review of heart disease trials and concluded that the majority enrolled too few women and that too little is know about the efficacy and potential side effects of heart drugs in women.
The researchers believe that this is because heart disease is still traditionally thought of as a ‘male’ condition, despite the fact that heart disease is the leading cause of death among American women. In fact, while more women than men die from heart disease in the USA, women are less likely to receive drug treatment or surgery following a heart attack.
“Because too few women participate in heart disease trials, we are not sure whether they really benefit from some of the therapeutic strategies that have shown clinical benefit in trials conducted predominantly in men,” explains Dr Stangl.
The article highlights several areas of heart disease research where gender-specific effects have been noted. For example, aspirin is thought to be less effective in preventing heart attacks in female patients and digitalis, given to heart failure patients, is associated with a higher risk of death in women. In addition, women are twice as likely as men to suffer a persistent cough when treated with angiotensin converting enzyme (ACE) inhibitors.
“Because too few women participate in heart disease trials we are not sure whether they really benefit from some therapeutic strategies that have shown clinical benefit in trials conducted predominantly in men.”
Since so little data is available on drug effects in women, it is not clear whether differences are directly due to gender or whether at least some are due to the relative overdosing of women due to their smaller body size.
Dr Stangl comments that: “For example, we have no prospective data for digitalis in female patients. It's unclear whether it is really linked to increased mortality among women or whether this increase is an effect only of an overdose, and therefore whether they would benefit from lower doses adapted to their weight.”
In light of these problems, the authors recommend that more attention be directed at gender-specific differences in heart disease and response to drug treatments. Most studies analyse these effects only retrospectively, which Dr Stangl feels is unacceptable, stating
“It is essential that trials are designed to provide the necessary data so that researchers know from the outset that they will be able to analyze factors that could contribute to different outcomes for men and women, such as hormonal aspects, possible effects of drug dosage and known differences in biochemical and physiological responses between men and women.”
Vaginal administration of emergency contraception appears feasible
A small study, published recently in Fertility and Sterility, has suggested that emergency contraception may be effective when delivered vaginally.
Nine regularly menstruating women were given double the standard dose of emergency contraception vaginally followed, after a 1-week wash-out period, by the standard dose orally. The vaginal hormones were self-administered and the women were asked to restrict their physical activity in the following hours.
The presumed mode of action of emergency contraception is a transient inhibition of gonadotropin, preventing ovulation. The women's gonadotropin levels were monitored for 24 h after hormone administration. The researchers found that vaginal and oral delivery produced the same drop in blood gonadotropin levels.
Vaginal administration might help prevent the side effects of nausea and vomiting that effect at least one in four women using emergency contraception. Dr Elirian Mor, lead author of the study, notes that “In theory, the vaginal route should perhaps be beneficial or preferable.”
in brief…
Amsterdam LL, Gentry W, Jobanputra S et al.: Fertil. Steril. 84(2) 300–304 (2005).
In a prospective, open-label Phase II clinical trial, researchers investigated the effect of the aromatase inhibitor anastrazole on pelvic pain caused by endometriosis. A total of 15 premenopausal women with documented refractory endometriosis were given 1 mg anastrazole plus a combined oral contraceptive daily for 6 months, following a 1-month wash-out period of previously prescribed hormonal treatments. Of the 15 women, 14 showed significant pain relief, based on analog pain scales. Few side effects were reported. The authors conclude that aromatase inhibitors warrant further investigation in the treatment of endometriosis.
Green MC, Buzdar AU, Smith T et al.: J. Clin. Oncol. (2005) [Epub ahead of print].
The study compared once-weekly with once every 3 weeks administration of paclitaxel in operable breast cancer patients. A total of 258 women with Stage I–IIIA breast cancer were randomized to receive paclitaxel either once weekly (12 doses) or once every 3 weeks (4 cycles), followed by standard doses of 5-fluorouracil–doxorubicin–cyclophosphamide (FAC) every 3 weeks for four cycles. Women receiving once-weekly paclitaxel followed by FAC had a 28% higher pathologic complete response rate (pCR), compared with those receiving the standard once every 3 weeks paclitaxel followed by FAC.
Aloia JF, Talwar SA, Pollack S, Yeh J: Arch. Intern. Med. 165(14), 1618–1623 (2005).
Demonstrates that vitamin D supplements have little or no benefit on bone mineral density (BMD) in calcium-replete postmenopausal African–American women. The randomized, placebo-controlled, double-blind trial assigned 208 healthy black women aged 50–75 years to receive either 20 mg vitamin D or placebo, with all women receiving calcium supplements to achieve a 1200–1500 mg daily calcium intake. No difference in bone loss or bone turnover markers was observed between the two groups. The authors recommend further studies to determine the applicability of these results to other ethnic groups.
Hope for early detection of pre-eclampsia
Researchers from the Sunnybrook and Women's College Health Sciences Center, Canada, have discovered a simple blood test for pre-eclampsia which may be able to detect the condition in early pregnancy.
Pre-eclampsia affects over 8% of women in the later stages of pregnancy and doctors have long hoped for a predictive test to detect the disease prior to the onset of symptoms. “We're really excited about this finding,” enthused study author Dr Clifford Librach “I think it's really an advance in this area and something we hope will prevent this disease in the future.”
The study, published in the American Journal of Obstetrics and Gynecology, compared 12 women who suffered from pre-eclampsia with 12 who had normal pregnancies. Researchers found that women who went on to develop pre-eclampsia had lower plasma levels of human leukocyte antigen (HLA)-G early in pregnancy. HLA-G is an antibody secreted by the placenta and involved in protecting the fetus from the maternal immune response.
The authors hope that earlier detection could lead to better treatment of pre-eclampsia. Although there are currently few treatment options available for the condition, doctors could monitor at-risk women more carefully and might even chose to induce an earlier birth. In addition, early detection would enable a better study of the condition and might help to develop potential treatments.
Librach cautioned that “More studies on larger numbers of pregnant women need to be done to determine if this test can be used on a routine basis,” and added that his team hope to begin clinical trials of the test within a few years.
Removal of ovaries at hysterectomy may lower long-term survival
It is commonly recommended that women over the age of 40–45 years undergoing hysterectomy have their ovaries removed to prevent any future risk of ovarian cancer. However, a new study by researchers at the University of California, LA, USA suggests that for women under the age of 65 years with an average risk of ovarian cancer, overall survival may be increased by leaving both ovaries in place.
The analysis showed that women who had their ovaries removed before the age of 55 years had a nearly 9% greater risk of dying by the age of 80. For those whose ovaries were removed between the ages of 55 and 59 years, the risk is smaller, around 4%.
The authors suggest that hormones released by the ovaries may exert a protective effect on bones and, in particular, the cardiovascular system. The ovaries continue to produce hormones even after menopause.
Lead author, Dr William H Parker, points out that “Women are living longer and the major killer of women is heart disease, taking 25 times more women's lives than ovarian cancer,” and added “I think we need to look at the big picture.”
He emphasized; however, that “these results, of course, do not apply to women at high risk of ovarian cancer.”
High dairy consumption may increase risk of ovarian cancer
A link between the consumption of milk products and ovarian cancer has been suspected since the late 1980s. A recent meta-analysis of 21 studies suggests that there may be some evidence for the association, although some studies showed conflicting results.
Dr Susanna Larsson and colleagues at the Karolinska Institute, Sweden, analyzed the results of 18 case-control and three cohort studies.
There were important difference between the results of different study designs, with case-control studies providing conflicting results. Overall, case-control studies showed that only high-fat milk consumption was positively associated with ovarian cancer, with low-fat milk consumption negatively associated. In contrast, prospective cohort studies consistently demonstrated an increased risk of ovarian cancer with greater milk consumption.
A new study published in the International Journal of Cancer provides some support for the hypothesis that milk and lactose may be linked to ovarian cancer
The authors conclude that “prospective cohort studies, but not case-control studies, support the hypothesis that high intakes of dairy foods and lactose may increase the risk of ovarian cancer.” These differences may be related to selection or recall bias.
It is hypothesized that lactose may be the mediator of this increased risk and the authors suggest that an increase in lactose consumption of 10 g (equivalent to a glass of milk) daily may increase ovarian cancer risk by 13%.
However, the authors do not recommend that women cut their milk intake. “Although milk consumption might increase the risk of ovarian cancer, consumption of milk has other potential benefits,” Dr Larsson stated “for instance, there is strong evidence that high consumption of milk may reduce the risk of colorectal cancer. There is also limited evidence that consumption of low-fat dairy foods may lower the risk of other diseases such as cardiovascular disease and Type 2 diabetes. Thus, I would not recommend women to stop drinking milk.”
Women with early breast cancer benefit by switching from tamoxifen to anastrozole
A study published in a recent issue of the Lancet has shown that switching drug treatments from tamoxifen to anastrozole after 2 years may reduce the risk of metastasis or recurrence by 40%.
The aromatase inhibitors, including anastrozole, have been previously shown to be more effective than tamoxifen in preventing recurrence of hormone-sensitive breast cancer in postmenopausal women, but the effect of switching drugs in women already taking tamoxifen remains unclear.
More than 3000 postmenopausal women who had been taking tamoxifen for 2 years were randomized to either switch to anastrozole or continue with tamoxifen for the next 3 years. At a median follow up of 28 months, women in the anastrozole group were shown to have a lower rate of recurrence and spread of the cancer.
“Switching from tamoxifen to anastrozole after 2 years is more beneficial for the patients than staying on tamoxifen,” stated lead researcher Prof Raimund Jakesz.
Anastrozole, as observed in previous studies, was associated with fewer cerebrovascular events and a lower rate of endometrial cancer. However, the incidence of fracture was significantly higher in the anastrozole group.
MR spectroscopy effective in distinguishing malignant breast tumors
Magnetic resonance (MR) spectroscopy has been demonstrated to improve the diagnostic accuracy of breast MR imaging. Spectroscopy takes only 7–10 min longer than standard MR imaging. It can detect choline-containing compounds found at higher levels in neoplastic breast tissue, allowing more accurate differentiation between malignant and benign tumors.
“Spectroscopy gives us an additional piece of information about the biochemical composition of the tumor,” noted senior author Prof Michael Garwood, University of Minnesota, MN, USA. “When the standard MR imaging exam is inconclusive, the spectroscopy measurement can improve the rate of detecting a canceros breast tumor.”
In a study published in a recent edition of Radiology, four radiologists retrospectively examined a total of 55 cases that had been previously confirmed by biopsy. They evaluated the cases first by standard MR imaging alone, and then with additional data from MR spectroscopy. MR spectroscopy improved the sensitivity, specificity, accuracy and agreement of the radiologists.
“Adding spectroscopy to breast MR examinations will not only reduce concern over possible missed cancers and unnecessary biopsy procedures, it may also improve the efficiency and quality of patient care,” concluded study author Dr Sina Meisamy.
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