Commercial opportunists encourage new parents to have their baby's cord blood stored for the next 25 years in case it could save his or her life in the future. Indeed, stem cell transplants from cord blood are used for the equivalent of bone marrow donations, often to patients with leukaemia. There may also be future advances where mesenchymal cells could be useful in treating chronic disorders and these potential applications have encouraged private businesses to lure the up-front costs of £1500 for the collection and storage of neonates' cord blood.
But the odds of the blood ever being used are low - estimated to be between 1 : 2 700 and 1 : 20 000 - and the commonest indication, childhood leukaemia, may require stem cells from a donor who does not have the carcinogenic mutation. Also, insufficient blood is available, so cord banks offer a more realistic solution and that is the view of all recognised expert groups, including the Royal College of Obstetricians and Gynaecologists. The problem is that cord banks developed altruistically have not taken off in the public sector, with less than 1% of live births contributing their cord blood in Europe.
A possible public / private partnership has been initiated by Virgin Health in the UK whereby, for the same cost, 20% of the blood is set aside for personal use and 80% donated to a communal bank (Fisk & Atun BMJ 2008;336:642-4). It is an intriguing proposition and may offer an alternative for those wishing to protect their own interests - no matter how remote - and assist those less financially well-off.
31 May, 2008
10 April, 2008
Assisted reproduction and multiple pregnancies
Multiple pregnancies resulting from assisted reproductive manoeuvres are often blamed for the rising preterm delivery rates in developed countries. Indeed, a multiple pregnancy is deemed to be the most significant risk of in-vitro fertilisation.
Transferring two or more embryos at the day 2 single-cleavage stage results in higher pregnancy rates per cycle, but also more multiple pregnancies. It now appears that transferring a single embryo at a later stage of in-vitro development (day 5) might lead to higher implantation rates, together with lowered multiple pregnancy rates, especially in women with a good prognosis. The philosophy is that by selecting women who are likely to have successful outcomes (because at least four eight-cell embryos of quality are achieved) and allowing for the development of their embryos to the blastocyst stage prior to implantation of single embryos, better clinical pregnancy rates could be achieved.
Whether such a policy in a large assisted conception unit would be feasible and give superior results is not known. To test the hypothesis, Khalaf et al (BJOG 2008;115:385-90) changed their guidelines and recorded their results for 18 months before and after the implementation of the new protocols. Despite only a selected group of patients fulfilling the criteria for single blastocyst transfer, they improved their clinical pregnancy rates from 27% to 32% while reducing their multiple pregnancy rates from 32% to 17%.
It is therefore feasible to use selective single embryo transfers in a busy IVF unit without sacrificing overall pregnancy rates and at the same time reducing twin and higher order multiple pregnancy risks. The policy had the extra spin-off of having more supernumerary embryos for cryopreservation and later use.
A Canadian study has found that singleton preterm babies and multiple birth babies have similar outcomes at the same gestational age, except for multiples having a greater predisposition to respiratory distress (Qui et al Obstet Gynecol 2008;111:365-71).
The extra costs of multiple pregnancies are considerable. As Wood points out (BJOG 2008;115:416) a twin pregnancy costs £1826 more than a low-risk singleton in antenatal and intrapartum care but other expenses have to be added in such as neonatal intensive care which could add another £3500 plus further infant in-patient care at £4800. These figures do not take into account other costs should complications arise like postnatal depression, a handicapped survivor never mind the emotional and societal costs of the stresses of ongoing care. A proper audit is indeed sobering.
Elective delivery of twins can safely include a vaginal option according to Schmitz et al who describe their experience in a French tertiary referral unit (Obstet Gynecol 2008;111:695-703). With an active intervention policy aimed at facilitating the delivery of the second twin about 5 minutes after the first, they had morbidity and mortality rates similar to those delivered by caesarean section.
Transferring two or more embryos at the day 2 single-cleavage stage results in higher pregnancy rates per cycle, but also more multiple pregnancies. It now appears that transferring a single embryo at a later stage of in-vitro development (day 5) might lead to higher implantation rates, together with lowered multiple pregnancy rates, especially in women with a good prognosis. The philosophy is that by selecting women who are likely to have successful outcomes (because at least four eight-cell embryos of quality are achieved) and allowing for the development of their embryos to the blastocyst stage prior to implantation of single embryos, better clinical pregnancy rates could be achieved.
Whether such a policy in a large assisted conception unit would be feasible and give superior results is not known. To test the hypothesis, Khalaf et al (BJOG 2008;115:385-90) changed their guidelines and recorded their results for 18 months before and after the implementation of the new protocols. Despite only a selected group of patients fulfilling the criteria for single blastocyst transfer, they improved their clinical pregnancy rates from 27% to 32% while reducing their multiple pregnancy rates from 32% to 17%.
It is therefore feasible to use selective single embryo transfers in a busy IVF unit without sacrificing overall pregnancy rates and at the same time reducing twin and higher order multiple pregnancy risks. The policy had the extra spin-off of having more supernumerary embryos for cryopreservation and later use.
A Canadian study has found that singleton preterm babies and multiple birth babies have similar outcomes at the same gestational age, except for multiples having a greater predisposition to respiratory distress (Qui et al Obstet Gynecol 2008;111:365-71).
The extra costs of multiple pregnancies are considerable. As Wood points out (BJOG 2008;115:416) a twin pregnancy costs £1826 more than a low-risk singleton in antenatal and intrapartum care but other expenses have to be added in such as neonatal intensive care which could add another £3500 plus further infant in-patient care at £4800. These figures do not take into account other costs should complications arise like postnatal depression, a handicapped survivor never mind the emotional and societal costs of the stresses of ongoing care. A proper audit is indeed sobering.
Elective delivery of twins can safely include a vaginal option according to Schmitz et al who describe their experience in a French tertiary referral unit (Obstet Gynecol 2008;111:695-703). With an active intervention policy aimed at facilitating the delivery of the second twin about 5 minutes after the first, they had morbidity and mortality rates similar to those delivered by caesarean section.
08 April, 2008
New JASS out
Much is being published on preventative measures.
The journals carry large, long-term studies which show that antenatal supplementation with broad-spectrum vitamin nutrients are superior to iron plus folate alone in reducing the incidence of how birth-weight in developing countries.
Bolstering nutrition in early childhood also has long-term benefits in terms of greater earning capacity in adulthood. Breastfeeding and basic hygiene are cheap and effective interventions (Lancet 2008;371 Haddinott et al 411-6, Bhutto et al 417-40, Vaidya et al 492-9, Bryce et al 510-26, Ruel et al 588-95, Morris et al 608-21).
Later in life smoking is the most common preventable cause of death. It killed 100 million people last century and is predicted to kill 1 billion this century. Half of all smokers will die prematurely, with men's lives being shortened by 6 years and women's by 8 years (NEJM 2008:doi:10.1056) (Britton & Edmunds pp 441-5).
If you doubted the link between obesity and cancer, the article by Renehan et al (Lancet 2008;371:569-75 will convince you of the association.
Meanwhile JASS this month is dominated by twins and embolic phenomena. It's fascinating what turns up serendipitously!
The journals carry large, long-term studies which show that antenatal supplementation with broad-spectrum vitamin nutrients are superior to iron plus folate alone in reducing the incidence of how birth-weight in developing countries.
Bolstering nutrition in early childhood also has long-term benefits in terms of greater earning capacity in adulthood. Breastfeeding and basic hygiene are cheap and effective interventions (Lancet 2008;371 Haddinott et al 411-6, Bhutto et al 417-40, Vaidya et al 492-9, Bryce et al 510-26, Ruel et al 588-95, Morris et al 608-21).
Later in life smoking is the most common preventable cause of death. It killed 100 million people last century and is predicted to kill 1 billion this century. Half of all smokers will die prematurely, with men's lives being shortened by 6 years and women's by 8 years (NEJM 2008:doi:10.1056) (Britton & Edmunds pp 441-5).
If you doubted the link between obesity and cancer, the article by Renehan et al (Lancet 2008;371:569-75 will convince you of the association.
Meanwhile JASS this month is dominated by twins and embolic phenomena. It's fascinating what turns up serendipitously!
18 March, 2008
Latest JASS
The messages from this month's summaries are hugely important from the international perspective.
Modern research in the epidemiological field would have been unthinkable last century because the long-term data would not have been available and the resources to capture it unaffordable. Massive financial and human investment in nutritional studies, plus the technology to interpret the information, are leading to global conclusions.
The macro- and micro-nutrition of mothers and children up to two years of age are clearly shown to determine long-term outcomes, while longitudinal studies of oral contraceptive (OC) use forty years ago are now affecting old women's health.
Concepts such as disability-adjusted life-years (DALYs) and intra-uterine settings are just the start as mega- and meta-analysis drive our views to include new confounding variables in our assessments in Obstetrics and Gynaecology. The positive news about OCs must surely eventually lead to their wider and easier availability which will breach so many existing hindrances to women's health.
Modern research in the epidemiological field would have been unthinkable last century because the long-term data would not have been available and the resources to capture it unaffordable. Massive financial and human investment in nutritional studies, plus the technology to interpret the information, are leading to global conclusions.
The macro- and micro-nutrition of mothers and children up to two years of age are clearly shown to determine long-term outcomes, while longitudinal studies of oral contraceptive (OC) use forty years ago are now affecting old women's health.
Concepts such as disability-adjusted life-years (DALYs) and intra-uterine settings are just the start as mega- and meta-analysis drive our views to include new confounding variables in our assessments in Obstetrics and Gynaecology. The positive news about OCs must surely eventually lead to their wider and easier availability which will breach so many existing hindrances to women's health.
10 March, 2008
05 March, 2008
HRT and breast cancer
The role of hormonal replacement therapy is controversial in the development of breast cancer. What does seem clear is that combined estrogen with progesterone taken orally either continually or sequentially does raise the risk by a quarter to a third if taken over a decade. Looking more closely into this group of women, it appears that C-19 progestins have a lower risk than C-21 progestins and the mechanism of action may be the potentiation of the proliferative effect of estrogens in breast tissue.
In contrast, taking estrogens alone or the delivery of estrogens with progesterone transdermally does not increase the risk of breast cancer (Opatrny et al BJOG 2008;115:169-75). The authors carried out a large observational case-control study on UK women with a mean age of 61 years that takes into account the hormone therapy women took at all stages of their post-menopausal lives as the Women's Health Initiative (WHI) study caused many to swap preparations. This new data confirms the estrogen-only arm of findings of the WHI study which showed no increased risk of breast cancer.
It is interesting that transdermal preparations were not associated with increased risk either. They provide constant low hormone levels in the blood which avoids hepatic protein synthesis which does occur with the oral route, causing peaks and troughs from one dose to the next. Transdermal estrogens alone or with progesterone did not raise the risk of breast cancer.
Tibolone is a selective tissue estrogen activity regulator which has estrogenic activity on the vagina and bone without similar effects on breast and endometrial tissue. The study summarised here showed that women using tibolone alone were not at increased risk of breast cancer but the numbers were small.
Information continues to become available showing that selected prescriptions of replacement hormones should be tailored to each woman's requirements in terms of the type of medication, the dosage, the route of administration and the duration of use if unwanted side-effects are to be avoided.
In contrast, taking estrogens alone or the delivery of estrogens with progesterone transdermally does not increase the risk of breast cancer (Opatrny et al BJOG 2008;115:169-75). The authors carried out a large observational case-control study on UK women with a mean age of 61 years that takes into account the hormone therapy women took at all stages of their post-menopausal lives as the Women's Health Initiative (WHI) study caused many to swap preparations. This new data confirms the estrogen-only arm of findings of the WHI study which showed no increased risk of breast cancer.
It is interesting that transdermal preparations were not associated with increased risk either. They provide constant low hormone levels in the blood which avoids hepatic protein synthesis which does occur with the oral route, causing peaks and troughs from one dose to the next. Transdermal estrogens alone or with progesterone did not raise the risk of breast cancer.
Tibolone is a selective tissue estrogen activity regulator which has estrogenic activity on the vagina and bone without similar effects on breast and endometrial tissue. The study summarised here showed that women using tibolone alone were not at increased risk of breast cancer but the numbers were small.
Information continues to become available showing that selected prescriptions of replacement hormones should be tailored to each woman's requirements in terms of the type of medication, the dosage, the route of administration and the duration of use if unwanted side-effects are to be avoided.
06 February, 2008
Urban legends
The end-of-year BMJ is a light-hearted issue which allows us to raise our eyes above the temperature charts and dwell on the funny side of our profession. Vreeman & Carroll (BMJ 2007;335:1288-9) bust a few medical myths that we may have wondered about:
Drink 8 glasses of water a day - not necessary. There is far more fluid in our food than we realise and our thirst signals when more is needed.
We use 10% of our brains - no areas of our brains are inactive for long despite many functions being localised.
Hair and fingernails grow after death - untrue but skin retraction from desiccation can give that appearance.
Reading in dim light ruins your eyes - poor lighting may make restaurant menus difficult to read but by next morning your eyes will be fine.
Shaving makes hair grow faster - shaving your chin or your legs removes the dead part of the hair and does not encourage growth.
Mobile phones are dangerous in hospitals - no serious consequences of mobile (cellular) phone use in hospitals have been reported and certainly no deaths.
Conversely, the use of mobile phones reduces errors from delays in communication.
Eating turkey makes you drowsy - turkey contains no specific sedatives but usually forms part of a large meal, redirecting blood flow from the brain to the abdomen, causing drowsiness.
Drink 8 glasses of water a day - not necessary. There is far more fluid in our food than we realise and our thirst signals when more is needed.
We use 10% of our brains - no areas of our brains are inactive for long despite many functions being localised.
Hair and fingernails grow after death - untrue but skin retraction from desiccation can give that appearance.
Reading in dim light ruins your eyes - poor lighting may make restaurant menus difficult to read but by next morning your eyes will be fine.
Shaving makes hair grow faster - shaving your chin or your legs removes the dead part of the hair and does not encourage growth.
Mobile phones are dangerous in hospitals - no serious consequences of mobile (cellular) phone use in hospitals have been reported and certainly no deaths.
Conversely, the use of mobile phones reduces errors from delays in communication.
Eating turkey makes you drowsy - turkey contains no specific sedatives but usually forms part of a large meal, redirecting blood flow from the brain to the abdomen, causing drowsiness.
08 January, 2008
OCs and cervical cancer
Overall oral contraceptives are not associated with an increased risk of cancer. Since they prevent pregnancy and thus the risk of maternal mortality, it is far safer for a woman to take OCs than not take them.
But within these broad statements are detailed changes of risk of various conditions which have been studied to confirm or refute the role of combined estrogen and progesterone medication in their aetiology. One such condition is cervical cancer and OCs have long been linked to its increased risk, with some suggesting their carcinogenic role (Sasieni Lancet 2007;370:1591-2).
Despite the causative nature of HPV in cervical cancer, by no means all such infections lead to malignancy, so the quest is now to find what causes some HPV infections to end up as precancerous or invasive cancer while others regress harmlessly.
Given that recurrent HPV infections are part of the process, contraceptive use has been scrutinised to see if barrier methods reduce risk or hormonal methods increase the risk of recurrent infection. Data have now been published for combined OC use which give consistent results from all around the world by the International Collaboration of Epidemiological Studies of Cervical Cancer - Lancet 2007;370:1609-21. They have shown that using OCs for 5 to 10 years doubles the risk, but this diminishes soon after stopping their use and is negligible after a decade.
The authors point out the absolute risks remain very small and the other factors such as screening, smoking and other infections - especially those associated with altered immunity - are more important in the long-term. So, for women taking OCs in their twenties and thirties in developed countries, the additional risk from OCs of eventually developing cervical cancer is very small - something of the order of 0.002% and, for a woman in sub-Saharan Africa, this rises to 0.4%.
In perspective, OCs and other hormones do fit into the complex pathology of cervical cancer but their aetiological role is minor - in the extreme.
But within these broad statements are detailed changes of risk of various conditions which have been studied to confirm or refute the role of combined estrogen and progesterone medication in their aetiology. One such condition is cervical cancer and OCs have long been linked to its increased risk, with some suggesting their carcinogenic role (Sasieni Lancet 2007;370:1591-2).
Despite the causative nature of HPV in cervical cancer, by no means all such infections lead to malignancy, so the quest is now to find what causes some HPV infections to end up as precancerous or invasive cancer while others regress harmlessly.
Given that recurrent HPV infections are part of the process, contraceptive use has been scrutinised to see if barrier methods reduce risk or hormonal methods increase the risk of recurrent infection. Data have now been published for combined OC use which give consistent results from all around the world by the International Collaboration of Epidemiological Studies of Cervical Cancer - Lancet 2007;370:1609-21. They have shown that using OCs for 5 to 10 years doubles the risk, but this diminishes soon after stopping their use and is negligible after a decade.
The authors point out the absolute risks remain very small and the other factors such as screening, smoking and other infections - especially those associated with altered immunity - are more important in the long-term. So, for women taking OCs in their twenties and thirties in developed countries, the additional risk from OCs of eventually developing cervical cancer is very small - something of the order of 0.002% and, for a woman in sub-Saharan Africa, this rises to 0.4%.
In perspective, OCs and other hormones do fit into the complex pathology of cervical cancer but their aetiological role is minor - in the extreme.
04 December, 2007
HPV testing
The HPV circus is still in town with plenty of sound and fury. Before we climb on the bandwagon and start expensive HPV DNA testing - as we are encouraged to do by commercial interests - let us be quite sure we are acting in our patients' best interests and not using technological improvements for the sake of science.
As our editorial points out, healthy young women will not thank you for a cancer scare, no matter how diligently you explain its significance. The evidence does not exist that HPV DNA screening reduces deaths from cervical cancer.
There is plenty else to amaze or amuse as the festive season approaches - so hang onto your sense of humour.
The following pieces are recommended reading for subspecialists and those in training:
Diagnosis and management of cervical cancer. Petignat & Roy BMJ 2007;335:765-8
Epilepsy in pregnancy. Thomson & Hiilesmaa BMJ 2007;335:769-73
As our editorial points out, healthy young women will not thank you for a cancer scare, no matter how diligently you explain its significance. The evidence does not exist that HPV DNA screening reduces deaths from cervical cancer.
There is plenty else to amaze or amuse as the festive season approaches - so hang onto your sense of humour.
The following pieces are recommended reading for subspecialists and those in training:
Diagnosis and management of cervical cancer. Petignat & Roy BMJ 2007;335:765-8
Epilepsy in pregnancy. Thomson & Hiilesmaa BMJ 2007;335:769-73
06 November, 2007
Cancer and Oral Contraception
Do oral contraceptives increase the risk of cancer? The answer is no, but it has taken 40 years to prove it. In 1968 GPs recruited a large group of women who had, or had not, taken oral contraceptives and followed them to see if the pill had carcinogenic effects.
The UK Royal College of GPs has now published the results of over a million women-years and the outcomes are reassuring (Hannaford et al BMJ 2007;335:651-4).
Most of the 46 000 women are now post-menopausal and moving into the years when cancers are more common but pill use is more distant, so the detection of protection or enhancement of risk is now measurable.
Overall, pill-users had a lower risk of cancers of the colon, rectum, uterus, ovaries and tumours of unknown site. The differences were statistically significant trends with absolute values of 1 to 5 per 10 000 women years. The authors believe that today's lower doses of estrogen will have similar effects, so we can reassure our patients that there are benefits rather than risks as far as cancer and the pill are concerned.
The UK Royal College of GPs has now published the results of over a million women-years and the outcomes are reassuring (Hannaford et al BMJ 2007;335:651-4).
Most of the 46 000 women are now post-menopausal and moving into the years when cancers are more common but pill use is more distant, so the detection of protection or enhancement of risk is now measurable.
Overall, pill-users had a lower risk of cancers of the colon, rectum, uterus, ovaries and tumours of unknown site. The differences were statistically significant trends with absolute values of 1 to 5 per 10 000 women years. The authors believe that today's lower doses of estrogen will have similar effects, so we can reassure our patients that there are benefits rather than risks as far as cancer and the pill are concerned.
24 October, 2007
HPV vaccine policy
HIV vaccines are receiving ongoing high profile. Their potential is huge but the implementation of vaccination programmes the source of rich debate (BMJ 2007;335 Lo 357-8, Raffle 375-7 & Franco 378-9).
The first argument is that existing cervical cancer screening programmes in developed countries reduce deaths by 80% and it is difficult to argue with these success rates. The costs may even come down with HPV triaged follow up, and the expenditure on a vaccine initiative is formidable. There is no doubt the conventional screening policies will be required on an ongoing basis, but with the opportunity for protecting future generations from primary HPV infection and preventing precancerous and cancerous lesions is too inviting to reject.
The second point is those who would benefit most are the at-risk populations, all in developing countries. Again implementation would be the most challenging but the rewards the greatest.
Finally, the attention to the benefits of screening and prophylaxis will probably be the greatest spin-off. The debate, the rhetoric, the policies, the arguments for and against, the money, the political stances, the religious views and the medical science all contribute to the opening of discussions about women's health.
Should we not all engage as vociferously as we dare on promoting interaction on sexual and adolescent health questions and provide the medical science to inform opinion?
This is an entrée not to be missed.
The first argument is that existing cervical cancer screening programmes in developed countries reduce deaths by 80% and it is difficult to argue with these success rates. The costs may even come down with HPV triaged follow up, and the expenditure on a vaccine initiative is formidable. There is no doubt the conventional screening policies will be required on an ongoing basis, but with the opportunity for protecting future generations from primary HPV infection and preventing precancerous and cancerous lesions is too inviting to reject.
The second point is those who would benefit most are the at-risk populations, all in developing countries. Again implementation would be the most challenging but the rewards the greatest.
Finally, the attention to the benefits of screening and prophylaxis will probably be the greatest spin-off. The debate, the rhetoric, the policies, the arguments for and against, the money, the political stances, the religious views and the medical science all contribute to the opening of discussions about women's health.
Should we not all engage as vociferously as we dare on promoting interaction on sexual and adolescent health questions and provide the medical science to inform opinion?
This is an entrée not to be missed.
04 October, 2007
Soy phytoestrogens
Natural estrogens have great appeal to women as an alternate to conventional hormones at and beyond the menopause. Concerns about the negative effects of standard drugs persuade some women to try phytoestrogens as a “softer option”.
It is difficult for clinicians to advise on such preparations as evidence of benefit - and more importantly harm - is lacking, and it has taken massive trials to uncover the small absolute detrimental effects of estrogens. Until equally stringent trials show the safety of phytoestrogens we will have to rely on smaller studies to show the way.
Marini et al (Ann Int Med 2007;146:839-47) have demonstrated in a RCT of 400 women that genistein, which is found in soy products, increases bone mineral density in osteopenic postmenopausal women. 54 mg of genistein daily for 2 years had positive effects on bone density and turnover compared with placebo, opening the way for long-term trials on fracture effects as well as uterine and breast safety.
It is difficult for clinicians to advise on such preparations as evidence of benefit - and more importantly harm - is lacking, and it has taken massive trials to uncover the small absolute detrimental effects of estrogens. Until equally stringent trials show the safety of phytoestrogens we will have to rely on smaller studies to show the way.
Marini et al (Ann Int Med 2007;146:839-47) have demonstrated in a RCT of 400 women that genistein, which is found in soy products, increases bone mineral density in osteopenic postmenopausal women. 54 mg of genistein daily for 2 years had positive effects on bone density and turnover compared with placebo, opening the way for long-term trials on fracture effects as well as uterine and breast safety.
07 September, 2007
Diet and health
The long-term prognosis for breast cancer survivors continues to improve. Better treatment, adjuvant chemo- and hormonal therapies offer women an excellent outlook, especially if the disease is detected early.
In addition, support groups give psychological comfort, exercise seems to be beneficial, and now a large study has looked at diet and survival. Pierce et al (JAMA 2007;298:289-98) allocated women after early stage breast cancer care to either a diet very high in fruit, vegetables and fibre but low in fat or a comparison dietary pattern which recommended “5-A-Day” fruit and vegetables.
The “extra fruit, fibre 'n veg” with low fat did not make a difference to recurrence, metastases or all-cause mortality over a period of seven years. Perhaps if the control group had been given no dietary instructions, and gained weight, there might have been a difference but failing to advise women about diet would be considered unethical. Where patients gain weight by not balancing intake and expenditure, the prognosis is poorer, so energy balance may be more important than extreme diets (Grapstur & Khan pp 335-6).
In addition, support groups give psychological comfort, exercise seems to be beneficial, and now a large study has looked at diet and survival. Pierce et al (JAMA 2007;298:289-98) allocated women after early stage breast cancer care to either a diet very high in fruit, vegetables and fibre but low in fat or a comparison dietary pattern which recommended “5-A-Day” fruit and vegetables.
The “extra fruit, fibre 'n veg” with low fat did not make a difference to recurrence, metastases or all-cause mortality over a period of seven years. Perhaps if the control group had been given no dietary instructions, and gained weight, there might have been a difference but failing to advise women about diet would be considered unethical. Where patients gain weight by not balancing intake and expenditure, the prognosis is poorer, so energy balance may be more important than extreme diets (Grapstur & Khan pp 335-6).
08 August, 2007
Depression in pregnancy
Women are more likely than men to suffer from depression, especially during their reproductive years. Rates of depression are higher where stressful circumstances exist such as poverty, lack of education, sexual inequality, poor social support and in pregnancy. Single and adolescent pregnant women are especially at risk.
Pregnancy is a socially and physiologically demanding time and a woman who is just coping with the stresses of life may find the additional burden unmanageable. Mood regulation is modified by sex steroids, specifically the cortisol stress system mediated via the hypothalamic-pituitary-adrenal axis which is overactive in depressed people.
In developed countries, the rate of depression in pregnancy is at least 10% and double that in poorer countries. Irrespective of their socio-economic status, women with affective disorders have a high relapse rate in pregnancy which, in turn, is reflected in poorer maternal and fetal outcomes - mostly early delivery and growth restriction. Again, the common pathway of depression and social adversity is likely to be through the cortisol stress hormone system (O'Keane & Marsh BMJ 2007;334:1003-5).
Given these high rates of occurrence, depression should be specifically enquired about antenatally and actively managed if present. Since two-thirds of women stopping antidepressants during pregnancy will relapse, discontinuation is seldom advisable as the resultant depression can lead to unhealthy behaviours such as smoking, drinking alcohol, substance abuse and poor clinic attendance. About a quarter of those remaining on treatment will relapse, so surveillance levels must remain high.
The teratogenicity of antidepressants has been prominent in the journals recently. Selective serotonin reuptake inhibitors (SSRIs) were introduced in the 1980s as safe mood elevators because of their reasonably rapid onset of action, which is ten days according to the latest reports, plus fewer side effects and lower risk when taken in overdose. Nevertheless, there were incidental reports of birth defects such as nervous system or cardiac abnormalities, and cautions were issued. Now two large studies are reported in NEJM (Louik et al 2007;356:2675-83 and Alwan et al 2007;356:2684-92) which are case-controlled evaluations showing a small absolute risk of SSRIs being causative of defects if taken in the first trimester. These are certainly nothing like the risk posed by thalidomide or isotretinoin. In the US the use of these drugs is increasing and the latest data suggest that 10% of all pregnant women are taking an SSRI (Cooper et al AJOG 2007;196:544-5).
In an editorial, Greene (NEJM 2007;356:2732-3) says it would be pleasing to say there is no risk from SSRIs, but that is not possible. To quote from these major studies, “it is important to keep in perspective that the absolute risks of these rare defects are small” and “the absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy”.
Pregnancy is a socially and physiologically demanding time and a woman who is just coping with the stresses of life may find the additional burden unmanageable. Mood regulation is modified by sex steroids, specifically the cortisol stress system mediated via the hypothalamic-pituitary-adrenal axis which is overactive in depressed people.
In developed countries, the rate of depression in pregnancy is at least 10% and double that in poorer countries. Irrespective of their socio-economic status, women with affective disorders have a high relapse rate in pregnancy which, in turn, is reflected in poorer maternal and fetal outcomes - mostly early delivery and growth restriction. Again, the common pathway of depression and social adversity is likely to be through the cortisol stress hormone system (O'Keane & Marsh BMJ 2007;334:1003-5).
Given these high rates of occurrence, depression should be specifically enquired about antenatally and actively managed if present. Since two-thirds of women stopping antidepressants during pregnancy will relapse, discontinuation is seldom advisable as the resultant depression can lead to unhealthy behaviours such as smoking, drinking alcohol, substance abuse and poor clinic attendance. About a quarter of those remaining on treatment will relapse, so surveillance levels must remain high.
The teratogenicity of antidepressants has been prominent in the journals recently. Selective serotonin reuptake inhibitors (SSRIs) were introduced in the 1980s as safe mood elevators because of their reasonably rapid onset of action, which is ten days according to the latest reports, plus fewer side effects and lower risk when taken in overdose. Nevertheless, there were incidental reports of birth defects such as nervous system or cardiac abnormalities, and cautions were issued. Now two large studies are reported in NEJM (Louik et al 2007;356:2675-83 and Alwan et al 2007;356:2684-92) which are case-controlled evaluations showing a small absolute risk of SSRIs being causative of defects if taken in the first trimester. These are certainly nothing like the risk posed by thalidomide or isotretinoin. In the US the use of these drugs is increasing and the latest data suggest that 10% of all pregnant women are taking an SSRI (Cooper et al AJOG 2007;196:544-5).
In an editorial, Greene (NEJM 2007;356:2732-3) says it would be pleasing to say there is no risk from SSRIs, but that is not possible. To quote from these major studies, “it is important to keep in perspective that the absolute risks of these rare defects are small” and “the absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy”.
04 July, 2007
Aspirin and colorectal cancer
Many studies have shown that the regular use of aspirin reduces the risk of colorectal neoplasms. Quite how this works is not clear but it is thought to be related to prostaglandin metabolism or, more specifically, to aspirin's ability to inhibit the enzyme cyclo-oxygenase-2 (COX-2).
If this is the mechanism by which aspirin reduces colorectal cancers then it would be cancers that over-express COX-2 that would occur less frequently in aspirin users. Chan et al (NEJM 2007;356:2131-42) looked at this theory by histochemical assays of cancers removed from men and women in two large surveys and matched these against aspirin intake. They found that cancers that over-express COX-2 were reduced by aspirin but not cancers that had weak COX-2 expression.
The effect was found relative to increasing aspirin dose and duration of use. Flossmann et al (Lancet 2007;369:1603-13) showed that 300mg per day for 5 years is effective in primary prevention but the latency time is 10 years so patients have to be dedicated to their health.
If this is the mechanism by which aspirin reduces colorectal cancers then it would be cancers that over-express COX-2 that would occur less frequently in aspirin users. Chan et al (NEJM 2007;356:2131-42) looked at this theory by histochemical assays of cancers removed from men and women in two large surveys and matched these against aspirin intake. They found that cancers that over-express COX-2 were reduced by aspirin but not cancers that had weak COX-2 expression.
The effect was found relative to increasing aspirin dose and duration of use. Flossmann et al (Lancet 2007;369:1603-13) showed that 300mg per day for 5 years is effective in primary prevention but the latency time is 10 years so patients have to be dedicated to their health.
30 June, 2007
Does Viagra work for women?
This is a deliberately provocative title. A more accurate heading would be: Does improving a man's erectile dysfunction improve his partner's sexual satisfaction?
The intuitive response is that it should. If a man's problem is reduced, confidence, frequency and performance could be expected to improve, resulting in the couple's greater enjoyment of sex and the woman being more satisfied with this aspect of their relationship.
But sexual function does not work in straight lines. For example, when a man experiences erectile dysfunction (ED), he may be embarrassed or fear ridicule and withdraw, starting a series of events in his partner's mind about self-blame or being unattractive which can reduce her confidence or may arouse suspicions of unfaithfulness. Because the age at which men seek aid for ED is about 58 years and their partners' age about 54 years, these events are likely to coincide with her menopause with its attendant loss of libido and physical symptoms.
For these reasons, research is complex in the field of women's satisfaction from sildenafil (Viagra ® - Pfizer) treatment of men. However, Heiman et al (BJOG 2007;114:437-47) were able to carry out such a study comparing sildenafil with placebo and measuring the woman's perception of outcomes. Unsurprisingly, provided the woman had no dysfunction herself, her satisfaction with their sexual relationship improved significantly if he received sildenafil compared with those whose partners received the placebo. The scores were better for overall satisfaction as well as more detailed questions probing erectile function, orgasmic function, libido, arousal and intercourse satisfaction.
Side effects in the men were infrequent and mild to moderate. Maybe the manufacturers can add another side-effect - increased partner satisfaction?
The intuitive response is that it should. If a man's problem is reduced, confidence, frequency and performance could be expected to improve, resulting in the couple's greater enjoyment of sex and the woman being more satisfied with this aspect of their relationship.
But sexual function does not work in straight lines. For example, when a man experiences erectile dysfunction (ED), he may be embarrassed or fear ridicule and withdraw, starting a series of events in his partner's mind about self-blame or being unattractive which can reduce her confidence or may arouse suspicions of unfaithfulness. Because the age at which men seek aid for ED is about 58 years and their partners' age about 54 years, these events are likely to coincide with her menopause with its attendant loss of libido and physical symptoms.
For these reasons, research is complex in the field of women's satisfaction from sildenafil (Viagra ® - Pfizer) treatment of men. However, Heiman et al (BJOG 2007;114:437-47) were able to carry out such a study comparing sildenafil with placebo and measuring the woman's perception of outcomes. Unsurprisingly, provided the woman had no dysfunction herself, her satisfaction with their sexual relationship improved significantly if he received sildenafil compared with those whose partners received the placebo. The scores were better for overall satisfaction as well as more detailed questions probing erectile function, orgasmic function, libido, arousal and intercourse satisfaction.
Side effects in the men were infrequent and mild to moderate. Maybe the manufacturers can add another side-effect - increased partner satisfaction?
28 June, 2007
Simple health tips - salt
Adult women and men, who reduce their salt intake, reduce their blood pressure. This effect is independent of age, race, baseline blood pressure or body mass. Such information has been around for years but a study by Cook et al (BMJ 2007;334:885-8) now shows that this leads to a long-term reduction in cardiovascular events.
We should restrict our daily intake to 5g per day, or less. We can reduce what we add to our food and support the profession's efforts to have salt levels on foods labeled. Legislation would help and the new data will add weight to the arguments encouraging less salt in prepared foods and declaring how much there is, so prudent purchasing is possible.
We should restrict our daily intake to 5g per day, or less. We can reduce what we add to our food and support the profession's efforts to have salt levels on foods labeled. Legislation would help and the new data will add weight to the arguments encouraging less salt in prepared foods and declaring how much there is, so prudent purchasing is possible.
04 June, 2007
HRT and breast cancer
Breast cancer risk is not increased in estrogen-only HRT but when estrogens are combined with progestins, there is a raised risk that is cumulative. However, there is no evidence of increased mortality and after quitting HRT risk ratios return to normal.
If these data are correct, and if there is a causal or unmasking effect of hormonal therapy on breast cancer, then the rapid reduction in HRT use in America following the Women Health Initiative trial results would have led to a concomitant reduction in cancers detected.
Ravdin et al (NEJM 2007;356:1670-4) report that such a drop in estrogen-receptor-positive breast cancers did occur in 2002-2003 as the number of prescriptions fell from about 50 million to 25 million. This change occurred in postmenopausal women only, strongly implying an association with hormone therapy. The change was of the order of 7% relative risk and the incidence levelled off thereafter.
These findings support a link between combined hormone therapy and breast cancer, but the interpretation should be cautious. The observations concern a particular set of products, a particular age group and a particular type of breast cancer.
The absolute risk of breast cancer for any woman considering hormonal therapy in America remains around 0.30% per annum and this changes to 0.36% per annum on HRT and the effects are cumulative.
This sort of evidence moves our collective wisdom forward but does not answer other questions, such as will these incidences start to rise as the occult cancers reveal themselves later? Or will other forms of hormonal therapy remain free of breast cancer “encouragement”?
So where is the evidence that taking HRT for 10 years after the menopause is harmful?
Is this another example of medicine discovering a magic bullet that is first hailed, then discredited and then, finally, finds its appropriate niche?
JASS certainly believes that the notion of “feminine forever” was a grossly optimistic concept but, equally, there has been an over-reaction to the harmful effects of HRT because of inappropriate hormones given to women long past their menopause - and who were not in the best of health.
Perhaps the pendulum is reaching sanity and hormonal therapy will be useful in the treatment of menopausal symptoms AND offer protection against chronic conditions if used appropriately in terms of initiation, dose, mode of delivery and duration which may well turn out to be 10 years.
The bottom line in 2007 is that starting therapy at the menopause and continuing for a number of years carries little, if any, risk in healthy women. The experts appear in equipoise so it is up to women and their advisors to decide.
It seems clear that initiating combined HRT in women 10 years or more after their menopause does not turn back the clock and probably, on balance, does harm.
If these data are correct, and if there is a causal or unmasking effect of hormonal therapy on breast cancer, then the rapid reduction in HRT use in America following the Women Health Initiative trial results would have led to a concomitant reduction in cancers detected.
Ravdin et al (NEJM 2007;356:1670-4) report that such a drop in estrogen-receptor-positive breast cancers did occur in 2002-2003 as the number of prescriptions fell from about 50 million to 25 million. This change occurred in postmenopausal women only, strongly implying an association with hormone therapy. The change was of the order of 7% relative risk and the incidence levelled off thereafter.
These findings support a link between combined hormone therapy and breast cancer, but the interpretation should be cautious. The observations concern a particular set of products, a particular age group and a particular type of breast cancer.
The absolute risk of breast cancer for any woman considering hormonal therapy in America remains around 0.30% per annum and this changes to 0.36% per annum on HRT and the effects are cumulative.
This sort of evidence moves our collective wisdom forward but does not answer other questions, such as will these incidences start to rise as the occult cancers reveal themselves later? Or will other forms of hormonal therapy remain free of breast cancer “encouragement”?
So where is the evidence that taking HRT for 10 years after the menopause is harmful?
Is this another example of medicine discovering a magic bullet that is first hailed, then discredited and then, finally, finds its appropriate niche?
JASS certainly believes that the notion of “feminine forever” was a grossly optimistic concept but, equally, there has been an over-reaction to the harmful effects of HRT because of inappropriate hormones given to women long past their menopause - and who were not in the best of health.
Perhaps the pendulum is reaching sanity and hormonal therapy will be useful in the treatment of menopausal symptoms AND offer protection against chronic conditions if used appropriately in terms of initiation, dose, mode of delivery and duration which may well turn out to be 10 years.
The bottom line in 2007 is that starting therapy at the menopause and continuing for a number of years carries little, if any, risk in healthy women. The experts appear in equipoise so it is up to women and their advisors to decide.
It seems clear that initiating combined HRT in women 10 years or more after their menopause does not turn back the clock and probably, on balance, does harm.
17 May, 2007
Donating eggs
Women donate eggs for two reasons. Firstly for other women to conceive and, secondly, for research. Both are dogged by controversy on medical, societal and financial grounds. The US and the UK are currently trying to create guidelines and legislation that will allow workers in assisted reproduction and laboratory research to operate without fear of prosecution.
Infertile women undergoing IVF are usually given some form of gonadotropin-releasing hormone to stimulate multiple oocyte production. This hyperstimulation and harvesting results in more oocytes than can be used in fertilisation and embryo transfer in any given cycle, so there are spare oocytes for later use by the woman, or for donation.
Whether the stimulation should be with GnRH agonists or antagonists is one debate and another is whether one or two embryos should be transferred. What is not in question is that the demand for oocytes far exceeds supply. Women below the age of 35 years have significantly higher IVF success rates than older women, precisely the group who are now more often seeking reproductive assistance. The result is that the donation or sale of oocytes has become a big issue.
Clearly the unauthorised harvesting of oocytes is illegal as an Israeli doctor has found to his cost (BMJ 2007;334:557), but what about consented donations to infertile women? The free donation of “extra ova” from women to their infertile fellow patients seems straight-forward enough, but already the problem of incentives has arisen. In private clinics, can these spare oocytes be bought or can the woman be given a discount for her treatment if she donates? This discount for donation occurs in the UK where 75% of all IVF procedures are funded by the patients themselves despite decrees that all infertile couples are entitled to four IVF cycles within the NHS (Ledger Lancet 2007;369:717-8). Moving further along the continuum, is it acceptable for a woman who has no fertility problems to supply oocytes for payment? In the US it is, where thousands of babies are born annually from oocytes acquired from women who receive an average of $5 000 per harvest (Spar NEJM 2007;356:1289-91).
The UK has the Human Fertilisation and Embryology Authority which is the regulator of IVF treatment. It has now ruled that altruistic oocyte donation, in conjunction with fertility treatment or not, is acceptable. The report by Mayor (BMJ 2007;334:445) made no mention of discounts for donations in the private sector - also known as “egg sharing” - so compensation for co-operation remains a grey area. Other places such as Singapore, Israel and South Korea allow donations but without payment or personal benefit.
The role of oocytes in research is more complex, despite the fact they may not be bought for study purposes. Research falls into two categories - infertility or stem cell research. The former is not as contentious, despite using human reproductive material, but the latter is highly controversial using somatic-cell nuclear transfer (SCNT) to create lines of stem cells from which the US administration has withheld federal funding. The arguments go that without payment women will not donate oocytes for research but, attracted by pay, women could be tempted to “sell their eggs” in a competitive market to their own potential detriment.
Infertile women undergoing IVF are usually given some form of gonadotropin-releasing hormone to stimulate multiple oocyte production. This hyperstimulation and harvesting results in more oocytes than can be used in fertilisation and embryo transfer in any given cycle, so there are spare oocytes for later use by the woman, or for donation.
Whether the stimulation should be with GnRH agonists or antagonists is one debate and another is whether one or two embryos should be transferred. What is not in question is that the demand for oocytes far exceeds supply. Women below the age of 35 years have significantly higher IVF success rates than older women, precisely the group who are now more often seeking reproductive assistance. The result is that the donation or sale of oocytes has become a big issue.
Clearly the unauthorised harvesting of oocytes is illegal as an Israeli doctor has found to his cost (BMJ 2007;334:557), but what about consented donations to infertile women? The free donation of “extra ova” from women to their infertile fellow patients seems straight-forward enough, but already the problem of incentives has arisen. In private clinics, can these spare oocytes be bought or can the woman be given a discount for her treatment if she donates? This discount for donation occurs in the UK where 75% of all IVF procedures are funded by the patients themselves despite decrees that all infertile couples are entitled to four IVF cycles within the NHS (Ledger Lancet 2007;369:717-8). Moving further along the continuum, is it acceptable for a woman who has no fertility problems to supply oocytes for payment? In the US it is, where thousands of babies are born annually from oocytes acquired from women who receive an average of $5 000 per harvest (Spar NEJM 2007;356:1289-91).
The UK has the Human Fertilisation and Embryology Authority which is the regulator of IVF treatment. It has now ruled that altruistic oocyte donation, in conjunction with fertility treatment or not, is acceptable. The report by Mayor (BMJ 2007;334:445) made no mention of discounts for donations in the private sector - also known as “egg sharing” - so compensation for co-operation remains a grey area. Other places such as Singapore, Israel and South Korea allow donations but without payment or personal benefit.
The role of oocytes in research is more complex, despite the fact they may not be bought for study purposes. Research falls into two categories - infertility or stem cell research. The former is not as contentious, despite using human reproductive material, but the latter is highly controversial using somatic-cell nuclear transfer (SCNT) to create lines of stem cells from which the US administration has withheld federal funding. The arguments go that without payment women will not donate oocytes for research but, attracted by pay, women could be tempted to “sell their eggs” in a competitive market to their own potential detriment.
15 May, 2007
OCs and ovarian cancer
Oral contraceptives (OCs) are known to decrease a woman's risk of developing epithelial ovarian cancer. However, the dose of estrogens and progestins in OCs have come down in recent years so it is unclear if the protection previously offered still holds.
Lurie et al (Obstets Gynecol 2007;109:597-607) conducted a case-controlled study on over 700 women with epithelial ovarian cancer that took into account the woman's OC history and matched them with controls who may or may not have used OCs. Their results were conclusive. OCs were effective in decreasing the risk of cancer and the lowest formulations offered the strongest protection. The authors postulate that the antiovulatory mechanisms of OCs are the key factor in reducing malignancy rates and that women taking the lower dose pills are more likely to be compliant compared to high-dose users.
Consistency of use, rather than the hormonal dose probably explains the effect and a reduction in ovarian cancers may well continue due to OC use.
Lurie et al (Obstets Gynecol 2007;109:597-607) conducted a case-controlled study on over 700 women with epithelial ovarian cancer that took into account the woman's OC history and matched them with controls who may or may not have used OCs. Their results were conclusive. OCs were effective in decreasing the risk of cancer and the lowest formulations offered the strongest protection. The authors postulate that the antiovulatory mechanisms of OCs are the key factor in reducing malignancy rates and that women taking the lower dose pills are more likely to be compliant compared to high-dose users.
Consistency of use, rather than the hormonal dose probably explains the effect and a reduction in ovarian cancers may well continue due to OC use.
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