Abstract
Initial findings from a UK trial suggests that the screening methods under investigation are suitable for use on a large scale and are able to successfully identify ovarian cancers
UK trial provides encouraging results for ovarian cancer screening
The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a randomized, controlled trial being conducted over the next 5 years to assess the feasibility and effectiveness of a national screening program for ovarian cancer in the UK. The Lancet Oncology has recently published the results of the prevalence (initial) screen in UKCTOCS, which tested the viability of the CA125 blood test and transvaginal ultrasound methods of screening, and the outcome is encouraging. “The early results suggest that both types of screening can be used on a large scale and both successfully identify ovarian cancers,” states Usha Menon, coordinator of the trial.
Over the course of 4 years, the UKCTOCS trial recruited 202,638 postmenopausal women and randomly assigned them to no treatment; annual CA125 blood screening with transvaginal ultrasound scan (USS) as a second-line test (multimodal screening [MMS]); or annual screening with transvaginal ultrasound alone in the ratio of 2:1:1. Women with abnormal screens had repeat tests and those with continued abnormality in repeat screens were recommended for clinical evaluation and surgery.
The prevalence screen demonstrated that both the MMS and USS screening methods were effective in detecting ovarian cancer. In the MMS and USS groups, 8.7 and 12.0% of women required a repeat test, respectively. A total of 42 primary ovarian and tubal cancers were detected in the MMS group and 45 in the USS group, including 28 borderline tumors (eight MMS and 20 USS). Overall, the screening program identified 58 invasive cancers, 28 of which were detected at stage I/II of the disease, with no difference in stage distribution between the two methods. A further 13 women developed primary ovarian cancer within 1 year after the screen. Sensitivity values for detection of primary invasive epithelial ovarian and tubal cancers were 89.5% for the MMS method and 75.0% for the USS method, suggesting that both have potential as ovarian cancer screens. The MMS method was significantly more successful at distinguishing between malignant and benign ovarian growths; however, USS detected a higher number of benign abnormalities, thus prompting higher numbers of repeat tests and unnecessary surgery.
The initial results of the trial are promising, and according to the authors of the study, establish that these screening strategies are feasible. However, lead researcher Ian Jacobs (University College London Institute for Women's Health, UK) emphasizes that this is just the first set of results from a trial that will carry on until 2012, with follow-up until 2014. He stresses, “there is a long way to go before we have firm evidence as to whether or not screening is able to detect cancer early enough to save lives.” The initial screen suggests that the methods tested are viable but the investigation into whether screening for ovarian cancer can reduce mortality continues. Jacobs also comments, “it will be essential to balance any benefits offered by screening with the downside, as it is recognized that screening can cause anxiety and lead to some unnecessary operations.” The full results of the UKCTOCS trial are due in 2015.
Source: Menon U, Gentry-Maharaj A, Hallett R et al.: Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 10(4), 327–340 (2009).
in brief…
A recent case–control study was conducted to determine the association between migraine and cardiovascular disease during pregnancy. Researchers conducted analysis on 33,956 pregnancies associated with migraines from 2000 to 2003. Diagnoses that were jointly associated with migraine codes during pregnancy (excluding pre-eclampsia) were stroke (OR: 15.05; 95% CI: 8.26–27.4), myocardial infarction/heart disease (OR: 2.11; 95% CI: 1.76–2.54), pulmonary embolus/venous thromboembolism (OR: 3.23; 95% CI: 2.06–7.07) and hypertension (OR: 8.61; 95% CI: 6.43–11.54), as well as pre-eclampsia/gestational hypertension (OR: 2.29; 95% CI: 2.13–2.46), smoking (OR: 2.85; 95% CI: 2.53–3.21) and diabetes (OR: 1.96; 95% CI: 1.64–2.35). The authors conclude that in this large, population-based sample of pregnant women admitted to hospital, a strong relation existed between active peripartum migraine and vascular diagnoses during pregnancy. However, they note that since the data do not allow causality to be established, prospective studies of pregnant women are needed to further explore this association.
A total of 28 hospitals in The Netherlands and Belgium were used as the setting for a recent study that investigating the incidence of serious maternal complications following the use of various tocolytic drugs for the treatment of preterm labor in routine clinical situations. A total of 1920 consecutive women were enrolled in the study. Of these women, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%) and 311 combined courses (16.2%). Adverse drug reactions were categorized as serious or mild in each of the 14 cases. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a β adrenoceptor agonist was 22.0 (95% CI: 3.6–138.0) and for single treatment with a calcium antagonist was 12 (90% CI: 1.9–69). Multiple drug tocolysis resulted in five serious adverse drug reactions (1.6%). Indometacin and atosiban were the only drugs not associated with serious adverse drug reactions. The authors conclude that a direct comparison of the effectiveness of nifedipine and atosiban in postponing preterm delivery is needed.
Female testosterone patch may be ineffective
A recent review of a number of studies investigating the effects of Intrinsa™ testosterone patch for female sexual dysfunction has found that the patch may not actually boost sex drive.
“…the majority of the trials lasted less than 6 months, thus conclusions regarding long-term safety could not be made.”
Intrinsa is licensed for use in Europe for the treatment of women who have undergone surgically induced menopause as a result of womb and ovary removal, and who are subsequently experiencing a reduced sex drive. This condition is known as hypoactive sexual desire disorder (HSDD). Some studies suggest that a decreased sex drive after menopause may be owing to low levels of circulating testosterone.
“The studies also demonstrated a large placebo response, where many women who were not treated with the patch reported an increase in sex drive.”
Ike Iheanacho, editor of Drug and Therapeutics Bulletin, and colleagues reviewed a number of studies that evaluated the use of Intrinsa among nearly 4000 women with HSDD. The analysis revealed that the majority of the trials lasted less than 6 months, thus conclusions regarding long-term safety could not be made. In addition, the mental and physical condition of the study subjects was not taken into consideration, and it is possible that these parameters may also have affected sex drive. The studies also demonstrated a large placebo response, where many women who were not treated with the patch reported an increase in sex drive. Side-effect rates were also high, with the two key trials reporting side-effect rates of approximately 75%. Most of these were due to skin reactions at the site of application. Other effects included acne, excess hair (hirsutism), hair loss (alopecia), breast pain, weight gain, insomnia, voice deepening and migraine.
“…the long-term safety of the treatment is unknown. Unwanted side effects are common and not always reversible. For all these reasons, we cannot recommend Intrinsa for use in women with sexual dysfunction…”
“The published evidence so far is based on highly selected women and only shows small improvements in sexual parameters and large placebo responses,” comments Iheanacho. “Also, the long-term safety of the treatment is unknown. Unwanted side effects are common and not always reversible. For all these reasons, we cannot recommend Intrinsa for use in women with sexual dysfunction,” he concluded.
Source: [No authors listed] Testosterone patches for female sexual dysfunction. Drug Ther. Bull. 47(3), 30–34 (2009).
About the Bulletin Board
The Bulletin Board highlights some of the most important events and research in the field of women's health. If you have newsworthy information, please contact:
Rebecca Owen, Commissioning Editor, Women's Health Future Medicine Ltd, Unitec House, 2 Albert Place, London N3 1QB, UK, Tel.: +44 (0)20 8371 6090; Fax: +44 (0)20 8343 2313;
GYNECARE PROLIFT+M™ pelvic floor repair system available in the USA for pelvic organ prolapse surgery
Ethicon Women's Health & Urology, part of the Johnson & Johnson company Ethicon Inc., have announced that their GYNECARE PROLIFT+M™ pelvic floor repair system is now available for use in the USA for the surgical treatment of pelvic organ prolapse.
The GYNECARE PROLIFT+M system is indicated for the reinforcement and long-term stabilization of the pelvic floor tissue, either to provide support or act as a bridging material in women undergoing prolapse surgery.
An important feature of the kit is a partially absorbable mesh implant, thought to increase biocompatibility and patient comfort compared with other meshes. Implanted using the tension-free vaginal mesh technique, the lightweight mesh enables easier application owing to an increased resistance to wrinkling and folding, and has increased longitudinal elasticity, making the mesh more pliable after surgery. The polypropylene mesh is also less dense with larger pores, which may decrease the amount of reactive scar formation and reduce inflammatory response during healing.
Salil Khandwala, Clinical Associate Professor at Wayne State University, MI, USA, comments: “Thousands of women have been treated successfully with the GYNECARE PROLIFT+M system for pelvic organ prolapse. With GYNECARE PROLIFT+M, surgeons now have an option that is specifically designed to offer patients even higher levels of comfort with improved biocompatibility to work with the body's natural healing process while correcting the prolapse.”
Source: Johnson & Johnson: www.jnj.com/connect/news/all/20090312_140000
Vaginal glycerol monolaurate gel prevents mucosal spread of simian immunodeficiency virus in a monkey model
Researchers at the University of Minnesota, MN, USA, have reported that a novel antimicrobial gel has been shown to prevent AIDS onset in a monkey model, paving the way for a potential new treatment option for the disease in humans.
“We thought if we could modulate the immune response at the portal of HIV entry, we could block sexual transmission,” explains Ashley T Haase, Professor of microbiology at the university and lead author of the study. “The results (with the gel) are very encouraging. They point to a novel avenue to prevent sexual transmission of HIV.”
The anti-HIV ingredient in the gel is glycerol monolaurate (GML), normally found in breast milk and US FDA-approved for use in many cosmetics and medicines. GML is believed to be toxic to many classes of microbes, including those responsible for vaginal yeast infections and several sexually transmitted diseases. These attributes have also led other researchers to suggest that GML could be used as a possible additive to tampons to prevent the bacterial disease responsible for toxic shock syndrome.
Patrick Schlievert, coauthor of the study, discovered that GML had many characteristics that might allow it to block HIV transmission and systemic spread through the body. The research group administered daily treatments of GML to five rhesus macaque monkeys before subjecting them to fatal doses of simian immunodeficiency virus, a primate HIV equivalent, into the vaginas of the monkeys. A control group of four animals were given a gel without GML.
All of the control group animals became infected with the AIDS virus. Those in the active group remained disease-free at the end of the short study period, although one of the monkeys showed signs of infection several months later.
With future human use borne in mind, GML was mixed with KY Warming Liquid, an over-the-counter product widely used as a personal lubricant. “What was done was to combine two FDA-approved medical devices to create another approved device,” explains Schlievert.
There is still much work to be done in animal models before a GML gel could be ready for human tests. Many HIV drugs consist of a ‘cocktail’ of different therapeutic agents with different modes of action. “GML could be part of a combined strategy with another vaginal microbicide, such as PRO 2000, with a different mechanism of action,” suggests Haase.
Source: Li Q, Estes JD, Schlievert PM et al.: Glycerol monolaurate prevents mucosal SIV transmission. DOI: 10.1038/nature07831. Nature (2009) (Epub ahead of print).