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Obesity and cancer risk

  1. Top of page
  2. Obesity and cancer risk
  3. The ORACLE revisited
  4. Misoprostol inserts and induction
  5. Cervical treatments and pregnancy outcomes
  6. Acne and new regimens
  7. The cost of time saving

There is an increasing risk of cancer with increasing body mass index (BMI) in women. Obese women have a significantly higher risk of endometrial, breast and colon cancer compared with nonobese women. Endometrial malignancy has the highest association with rising weight, with women of a BMI between 30 and 35 kg/m2 having a five-fold greater risk than slim women.

There is concern in the USA about weight trends with the latest figures showing two-thirds of the population being overweight or obese—double the number 50 years before. Although the majority of Americans are aware that obesity is a health problem, only half acknowledge that it is linked to increased cancer risks. Soliman et al. (Obstet Gynecol 2008;112:835–42) surveyed US women about their knowledge of obesity and cancer. Although the majority of women recruited had at least high school education, less than half (42%) were aware of the endometrial cancer risks, with only slightly higher percentages knowing of the breast and colon raised risks.

It is entirely possible that half of your patients are equally unaware. Is this not a major educational opportunity?

The ORACLE revisited

  1. Top of page
  2. Obesity and cancer risk
  3. The ORACLE revisited
  4. Misoprostol inserts and induction
  5. Cervical treatments and pregnancy outcomes
  6. Acne and new regimens
  7. The cost of time saving

The ORACLE trials on the use of antibiotics in the treatment of preterm labour were concluded 7 years ago. They showed possible short-term benefit of erythromycin use in ruptured membranes situations in some of the secondary outcomes, but no major advantages over placebo, and certainly, co-amoxiclav was contraindicated.

These findings lead to the extended use of erythromycin perinatally to the point where resistant strains of group B streptococci are appearing and overuse is being warned against. More worrying, however, are the long-term results of antibiotic use in the children whose mothers were treated for sometimes the presumptive diagnosis of preterm labour with intact membrane in the ORACLE II trial (Kenyon et al., Lancet 2008;372:1319–27). It turns out that those in utero when erythromycin was given were more at risk of developing cerebral palsy than those exposed to placebo. Co-amoxiclav was also implicated, with the combination seeming to have a cumulative effect on cerebral palsy incidence and functional impairment. Fortunately, the follow up by the same authors of the ORACLE I trial survivors for the use of antibiotics in the face of preterm rupture of membranes showed no such negative effects (Lancet 2008;372:1310–18).

These results are sharp reminders of the possible detrimental effects of drugs used at any stage of pregnancy (Bedford Russell and Steer, Lancet 2008;372:1276–8). Antibiotics must be used when there are signs and symptoms of chorioamnionitis but not routinely for the treatment of preterm labour with intact membranes.

Misoprostol inserts and induction

  1. Top of page
  2. Obesity and cancer risk
  3. The ORACLE revisited
  4. Misoprostol inserts and induction
  5. Cervical treatments and pregnancy outcomes
  6. Acne and new regimens
  7. The cost of time saving

Publications continue to appear about misoprostol for the induction of labour. Such use is ‘off label’ as it is not licensed or manufactured for either intravaginal or oral use for cervical ripening or the induction of labour. There are concerns about its absorption, the accuracy of dosages when tablets are divided, vaginal release characteristics, reversibility and uterine hyperstimulation.

Misoprostol has not been subject to rigorous safety trials sufficient to have it registered with the United States Food and Drug Administration, so the legal use situation remains unclear. A study published by Wing for the Misoprostol Vaginal Insert Consortium adds welcome data about its use, comparing its efficacy with dinoprostone inserts (Obstet Gynecol 2008;112:801–12). In this trial, specially prepared misoprostol inserts were used that had undergone phase II testing to check linear, controlled and continuous release after vaginal insertion. The inserts contained measured amounts of 50 or 100 micrograms of misoprostol and used retrieval tape technology, which allowed the insert to be removed to halt further absorption if adverse reactions occurred. All women signed informed consent and had normal cardiotocographic tracings prior to commencement, with continuous monitoring throughout the study. The insert was removed if hyperstimulation occurred or nonreassuring fetal heart rate patterns were observed.

The 50 and 100 micrograms inserts were compared with 10 mg of dinoprostone, which looked identical to ensure blinding. The 100 micrograms insert gave an absorption co-efficient approximately equal to a 25 micrograms misoprostol fragment inserted every 6 hours, which is a conservative regimen. More than 1300 women were recruited in 49 institutions across the USA with review board approval to participate in the research, and the subjects were carefully chosen to exclude high parity, previous uterine surgery, serious obstetric complications or a compromised fetus. All participants had Bishop scores of 4 or less with a clear indication to proceed with induction of labour. Once labour was established, the insert was removed or after 24 hours.

The results showed that 100 micrograms of misoprostol and 10 mg of dinoprostone were similar in their time to vaginal delivery, frequency of removal for adverse events (13%) and other outcomes. The lower dose of misoprostol had a one-third longer time to delivery and half the adverse events with half the likelihood of hyperstimulation (3 and 6%). All other outcomes, including caesarean section rates of 27%, were similar in the three groups.

Under these rigorous trial conditions, including the possibility of removing the insert, 100 micrograms of misoprostol performs almost identically to 10 mg dinoprostone for cervical ripening and induction in low-risk pregnancies. The 50micrograms dose of misoprostol has slightly better safety outcome measures but a longer initiation to delivery time and an equally high caesarean section incidence. The high caesarean section rate was only related to drug effects in less than 2% of all cases, so it seems that the low threshold to resort to abdominal delivery is generated by factors other than uterotonic agents.

The researchers believe that this precisely dosed, retrievable insert with controlled release is a safe induction agent under full monitoring conditions and where Good Clinical Practice standards are applied.

These are the criteria under which safe misoprostol induction can be carried out.

Cervical treatments and pregnancy outcomes

  1. Top of page
  2. Obesity and cancer risk
  3. The ORACLE revisited
  4. Misoprostol inserts and induction
  5. Cervical treatments and pregnancy outcomes
  6. Acne and new regimens
  7. The cost of time saving

Premalignant cervical lesions are treated with excision or ablation. Cervical intraepithelial neoplasia caused by oncogenic strains of the human papillomavirus can be low grade, in which case observational follow up is sufficient, or high grade when eradication is indicated.

It seems as if the more aggressive the eradication, the greater the effect on subsequent pregnancy outcomes with conisation at one end of the spectrum and more superficial ablation with laser or cryotherapy at the other. The minimum amount of tissue should be removed or destroyed as long-term follow up of women undergoing conisation reveal higher incidences of preterm births that were not observed when women with similar lesions were treated after pregnancy. These data from Norway suggest that it is the surgery rather than the disease that is the culprit (Albrechtsen et al., BMJ 2008;337:803–5).

In a meta-analysis (Arbyn et al., BMJ 2008;337:798–803) and an editorial (Jakobsson and Bruinsma, BMJ 2008;337:769–70), there appears to be consensus that cold knife conisation has the most serious consequences in pregnancy, followed by laser conisation, radical diathermy and large loop excision of the transformation zone, while the ablative techniques did not have similar associations.

Gynaecological oncologists are aware of these risks and more conservative treatments are used where possible—with judicious timing.

Acne and new regimens

  1. Top of page
  2. Obesity and cancer risk
  3. The ORACLE revisited
  4. Misoprostol inserts and induction
  5. Cervical treatments and pregnancy outcomes
  6. Acne and new regimens
  7. The cost of time saving

Androgen overproduction is a contributory factor for acne in women. It leads to excess keratinisation of hair follicles and increased sebum production, which are part of the pathogenesis of the disorder. Oral contraceptives (OCs) can offer an alternative hormonal environment with the estradiol component inducing the synthesis of sex hormone-binding globulins, an effect that seems not to be off-set by the new progestins.

Specifically, drospirenone is a new progesterone with antimineralocorticoid plus anti-androgenic properties similar to spironolactone and has been shown to offer relief from emotional and physical symptoms in the premenstrual dysphoric disorder. A preparation of 3 mg of drospirenone with 20 micrograms of ethinyl estradiol given on a 24 days on cycle and 4 days off cycle has proved effective in symptom relief and cycle regulation, and now Maloney et al. report on its efficacy in managing moderate acne vulgaris (Obstet Gynecol 2008;112:773–81). The researchers conducted a placebo-controlled trial over 6 months and found significant improvements in skin condition in those taking the active pills compared with placebo.

One-third improved on the inert pills, but one-half improved on the drospirenone/estradiol combination with a three-fold increased likelihood of their skin being assessed as ‘clear or nearly clear’ on the hormonal regimen. Those on the OCs had a slight decrease in body weight, whereas those on the placebo had a modest increase.

The cost of time saving

  1. Top of page
  2. Obesity and cancer risk
  3. The ORACLE revisited
  4. Misoprostol inserts and induction
  5. Cervical treatments and pregnancy outcomes
  6. Acne and new regimens
  7. The cost of time saving

In developed countries, people turn their clocks forward in spring and backwards in autumn. Forward-turning in spring means an hour is ‘lost’, which usually means an hour less sleep and this reduction can be stressful until people’s physiology adjusts. But can losing 1 hour of rest have a real effect? It seems so if the incidence of myocardial infarcts is anything to go by.

Janszky and Ljung from Sweden (NEJM 2008;359:1966–8) show that coronary events are more common when people are deprived of their extra hour when they turn their clocks forward. Hospital admissions for infarcts rose significantly across the land, especially 2 days after change-over compared with 2 weeks earlier or 2 weeks later. The effect was consistent over many years and most pronounced in people younger than 65 years.

As if to prove the point, the opposite effect was found in autumn when the Swedes had fewer than average heart attacks immediately after the ‘extra hour’ was added. The work suggests that there are subtle relationships between sleep patterns, stress and cardiac events.

Footnotes
  1. These snippets are extracts from a monthly service called the Journal Article Summary Service. It is a service that summarises all that is new in obstetrics and gynaecology over the preceding month. If you would like to know the details of how to subscribe, please email the editor Athol Kent at atholkent@mweb.co.za or visit the website www.jassonline.com.