Gynaecology Details Flashcards
Buys et al (PLCO)
Effect of screening on ovarian cancer mortality (Prostate, Lung Colorectal and Ovarian cancer screening), JAMA 2011
Methodology: Multicenter Randomised controlled trial, 78,000 women 55-74 years were randomised to annual screening (TV USS and Ca-125) or usual care, with subsequent followup for 13 years to assess the number of women diagnosed with and dying from ovarian cancer.
Results: There was no significant difference in diagnosis of ovarian cancer or mortality from ovarian cancer between the groups, but there was significantly more oophorectomies in the screening group - the women who had screening had a large number of false positive results, and of the women who had surgery 15% had a serious complication. The majority of cancers in both groups were serous cystadenocarcinomas, and the majority in both groups were high grade, screening did not make a difference to stage at diagnosis.
Conclusions: Screening with annual Ca125 and USS does not significantly improve diagnosis or mortality from ovarian cancer, and is not effective to detect cancer at an earlier stage. It does increase the risk of oophorectomy.
Strengths: very large number of women enrolled, long duration of follow up
Weaknesses: The study did not compare whether the surgery was performed by a generalist or gynae-onc specialist, which have been shown to be related to ovarian cancer survival.
Janda et al / LACE
Laparoscopic Approach to Cancer of the Endometrium
Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy of disease free survival in women with stage 1 endometrial cancer, JAMA 2017
Methodology: International Randomised trial of 700 women with stage 1 EAC of endometrium, allocated to TAH or TLH (with or without lymph node dissection according to usual treatment), all centres were tertiary gynaecology cancer treatment centres and surgeons had to be proficient in TLH.
Results: Disease free survival was not significantly different between the two groups after 4.5 years, 81.6% TLH vs 81.3% TAH disease free survival, and equivalent overall survival.
Conclusions: Laparoscopic Approach to Cancer of the Endometrium (stage 1) has no difference in recurrence or survival compared to TAH, with benefits for hospital stay, recovery, quality of life, and adverse events, so should be considered as a standard approach.
Strengths: Large number of participants, randomised trial.
Weaknesses: Lymph node dissection was at the discretion of the surgeon, so varied and was performed less in TLH.
Million Women Study
Breast cancer and HRT in the Million Women Study, Lancet 2003
Methodology: Multicenter Cohort study. Of the >1mil women in the cohort, 550,000 aged 50-64 had ever used HRT according to their questionnaire, and had routine (3 yearly) mammography. All women were analysed based on age, menopausal status, parity, family history of breast cancer, BMI, and deprivation index, as well as type and duration of HRT use, and then followed up over 2-5 years for incidence of breast cancer and mortality.
Results: Current use of HRT, specifically combined HRT, increases risk of breast cancer and death from breast cancer. Combined oestrogen + progesterone for >10 years RR 2.31. Risk increases with increased duration of use, and is not significant after ceasing HRT. Risk does not change mode of delivery or continuous vs cyclical. 10 years of combined HRT use is estimated to result in 19 additional cancers per 1000 women.
Conclusions: Current use of HRT is associated with an increased risk of breast cancer and death from breast cancer, the risk increases with duration of use and is higher in combination HRT than oestrogen alone.
Strengths: Very large number of participants
Weaknesses: Cohort study not randomised
Parker / Ovarian conservation at Hysterectomy
Ovarian conservation at the time of Hysterectomy for benign disease, O&G 2005
Methodology: Model study (hypothetical healthy women, not actual people) based on published data in relation to risk of different outcomes like coronary heart disease and stroke, with or without oophorectomy, then modelled to reflect the possible decision of oophorectomy or ovarian conservation between ages of 40 and 80, and the eventual risk profile of mortality over time.
Results: Women undergoing hysterectomy with oophorectomy before age 55 has 8.5% excess mortality by the age of 80. Benefit in younger women is due to coronary heart disease, and then in older women also related to hip fractures. Note that hysterectomy itself confers benefit for risk of ovarian cancer, with or without oophorectomy.
Conclusions: In women undergoing hysterectomy for benign disease, ovarian conservation benefits long term survival, particularly women before age 55 undergoing oophorectomy having significantly excess mortality by the age of 80. After age 65 the risks and benefits approximate each other.
Strengths:
Weaknesses:
Womens Health Initiative 2002
Risks and benefits of oestrogen plus progestin in healthy postmenopausal women, 2002
Methodology: Multicenter Randomised controlled trial. 16,000 women, average 63yo, postmenopausal (majority >10 years PM), with a uterus at baseline, were allocated to oral conjugated equine oestrogen + MDPA or placebo, underwent 6 monthly follow up for 5 years, with discontinuation if they developed cancer or other adverse outcomes.
Results: The trial was ceased early, with an average of 5 years follow up, due to safety data showing an increased risk of breast cancer in the treatment group, hazard ratio 1.26. 2x increased risk of VTE. No significant difference in rates of CHD, Stroke, endometrial cancer. Reduction in rates of hip fractures. There was possibly a reduction in colorectal cancer.
Conclusions: In postmenopausal women, the initiation of combined HRT increased risk of breast cancer and VTE, which outweighed the reduction in risk of fractures.
Strengths: large number of participants, blinded
Weaknesses: the study mostly involved women >60yo and postmenopausal >10 years, more recent data suggests negative effects less concerning if HRT started younger/closer to menopause.
Womens Health Initiative 2004
Effects of conjugated equine oestrogen in postmenopausal women with hysterectomy, JAMA 2004
Methodology: Multicenter Randomised controlled trial. 10,000 women, postmenopausal, with a prior hysterectomy, were allocated to oestrogen or placebo, then followed up for an average of 7 years, during which time over 50% stopped taking the study medication.
Results: Significantly increased risk of stroke with oestrogen, and significantly decreased risk of hip fracture. No difference in CHD, breast cancer, colorectal cancer, or all cause mortality.
Conclusions: Oestrogen HRT after hysterectomy increases risk of stroke, but decreases risk of hip fractures, and does not increase risk of CHD. Overall, there is no difference in all cause mortality or chronic disease prevention.
Strengths: large number of participants, double blinded.
Weaknesses: High rates of discontinuation.
SPIN
Scottish Pregnancy INtervention study. LMWH and LDA in women with recurrent miscarriage, American society of haematology, 2010
Methodology: International Randomised controlled trial, 290 women with 2 or more consecutive losses <24/40 without known cause, and excluding antiphospholipid syndrome or thrombotic disorders, were randomised at <7/40 current pregnancy to either LMWH 40mg SC + LDA 75mg daily with intensive pregnancy surveillance, or Control intensive pregnancy surveillance, which included fortnightly ultrasound until 12/40 then monthly until 28/40.
Results: The pregnancy loss rate was not significantly different between the two groups. Serious adverse events (APH, PPH) were similar, but treatment group had more minor adverse events.
Conclusions: Pregnancy loss in women with recurrent miscarriage without antiphospholipid syndrome is not reduced by LDA and LMWH.
Strengths: intention to treat analysis
Weaknesses: Not blinded, no placebo, small population size. Authors were funded by drug company.
Kaandorp
Aspirin plus Heparin or Aspirin alone in women with recurrent miscarriage, NEJM 2010
Methodology: Multicenter Randomised controlled trial, 360 women with 2 or more pregnancy losses <20/40 without known cause, <6/40 in current pregnancy, allocated to LDA 80mg + LMWH, or LDA 80mg alone, or placebo tablet. The placebo group had higher alcohol intake.
Results: There was no significant difference in live birth rate between the three groups. There was no difference in miscarriage or IUFD rate, and no difference in obstetric complications, including rates of pre-eclampsia. The combination group delivered about 1 week earlier than the aspirin alone or placebo groups, but there was not an increase in preterm births.
Conclusions: Aspirin alone or with LMWH does not improve live birth rate for unexplained recurrent miscarriage.
Strengths: intention to treat analysis
Weaknesses: small number of participants, heparin was not blinded or placebo controlled, the drugs were provided by pharmaceutical company.
Zhang et al
Medical management with misoprostol vs Surgical management for early pregnancy failure, NEJM 2005
Methodology: Multicenter Randomised controlled trial. 650 women, average 7.6 weeks gestation, with first trimester pregnancy failure, were allocated in a 3:1 ratio to Misoprostol (800mcg PV on day 1 then 3 if required, then ‘failed’ and vacuum on day 8), or Control immediate vacuum aspiration.
Results: 71% of Misoprostol group had complete expulsion by day 3, and 84% by day 8. Anembryonic pregnancy had lower rates of success. 3% of Vacuum needed repeat aspiration. No significant difference in haemorrhage or endometritis. Misoprostol was acceptable to women, but was associated with higher rates of side effects (pain, nausea/vomit)
Conclusions: Misoprostol is effective (71% by day 3) and acceptable to women for management of first trimester miscarriage, with similar rates of haemorrhage and endometritis but higher side effects than surgical management.
Strengths:
Weaknesses: More intensive follow up than standard protocol for medical management possibly led to improved outcomes.
Secura
Provision of no-cost, long-acting contraception and teenage pregnancy, NEJM 2014
Methodology: Multicenter Cohort study, 1400 girls aged 14-17 who wanted contraception, no desire for pregnancy in next 12 months, sexually active or planning to be (48% had a previous unintentional pregnancy), were educated about reversible contraception, offered choice of LARC or other method free of charge, then followed for 2-3 years and results were compared to the national (USA) population rates.
Results: High rates of uptake of LARCs among these young women (72%), with low failure rates for LARCs compared to other methods. Compared to both the general USA population and the ‘sexually experienced’ population, the study cohort had significantly less pregnancies, abortions and births. At 24 months, 2/3rds of LARC methods were still being used.
Conclusions: LARCs are an acceptable method of contraception for young women and provide a significant reduction in teen pregnancy, abortion and birth compared to the USA national average, when financial and access barriers are removed.
Strengths: High follow up rates.
Weaknesses: non-randomised study, USA not necessarily a generalisable population.
