Large loop excision of transformation zone and cervical length in the prediction of spontaneous preterm delivery.

OBJECTIVES: To investigate the association between previous large loop excision of transformation zone (LLETZ) and risk for subsequent spontaneous preterm delivery (sPD) and whether this effect is reflected in the measurement of cervical length at mid-gestation. DESIGN AND SETTING: A secondary analysis of data from women recruited for clinical trials of interventions to prevent preterm labour. POPULATION: A total of 26,867 women with singleton pregnancies attending for routine antenatal care. METHODS: Transvaginal sonographic measurement of cervical length was carried out at 20(+0) to 24(+6) weeks. Logistic regression analysis was used to determine the significant predictors of sPD among maternal characteristics, obstetric history, previous history of LLETZ and cervical length. MAIN OUTCOME MEASURES: Spontaneous preterm delivery. RESULTS: In the 473 women who had undergone LLETZ, compared with the 25,772 without a history of LLETZ, the rate of sPD before 34 weeks of gestation was higher (3.4 versus 1.3%, P = 0.0002) and the median cervical length was shorter (32 mm versus 34 mm, P < 0.0001). Regression analysis demonstrated that in the prediction of sPD there were significant contributions from racial origin, cigarette smoking, previous preterm delivery and LLETZ and the detection rate of sPD was 29.8%, at a false-positive rate of 10%. However, after addition of cervical length, LLETZ did not remain a significant predictor in the model, which detected 52.6% of sPD, at a false-positive rate of 10%. CONCLUSIONS: LLETZ increases the risk of sPD, even after adjustment for maternal risk factors. The effect of a previous LLETZ on sPD in a subsequent pregnancy is reflected in the measurement of cervical length at mid-gestation.

Cervical screening in under 25s: a high-risk young population.

OBJECTIVE: The changes to the UK NHS cervical screening programme launched in April 2004 recommend that the first cytological screening should be undertaken at the age of 25 years rather than at 20 years. This study analyses Papanicolaou smear diagnoses of women under 25 years in Lewisham Borough of London to determine the incidence of cervical intraepithelial neoplasia (CIN) in this age group. There are concerns that delaying the onset of cervical screening in this population may increase the risk of cervical cancer. STUDY DESIGN: Pap smear results of 2793 women (2617 between 20 and 24 years and 176 below 20 years) over a period of 1 year from 1 April 2003 to 31 March 2004 were analysed. Appropriate colposcopy referrals and the results of cervical biopsies performed were followed up. RESULTS: Of the 2793 cervical smears analysed: 1997 (71.5%) were normal; 375 (13.4%) inadequate; 144 (5.1%) borderline; 208 (7.4%) showed mild dyskaryosis and 69 (2.5%) showed high-grade lesions (moderate to severe dyskaryosis). One hundred and eighty-two women were referred to colposcopy: 34% showed histological evidence of high-grade precancerous lesions (CIN 2 or 3); 27% CIN 1 and 0.5% koilocytosis only. Thirteen percent had normal colposcopy while 22% did not attend. CONCLUSION: The Lewisham population of young women under the age of 25 years is vulnerable to potential precancerous cervical lesions. This may reflect a high level of sexual activity among the young girls. Absence of screening in this age group may miss these high-grade cervical lesions that could progress to cervical cancer in the near future. We reinforce the importance of cervical screening in the highly vulnerable sexually active population under 25.

A randomized study of tibolone on bone mineral density in osteoporotic postmenopausal women with previous fractures.

OBJECTIVE: To investigate the effects of tibolone on trabecular and cortical bone mineral density and on indices of calcium metabolism in postmenopausal women with previous fractures. METHODS: In a 2-year, randomized, double-blind, placebo-controlled, bicenter study, 45 women were treated with tibolone and 43 with placebo. All subjects received 800 mg of calcium daily. Trabecular bone mineral density of lumbar spine (L1 to L4) and cortical bone mass at the femoral neck were assessed by dual energy x-ray absorptiometry at baseline and at 6-month intervals. Serum and urinary bone biochemistry variables were also assessed. RESULTS: After 2 years, subjects in the tibolone group gained 6.9% bone mass at lumbar spine and 4.5% at femoral neck, and respective increases from baseline in the placebo group were 2.7% and 1.4%. Tibolone-treated patients gained statistically significantly more bone mass than placebo-treated patients in the spine and femur. Urinary calcium: creatinine and hydroxyproline:creatinine ratios, as well as serum alkaline phosphatase and phosphate levels, were significantly reduced with tibolone compared with placebo. CONCLUSION: Tibolone induced a significant increase in trabecular (lumbar spine) and cortical (femoral neck) bone mass in postmenopausal osteoporotic women compared to placebo, suggesting its potential to treat postmenopausal osteoporosis.

Efficacy and tolerance of Menorest compared to Premarin in the treatment of postmenopausal women. A randomised, multicentre, double-blind, double-dummy study.

Two-hundred and fourteen (214) menopausal women with moderate to severe vasomotor symptoms, aged 40-65 years, were randomised. After a 4-week treatment-free period, each women received a continuous regimen of Menorest 50 twice weekly or Premarin 0.625 mg daily, for 12 weeks. Didrogesterone 10 mg was also given to all women for 12 days of every 28-day cycle. The objectives were to compare the efficacy and safety profiles of Menorest and an oral estrogen. A statistically significant reduction in the mean number of hot flushes occurred in each group compared to baseline with a decrease from 7.1 at baseline to 0.9 at 12 weeks in the Menorest group, and from 6.7 to 0.5 in the oral estrogen group; there was no statistically significant difference between the two groups (P = 0.36). With each successive treatment cycle, there was a continuous improvement in the number of hot flushes. The incidence and severity of menopausal symptoms were reduced in the same manner in both groups. There were no statistically significant differences in the mean plasma estradiol and estrone concentrations between the two treatment groups after 10 weeks of therapy. The mean estradiol to estrone ratio was similar in both groups, as was the number of adverse events observed. In summary, Menorest was as effective as an oral estrogen in alleviating menopausal symptoms.

HRT and long-term compliance: the efficacy and safety of Menorest.

Hormone replacement therapy (HRT) is perhaps the most important development in preventive medicine in the Western world for half a century, yet long-term compliance is notoriously poor. Up to 75% of women who start on HRT are reported to drop out within the first 6 months. Poor compliance may arise from a lack of awareness of the benefits of HRT, or from a number of common misconceptions, particularly the idea that HRT is ¿unnatural', and will cause weight gain, cancer, or unpleasant side effects. While side effects (usually progestogenic) may of course occur on HRT, they can usually be managed by a change in the regimen. Studies of the efficacy and safety of Menorest, an adhesive matrix transdermal system, used in combination with dydrogesterone for 12 days in each cycle, show it to be effective in relieving menopausal symptoms and increasing lumbar and spinal bone mass. Menorest was as effective and well-tolerated as a reference oral treatment (conjugated estrogens), and its twice weekly application may be considered to promote compliance.

Randomised trial of hypan versus gemeprost in cervical preparation prior to second trimester termination of pregnancy.

PIP: The findings of a preliminary study of women undergoing second-trimester dilatation and evacuation for pregnancy termination suggest that hypan produces better cervical preparation than the more commonly used prostaglandin gemeprost. All 50 subjects were between 15-20 weeks' gestation. The 25 women who were randomly assigned to the gemeprost group had a 1 mg vaginal pessary inserted in the posterior fornix 4-6 hours before abortion; an additional 1 mg pessary was inserted 2-4 hours before the procedure in nulliparous women. The 25 women in the hypan group had either a 3 x 55 mm dilator (15-17 weeks' gestation) or a 4 x 65 mm dilator (18-20 weeks' gestation) inserted in the cervix 24 hours pre-operatively. The mean pre-dilatation cervical diameter was significantly greater (p 0.0001) in the hypan group (14.5 mm) than the gemeprost group (8.7 mm). Also significantly greater (p 0.01) was the mean post-dilatation cervical diameter: 19.3 mm for hypan compared to 17.1 for gemeprost. Dilatation was rated as easy by 21 women in the hypan group compared to only 10 in the gemeprost group. In the hypan group, 24 women reported no pre-operative pain and 23 experienced no post-operative pain; in the gemeprost group, these numbers were 15 and 14, respectively. There were 4 cases of pre-operative bleeding among gemeprost acceptors but none in the hypan group. Finally, at the 6-week follow-up, 1 patient in the gemeprost group reported she had required evacuation of retained products of conception and 1 woman in the hypan group had been treated with antibiotics for a urinary tract infection. Although hypan, unlike gemeprost, requires insertion by a trained physician or nurse, its substantially lower cost, better cervical preparation, and lack of side effects justify its more widespread use.^ieng

Efficacy and safety of Menorest (50 mikrog/day) compared to Premarin 0.625 mg in the treatment of menopausal symptoms and the prevention of bone loss, in menopausal women. A single-center, comparative, randomized, double-blind, double-dummy study.

Thirty-two (32) menopausal women were entered into the study (16 in each treatment group), of whom 24 completed the study. The objectives were to compare the long-term efficacy and the local and systemic tolerance of Menorest and Premarin in the control of menopausal symptoms, and the prevention of bone loss. After a 4-week treatment-free run-in period, patients were treated with continuous estrogen therapy (a twice weekly application with Menorest 50 or a daily oral administration of Premarin 0.625 mg) for one year. Patients were also given 20 mg oral Dydrogesterone per day for the last 12 days of each 28 day cycle of treatment. The main efficacy criterion was the reduction in the mean number of hot flushes per day at 12 months compared to baseline. This study was also considered as a pilot study to collect data on changes in the bone mineral density of the lumbar spine (L1-L4) assessments from baseline to week 30 and week 56. Menorest and Premarin were equally effective in the relief of menopausal symptoms over the 1-year period of treatment. The mean number of hot flushes per day decreased from 6.9 at baseline to 0.5 at 12 weeks and 0.1 at 12 months in the Menorest group, and from 7.0 to 0.3 and 0.0 in the Premarin group. Regarding the lumbar spine and hip densitometry results, Menorest prevented bone loss to the same extent as Premarin. This data confirms the positive action of estrogen, with oral in addition to transdermal administration on both trabecular and cortical BMD over 1 year of treatment. Tolerance was similar, with approximately the same number of patients with AEs, severe AEs and related to study drug AEs in both groups. There was one serious AE (breast carcinoma) diagnosed after 6-months of treatment. Chemotherapy and radiotherapy was initiated prior to surgery. According to the investigator it was not related to study drug and must have been present prior to study start. Menorest 50 and Premarin 0.625 were equally effective over the 1-year treatment period in reducing the mean number of hot flushes and the severity score of menopausal symptoms, including vasomotor, psychological and urogenital symptoms.

A randomised comparison over 8 months of 100 micrograms and 200 micrograms twice weekly doses of transdermal oestradiol in the treatment of severe premenstrual syndrome.

OBJECTIVE: To determine the efficacy of a 100 micrograms twice weekly dose of Estraderm TTS compared with a 200 micrograms dose in the treatment of severe PMS, and to determine the overall acceptability of the treatment. To determine the serum oestradiol levels produced by the two doses of Estraderm and to discover whether the lower dose suppresses ovulation. DESIGN: Main: randomised, prospective, comparative study. Subsidiary: cross-sectional and prospective. SETTING: Premenstrual syndrome clinic in teaching hospital. SUBJECTS: Women with severe PMS confirmed by prospective daily symptom recording. INTERVENTIONS: Estraderm TTS at a dose of either 100 or 200 micrograms twice weekly continuously with either dydrogesterone 10 mg or medroxyprogesterone acetate 5 mg, from day 17 to day 26 of each cycle. MAIN OUTCOME MEASURES: Main: change in total, exponentially smoothed, average maximum score (total-ESAmax) of 10 common premenstrual syndrome symptoms derived from Trigg's trend analysis and patient satisfaction. Subsidiary: plasma oestradiol and day 21 progesterone levels. RESULTS: Main: no difference in change in total-ESAmax between Estraderm 100 micrograms and 200 micrograms groups. Greater drop-out rate and greater incidence of side effects attributed to oestrogen in higher dosage group. Satisfaction rate of 45% to 57% at eight months. Subsidiary: 1. Mean (95% CI) oestradiol level of 300 pmol/l (255 to 345) with Estraderm 100 micrograms and 573 (494 to 693) with Estraderm 200 micrograms; 2. Estraderm 100 micrograms suppresses mid-luteal progesterone from a mean (95% CI) of 35.5 (28.4 to 42.7) to 3.4 (2.4 to 4.5). CONCLUSIONS: Estraderm TTS 100 micrograms twice weekly is as effective as 200 micrograms twice weekly in reducing symptom levels in severe premenstrual syndrome but is better tolerated. Estraderm 100 micrograms suppresses ovulation and results in a mean plasma oestradiol level similar to that observed in a spontaneous cycle.

Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study.

The anxiety regarding no-bleed regimens is that breakthrough bleeding and endometrial hyperplasia may occur. We aimed to demonstrate that 25 mg oestradiol implants can be adequately opposed by a low dose of progestogen protecting against osteoporosis. Twenty-two patients were recruited to the study. The mean age was 62 years and body mass index of 26.5. Median oestradiol rose from 77 pmol/L at baseline to 275 pmol/L at one year. Median endometrial thickness remained unchanged at 4 mm and only two women withdrew with bleeding problems. There was one case of proliferative endometrium at one year--all others samples were either atrophic or secretory. Lumbar bone density (L2-L4) rose significantly from 0.939 to 0.992 g/cm2 (6%, P = 0.005) and the total femoral density rose from 0.872 to 0.890 g/cm2 (+2.1%). Bone formation markers increased significantly (serum type 1 procollagen C terminal peptide, P1CP = 112-114, P = 0.0376) and bone resorption fell (serum type 1 collagen C terminal telopeptide, 1CTP = 3.0-2.9, P = 0.2863). E25 implants and low dose progestogen appear to avoid endometrial hyperplasia and bleeding problems while increasing bone density.