Erkki Kujansuu

Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial

BACKGROUND Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness. METHODS Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel-releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat. FINDINGS In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group. INTERPRETATION The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder.

Low dose acetylsalicylic acid in prevention of pregnancy‐induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches

Objective To evaluate the efficacy of low‐dose acetylsalicylic acid in the prevention of pregnancy‐induced hypertension and intrauterine growth retardation in high‐risk pregnancies as determined by transvaginal Doppler ultrasound study of the uterine arteries at 12 to 14 weeks of gestation.

Gabapentin for the prevention of postoperative pain after vaginal hysterectomy

&NA; Gabapentin alleviates and/or prevents acute nociceptive and inflammatory pain both in animals and volunteers, especially when given before trauma. Gabapentin might also reduce postoperative pain. To test the hypothesis that gabapentin reduces the postoperative need for additional pain treatment (postoperative opioid sparing effect of gabapentin in humans), we gave 1200 mg of gabapentin or 15 mg of oxazepam (active placebo) 2.5 h prior to induction of anaesthesia to patients undergoing elective vaginal hysterectomy in an active placebo‐controlled, double blind, randomised study. Gabapentin reduced the need for additional postoperative pain treatment (PCA boluses of 50 &mgr;g of fentanyl) by 40% during the first 20 postoperative hours. During the first 2 postoperative hours pain scores at rest and worst pain score (VAS 0–100 mm) were significantly higher in the active placebo group compared to the gabapentin‐treated patients. Additionally, pretreatment with gabapentin reduced the degree of postoperative nausea and incidence of vomiting/retching possibly either due to the diminished need for postoperative pain treatment with opioids or because of an anti‐emetic effect of gabapentin itself. No preoperative differences between the two groups were encountered with respect to the side effects of the premedication. However, 15 mg oxazepam was more effective in relieving preoperative anxiety than 1200 mg gabapentin.

In vitro fertilization in patients with ovarian endometriomas.

Objective. The objective of the study was to establish whether operative treatment of recurrent ovarian endometriosis improves the prognosis of in vitro fertilization.

Cytosol estrogen and progestin receptors in endometrial carcinoma of patients treated with surgery, radiotherapy, and progestin. Clinical correlates

Cytosol progestin (PR) and estrogen receptor (ER) concentrations were measured in 114 endometrial carcinoma specimens from 109 patients; these levels were correlated with clinical and histopathologic characteristics, and with clinical outcome in 44 patients followed for at least two years after the primary therapy consisting of surgery, irradiation and adjuvant administration of progestin. Eighty percent of all specimens were simultaneously PR‐ and ER‐positive (≥6 fmol and ≥3 fmol/mg protein, respectively) whereas 10% were both PR‐ and ER‐negative. Early clinical stages (I and II) were more often receptor‐positive, and the receptor concentration in these tumors was higher than in advanced or recurrent disease. The same was the case for superficial as compared with deeply invasive lesions. Both PR and ER concentrations in well or moderately differentiated tumors were higher than in anaplastic carcinomas. PR and ER concentrations did not correlate with the age or menopausal status, body weight or carbohydrate metabolism of the patients. In the patient group followed up for two years or more, the receptor‐poor tumors tended to behave more aggressively than did receptor‐rich malignancies in relation to patient survival. The measurement of PR and ER concentrations in advanced endometrial carcinoma has been proved useful in the selection of hormonal or cytotoxic chemotherapy. The current results advocate their use as prognostic risk factors which might be useful in selection of the most efficient treatment modalities for individual patients.

Prognostic factors in controlled ovarian hyperstimulation

OBJECTIVE To determine whether the number of retrieved oocytes and the required amount of gonadotropins per oocyte in IVF treatment can be predicted with use of the following independent predictive variables: age, parity, cause of infertility, body mass index, day 3-5 FSH, E2, inhibin B, ovarian volume, the number of follicles, and intraovarian and uterine artery vascular resistance measured by ultrasonography before ovarian hyperstimulation. DESIGN A retrospective analysis. SETTING University hospital infertility clinic. PATIENT(S) Seventy-four consecutive women attending the university hospital infertility clinic for IVF treatment. INTERVENTION(S) The investigated factors were measured on day 3-5 of the cycle, in which luteal phase suppression was begun before ovarian hyperstimulation preparatory to IVF. MAIN OUTCOME MEASURE(S) The amount of gonadotropins required per oocyte and the number of retrieved oocytes were correlated with the predictive factors in stepwise regression analysis. RESULT(S) The best predictive factors for the number of oocytes retrieved were FSH, inhibin B, and parity, explaining 25% of the ovarian response. Intraovarian vascular resistance, parity, FSH, and inhibin B best predicted the amount of gonadotropins needed, explaining 44% of the variation. CONCLUSION(S) FSH, inhibin B, and parity were the independent predictive factors for the number of retrieved oocytes. The same factors and intraovarian vascular resistance predicted the required amount of gonadotropins per oocyte. The main part of the ovarian response cannot be predicted using the factors investigated.

Tension-free vaginal tape and laparoscopic mesh colposuspension for stress Urinary incontinence

OBJECTIVE: To compare objective and subjective outcomes after the tension-free vaginal tape procedure (TVT) with laparoscopic mesh colposuspension as a primary treatment for female stress urinary incontinence. Objective outcome measures were stress test and 48-hour pad test. METHODS: In 6 departments of gynecology in Finland, including 4 university teaching hospitals and 2 central hospitals, 128 women with urodynamic stress incontinence were randomly allocated to 2 treatment groups. Seventy were treated with TVT and 51 by means of laparoscopic mesh colposuspension. There were 7 dropouts. Inclusion criteria were history of stress incontinence, positive stress test, and urodynamic conformation of stress incontinence. Exclusion criteria were age older than 70 years, previous incontinence surgery, more than 3 episodes of urinary tract infection within the last 2 years, coincident other gynecological surgery, body mass index more than 32 kg/m2, urethral closure pressure less than 20 cm H2O, and residual volume more than 100 mL in preoperative urodynamic evaluation. Assessment took place before treatment and at 12 months postoperatively with the cough stress test, Urge Score, 48-hour pad test, Kings College Health Questionnaire, Visual Analog Scale, and Urinary Incontinence Severity Score. RESULTS: When negative stress test was used as criteria for cure, 85.7% of women in the TVT group and 56.9% in the laparoscopic mesh colposuspension group were objectively cured. Subject satisfaction was significantly better after the TVT procedure than after laparoscopic mesh colposuspension. CONCLUSION: Treatment with TVT results in higher objective and subjective cure rates at 1 year than treatment by means of laparoscopic mesh colposuspension. LEVEL OF EVIDENCE: I

Hysterectomy trends in Finland in 1987-1995--a register based analysis.

BACKGROUND The study objective was to identify trends in the use of hysterectomy by nationwide register based analysis in Finland. METHODS All women (n=89,069) undergoing hysterectomy in 1987-1995 according to the Finnish Hospital Discharge Register were the numerator. The annual denominator data were obtained from the population database of Statistics Finland. RESULTS From 1987 to 1992 the hysterectomy rate increased by 22%, from 340 to 414 per 100,000 females, almost half of this being attributable to the changing age structure. From 1993 on, ambiguity in coding laparoscopically assisted vaginal hysterectomies prohibited detailed analyses. However, the overall trend continued at least among women 50 years and over until 1995. The age-adjusted 12% increase from 1987 to 1992 coincided with a rapid increase in operation rates in postmenopausal groups (60% or more among women aged 55 59 and 70-79 years). Among women aged 55-64 years, operations for fibroids and uterine bleeding more than doubled, suggesting an influence of increased use of estrogen replacement therapy. Among all women, operations due to bleeding disorders and genital prolapse showed the largest increase (41% and 42% respectively). Bilateral oophorectomy became more common in all age groups over 46 years. CONCLUSIONS There was a modest increase in the overall hysterectomy rate. However, the operation became far more common in postmenopausal women, possibly due to the growing use of estrogen replacement therapy. Register data can be used for describing changes in clinical practice, but other methods are needed to confirm the causal relationships underlying the changes.

Spontaneous luteinizing hormone surge and cleavage of in vitro fertilized embryos

The importance of monitoring luteinizing hormone (LH) secretion during gonadotropin stimulation remains controversial. In the present study, the authors evaluated the occurrence of spontaneous LH surges in 170 cycles stimulated by clomiphene citrate and human menopausal gonadotropin, and correlated the success rate of embryo cleavage to the time interval between the occurrence of the LH surge peak value and the time of human chorionic gonadotropin (hCG) administration. LH was quantitated from urine by an avidin-biotin enzyme immunoassay. The results indicated that a spontaneous LH surge occurred in 18% of the cycles. The number of oocytes recovered was not affected by the occurrence of a spontaneous LH surge. In 12% of all cases, the spontaneous LH surge occurred less than 12 hours before the administration of hCG, and in these cases embryo cleavage was not reduced. In 6% of all cases, the spontaneous LH surge occurred over 12 hours before hCG administration, and in these cases embryo cleavage was reduced significantly.

Diagnosis and treatment of menorrhagia

One‐third of all women experience heavy menstrual bleeding at some point in their life. In western countries, about 5% of women of reproductive age will seek help for menorrhagia annually. Half of all women who consult for hypermenorrhea have some uterine abnormality, most often fibroids (among patients under 40 years of age) and endometrial polyps (above 40 years of age). Appropriate treatment considerably improves the quality of life of these patients, and it is important to make a rigorous assessment of the patient to provide the best treatment options. This guideline provides instructions on how to examine and treat women of fertile age who have menorrhagia. The subjects own assessment of the amount of menstrual blood loss does not generally reflect the true amount. All patients should undergo a pelvic examination and, if the menstrual pattern has changed substantially or if anaemia is present, a vaginal sonography should be carried out as the most important supplemental examination. Vaginal sonography combined with an endometrial biopsy is a reliable method for diagnosing endometrial hyperplasia or carcinoma, but it is insufficient for diagnosing endometrial polyps and fibroids; these can be diagnosed more reliably by sonohysterography or hysteroscopy. Non‐steroidal anti‐inflammatory drugs and tranexamic acid reduce menstrual blood loss by 20–60%, and the effectiveness of a hormonal intrauterine system (IUS) is comparable with that of endometrial ablation or hysterectomy. Cyclic progestogens do not significantly reduce menstrual bleeding of women who ovulate. Treatment should be started with one of the drug therapies, i.e. the IUS, tranexamic acid, anti‐inflammatory drugs, or oral contraceptive. Drug treatment should be used and evaluated before surgical interventions are considered. With an effective training and feedback system, it is possible to organise the diagnostics, medical treatment and follow‐up of heavy menstrual bleeding in the primary health care setting or in outpatient clinics, which reduces the burden on specialist health care.