Ritva Hurskainen

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.

Hysteroscopic tubal sterilization: a systematic review of the Essure system

OBJECTIVE To update the evidence of the efficacy and safety of the Essure system. Female sterilization has undergone changes in the last decade. Besides laparoscopic tubal occlusion, the Essure system is now a viable option, with about 200,000 women sterilized using this method. DESIGN The review is based on the report of the Alberta Heritage Foundation for Medical Research and completed with systematic literature searches up to April 8, 2008. SETTING The Managed Uptake of Medical Methods program of the Finnish National Research and Development Center for Health and Welfare. PATIENT(S) Women over 30 years, who had been sterilized by the Essure method. INTERVENTION(S) Hysteroscopic tubal sterilization using Essure system. MAIN OUTCOME MEASURE(S) Efficacy/effectiveness, adverse events, costs. RESULT(S) Sterilization by Essure can be performed under local anesthesia or with oral analgesics in ambulatory settings. However, sterilization is not immediate and women must use additional contraception for 3 months until permanent tubal occlusion is verified by transvaginal ultrasound, hysterosalpingosonography, hysterosalpingography, or pelvic radiography. The evidence on efficacy and safety is mainly available from short follow-up case series but shows good efficacy and safety of the Essure system. Only a few small risks are associated with the procedure. Two economic studies, one of which implemented Essure as an in-office procedure, suggest that Essure could be more cost-effective than laparoscopic sterilization, but more information on the total cost is needed. CONCLUSION(S) The Essure system appears to be safe, permanent, irreversible, and a less invasive method of contraception compared with laparoscopic sterilization.

Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland.

OBJECTIVE: To examine the association between premenopausal use of the levonorgestrel-releasing intrauterine system and cancer incidence in Finland with a special focus on endometrial adenocarcinoma. METHODS: All Finnish women aged 30–49 years using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia in 1994–2007 (n=93,843) were identified from the National Reimbursement Registry and linked to the Finnish Cancer Registry data. The incidence of cancers in levonorgestrel-releasing intrauterine system users was compared with that in the general population. RESULTS: A total of 2,781 cancer cases were detected in levonorgestrel-releasing intrauterine system users during the follow-up of 855,324 women-years. The standardized incidence ratio (observed-to-expected ratio) for endometrial adenocarcinoma was 0.50 (95% confidence interval [CI] 0.35–0.70; 34 observed compared with 68 expected cases) after the first levonorgestrel-releasing intrauterine system purchase and 0.25 (95% CI 0.05–0.73; three observed compared with 12 expected cases) after two purchases. The standardized incidence ratio for ovarian cancer was 0.60 (95% CI 0.45–0.76; 59 observed compared with 99 expected cases), for pancreatic cancer 0.50 (95% CI 0.28–0.81; 15 observed compared with 30 expected cases), and for lung cancer 0.68 (95% CI 0.49–0.91; 43 observed compared with 63 expected cases). The standardized incidence ratio for breast cancer among all levonorgestrel-releasing intrauterine system users was 1.19 (95% CI 1.13–1.25; 1,542 observed compared with 1,292 expected cases). CONCLUSION: The levonorgestrel-releasing intrauterine system may have a protective effect against endometrial malignant transformation. Using the levonorgestrel-releasing intrauterine system for treatment of menorrhagia during reproductive years was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers than expected. Levonorgestrel-releasing intrauterine system use was associated with a higher than expected incidence of breast cancer. LEVEL OF EVIDENCE: II

Double-blind, randomized, placebo-controlled study on the effect of misoprostol on ease of consecutive insertion of the levonorgestrel-releasing intrauterine system

BACKGROUND Misoprostol has been studied intensively to produce cervical dilatation. To date, no studies have evaluated the effectiveness, safety or acceptability of this treatment for repeat intrauterine device insertions. STUDY DESIGN This study was a randomized, double-blind, placebo-controlled trial on the consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS). Women who had used their first LNG-IUS for 4 years and 3 to 9 months and opted for an immediate replacement with a second LNG-IUS received a single sublingual dose of 400 mcg misoprostol or placebo 3 h prior to the LNG-IUS insertion. RESULTS The proportion of easy insertions as judged by the investigator was 93% (40/43) in subjects randomized to misoprostol and 91% (42/46) in the placebo group (p=1.0 for the difference of proportions). No or mild pain at insertion was reported by 37% and 35% of subjects in the misoprostol and placebo groups, respectively. However, adverse events related to the study drug were more common in the misoprostol group. CONCLUSION Sublingual misoprostol did not have a significant effect on the ease of insertion in subjects having a repeat insertion of the LNG-IUS.

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.

The effect of hysterectomy or levonorgestrel-releasing intrauterine system on sexual functioning among women with menorrhagia : a 5-year randomised controlled trial

Objective  To compare among women with menorrhagia the effect of hysterectomy or levonorgestrel‐releasing intrauterine system (LNG‐IUS) on sexual functioning .

Cost-utility of levonorgestrel intrauterine system compared with hysterectomy and second generation endometrial ablative techniques in managing patients with menorrhagia in the UK

ABSTRACT Objective: To estimate the cost-utility of levonorgestrel intrauterine system (LNG-IUS; Mirena*) compared to second generation endometrial ablative techniques [i.e. microwave endometrial ablation (MEA) and thermal balloon endometrial ablation (TBEA)] and hysterectomy in the UK. Methods: Clinical and utility data from a 5-year randomised controlled trial comparing LNG-IUS with hysterectomy were combined with further data from published studies to construct a state-transition (Markov) model. The model depicted the movement of patients between health states over 5 years following treatment for menorrhagia. The model was used to estimate the cost-utility of LNG-IUS followed by ablation (L-A); LNG-IUS followed by hysterectomy (L-H); immediate ablation (MEA or TBEA) and immediate hysterectomy in the UK at 2004/2005 prices, from the perspective of the UKs National Health Service (NHS). Main outcome measures and results: The expected 5-yearly cost of treating menorrhagia with L-A, L-H, TBEA, MEA and hysterectomy was estimated to be £828, £1355, £1679, £1812 and £2983 per patient respectively and the expected level of health gain to be 4.14, 4.12, 4.13, 4.13 and 4.01 QALYs per patient respectively. LNG-IUS followed by ablation dominated all the alternative treatments. Hysterectomy was dominated by the alternative treatments. Sensitivity analysis found the model to be sensitive to the quality of life data used. Conclusion: Within the models limitations, LNG-IUS followed by ablation appears to offer the NHS a cost-effective treatment for menorrhagia, when compared to immediate surgery, affording the NHS a less expensive treatment modality without detrimental effects on resulting health gain.

Levonorgestrel-releasing intrauterine system in the treatment of heavy menstrual bleeding.

Purpose of review Menorrhagia is a frequent reason for women to seek medical care and an increasingly common health problem. The levonorgestrel-releasing intrauterine system is an effective medical treatment for menorrhagia. Emerging clinical and research evidence suggests that this new treatment modality has major health benefits. Recent findings The levonorgestrel-releasing intrauterine system is a cost-effective treatment modality for menorrhagia. The quality of life improves significantly which is comparable to that gained with hysterectomy. The costs are about half those of hysterectomy after 5 years of follow-up. Unscheduled breakthrough bleeding is the most common side effect of the treatment. There are different new theories about the mechanism underlying this problem. Women with endometriosis or fibroids also benefit from this treatment. Summary Because menorrhagia is often a reason for seeking medical attention, it is important to consider the outcomes and costs to provide the most appropriate care. The levonorgestrel-releasing intrauterine system improves health-related quality of life significantly at relatively low cost. It is the most effective medical treatment for menorrhagia and comparable to surgical interventions. The system is not associated with serious complications. Although not all women are successfully treated, about 60% avoid hysterectomy and are satisfied with the treatment. Thus, the levonorgestrel-releasing intrauterine system should be the first line of treatment for heavy menstrual bleeding.

Combined laboratory and diary method for objective assessment of menstrual blood loss

BACKGROUND To develop an objective measurement system for menstrual blood loss applicable in clinical practice. METHODS One hundred and fifty-six patients were enrolled in a randomized trial of the treatment of menorrhagia in all five gynecology departments of the university teaching hospitals in Finland. Correlation between venous blood hemoglobin concentration (Hb) and absorbance at 564 nm (A564) was investigated in experiments with blood samples. Amount of collected menstrual blood and menstrual diary data were analyzed. RESULT Hb concentration and A564 of the blood were linearly correlated (r=0.99). One hundred and fifty-four women (99%) returned used sanitary protection and menstrual diaries. On average, 12% (range 0-57%) of menstrual blood was lost during collection. The median amount of blood recovered from sanitary protection was 89 ml (range 14-724 ml), with 58% (n=90) of the women exceeding 80 ml per cycle. When the spilled blood was taken into account, the corresponding figures were 104 ml (range 15-724 ml) and 66% (n= 101). CONCLUSIONS The spectrophotometric measurement of venous blood in the conventional alkaline hematin method can be replaced by measurement of Hb concentration. All blood incompletely collected should be recorded. Objective measurement of menstrual blood loss can be applied in routine clinical practice.

Levonorgestrel-releasing intrauterine system or hysterectomy in the treatment of essential menorrhagia: predictors of outcome

Levonorgestrel‐releasing intrauterine system (LNG‐IUS) has been advocated as an effective alternative to hysterectomy in the treatment of menorrhagia. The outcome predictors have been poorly known. In this study the amount of menstrual blood loss (MBL) turned out to be the single most important outcome predictor of these treatments. However, the treatment with LNG‐IUS seemed to be an appropriate alternative to hysterectomy for all women who perceived their MBL heavy.