Levonorgestrel intrauterine system superior for controlling menorrhagia

The levonorgestrel-releasing intrauterine system is superior to a variety of medical therapies at improving quality of life for women with menorrhagia, according to a report published online Jan. 10 in the New England Journal of Medicine.

In a randomized clinical trial that followed 571 subjects for 2 years, levonorgestrel-IUS (Mirena, Bayer HealthCare) was more effective than the usual medical treatments at combating the adverse effects of heavy menstrual bleeding on women’s daily lives, as well as at improving their psychological and physical well-being, said Dr. Janesh Gupta of the University of Birmingham (England) and his associates for the ECLIPSE (Effectiveness and Cost-Effectiveness of Levonorgestrel-Containing Intrauterine System in Primary Care against Standard Treatment for Menorrhagia) Trial Collaborative Group.

Previous studies gauging the effectiveness of various treatments for menorrhagia have focused on their control of menstrual blood loss, but there is great discordance between objective measures of blood loss and women’s perception of the amount they bleed. "Only about half the women with menorrhagia who present to health care providers have blood loss greater than the traditional threshold of 80 mL per menstrual cycle," the investigators wrote.

Moreover, the amount of bleeding doesn’t correlate with a woman’s experience of what is burdensome for her. "Clinical guidelines now advocate a shift in emphasis from the amount of menstrual blood loss to the more patient-centered definition of heavy menstrual bleeding that interferes with a woman’s physical, emotional, and social life," they noted.

Dr. Gupta and his colleagues compared levonorgestrel-IUS with standard medical therapies using these factors rather than the amount of blood loss as the primary outcome measures. They assessed the effect of menorrhagia on six domains of daily life – practical difficulties, social life, psychological health, physical health, work and daily routine, and family life and relationships – using the condition-specific Menorrhagia Multi-Attribute Scale (MMAS). Scores on the MMAS can range from 0 ("severely affected") to 100 ("not affected at all").

The researchers also assessed general health-related quality of life using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which also has a 100-point scoring system, and the EuroQOL Group 5-Dimension Self-Report Questionnaire (EQ-5D), which has two 100-point scores. They used the Sexual Activity Questionnaire to measure pleasure and discomfort associated with sex, as well as the frequency of sexual activity, relative to the patient’s usual levels.

The study subjects were women aged 25-50 years who presented with menorrhagia to their primary care physicians at 63 U.K. medical centers during a 4-year period. These women were randomly assigned to receive either levonorgestrel-IUS (285 subjects) or medical therapies (286 subjects) such as mefenamic acid, tranexamic acid, norethindrone, estrogen-progestogen OCs, progesterone-only OCs, medroxyprogesterone acetate injections, or some combination of these. The medical treatments were chosen by the patient and her physician according to her contraceptive needs and wishes regarding hormonal therapy.

The two study groups were balanced with respect to subject age (younger than or older than 35 years), body-mass index (over or under 25), duration of symptoms (less than or more than 1 year), need for contraception (yes or no), and the presence or absence of menstrual pain.

The primary outcome measure was improvement on MMAS scores after 2 years of follow-up. These scores improved in all patients, but the improvement in all six domains of the MMAS was significantly greater among women in the levonorgestrel-IUS group, not just at 2 years but at every time point that was assessed.

The mean difference between baseline and final MMAS scores was 13.4 points for these women, a change that was both statistically significant and clinically meaningful. This represents an improvement from being substantially affected to minimally affected by menorrhagia, or from being minimally affected to being completely unaffected.

A sensitivity analysis was performed that included only study subjects who did not cross over from their assigned treatment to a different treatment. This analysis confirmed the findings of the main analysis, showing an improvement of 17.8 points in MMAS scores in women given levonorgestrel-IUS.

Similarly, scores on the SF-36 favored levonorgestrel-IUS over standard medical therapy at all time points in seven of the eight domains assessed, the investigators said (N. Engl. J. Med. 2013 Jan. 10 [doi:10.1056/NEJMoa1204724]).

The two study groups did not differ significantly on EQ-5D scores or on any factor in the Sexual Activity Questionnaire.

The frequency of surgical interventions for menorrhagia during follow-up also did not differ significantly, with 6% of both study groups undergoing hysterectomy; endometrial ablation was performed in 4% of the levonorgestrel-IUS patients and 6% of the medical treatment–group patients.

Given that menorrhagia often persists for years, longer follow-up of these study subjects is planned. Additional intention-to-treat analyses will be done at 5 and 10 years, Dr. Gupta and his associates said.

This study was supported by the National Institute of Health Research Health Technology Assessment Programme. Dr. Gupta reported ties to Hodder Arnold Publishing, Ethicon Gynecare, and Femcare-Nikomed.

The levonorgestrel-releasing intrauterine system is superior to a variety of medical therapies at improving quality of life for women with menorrhagia, according to a report published online Jan. 10 in the New England Journal of Medicine.

In a randomized clinical trial that followed 571 subjects for 2 years, levonorgestrel-IUS (Mirena, Bayer HealthCare) was more effective than the usual medical treatments at combating the adverse effects of heavy menstrual bleeding on women’s daily lives, as well as at improving their psychological and physical well-being, said Dr. Janesh Gupta of the University of Birmingham (England) and his associates for the ECLIPSE (Effectiveness and Cost-Effectiveness of Levonorgestrel-Containing Intrauterine System in Primary Care against Standard Treatment for Menorrhagia) Trial Collaborative Group.

Previous studies gauging the effectiveness of various treatments for menorrhagia have focused on their control of menstrual blood loss, but there is great discordance between objective measures of blood loss and women’s perception of the amount they bleed. "Only about half the women with menorrhagia who present to health care providers have blood loss greater than the traditional threshold of 80 mL per menstrual cycle," the investigators wrote.

Moreover, the amount of bleeding doesn’t correlate with a woman’s experience of what is burdensome for her. "Clinical guidelines now advocate a shift in emphasis from the amount of menstrual blood loss to the more patient-centered definition of heavy menstrual bleeding that interferes with a woman’s physical, emotional, and social life," they noted.

Dr. Gupta and his colleagues compared levonorgestrel-IUS with standard medical therapies using these factors rather than the amount of blood loss as the primary outcome measures. They assessed the effect of menorrhagia on six domains of daily life – practical difficulties, social life, psychological health, physical health, work and daily routine, and family life and relationships – using the condition-specific Menorrhagia Multi-Attribute Scale (MMAS). Scores on the MMAS can range from 0 ("severely affected") to 100 ("not affected at all").

The researchers also assessed general health-related quality of life using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which also has a 100-point scoring system, and the EuroQOL Group 5-Dimension Self-Report Questionnaire (EQ-5D), which has two 100-point scores. They used the Sexual Activity Questionnaire to measure pleasure and discomfort associated with sex, as well as the frequency of sexual activity, relative to the patient’s usual levels.

The study subjects were women aged 25-50 years who presented with menorrhagia to their primary care physicians at 63 U.K. medical centers during a 4-year period. These women were randomly assigned to receive either levonorgestrel-IUS (285 subjects) or medical therapies (286 subjects) such as mefenamic acid, tranexamic acid, norethindrone, estrogen-progestogen OCs, progesterone-only OCs, medroxyprogesterone acetate injections, or some combination of these. The medical treatments were chosen by the patient and her physician according to her contraceptive needs and wishes regarding hormonal therapy.

The two study groups were balanced with respect to subject age (younger than or older than 35 years), body-mass index (over or under 25), duration of symptoms (less than or more than 1 year), need for contraception (yes or no), and the presence or absence of menstrual pain.

The primary outcome measure was improvement on MMAS scores after 2 years of follow-up. These scores improved in all patients, but the improvement in all six domains of the MMAS was significantly greater among women in the levonorgestrel-IUS group, not just at 2 years but at every time point that was assessed.

The mean difference between baseline and final MMAS scores was 13.4 points for these women, a change that was both statistically significant and clinically meaningful. This represents an improvement from being substantially affected to minimally affected by menorrhagia, or from being minimally affected to being completely unaffected.

A sensitivity analysis was performed that included only study subjects who did not cross over from their assigned treatment to a different treatment. This analysis confirmed the findings of the main analysis, showing an improvement of 17.8 points in MMAS scores in women given levonorgestrel-IUS.

Similarly, scores on the SF-36 favored levonorgestrel-IUS over standard medical therapy at all time points in seven of the eight domains assessed, the investigators said (N. Engl. J. Med. 2013 Jan. 10 [doi:10.1056/NEJMoa1204724]).

The two study groups did not differ significantly on EQ-5D scores or on any factor in the Sexual Activity Questionnaire.

The frequency of surgical interventions for menorrhagia during follow-up also did not differ significantly, with 6% of both study groups undergoing hysterectomy; endometrial ablation was performed in 4% of the levonorgestrel-IUS patients and 6% of the medical treatment–group patients.

Given that menorrhagia often persists for years, longer follow-up of these study subjects is planned. Additional intention-to-treat analyses will be done at 5 and 10 years, Dr. Gupta and his associates said.

This study was supported by the National Institute of Health Research Health Technology Assessment Programme. Dr. Gupta reported ties to Hodder Arnold Publishing, Ethicon Gynecare, and Femcare-Nikomed.

The levonorgestrel-releasing intrauterine system is superior to a variety of medical therapies at improving quality of life for women with menorrhagia, according to a report published online Jan. 10 in the New England Journal of Medicine.

In a randomized clinical trial that followed 571 subjects for 2 years, levonorgestrel-IUS (Mirena, Bayer HealthCare) was more effective than the usual medical treatments at combating the adverse effects of heavy menstrual bleeding on women’s daily lives, as well as at improving their psychological and physical well-being, said Dr. Janesh Gupta of the University of Birmingham (England) and his associates for the ECLIPSE (Effectiveness and Cost-Effectiveness of Levonorgestrel-Containing Intrauterine System in Primary Care against Standard Treatment for Menorrhagia) Trial Collaborative Group.

Previous studies gauging the effectiveness of various treatments for menorrhagia have focused on their control of menstrual blood loss, but there is great discordance between objective measures of blood loss and women’s perception of the amount they bleed. "Only about half the women with menorrhagia who present to health care providers have blood loss greater than the traditional threshold of 80 mL per menstrual cycle," the investigators wrote.

Moreover, the amount of bleeding doesn’t correlate with a woman’s experience of what is burdensome for her. "Clinical guidelines now advocate a shift in emphasis from the amount of menstrual blood loss to the more patient-centered definition of heavy menstrual bleeding that interferes with a woman’s physical, emotional, and social life," they noted.

Dr. Gupta and his colleagues compared levonorgestrel-IUS with standard medical therapies using these factors rather than the amount of blood loss as the primary outcome measures. They assessed the effect of menorrhagia on six domains of daily life – practical difficulties, social life, psychological health, physical health, work and daily routine, and family life and relationships – using the condition-specific Menorrhagia Multi-Attribute Scale (MMAS). Scores on the MMAS can range from 0 ("severely affected") to 100 ("not affected at all").

The researchers also assessed general health-related quality of life using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which also has a 100-point scoring system, and the EuroQOL Group 5-Dimension Self-Report Questionnaire (EQ-5D), which has two 100-point scores. They used the Sexual Activity Questionnaire to measure pleasure and discomfort associated with sex, as well as the frequency of sexual activity, relative to the patient’s usual levels.

The study subjects were women aged 25-50 years who presented with menorrhagia to their primary care physicians at 63 U.K. medical centers during a 4-year period. These women were randomly assigned to receive either levonorgestrel-IUS (285 subjects) or medical therapies (286 subjects) such as mefenamic acid, tranexamic acid, norethindrone, estrogen-progestogen OCs, progesterone-only OCs, medroxyprogesterone acetate injections, or some combination of these. The medical treatments were chosen by the patient and her physician according to her contraceptive needs and wishes regarding hormonal therapy.

The two study groups were balanced with respect to subject age (younger than or older than 35 years), body-mass index (over or under 25), duration of symptoms (less than or more than 1 year), need for contraception (yes or no), and the presence or absence of menstrual pain.

The primary outcome measure was improvement on MMAS scores after 2 years of follow-up. These scores improved in all patients, but the improvement in all six domains of the MMAS was significantly greater among women in the levonorgestrel-IUS group, not just at 2 years but at every time point that was assessed.

The mean difference between baseline and final MMAS scores was 13.4 points for these women, a change that was both statistically significant and clinically meaningful. This represents an improvement from being substantially affected to minimally affected by menorrhagia, or from being minimally affected to being completely unaffected.

A sensitivity analysis was performed that included only study subjects who did not cross over from their assigned treatment to a different treatment. This analysis confirmed the findings of the main analysis, showing an improvement of 17.8 points in MMAS scores in women given levonorgestrel-IUS.

Similarly, scores on the SF-36 favored levonorgestrel-IUS over standard medical therapy at all time points in seven of the eight domains assessed, the investigators said (N. Engl. J. Med. 2013 Jan. 10 [doi:10.1056/NEJMoa1204724]).

The two study groups did not differ significantly on EQ-5D scores or on any factor in the Sexual Activity Questionnaire.

The frequency of surgical interventions for menorrhagia during follow-up also did not differ significantly, with 6% of both study groups undergoing hysterectomy; endometrial ablation was performed in 4% of the levonorgestrel-IUS patients and 6% of the medical treatment–group patients.

Given that menorrhagia often persists for years, longer follow-up of these study subjects is planned. Additional intention-to-treat analyses will be done at 5 and 10 years, Dr. Gupta and his associates said.

This study was supported by the National Institute of Health Research Health Technology Assessment Programme. Dr. Gupta reported ties to Hodder Arnold Publishing, Ethicon Gynecare, and Femcare-Nikomed.