A Randomized Controlled Trial of Oral Naproxen and Transdermal Estradiol for Bleeding in LNG-IUC
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|ClinicalTrials.gov Identifier: NCT00789802|
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : December 11, 2014
Last Update Posted : March 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Contraception Bleeding||Drug: transdermal estradiol Drug: naproxen Drug: oral placebo||Not Applicable|
The levonorgestrel intrauterine system (LNG-IUC) is one of the most effective, reversible methods of contraception currently available in the United States. User satisfaction is overall high , however the most often cited reason for discontinuation is irregular bleeding . The LNG-IUC has mainly progesteronic effects on the uterine cavity. Morphological changes of the endometrium are observed, including stromal pseudo-decidualization and glandular atrophy . These endometrial changes may contribute to the irregular uterine bleeding experienced by women using the LNG-IUC. Up to 14% of women will discontinue the LNG-IUC within the 5-year period due to abnormal bleeding and up to 66% of woman who request removal of the LNG-IUC will do so in the first 6 months of use . Women may be less likely to discontinue the LNG-IUC due to abnormal bleeding patterns if they are counseled appropriately beforehand, however the prospect of irregular bleeding with few options for management may dissuade some women from even trying the LNG-IUC. A recent Cochrane review identified the need for further investigation into the treatment of irregular uterine bleeding caused by progestin only contraception .
One treatment for progestin-induced irregular bleeding is the administration of nonsteroidal anti-inflammatory agents (NSAIDs). A 1999 study showed a significant decrease in the number of bleeding days in women using the levonorgestrel sub-dermal implant randomized to mefenamic acid 500 mg compared to placebo . A 2004 study found a 50% reduction in bleeding in depot medroxyprogesterone (DPMA) users randomized to mefenamic acid versus placebo . There have been no studies looking specifically at NSAIDs for the prevention or treatment of LNG-IUC related irregular bleeding. Naproxen is an antiprostaglandin that is commonly used in gynecological practice for relief of dysmenorrhea and has been used to treat menorrhagia. It is widely available, inexpensive, well-tolerated and has a low incidence of side effects.
Previous studies have also shown the administration of estrogen alone and estrogen-containing oral contraceptives to users of subdermal levonorgestrel implants (Norplant®) resulted in decreased frequency of irregular uterine bleeding , . A prior randomized, controlled trial found a 0.1mg estradiol patch resulted in the clinical improvement of abnormal bleeding, however this finding was not statistically significant . A randomized, controlled trial of DMPA users found the cyclic administration of 0.1mg estradiol patches did not decreases irregular menstrual bleeding . In this study, the cyclic use of estrogen may have resulted in lower or inconsistent serum estradiol levels. Additionally, the progestational mechanism of action is more similar between levonorgestrel subdermal implants and LNG-IUC than depot medroxyprogesterone. No study has specifically addressed estrogen for treatment of irregular bleeding with the LNG-IUC.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||129 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||A Randomized, Controlled Trial of Oral Naproxen and Transdermal Estradiol for Prevention of Unscheduled Bleeding in New Users of Levonorgestrel Intrauterine Contraception|
|Study Start Date :||November 2008|
|Actual Primary Completion Date :||January 2010|
|Actual Study Completion Date :||January 2011|
Experimental: transdermal estradiol
participants will be randomized to transdermal estradiol
Drug: transdermal estradiol
transdermal estradiol 0.1mg patch to be changed weekly for 12 weeks.
Other Name: Climara
Experimental: oral naproxen
participants will be randomized to oral naproxen
naproxen 500mg by mouth twice daily for the first 5 days of every 4 week period for a total of 12 weeks
Other Name: Naprosyn, Anaprox
Placebo Comparator: oral placebo
participants will be randomized to oral placebo
Drug: oral placebo
oral placebo to be taken by mouth twice daily for the first 5 days of a 4 week block for a total of 5 weeks
- Number of Bleeding and Spotting Days [ Time Frame: 12 weeks ]The median number of bleeding and spotting days reported at 12 weeks.
- Number of Bleeding Days Observed in Women With a LNG-IUC Treated With Naproxen, Estradiol and Placebo. [ Time Frame: 16 weeks ]Median number of bleeding days observed in women with a LNG-IUC treated with naproxen, estradiol and placebo at 16 weeks.
- Patient Satisfaction With the LNG-IUC at the End of the 12 Weeks Between the 3 Study Groups. [ Time Frame: 12 weeks ]To compare the level of patient satisfaction with the LNG-IUC at the end of the 12 weeks between the 3 study groups.
- Continuation Rates of the LNG-IUC at the End of the 12 Week Between the 3 Study Groups [ Time Frame: 12 weeks ]To compare continuation rates of the LNG-IUC at the end of the 12 week between the 3 study groups
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00789802
|United States, Missouri|
|Washington University School fo Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Tessa E Madden, MD||Washington University School of Medicine|