Clinical assessment of treatments for prolonged bleeding in users of norplantR implants

doi:10.1016/0010-7824(90)90094-C

Contraception

Volume 42, Issue 1, July 1990, Pages 97-109

https://doi.org/10.1016/0010-7824(90)90094-C Get rights and content

Abstract

The effectiveness of three drugs in controlling prolonged bleeding in the first year of NORPLANT^R implants use was tested. The drugs were levonorgestrel (L-Ng, 0.03 mg twice a day for 20 days), ethinylestradiol (EE, 0.05 mg per day for 20 days) and ibuprofen (Ib, 800 mg three times a day for 5 days) and were given orally. A control group received a placebo (PL, one pill of lactose for 20 days). Treatment should start each time a woman experienced eight consecutive days of bleeding or spotting. The 183 volunteers were not aware of the drug administered. A daily record of bleeding and spotting and of treatment intake was maintained. One-hundred-forty women completed the study period; 60 never used the prescribed treatment. Women treated with the three test drugs had significantly fewer bleeding and spotting days during the treated month and also throughout the study year than women using the placebo. The mean number of bleeding plus spotting days per actually treated subject in the first year was 77, 94, 101 and 129 days for the EE, Ib, L-Ng and PL groups, respectively. The administration of EE might help in the management of prolonged bleeding during the first year of NORPLANT^R implants use.

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Nearly 20% of women using contraception are using progestin-only contraception, including progestin-only pills, depot-medroxyprogesterone acetate, subdermal etonogestrel implants, and levonorgestrel intrauterine devices. This number will continue to grow with the increased provision of long-acting reversible contraception. Although overall satisfaction among women using progestin-only contraception is high, dissatisfaction and discontinuation may be associated with unscheduled bleeding and spotting. The exact etiology of irregular bleeding associated with progestin-containing contraceptives is not completely understood, yet several mechanisms have been suggested. Several therapies targeting these mechanisms have been evaluated with mixed results. This paper will review the physiology and management of unscheduled bleeding with progestin-containing contraceptives.
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We chose naproxen because it is inexpensive, is widely available in the United States, and can be taken twice daily. We administered the naproxen for the first 5 days of a 4-week period because this regimen had been investigated previously in several other studies of NSAIDS for the treatment of progestin-induced irregular bleeding.7,8,10 Women who were assigned to estradiol also started the patch the day after insertion (day 1) and used it continuously, changing the patch weekly.
The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system.
We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis.
There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84–0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17–1.34).
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Only one small study has looked at administration of low-dose oral progestogen (0.03 mg LNG twice daily for 20 days and up to 5 occasions in one year) in LNG implant users. The number of bleeding/spotting days was reduced but discontinuation and nonuse rates were high [49]. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) to treat irregular bleeding has been encouraged because arachidonic acid metabolism in the endometrium of progestogen-only contraceptive users may be disturbed [50] NSAIDS, however, have shown variable efficacy in LNG implant users.
The aim of this guidance is to review the management of unacceptable vaginal bleeding patterns in etonogestrel (ENG)-releasing contraceptive implant users concentrating, where possible, on the evidence for pharmacological treatments and identifying a pragmatic approach where this is not possible.
This article was developed in accordance with methodology used for producing Royal College of Obstetricians and Gynaecologists' Green Top Guidelines.
The Cochrane Library (including the Cochrane Database of Systematic Reviews, DARE and EMBASE) and Medline (1966–2010) were searched using the relevant MeSH terms, including all subheadings, and this was combined with a keyword search. Search words included “progestogen only contraceptives,” “contraceptive implants,” “progestogen implants,” “etonogestrel implants,” “irregular bleeding,” “unpredictable bleeding,” “bleeding irregularity” and “bleeding pattern,” and the search was limited to humans and English language. Enquiries for relevant information were also made to the pharmaceutical industry and researchers for missing studies.
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Implanon: A Review of the Literature With Recommendations for Clinical Management
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Phaliwong and Taneepanichskul36 found that mefenamic acid 500 mg three times daily for 5 days stopped Implanon users' bleeding within 7 days. Ibuprofen may be a more accessible drug for patients, and in a Norplant study, ibuprofen 800 mg three times daily for 5 days stopped bleeding although less rapidly than estrogen.38 Other nonsteroidal anti-inflammatory drugs might be tried, although aspirin was found to be ineffective in a large-scale trial of Norplant users.40
Implanon is a new implantable, progestin-only contraceptive which was approved in the United States in July 2006. Implanon is comprised of a single ethylene vinylacetate copolymer rod that is 4 cm long and 2 mm in diameter. It is inserted subdermally in the groove between the biceps and triceps of the nondominant arm. A literature review was conducted and side effects are discussed. Implanon offers promise as a high-efficacy, long-term contraceptive and can enhance the contraceptive options offered by the women's health care providers. Clinical trial data indicate that the device is both safe and effective.
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