Unscheduled bleeding is a common side effect of hormonal contraceptives, often leading to discontinuation. Comprehensive counseling before starting hormonal methods is crucial for improving user satisfaction. For persistent bleeding, common treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and estrogen alone or with progestin in oral contraceptives. Small studies suggest that doxycycline, mifepristone, tranexamic acid, tamoxifen, ulipristal acetate, and clomiphene citrate may reduce bleeding in various contraceptive users. Mifepristone and tranexamic acid show promise for users of depot medroxyprogesterone acetate, implants, and intrauterine devices. While NSAIDs and combined oral contraceptives are commonly used, alternative therapies offer potential, though evidence remains limited.
Key points
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Unscheduled bleeding while using hormonal contraception is common.
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Unscheduled bleeding on hormonal contraception does not decrease efficacy of the contraceptive method.
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Expectant management of unscheduled bleeding is the mainstay of treatment, as symptoms generally improve with continued use.
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Common medical treatments of unscheduled bleeding on hormonal contraception include non-steroidal anti-inflammatory drugs and estrogen alone or in combined oral contraceptives.
| CHCs | combined hormonal contraceptives |
| COC | combined oral contraceptives |
| DMPA | depot medroxyprogesterone acetate |
| DRSP | drospirenone |
| DSG | desogestrel |
| ENG | etonogestrel |
| IUDs | intrauterine devices |
| LNG | levonorgestrel |
| NSAIDs | non-steroidal anti-inflammatory drugs |
| POPs | progestin only pills |
| TXA | tranexamic acid |
| US SPR | United States Centers for Disease Control and Prevention Selected Practice Recommendations for Contraceptive Use |
Introduction
Unscheduled bleeding can occur with use of any form of hormonal contraception and lead to patient dissatisfaction. Unscheduled bleeding does not indicate decreased efficacy of the hormonal contraception and generally improves with continued use. However, dissatisfaction can lead to discontinuation. People may choose to be on hormonal contraception for myriad reasons—contraception, regulation of bleeding, amenorrhea, acne, and dysmenorrhea—therefore, if unscheduled bleeding leads to discontinuation, these other issues may no longer be addressed and managed.
Evaluation
It is imperative for all providers to set expectations for changes in bleeding patterns when initiating a new hormonal contraceptive method and to address the potential of unscheduled bleeding. Thorough counseling prior to the initiation of hormonal contraception reduces the dissatisfaction and discontinuation of the hormonal method. Specifically, providers should counsel that there is no decreased contraceptive efficacy with unscheduled bleeding and that the mainstay for treatment is continued use of the method. With almost all hormonal contraceptive methods, continued use does improve unscheduled bleeding over time.
Characterizing unscheduled bleeding may be challenging for providers and contraceptive users. The Belsey criteria, a standardized set of 5 bleeding categories with bleeding assessed over 90-day periods of hormonal contraceptive use, was proposed by the World Health Organization in 1986 for use in clinical trials and is the most common reporting scheme ( Table 1 ). However, these criteria do not report flow amount, nor do they differentiate based on whether bleeding is occurring during an expected or unexpected time. Newer recommendations for reporting of bleeding patterns put forth in 2022 take into consideration the user experience of bleeding, describing bleeding based on pattern, flow, and duration, and differentiate between contraceptive methods with expected predictable bleeding episodes and anticipated unpredictable bleeding episodes. For methods with expected predictable bleeding, such as combined hormonal contraceptives (CHCs), the occurrence of bleeding is divided into scheduled and unscheduled bleeding ( Fig. 1 ).
| Term | Definition |
|---|---|
| Amenorrhea | No bleeding or spotting during a 90-days reference period |
| Prolonged bleeding | Bleeding/spotting episodes lasting more than 14 days during a 90-days reference period |
| Frequent bleeding | More than 5 bleeding/spotting episodes during a 90-days reference period |
| Infrequent bleeding | 1 – 2 bleeding/spotting episodes during a 90-days reference period |
| Irregular bleeding | 3 – 5 bleeding/spotting episodes and < 3 bleeding/spotting-free intervals of 14 days or more during a 90-days reference period |
In all people who report unscheduled bleeding while using hormonal contraception, providers should initially consider an underlying health condition and initiate treatment, if identified. It is important to rule out pregnancy, even in people using highly effective methods of contraception, such as long-acting reversible contraceptive methods. If underlying health conditions are ruled out and the bleeding pattern is within expected patterns of the hormonal contraception in use, there is evidence for management to help stop or decrease these unscheduled bleeding episodes. As stated earlier, the mainstay of treatment is continued use, as increased duration of use will decrease unscheduled bleeding in most situations.
In this review, we will discuss how to manage unscheduled bleeding with all hormonal contraceptive methods. The United States Centers for Disease Control and Prevention Selected Practice Recommendations for Contraceptive Use (US SPR 2024) and additional evidence-based recommendations can be found in the primary literature.
Levonorgestrel intrauterine device (LNG IUD)
Currently, there are 4 hormonal intrauterine devices (IUDs) on the market. Mirena and Liletta both contain 52 mg levonorgestrel (LNG) (initial release rate of 20mcg LNG/day) and have similar bleeding patterns. , In contrast, Kyleena contains 19.5 mg LNG (initial release rate of 18.5mcg LNG/day) and Skyla contains 13.5 mg LNG , (initial release rate of 14 mg LNG/day).
Prior to IUD insertion, providers should counsel about expected bleeding patterns associated with hormonal IUDs. After insertion, side effects of spotting or light bleeding in first 3 to 6 months can be expected. In a study of the LNG 52 mg IUD, 44% of users reported amenorrhea after 6 months of use. This increased to 50% by 12 to 24 months of use. No evaluation is necessary for amenorrhea as this is a known side effect. In contrast, 35% of users had frequent or prolonged bleeding in the first 3 months after insertion, but this decreased to 4% at 12 months. This is a wide variation in bleeding patterns, and 6% of users had the LNG 52 mg IUD removed because of bothersome bleeding patterns.
While all hormonal IUDs can result in decreased overall bleeding and amenorrhea, IUDs with a lower LNG dose have lower rates of amenorrhea. Twelve percent of LNG 19.5 mg IUD users and 6% of LNG 13.5 mg IUD users report amenorrhea at 12 months. , Therefore, providers should counsel people on these differences in bleeding patterns when discussing about which LNG IUD to use.
Management
The 2 most significant components of management of unscheduled bleeding with LNG IUDs are pre-insertion counseling to set expectations and expectant management. Reassurance is a key and it is essential to counsel that unscheduled bleeding and amenorrhea do not alter the efficacy of the LNG IUD. Most unscheduled bleeding improves overtime, as noted by the increase in amenorrhea rates with the LNG 52 mg IUD. Most unscheduled bleeding does not require a workup, nor does it require treatment. However, for people who are bothered by the unscheduled bleeding, there are several medical options for users of LNG 52 IUDs ( Table 2 ). There are no studies that have evaluated unscheduled bleeding in the lower dose LNG IUDs.
| Medication | Dose | Duration of Use | Short-Term Effect on Bleeding | Long-Term Effect on Bleeding |
|---|---|---|---|---|
| Effective Treatments | ||||
| Naproxen | 500 mg BID | 5 days for 3 cycles | 10% decrease in number of bleeding days | No difference 4 weeks after treatment |
| Tranexamic acid | 500 mg TID | Start on second day of bleeding | 6 fewer bleeding days over 90-days study period | No difference after trial |
| Mifepristone | 100 mg daily | On day of insertion and every 30 days for 3 additional doses | Decrease in median duration of unscheduled bleeding and number of bleeding episodes | After 3 months, mifepristone group continued to report less intermenstrual bleeding (6 vs 15 days) |
| Ulipristal acetate | 50 mg daily | 3-days course starting 3 weeks after IUD insertion and repeated every 28 days | 3 fewer bleeding days after first cycle | Effect gone by second and third cycle and ulipristal acetate users had more bleeding |
| Ineffective Treatments | ||||
| Mefenamic acid | 500 mg TID | At start of bleeding episode | No difference in unscheduled bleeding dose | No difference |
| Estradiol | 0.1 mg patch placed 1 day after IUD insertion | Reapplied weekly for 12 weeks | Increase in unscheduled bleeding | No difference 4 weeks after treatment |
Progestin implants
Currently, in 2024, there is 1 available contraceptive implant in the US: the etonogestrel (ENG) 68 mg implant, Nexplanon. In other countries, a 2-rod LNG 150 mg implant is available. In 2002, the 6-rod LNG 216 mg implant was removed from the market.
Similar to the LNG IUD, there is a wide variety of possible bleeding patterns after insertion of the ENG 68 mg implant. These range from frequent but light unscheduled bleeding to amenorrhea. Unscheduled bleeding is extremely common in implant users and is the primary reason for 6% to 23% of users choosing implant removal. Twenty-two percent of implant users experience amenorrhea. 75% to 80% of implant users report unscheduled bleeding in the first 3 months of use. , Though unscheduled bleeding is common in implant users, bleeding is typically light, consisting of spotting or light bleeding; heavy bleeding is uncommon. Prior to implant insertion, people should be counseled about the high likelihood of unscheduled bleeding.
Management
The 2 most significant components of management of unscheduled bleeding in implant users are pre-insertion counseling to set expectations and expectant management. Reassurance is a key and it is essential to counsel that unscheduled bleeding and amenorrhea do not alter the efficacy of the implant. Most unscheduled bleeding does not require a workup, nor does it require treatment. However, for people who are bothered by the unscheduled bleeding, there are several medical options for ENG 68 mg implant users ( Table 3 ).
| Medication | Dose | Length of Time | Short-Term Effect on Bleeding | Long-Term Effect on Bleeding |
|---|---|---|---|---|
| Effective Treatments | ||||
| Nonsteroidal anti-inflammatory drugs , a | 5 – 7 days | Reduced bleeding | Effect may persist after treatment | |
| Celecoxib Mefenamic acid | 200 mg daily 500 mg TID | 5 days 7 days | Reduced bleeding | Effect may persist after treatment |
| Selective estrogen receptor modulators (tamoxifen) , a | 7 – 10 days | Reduced bleeding | Effect may persist after treatment | |
| Tamoxifen | 7 days | 5 fewer bleeding days and 15 more continuous days without bleeding compared to placebo | Effect may persist after treatment | |
| Combined oral contraceptive pills or estrogen alone , a | 20 – 30 μg of ethinyl estradiol | No guidance | Decrease bleeding | No difference in unscheduled bleeding after treatment |
| Combined oral contraceptive pills , | No dosing provided | 14 days | Decreased duration of bleeding episode compared to placebo (88% compared to 38%) | No difference in unscheduled bleeding after treatment |
| Estrogen alone | 20 – 30 μg ethinyl estradiol | 20 – 21 days | Decrease duration of bleeding episodes and length duration of time between bleeding episodes | No difference in unscheduled bleeding after treatment |
| Tranexamic acid , , a (1 RCT in six rod levonorgestrel implant) | 500 mg BID | 5 days | Significant reduction in bleeding during first week of treatment | No difference in unscheduled bleeding after treatment |
| Ulipristal acetate | 15 mg daily | 7 days | 5 fewer bleeding days in 30 days follow-up | No data |
| Doxycycline | Shorter time to cessation of unscheduled bleeding | No difference in unscheduled bleeding after treatment | ||
| Mifepristone , | 50 – 100 mg Not available in the US at these doses | Reduction in bleeding | Based on mechanism of action, may theoretically decrease efficacy of progestin implant | |
| Ineffective Treatments | ||||
| Estrogen patch | Does not improve bleeding patterns | |||
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