In cases of breakthrough bleeding without medical causes, is it better to change the estrogen formulation or the progesterone (progestin) component?

From the Guidelines

In cases of breakthrough bleeding without medical causes, it's generally better to change the progestin component first rather than the estrogen. When addressing breakthrough bleeding in hormonal contraception, the primary consideration should be the role of progestins in endometrial stabilization.

Key Considerations

• Breakthrough bleeding often results from inadequate endometrial stabilization, which is primarily the role of progestins 1.
• Progestins prevent excessive endometrial growth and provide structural stability to the endometrial lining, while estrogen primarily affects the proliferation phase.
• The approach to managing breakthrough bleeding should prioritize adjusting the progestin component, either by increasing the dose or switching to a more potent progestin such as levonorgestrel, desogestrel, or norgestimate 1.

Adjusting Progestin and Estrogen Components

• Common progestins in order of increasing potency include norethindrone, norethindrone acetate, levonorgestrel, desogestrel, and drospirenone.
• If changing the progestin doesn't resolve the bleeding, then consider adjusting the estrogen component by increasing the dose (typically from 20mcg to 30-35mcg ethinyl estradiol) or switching to a different estrogen type.
• It's crucial to maintain the new formulation for at least three months to allow the endometrium to adjust and properly evaluate the effectiveness of the change.

Evidence-Based Recommendations

• The most recent and highest quality study 1 supports the recommendation to prioritize changing the progestin component over the estrogen component in managing breakthrough bleeding.
• This approach is consistent with the understanding of the roles of progestins and estrogens in hormonal contraception and their effects on the endometrium.

From the FDA Drug Label

Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use The type and dose of progestogen may be important. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem

In cases of breakthrough bleeding without medical causes, changing the progestogen component may be considered, as the type and dose of progestogen may be important in addressing this issue. However, the decision to change the estrogen formulation or the progestogen component should be made on a case-by-case basis, considering the individual patient's needs and medical history 2.

• Key considerations include the type and dose of progestogen, as well as the patient's overall health and medical history.
• No conclusive evidence is provided to definitively recommend changing one component over the other.

From the Research

Breakthrough Bleeding Management

In cases of breakthrough bleeding without medical causes, the decision to change the estrogen formulation or the progesterone component depends on various factors.

• The study 3 suggests that if bleeding persists beyond three months, it can be treated with supplemental estrogen and/or a nonsteroidal anti-inflammatory drug (NSAID), or by changing to an oral contraceptive pill (OCP) with a higher estrogen content or to a different formulation.
• Another approach, as indicated in 4, is to correct abnormal bleeding by changing the progestogen, adjusting the progestogen or estrogen/progestogen doses, or switching the initial regimen to another formulation.

Progesterone vs. Estrogen Formulation Change

• The role of progesterone and progestogens in managing abnormal uterine bleeding is explored in 5, highlighting their use in regulating intermenstrual bleeding and decreasing heavy menstrual bleeding.
• However, as noted in 6, progestogens can have significant side effects, including elevations in breast cancer risk and diminished positive effects of estrogen on certain health aspects.
• The choice between changing the estrogen formulation or the progesterone component may depend on the individual woman's characteristics, risk factors, and the specific hormonal regimen being used, as suggested in 4.

Considerations for Management

• Before making any changes, it is essential to exclude any abnormal organic condition and identify women at higher risk for bleeding, as emphasized in 4.
• Tailoring the regimen to the needs of individual women and identifying those with a higher risk of bleeding can help diminish the occurrence of abnormal bleeding during hormone therapy, as proposed in 4.