Ethinyl Estradiol; Norethindrone with Dehydroepiandrosterone Interaction Details
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
Increased risk of estrogenic adverse effects
Interaction Summary
Combining dehydroepiandrosterone (DHEA) with estrogen may result in symptoms of estrogen excess. DHEA has increased endogenous estrogen levels in postmenopausal women. Pre- and post-menopausal women have effective enzymatic systems for the biotransformation of DHEA to C-19 and C-18 sex steroids , suggesting that increased estrogen levels may occur in all women regardless of menopausal status.
Severity
Minor
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
Concomitant use of dehydroepiandrosterone (DHEA) and estrogen is not recommended. Monitor for symptoms and adverse effects of estrogen excess in those patients who elect to combine therapies. Such symptoms include (but are not limited to) nausea, headache, intolerance to contact lenses, insomnia, chorea, cholasma, colitis, acute breakthrough or withdrawal bleeding, changes in menstrual flow, leukorrhea, and pancreatitis.
Mechanism Of Interaction
Additive estrogenic effect since dehydroepiandrosterone is enzymatically converted into C-19 and C-18 sex steroids
Literature Reports
A) Estrone and estradiol levels increased to two-times the basal value following four weeks of dehydroepiandrosterone (DHEA) 400 milligrams (mg) four times daily for 28 days in six postmenopausal women in a double-blind, placebo-controlled, crossover study. Subjects received DHEA or placebo for 28 days, followed by a 2-week washout period, then crossed over to the other treatment (DHEA or placebo). Estrone increased from 58.7 +/- 11.0 to 167.4 +/- 66.6 picomole/liter (pmol/L) and estradiol increased from 36.7 +/- 3.7 to 121.1 +/- 25.7 pmol/L. This corresponds to a maximal percent change of 214 +/- 67 percent and 181 +/- 29 percent for estrone and estradiol, respectively .
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
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Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
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