Selegiline and Estradiol Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Selegiline
Estradiol Topical
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increase in selegiline oral bioavailability and an increased risk of selegiline adverse reactions
Interaction Deep Dive
During a randomized study to determine the dose relationship of selegiline and its main metabolite, desmethylselegiline, female subjects who were receiving oral contraceptives had a Cmax and AUC that was 10- to 20-fold higher than subjects not receiving oral contraceptives. The marked elevation in the bioavailability of selegiline may result in a loss of selective inhibition of monoamine oxidase (MAO) type B, which would predispose the patient to hypertensive reactions after the intake of amines1.
Why it happens (mechanism)
Inhibition of selegiline first-pass metabolism to desmethylselegiline
Literature reports
1 report — tap to read
a) Eight healthy females, four using oral contraceptives, entered an open, four-period randomized study to characterize the dose relationship of selegiline and desmethylselegiline pharmacokinetics. Subjects ingested a single dose of 5 mg, 10 mg, 20 mg, or 40 mg of selegiline, with a washout period of at least two weeks between treatment phases. Although researchers were not looking for differences in the pharmacokinetics of selegiline between oral contraceptive users and non-users, there was a 20-fold increase in selegiline AUC in oral contraceptive users as compared with non-users. The median Cmax was more than 10 times higher in the group taking oral steroids. Desmethylselegiline AUC values were also higher in contraceptive users, although the increase was smaller in magnitude and did not reach statistical significance. The difference in the metabolic ratio between the two groups suggests that oral contraceptives inhibit the N-demethylation of selegiline to desmethylselegiline. The increase in selegiline bioavailability in oral contraceptive users may lead to loss of selective inhibition of monoamine oxidase type B, predisposing the patient to hypertensive reactions 1.
Common questions
Can I take Selegiline and Estradiol Topical together?
An increase in selegiline oral bioavailability and an increased risk of selegiline adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Selegiline and Estradiol Topical interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Selegiline or Estradiol Topical need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (1)
- Laine K, Antiila M, Helminen A, et al: Dose linearity study of selegiline pharmacokinetics after oral administration: evidence for strong drug interaction with female sex steroids. Br J Clin Pharmacol 1999; 47:249-254. PubMed
Keep reading about Selegiline
Keep reading about Estradiol Topical
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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