Pregnenolone + Drospirenone, Estetrol
Drospirenone, Estetrol brand name: Nextstellis.
Drospirenone, Estetrol falls into 3 drug categories that Pregnenolone can interact with; the most serious is rated moderate. Theoretically, taking pregnenolone might enhance the effects of estrogens.
Read the full interaction reportPregnenolone and Drospirenone, Estetrol
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Pregnenolone interacts with whole categories of medication. Drospirenone, Estetrol falls into 3 of those categories, so it can interact with Pregnenolone in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
ESTROGENS
1 of 3Why this applies to Drospirenone, Estetrol
Drospirenone, Estetrol falls under ESTROGENS — the group Pregnenolone interacts with.
Pregnenolone is a precursor for several steroid hormones, including estrogens.
Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
Nextstellis combines two hormones, drospirenone (a progestin) and estetrol (an estrogen). Here's the concern with pregnenolone: your body can use it as a raw material to build its own estrogens. So in theory, adding pregnenolone on top of your birth control could nudge your total estrogen activity a little higher.
I want to be honest about how soft this is. It's based on how these hormones work on paper (theoretical), not on real patient studies, so we don't actually know if it matters day to day. If anything did shift, you might notice estrogen-type effects like breast tenderness, nausea, bloating, or headaches. Because it's still a hormone stacked on a hormone, please run it by your pharmacist or doctor before combining them rather than guessing.
- Devlin TM, ed. Textbook of Biochemistry With Clinical Correlations. third ed. New York: Wiley-Liss Inc., 1992.
PROGESTIN
2 of 3Drospirenone, Estetrol also falls under PROGESTIN.
Pregnenolone is a precursor for several steroid hormones, including progestin.
Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
Nextstellis is a birth control pill that combines a progestin (drospirenone) with an estrogen (estetrol). Here's the idea behind this interaction: pregnenolone is an upstream hormone your body can turn into other steroid hormones, including progestin-like ones. So in theory, adding it on top of your pill could nudge progestin-type effects a little higher. That might show up as more spotting, breast tenderness, bloating, or mood changes.
I want to be honest with you though, this is purely theoretical and based on how these hormones are built, not on real studies in people. We don't have evidence it actually causes problems. Since pregnenolone is itself a hormone, it's worth a quick chat with your pharmacist or doctor before combining the two.
- Devlin TM, ed. Textbook of Biochemistry With Clinical Correlations. third ed. New York: Wiley-Liss Inc., 1992.
PROGESTERONE
3 of 3Drospirenone, Estetrol also falls under PROGESTERONE.
In humans, some research shows that oral administration of pregnenolone can increase levels of progesterone. However, other research shows no effect on progesterone levels. It is possible the impact of pregnenolone on progesterone levels may be dose dependent.
Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
Here's the thing to keep in mind with Nextstellis (your drospirenone and estetrol birth control pill). Because pregnenolone sits at the top of your body's hormone-making chain, it can be converted into other steroid hormones, including progesterone. The concern on file is mostly theoretical and based on pharmacology, with some human studies showing a small bump in progesterone and others showing no change at all. So this isn't a strong, well-proven interaction.
If pregnenolone did nudge your progesterone-like activity upward, you might notice more of the usual progestin-type effects, such as breast tenderness, bloating, mood shifts, or spotting. It's unlikely to be dramatic, but since this is a hormone-on-hormone situation, I'd run it by your pharmacist or doctor before combining them rather than guessing.
- Ritsner MS, Gibel A, Shleifer T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry 20 PubMed
- Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009;34(8):1885-903. PubMed
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
- ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
- PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
- UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
- AHigh-quality meta-analysis (quantitative systematic review).
- BCase-control study.
- CConsensus.
- DAnecdotal evidence.
These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.
Pregnenolone Also Interacts With Other Medications
Pregnenolone has 81 moderate known drug interactions in our database — the Drospirenone, Estetrol one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Pregnenolone
We haven’t checked that one against Pregnenolone yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Pregnenolone. Pick one to open its full report.
See Every Supplement That Interacts With Drospirenone, Estetrol
This page covers Pregnenolone only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Drospirenone, Estetrol page lists 245 supplements it has a documented interaction with, worst first, each one explained.
The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).
By severity: 6 major · 200 moderate · 39 minor.
From our pharmacist’s overview on the Drospirenone, Estetrol page
“The stakes with Nextstellis (drospirenone and estetrol) are the ones that come with any birth control pill, because an interaction that lowers its hormone levels can mean an unplanned pregnancy, and I would treat this list with genuine seriousness. Most of what is here changes how the body handles the hormones.”
Reviewed by 2 · Jul 18, 2026
Taking Pregnenolone as Part of a Dietary Supplement Product? Check It for Interactions
We hold 303 real supplement products containing Pregnenolone, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Pregnenolone. Your product may carry other ingredients that interact with Drospirenone, Estetrol too, on top of Pregnenolone — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Pregnenolone and Drospirenone, Estetrol Sit Against Everything Else
Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.
#307 of 1,452 supplements looked up here in the last 7 days
#1,207 of 2,830 medications looked up here in the last 7 days
Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.
About Pregnenolone
What is Pregnenolone?
- Memory and cognitive support
- Anxiety and stress
- Anti-aging
- Fatigue and low energy
- Mood support
Pregnenolone is a hormone your body makes naturally and a building block for other hormones like cortisol, DHEA, estrogen, and testosterone. It is sold as a supplement for memory, mood, and anti-aging, but solid human evidence for these uses is very limited. Because it is a hormone, talk with your pharmacist or doctor before using it.
Other Drugs & Pregnenolone
Browse every other medication we’ve checked against Pregnenolone — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
81 interactions
- Estradiol ›
- Norethindrone ›
- Testosterone ›
- Flurazepam ›
- Methyltestosterone ›
- Triazolam ›
- Temazepam ›
- Nitrazepam ›
- Conjugated Estrogens ›
- Diazepam ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Testosterone Undecanoate ›
- Clobazam ›
- Clonazepam ›
- Clorazepate ›
- Midazolam ›
- Progesterone (prescription Drug) ›
- Alprazolam ›
- Esterified Estrogens ›
- Estropipate ›
- Hydroxyprogesterone ›
- Megestrol Acetate ›
- Methyltestosterone Buccal ›
- Bromazepam ›
- Chlordiazepoxide ›
- Desogestrel ›
- Drospirenone ›
- Estazolam ›
- Estrogen ›
- Estrone ›
- Ethinyl Estradiol ›
- Halazepam ›
- Ketazolam ›
- Lorazepam ›
- Oestrogen ›
- Oxazepam ›
- Prasterone (prescription Drug) ›
- Prazepam ›
- Progesterone ›
- Quazepam ›
- Remimazolam Besylate ›
- Testosterone Enanthate ›
- Tibolone ›
- Ethinyl Estradiol, Norethindrone ›
- Ethinyl Estradiol, Levonorgestrel ›
- Ethinyl Estradiol, Norgestimate ›
- Ethinyl Estradiol, Desogestrel ›
- Ethinyl Estradiol, Norethindrone, Ferrous Fumarate ›
- Desogestrel, Ethinyl Estradiol ›
- Mestranol, Norethindrone ›
- Ethinyl Estradiol, Ethynodiol Diacetate ›
- Levonorgestrel, Ethinyl Estradiol ›
- Ethinyl Estradiol, Norgestrel ›
- Drospirenone, Ethinyl Estradiol ›
- Conjugated Estrogens, Medroxyprogesterone Acetate ›
- Conjugated Estrogens, Meprobamate ›
- Cyproterone Acetate, Ethinyl Estradiol ›
- Ethiny Estradiol, Levonorgestrel ›
- Norelgestromin, Ethinyl Estradiol ›
Showing 60 of 81 moderate interactions — see all 81 on the Pregnenolone page.
No interaction 2,748 drugs checked — show the list
We also checked Pregnenolone against these medications and found no known interaction in our sources. Open any page to confirm.
- Apixaban ›
- Levothyroxine ›
- Amlodipine ›
- Methylphenidate ›
- Warfarin ›
- Sertraline ›
- Losartan Potassium ›
- Metoprolol ›
- Aspirin ›
- Ivermectin ›
- Rivaroxaban ›
- Rosuvastatin ›
- Escitalopram ›
- Acetaminophen ›
- Tadalafil ›
- Clopidogrel ›
- Atorvastatin ›
- Docusate ›
- Valacyclovir ›
- Abemaciclib ›
- Hydroxyurea ›
- Methamphetamine ›
- Ibuprofen ›
- Sumatriptan ›
- Semaglutide ›
- Warfarin Sodium ›
- Tirzepatide ›
- Prednisone ›
- Propranolol ›
- Bupropion ›
- Lisdexamfetamine ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Acyclovir ›
- Bendamustine ›
- Amitriptyline ›
- Doxycycline ›
- Methotrexate ›
- Lamotrigine ›
- Fluoxetine ›
- Acetaminophen, Codeine ›
- Amphetamine ›
- Gabapentin ›
- Pregabalin ›
- Azithromycin ›
- Dextroamphetamine ›
- Isotretinoin ›
- Omeprazole ›
- Methylene Blue ›
- Quetiapine ›
- Amlodipine Besylate ›
- Duloxetine ›
- Letrozole ›
- Buspirone ›
- Citalopram ›
- Naproxen ›
- Ciprofloxacin ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
Showing the 60 most looked-up of 2,748 medications checked with no known interaction — see the full Pregnenolone list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.
Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC
Drospirenone, Estetrol Is Linked to Lower Levels of 7 Nutrients
Natural Medicines records Drospirenone, Estetrol as a medicine that can lower these. This is not an interaction with Pregnenolone — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Drospirenone, Estetrol nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Pregnenolone and Drospirenone, Estetrol Together: Common Questions
Can you take Pregnenolone with Drospirenone, Estetrol?
Why are there 3 interactions listed for Pregnenolone and Drospirenone, Estetrol?
How serious is the Pregnenolone and Drospirenone, Estetrol interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.