Conjugated Estrogens, Medroxyprogesterone Acetate & Nutrient Depletion
Also searched as Prempro, Premplus. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Conjugated Estrogens, Medroxyprogesterone Acetate has been associated with depletion of VITAMIN B6, VITAMIN C, ZINC and FOLIC ACID and 1 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Conjugated Estrogens, Medroxyprogesterone Acetate long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Conjugated Estrogens, Medroxyprogesterone Acetate pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Conjugated Estrogens, Medroxyprogesterone Acetate
Each record below is shown as published in our licensed clinical database, with its evidence rating and citations. Expand a section for food sources and talking points.
VITAMIN B6
Insignificant DepletionESTROGENS
Estrogens can interfere with vitamin B6 metabolism. Reduced plasma pyridoxal phosphate levels may occur with oral contraceptives and estrogen replacement therapy. It is suggested that low vitamin B6 levels contribute to depression, lethargy, and fatigue sometimes associated with oral contraceptives. But there is not reliable evidence that vitamin B6 supplements prevent or treat these symptoms. Also, there is some evidence that with low-dose estrogen contraceptives, levels return to normal despite continued therapy. In general, use of oral contraceptives or postmenopausal estrogens does not necessitate vitamin B6 supplementation. For information on foods that are rich in vitamin B6, see our chart.
Vitamin B6 is something your body uses to make brain chemicals and keep your nerves and energy metabolism running smoothly. Estrogen hormones like the ones in this combination can interfere with how the body processes B6, which may nudge blood levels slightly lower. That said, this is rated as an insignificant depletion, meaning the doses involved are unlikely to cause a real problem for most people, and routine supplementation is generally not considered necessary. If you ever notice unusual fatigue or mood changes while on this medication, it is worth bringing up with your pharmacist or doctor just to be safe.
What Vitamin B6 does & food sources
Vitamin B6 is involved in protein metabolism, neurotransmitter production, and red blood cell formation.
Common food sources:
- Poultry and fish
- Potatoes and starchy vegetables
- Bananas
- Fortified cereals
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
With some medications (for example, isoniazid), B6 is intentionally co-prescribed — follow your prescriber's plan. Otherwise, ask whether testing or supplementation is appropriate if you have symptoms like numbness or tingling.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Paradoxically, long-term high-dose B6 can itself cause nerve symptoms — this is a nutrient where more is definitely not better.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Avoid high-dose B6 without medical guidance; sustained high intakes can cause neuropathy.
Learn more about this nutrient: Vitamin B6 — uses, safety & interactions
References (6)
- Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4:423-40.
- Prasad AS, Lei KY, Moghissi KS, et al. Effect of oral contraceptives on nutrients. III. Vitamins B6, B12 and folic acid. Am J Obstet Gynecol 1976;125:1063-9. PubMed
- Butterworth CE. Interactions of nutrients with oral contraceptives and other drugs J Am Diet Assoc 1973;62:510-4.. DOI
- Tyrer LB. Nutrition and the pill. J Reprod Med 1984;29:547-50..
- Haspels AA, Bennink HJ, Schreurs WH. Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women. Maturitas 1978;1:15-20. . PubMed
- van der Vange N, van der Berg H, Kloosterboer HJ, Haspels AA. Effects of seven low-dose combined contraceptives on vitamin B6 status. Contraception 1989;40:377-84.. PubMed
VITAMIN C
Insignificant DepletionESTROGENS
Evidence on the effects of oral contraceptives and hormone replacement therapy on vitamin C levels is conflicting. It's suggested that estrogens can reduce vitamin C absorption or increase its breakdown, and that vitamin C stores are used to prevent oxidation of estrogens in tissue. This may only be clinically relevant in patients with very low intake of vitamin C. Supplements aren't necessary for people on estrogens who have an adequate dietary intake of vitamin C.
Vitamin C is something your immune system, skin, and tissue repair all depend on, so it matters to keep your levels steady. There is some research suggesting that estrogen hormones like those in this medication may slightly reduce how well the body absorbs vitamin C or may use it up a bit faster as the body processes estrogen. That said, the evidence here is mixed and the overall impact is rated as insignificant, meaning that for most people eating a reasonably balanced diet, this is not a concern worth worrying about. If your diet is very low in fruits and vegetables, it is worth a quick conversation with your pharmacist or doctor.
What Vitamin C does & food sources
Vitamin C is an antioxidant that supports the immune system, collagen formation, and iron absorption.
Common food sources:
- Citrus fruits
- Bell peppers
- Strawberries and kiwi
- Broccoli and Brussels sprouts
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Frank vitamin C deficiency is uncommon with a varied diet. If your diet is limited and you take an associated medication, ask your provider whether your intake is adequate.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Vitamin C is water-soluble and generally low-risk at food-level intakes; very high supplemental doses can cause stomach upset and may not add benefit.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Learn more about this nutrient: Vitamin C — uses, safety & interactions
References (9)
- Thorp VJ. Effect of oral contraceptive agents on vitamin and mineral requirements. J Am Diet Assoc 1980;76:581-4.. DOI
- Briggs M, Briggs M. Vitamin C requirements and oral contraceptives. Nature 1972;238:277. PubMed
- Rivers JM. Oral contraceptives and ascorbic acid. Am J Clin Nutr 1975;28:550-4. PubMed
- Hudiburgh NK, Milner AN. Influence of oral contraceptives on ascorbic acid and triglyceride status. J Am Diet Assoc 1979;75:19-22. DOI
- Weininger J, King JC. Effect of oral contraceptives on ascorbic acid status of young women consuming a constant diet. Nutr Rep Int 1977;15:255-64.
- McLeroy VJ, Schendel HE. Influence of oral contraceptives on ascorbic acid concentrations in healthy, sexually mature women. Am J Clin Nutr 1973;26:191-6. PubMed
- Rivers JM, Devine MM. Plasma ascorbic acid concentrations and oral contraceptives. Am J Clin Nutr 1972;25:684-9. PubMed
- Kuo SM, Lin CP. 17Beta-estradiol inhibition of ascorbic acid accumulation in human intestinal Caco-2 cells. Eur J Pharmacol 1998;361:253-9.
- Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
ZINC
Insignificant DepletionESTROGENS
Research on the effects of estrogens on plasma zinc levels is conflicting. Some studies report decreased levels, while others show no change. Estrogen-induced decreases in serum albumin may reduce the amount of zinc carried in the blood. Also, the anabolic effects of estrogens increase protein synthesis and use of zinc as an enzyme cofactor, increasing the amount of zinc taken up and retained by tissues. There is no reliable evidence that estrogens increase zinc excretion. Therefore, supplements generally are not necessary.
Zinc helps your body run hundreds of enzymes and supports immune function and wound healing. With estrogen-containing medications like this one, the picture is actually a bit complicated: estrogens may shift zinc from the bloodstream into body tissues (where it gets used for building proteins), rather than truly depleting it. Research is mixed, with some studies showing lower blood zinc levels and others showing no change at all. Because the overall evidence points to an insignificant effect, most people on this medication do not need to worry about zinc or take a supplement, but your pharmacist or doctor can address any specific concerns.
What Zinc does & food sources
Zinc supports immune function, wound healing, taste and smell, and many enzyme systems.
Common food sources:
- Meat and shellfish (especially oysters)
- Beans and lentils
- Nuts and seeds
- Whole grains
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask about zinc status if you take an associated medication long-term and notice slow wound healing, frequent infections, or taste changes — a clinician can decide whether testing or an empiric plan makes sense.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Zinc competes with copper for absorption — long-term, higher-dose zinc without medical guidance can cause copper deficiency. Zinc also binds some antibiotics in the gut, so dose timing matters.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Keep zinc doses moderate and time them away from interacting medications — ask your pharmacist.
Learn more about this nutrient: Zinc — uses, safety & interactions
References (11)
- Tyrer LB. Nutrition and the pill. J Reprod Med 1984;29:547-50..
- King JC. Do women using oral contraceptive agents require extra zinc? J Nutr 1987;117:217-9. PubMed
- Smith JC, Brown ED. Effects of oral contraceptive agents on trace element metabolism - a review. In: Prasad AS (ed). Trace Elements in Human Health and Disease. Vol.II, Essential and Toxic Elements. New York: Academic Press, 1976. 315-45. DOI
- Prasad AS, Oberleas D, Lei KY, et al. Effect of oral contraceptive agents on nutrients: I. Minerals. Am J Clin Nutr 1975;28:377-84. PubMed
- Prema K, Ramalakshmi Ba, Babu S. Serum copper and zinc in hormonal contraceptive users. Fertil Steril 1980;33;267-71. PubMed
- Webb JL. Nutritional effects of oral contraceptive use: A review. J Reprod Med 1080;25:150.
- Vir SC, Love AH. Zinc and copper nutriture of women taking oral contraceptive agents. Am J Clin Nutr 1981;34:1479-83. PubMed
- Hinks LJ, Clayton BE, Lloyd RS. Zinc and copper concentrations in leukocytes and erythrocytes in healthy adults and the effect of oral contraceptives. J Clin Pathol 1983;36:1016-21.
- Chilvers DC, Jones MM, Selby PL, et al. Effects of oral ethinyl oestradiol and norethisterone on plasma copper and zinc complexes in post-menopausal women. Hormone Metab Res 1985;17:532-5. PubMed
- Powell-Beard L, Lei KY, Shenker L. Effect of long-term oral contraceptive therapy before pregnancy on maternal and fetal zinc and copper status. Obstet Gynecol 1987;69:26-32.
- Liukko P, Erkkola R, Pakarinen P, et al. Trace elements during 2 years' oral contraception with low-estrogen preparations. Gynecol Obstet Invest 1988;25:113-7. PubMed
FOLIC ACID
Moderate DepletionESTROGENS
Reduced serum and red blood cell folate levels can occur with the use of conjugated estrogens (Premarin) or oral contraceptives, although this is unlikely with adequate dietary folate intake. There are rare reports of megaloblastic anemia associated with oral contraceptive use, usually in patients with other conditions contributing to folate deficiency. Possible mechanisms by which estrogens contribute to folate deficiency include reduced absorption of dietary folate, increased excretion, induction of liver enzymes, and increased protein binding of folate in serum. There is some evidence that oral contraceptives can increase the rate of progression of cervical dysplasia to cervical cancer, and that folic acid can slow or reverse this dysplasia. Advise patients taking oral contraceptives or other estrogens to maintain a good dietary intake of folate. Recommend supplements only for those with inadequate dietary intake or other conditions that contribute to folate deficiency, and for those diagnosed with, or at increased risk for, cervical dysplasia. For information on foods that are rich in folate, see our chart.
Folic acid is a B vitamin your body uses to build healthy cells, including red blood cells and the cells lining your cervix. The estrogen in this combination therapy may lower your folate levels through a few possible routes, including making it harder to absorb from food, causing the kidneys to excrete more of it, or changing how the liver processes it. For most people who eat a reasonably folate-rich diet, this is not cause for alarm, but long-term users with poor dietary intake or other risk factors may want to ask their pharmacist or doctor whether a folic acid supplement makes sense for them.
What Folic acid (folate) does & food sources
Folate is needed for cell division, red blood cell formation, and healthy fetal development.
Common food sources:
- Leafy green vegetables
- Beans, lentils, and peas
- Fortified grains and cereals
- Citrus fruits
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask your provider whether folate monitoring or supplementation is appropriate for you — this matters most before and during pregnancy, and with long-term use of certain seizure or arthritis medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Folate needs are individual. With some medications (for example, methotrexate), folic acid is often prescribed deliberately on a specific schedule — follow your prescriber's instructions rather than adding your own.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: High-dose folic acid can mask vitamin B12 deficiency, so the two are often evaluated together.
Learn more about this nutrient: Folic Acid — uses, safety & interactions
References (9)
- Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4:423-40.
- Prasad AS, Lei KY, Moghissi KS, et al. Effect of oral contraceptives on nutrients. III. Vitamins B6, B12 and folic acid. Am J Obstet Gynecol 1976;125:1063-9. PubMed
- Grace E, Emans SJ, Drum DE. Hematologic abnormalities in adolescents who take oral contraceptive pills. J Pediatrics 1982;101:771-4. PubMed
- Green TJ, Houghton LA, Donovan U, et al. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females. J Am Diet Assoc 1998;98:49-55. PubMed
- Shojania AM. Oral contraceptives: effect on folate and vitamin B12 metabolism. Can Med Assoc J 1982;126:244-7.
- Mooij PN, Thomas CM, Doesburg WH, Eskes TK. Multivitamin supplementation in oral contraceptive users. Contraception 1991;44:277-88. PubMed
- Barone C, Bartoloni C, Ghirlanda G, Gentiloni N. Megaloblastic anemia due to folic acid deficiency after oral contraceptives. Haematologica 1979;64:190-5.
- Butterworth CE, Hatch KD, Gore H, Mueller H, Krumdieck CL. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr 1982;35:73-82. PubMed
- Check WA. Folate for oral contraceptive users may reduce cervical cancer risk. J Am Med Assoc 1980;244:633-4. DOI
MAGNESIUM
Moderate DepletionESTROGENS
Estrogens enhance magnesium uptake by soft tissues and bones, lowering serum levels. There appears to be an inverse relationship between estrogen levels and magnesium serum levels. Estrogen therapy, including the use of oral contraceptives, lowers serum magnesium levels and can cause hypomagnesemia, which may contribute to thromboembolic complications associated with estrogens. For information on foods that are rich in magnesium, see our chart.
Magnesium helps keep your muscles working, your heart rhythm steady, and your bones strong. With conjugated estrogens and medroxyprogesterone, the estrogen component appears to push magnesium out of the bloodstream and into body tissues like bone and soft tissue, which can leave circulating levels lower than they should be. This is rated a moderate concern, meaning some people on long-term hormone therapy do end up needing extra magnesium. It is worth bringing up with your pharmacist or doctor, especially if you notice muscle cramps, fatigue, or other symptoms that might point to low levels.
What Magnesium does & food sources
Magnesium is involved in muscle and nerve function, heart rhythm, blood sugar control, and bone health.
Common food sources:
- Nuts and seeds (almonds, pumpkin seeds)
- Whole grains
- Leafy green vegetables
- Beans and legumes
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask whether a magnesium level is worth checking if you take an associated medication long-term — particularly with symptoms like muscle cramps, twitching, or palpitations. Blood levels do not always reflect total body stores, which is worth discussing too.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Magnesium supplements come in many forms and can cause loose stools at higher doses. They can also bind some medications in the gut (certain antibiotics, thyroid medication), so timing matters — check with your pharmacist.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Magnesium supplementation can be risky in kidney disease, where magnesium can accumulate — always check with a clinician first if your kidney function is reduced.
Learn more about this nutrient: Magnesium — uses, safety & interactions
References (4)
- Seelig MS. Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. Magnes Res 1990;3:197-215..
- Seelig MS. Interrelationship of magnesium and estrogen in cardiovascular and bone disorders, eclampsia, migraine, and premenstrual syndrome. J Am Coll Nutr 1993;12:442-58.. PubMed
- Muneyyirci-Delale O, Nacharaju VL, Dalloul M, et al. Serum ionized magnesium and calcium in women after menopause: inverse relation of estrogen with ionized magnesium. Fertil Steril 1999;71:869-72.. PubMed
- Stanton MF, Lowenstein FW. Serum magnesium in women during pregnancy, while taking contraceptives, and after menopause. J Am Coll Nutr 1987;6:313-9.. PubMed
This tool is educational and is not a substitute for professional medical advice. An association is not a diagnosis and does not mean a deficiency will occur. Always talk to your pharmacist or healthcare provider before starting, stopping, or changing any medication or supplement.
Disclaimer: This checker finds which nutrients might be depleted by prescription or over-the-counter medications. Each nutrient depletion issue is rated based on clinical significance. Use your own professional judgment prior to making clinical decisions.© 2026 Therapeutic Research Center Licensed records refresh weekly · last updated July 3, 2026.
More about Conjugated Estrogens, Medroxyprogesterone Acetate
What drug-induced nutrient depletion means
Some medications can, over time, lower the levels of certain vitamins, minerals, or other nutrients — through reduced absorption, increased loss, or changes in how the body uses them.
Association is not deficiency
An entry here means a depletion has been reported or studied — not that it happens to everyone, or that you are deficient. Dose, duration, diet, and your own health all matter.
Evidence varies by pair
Some drug–nutrient links (like metformin and vitamin B12) are well studied; others rest on limited or preliminary research. Each entry shows the evidence rating from our licensed clinical database.
When to ask about labs
If you take an associated medication long-term, ask your healthcare provider whether monitoring is appropriate for you. Not everyone needs testing — your provider can weigh your dose, duration, and symptoms.
Don't self-supplement blindly
Supplements are not risk-free: some can interact with medications, and some (like potassium or magnesium) can be risky with kidney disease. Talk to your pharmacist before adding anything.
Never stop a medication over this
These medications are prescribed for good reasons, and the benefit usually far outweighs a manageable nutrient consideration. Any change belongs in a conversation with your prescriber.
Food first, usually
For many nutrients, a varied diet covers the gap. Each entry lists common food sources; a supplement is a decision to make with your pharmacist or provider, not a default.
Conjugated Estrogens, Medroxyprogesterone Acetate & nutrients: FAQs
Does Conjugated Estrogens, Medroxyprogesterone Acetate deplete VITAMIN B6?
Should I take a supplement because I take Conjugated Estrogens, Medroxyprogesterone Acetate?
Should I stop taking Conjugated Estrogens, Medroxyprogesterone Acetate?
Where does this information come from?
Questions about Conjugated Estrogens, Medroxyprogesterone Acetate and your nutrition?
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Sources & How We Checked
Nutrient depletion records for Conjugated Estrogens, Medroxyprogesterone Acetate are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for drug-induced nutrient depletions, supplements, and interactions — the basis for this page.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for medication overviews across the site.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.