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MyDeficiencies

Drospirenone

progestin-only oral contraceptive, estrogen-free

Also sold as Slynd.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Single-agent drospirenone has almost none of the classical drug-nutrient depletion machinery, and it has notably less than its combination-pill sibling. The label documents no chelation, gastric-pH, or transporter-mediated absorption interference (food does not affect absorption at all), no hepatic-enzyme-induction activity attributable to drospirenone itself (it is a CYP3A4 substrate, not a described inducer or inhibitor of any CYP450 enzyme), and no renal excretion of unchanged drug (elimination is via CYP3A4-mediated metabolism to two inactive metabolites, split roughly between feces and urine, with only trace unchanged drug in either). Because this product carries no ethinyl estradiol at all, the estrogen-driven mechanisms that produced real, Tier A, drug-specific findings in this database's dossier for the drospirenone/ethinyl estradiol combination pill, elevated serum copper via hepatic ceruloplasmin synthesis, elevated lipid peroxidation and oxidized LDL, and a rise in total 25-hydroxyvitamin D via estrogen-driven binding-protein synthesis, do not have a mechanistic basis here and must not be read across from that sibling product. This dossier's Fails verification section exists specifically to block that cross-contamination.

progestin-only oral contraceptive, estrogen-free · ATC G03AC10 (drospirenone) · also sold as Slynd · reviewed 2026-09-26. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Drospirenone in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
severe: ≥2 independent Tier A sources, this drug in the cohort, the nutrient/category directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
moderate: ≥1 Tier A source with this drug in the cohort showing a real deficit or effect, but bounded by exposure window, subgroup, frequency, or a functional rather than circulating change.
Yellow — Low
low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction findings.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: evidence gap: no Tier B/C evidence exists to support even a yellow grade, and no circulating claim exists to rebut as white. A disclosed gap in the literature or in what could be accessed this review, never reworded as reassurance.

What the research found

Potassium

Orange — Moderate

Evidence in: Tier A

Drospirenone's anti-mineralocorticoid activity creates a real, directly measured, low-frequency hyperkalemia risk in the general trial population, and a labeled higher risk in females also taking other potassium-elevating drugs or with impaired renal, hepatic, or adrenal function; it is not a concern established in isolated use with normal organ function and no interacting drugs.

Full detail and limits

What the grade means here: moderate: ≥1 Tier A source with this drug in the cohort showing a real deficit or effect, but bounded by exposure window, subgroup, frequency, or a functional rather than circulating change. Excess/retention, not depletion · Tier A

Limits on what this shows

  • Key negative/null findings: In the Kimble 2020 trial's overall population, hyperkalemia was uncommon (0.5%) and uniformly mild, arguing against a large, unconditional potassium effect in women without other risk factors. No hospitalization or severe hyperkalemia was reported in this trial.
  • At-risk subgroups: Concomitant ACE inhibitors, ARBs, potassium-sparing diuretics, potassium supplements, chronic NSAID use, heparin, aldosterone antagonists, strong CYP3A4 inhibitors; renal, hepatic, or adrenal impairment (the first two are separately labeled to raise drospirenone exposure itself, the latter two are outright contraindications).
  • Counter-evidence on record: The low overall incidence and uniformly mild severity in the Kimble 2020 trial is itself the main bounding evidence against an unconditional claim. This review could not access the Archer 2015 or Palacios 2019 phase 3 trial full texts (paywalled/blocked this session, see Sources) to check whether either reports additional potassium data; they are listed for context but not used as evidentiary support here.

Regulatory status

DailyMed SLYND SPL, Section 5.1: anti-mineralocorticoid activity "comparable to a 25 mg dose of spironolactone"; recommends checking serum potassium prior to starting treatment and during the first treatment cycle in females on chronic potassium-elevating medications. Section 4 contraindicates renal impairment and adrenal insufficiency. Section 7 names ACE inhibitors, ARBs, potassium-sparing diuretics, potassium supplements, heparin, aldosterone antagonists, NSAIDs, and strong CYP3A4 inhibitors (which raise drospirenone exposure itself) as risk-compounding co-medications.

Population evidence

Kimble et al. 2020, Contraception: X: 1-year, prospective, open-label, single-arm, multicenter phase 3 trial of SLYND (drospirenone 4 mg, 24/4-day regimen), N=1,006 enrolled, median exposure 168 days, maximum 364 days. Directly measured, labeled result: 5 women (0.5%) had asymptomatic hyperkalemia, all graded mild, with no hospitalizations and outcomes resolved or unknown; a further 6 women had a single blood-potassium elevation above the reference range without meeting the hyperkalemia diagnosis threshold. Separately, the SLYND label itself gives renal-impairment PK data: CLcr 30-49 mL/min produces drospirenone concentrations approximately 37% higher than normal renal function, and moderate hepatic impairment raises exposure roughly three-fold, both plausibly compounding the potassium effect in those subgroups, though neither PK finding is itself a potassium measurement.

Mechanism

Named. Drospirenone antagonizes the mineralocorticoid (aldosterone) receptor, blunting aldosterone-mediated renal potassium excretion and sodium reabsorption. This is the identical receptor-level mechanism graded in this database's companion drospirenone/ethinyl estradiol combination-pill dossier; see the Overlap map for how this shared mechanism is disclosed rather than double-counted across the two products.

Counter-evidence held on record

This is an excess/retention risk, not a depletion. Potassium supplementation is never indicated on the basis of taking this drug and would be the hazard, not the remedy. It is not established as a concern for healthy women with normal renal, hepatic, and adrenal function who are not also taking another potassium-affecting medication.

Calcium

Yellow — Low

See study details

SLYND works primarily by suppressing ovulation, which lowers a woman's own endogenous estradiol; the label states plainly that it is unknown whether this causes clinically relevant bone mineral density loss, and no trial has directly measured serum or ionized calcium in SLYND users.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction findings. Label-flagged, unstudied at the mineral level

Limits on what this shows

  • Key negative/null findings: None located; this is precisely the evidence gap the label itself discloses ("it is unknown"). No serum calcium, PTH, or DXA data exist to confirm or refute a measurable effect.
  • At-risk subgroups: Not defined by the label. By analogy to other estradiol-suppressing mechanisms in this database (GnRH agonists/antagonists), a longer duration of use and adolescent users still accruing peak bone mass would be the plausible higher-attention subgroups, though this is not demonstrated for SLYND specifically.
  • Counter-evidence on record: A skeletal outcome (BMD loss) must not be equated with a measured calcium deficiency (Hard Rule 2); this entry's point is that the same hormonal axis plausibly touches bone/calcium handling, not that a deficiency has been demonstrated. The label's own wording ("unknown if this may cause") is itself evidence of an unresolved question rather than an established effect.

Regulatory status

DailyMed SLYND SPL, Section 5.3, verbatim: "Treatment with SLYND leads to decreased estradiol serum levels. It is unknown if this may cause a clinically relevant loss of bone mineral density." This is a labeled uncertainty, not a demonstrated deficit or a DXA finding, and it is a distinct labeling approach from the combination product, which instead carries an added, exogenous estrogen and a different (and better-characterized) bone-density profile.

Population evidence

No SLYND-specific bone mineral density trial or serum calcium measurement was located in the sources accessible this session (the Kimble 2020 trial abstract did not report BMD or calcium data; the Palacios 2019 and Archer 2015 phase 3 trial full texts could not be opened, see Sources). This entry rests on the label's own disclosed uncertainty, not on a population study.

Mechanism

Named at the hormonal-axis level (mechanism F, hormonal disturbance): suppressing ovulation removes the woman's own cyclical estradiol production, and estrogen normally restrains osteoclast-mediated bone resorption; withdrawal of that restraint is the general endocrine mechanism by which hypoestrogenic states (menopause, other GnRH-axis suppression) are associated with bone loss. This review could not independently corroborate a SLYND-specific or drospirenone-only-specific quantitative bone-turnover-marker study this session; the mechanism is stated as established general endocrinology, not tied to a citation verified this session, following the same disclosed-reasoning approach used elsewhere in this database.

Counter-evidence held on record

No calcium dose is recommended here (see Monitoring panel and Scope and limits). This is a labeled open question about bone density, not a demonstrated calcium or vitamin D deficiency, and must not be conflated with the combination product's own, differently sourced bone-density profile.

Vitamin C

Not graded — disclosed evidence gap

See study details

No drospirenone-only or progestin-only-specific vitamin C data were located.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: the only drospirenone-related vitamin C findings this review is aware of come from the combination product's own oxidative-stress study, which is estrogen-containing and excluded here per the cohort test; this review did not independently reopen or reverify that source's vitamin C data this session and does not cite it. No progestin-only vitamin C literature was located via the searches this category received. No circulating claim specific to this product was independently verified this session.

Vitamin E

Not graded — disclosed evidence gap

See study details

No drospirenone-only or progestin-only-specific vitamin E data were located.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: no Tier A/B/C source measuring vitamin E status in drospirenone-only or progestin-only users was located this session. The DMPA rat oxidative-stress study located for the Oxidative stress entry above used co-administered vitamin C and E as an intervention/protective agent rather than measuring endogenous vitamin E status, so it does not itself support a depletion claim, and in any case studies a different progestin. No circulating claim specific to this product was independently verified this session.

Vitamin B2

Not graded — disclosed evidence gap

See study details

No drospirenone-only or progestin-only-specific riboflavin data were located.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: the classical erythrocyte-glutathione-reductase riboflavin literature for oral contraceptives is old, non-drug-stratified, and (based on this database's companion combination-product review) tied to formulations that predate and differ from drospirenone; this review did not independently reopen or reverify that literature this session and does not cite it here. No progestin-only-specific riboflavin data were located via the searches this category received this session. No circulating claim specific to this product was independently verified this session.

Zinc

Not graded — disclosed evidence gap

See study details

No drospirenone-only or progestin-only-specific zinc data were located; two targeted Crossref searches for progestogen-only contraceptives and trace elements (zinc, copper, iron) returned no matching studies at all.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: two separately phrased Crossref searches this session ("progestin-only pill copper ceruloplasmin" and "progestogen-only contraceptive trace elements zinc copper serum") returned zero studies measuring zinc, copper, or iron specifically in progestogen-only contraceptive users, a genuine and, across two independent query attempts, consistent literature gap rather than a single blocked attempt. The one identified serum-copper-and-zinc study in hormonal contraceptive users (Prema et al. 1980) predates drospirenone's 2001 approval by two decades and its formulation could not be confirmed as progestin-only from bibliographic metadata alone; it is not cited as evidence here. No circulating claim specific to this product was independently verified this session.

Magnesium

Not graded — disclosed evidence gap

See study details

No drospirenone-only or progestin-only-specific magnesium data were located, and the label's only mineral-adjacent content is the electrolyte-monitoring guidance for potassium, which does not mention magnesium.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: no Tier A/B/C source measuring magnesium status in drospirenone-only or progestin-only users was located this session. No circulating claim specific to this product was independently verified this session, though a generic "the pill depletes magnesium" claim is common in consumer wellness content generally.

Selenium

Not graded — disclosed evidence gap

See study details

No drospirenone-only or progestin-only-specific selenium data were located.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: no Tier A/B/C source measuring selenium status in drospirenone-only or progestin-only users was located this session. No circulating claim specific to this product was independently verified this session.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

No entry in this dossier measured mitochondrial capacity for this medication. That is a documented gap, not a finding of safety.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress

Yellow — Low

Evidence in: Tier B, different progestin

No human data exist for drospirenone in any formulation regarding oxidative stress outside the estrogen-containing combination product; a rat model using a different progestin (medroxyprogesterone acetate) found ovarian oxidative stress that vitamins C and E mitigated, offering weak, cross-molecule mechanistic plausibility only.

Full detail, limits and 2 references

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction findings. Yellow · Tier B, different progestin, animal model

Limits on what this shows

  • Key negative/null findings: None located specific to drospirenone; the entire evidence base for this entry is one animal study of a different molecule.
  • At-risk subgroups: Not established for any human population on any drospirenone-containing product.
  • Counter-evidence on record: The De Groote 2009 combination-product oxidative-stress signal (lipid peroxidation, oxidized LDL) is not evidence for this product: its own authors and this review's own reading of its title attribute the effect to the combined estrogen/progestin exposure, and single-agent drospirenone contains no estrogen. This distinction is the central reason this entry is graded a cautious yellow rather than reused at orange from the sibling dossier.

Regulatory status

Not addressed in the SLYND label.

Population evidence

Ismiyati, Wiyasa & Hidayati, 2016, Journal of Toxicology, DOI 10.1155/2016/3134105, PMID 26966434: rat model, depot medroxyprogesterone acetate (DMPA), a different progestin from drospirenone, examining ovarian oxidative stress and a protective effect of co-administered vitamins C and E. The full text was blocked (403) at the publisher this session, so this review could confirm only the bibliographic record and the summary description via Crossref metadata (species, drug, and general finding direction); specific marker values (e.g., malondialdehyde, superoxide dismutase levels) could not be independently verified and are not asserted here. The only drospirenone-specific oxidative-stress literature located (De Groote et al. 2009, Contraception, PMID 19631796, "Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress") studied the combination formulation (0.03 mg ethinylestradiol plus 3 mg drospirenone), confirmed by its own title, and is excluded as evidence for this single-agent product per the cohort test.

Mechanism

Plausible only, and only by extrapolation across both drug class (progestin) and species (rat, not human): synthetic progestins acting on ovarian tissue could theoretically generate reactive oxygen species independent of any estrogen co-exposure, which is the reasoning that would let a DMPA finding say anything at all about a different progestin like drospirenone. No mechanism specific to drospirenone's own chemistry was located.

Counter-evidence held on record

This is a cross-molecule, cross-species theoretical signal only, not evidence that drospirenone-only use raises oxidative stress in women. It is not grounds for antioxidant supplementation, and it must not be confused with the combination product's own, human, drospirenone-specific (but estrogen-driven) oxidative-stress finding, which does not apply to this estrogen-free product.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron

Not graded — disclosed evidence gap

See study details

No study directly measured ferritin, hemoglobin, or transferrin saturation in drospirenone-only users, and this product's bleeding profile does not establish the same reduced-blood-loss story documented for combined pills.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: no Tier A/B/C source measuring an iron marker in SLYND users was located, and no circulating claim specific to this product was independently verified. Unlike the combination product, where reduced menstrual blood loss under stable anovulation plausibly improves iron balance, SLYND's own phase 3 safety data (Kimble et al. 2020) reported metrorrhagia (irregular bleeding) as a common adverse event in 5.3% of 1,006 women, which does not by itself establish a reliable reduction in total blood loss the way the combination product's labeled bleeding data do. This review explicitly declines to extrapolate the combination product's iron-related finding to this drug; see the headline finding and the companion dossier's own bounded framing of that result. The Palacios 2019 and Archer 2015 phase 3 trial full texts, which might contain amenorrhea-rate or hemoglobin data, could not be opened this session (Wiley 403, PMC bot-verification, no open-access copy for the Contraception paper), disclosed as a tooling limitation rather than a confirmed absence of such data.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Yellow — Low

See study details

No drospirenone-specific or progestin-only-specific microbiome data exist. The one class-level longitudinal study this review could independently open found no change in gut microbial diversity or composition after oral contraceptive initiation, with only minor shifts in specific bacterial biosynthesis pathways.

Full detail, limits and 1 references

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction findings. Yellow · Tier C, formulation unspecified, mostly null

Limits on what this shows

  • Key negative/null findings: The null finding on diversity and composition is itself the main and most valuable result located for this category.
  • At-risk subgroups: None established.
  • Counter-evidence on record: None found contradicting this direction; the main limitation is that the source's formulation could not be confirmed as drospirenone-only, so this is class-level, Tier C evidence at best for this specific product.

Regulatory status

Not addressed in the SLYND label.

Population evidence

Hua et al. 2022, Journal of Medical Microbiology, DOI 10.1099/jmm.0.001512: longitudinal study, 10 healthy women, three timepoints (baseline, 1 month, and 6 months after oral contraceptive initiation); the formulation used was not specified in the accessible text, so this cannot be confirmed as drospirenone or even as progestin-only versus combined. Verbatim finding: "We observed no changes in the diversity or composition of the gut microbiome following OC initiation." Increases were detected in specific biosynthesis pathways (peptidoglycan and the amino acids lysine, threonine, methionine, and tryptophan) and the NAD salvage pathway; higher estradiol and SHBG correlated with a flavonoid-degrading bacterium, Eubacterium ramulus.

Mechanism

Plausible in theory only (mechanism class G; the "estrobolome" concept holds that gut bacteria influence estrogen recirculation), but the one study located tests whether the drug changes the microbiome and mostly finds that it does not. Because this entry's source's formulation is unconfirmed, and because SLYND itself adds no exogenous estrogen (it suppresses the woman's own estradiol instead), the estrobolome mechanism is, if anything, less applicable here than to an estrogen-containing product.

Counter-evidence held on record

The popular "birth control disrupts your gut microbiome" claim is not well supported for hormonal contraceptives generally in the one study located, and has no drospirenone-only-specific data in either direction.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization

Not graded — disclosed evidence gap

See study details

No hemoglobin, hematocrit, or oxygen-carrying-capacity data specific to drospirenone-only use were located in the sources this review could open.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: the Kimble et al. 2020 trial states that "hematology, serum biochemistry and urinalysis" were assessed as part of standard safety labs, but the accessible summary of that trial did not report specific hemoglobin, hematocrit, or anemia findings, so this review cannot confirm either a positive or a null result from it. No other Tier A/B/C source, and no independently verified circulating claim, was located for this category. This is a disclosed gap in what could be extracted from the accessible source, not a confirmed null finding, and not a finding of safety.

ATP production

Not graded — disclosed evidence gap

See study details

No study has measured ATP production or cellular energy output in users of drospirenone in any formulation, or in progestin-only contraceptive users generally.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Evidence gap

Limits on what this shows

  • Why no grade: Dual condition met: repeated PubMed searches (progestin plus mitochondrial function/ATP) returned only unrelated basic-science literature on progesterone's role in steroidogenic ATP synthesis within ovarian and testicular cells, none of which measures a contraceptive drug's effect on ATP production in a treated population. No circulating consumer claim specific to this product was independently verified this session (a generic "birth control drains your energy" claim is common in consumer wellness content, but this review could not independently open a specific source making that claim for drospirenone or progestin-only pills this session, so it is not rebutted as white here). A fatigue adverse-event listing, if present on the label, would be a symptom report, not a bioenergetic measurement, and is not treated as evidence either way.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Mitochondrial burden (liver mitochondrial activity claim)

    Where it comes from: Jonderko et al. 2013, "Combined oral contraceptives affect liver mitochondrial activity" (Eur J Contracept Reprod Health Care), is the one candidate source this dossier's original review identified for this category. A reader could reasonably, but incorrectly, read its title alone as evidence that any drospirenone-containing product affects liver mitochondrial activity.

    Why it fails: Re-opened on revision via OpenAlex abstract reconstruction and Crossref metadata (the publisher page and PubMed remained blocked, and Unpaywall confirms no open-access copy exists). The reconstructed abstract shows the study cohort was women on combined oral contraceptives containing ethinylestradiol, tested by a ¹³C-alpha-ketoisocaproic-acid breath test during active pill use versus withdrawal bleeding (26.8±1.6%/h vs. 23.5±1.2%/h, p=0.012); no drospirenone-only or progestin-only arm was studied, and the authors' own stated conclusion is that "metabolism of ethinylestradiol augments liver mitochondrial metabolic activity," an estrogen-specific mechanism. Single-agent SLYND contains no ethinyl estradiol or any exogenous estrogen, so the documented mechanism is ruled out by this product's own chemistry, not merely differing in degree. Separately, dedicated Crossref searches this revision for drospirenone-and-mitochondria and for medroxyprogesterone-acetate-and-mitochondrial (the same proxy progestin used in the Oxidative stress entry above) returned no studies of any tier connecting a progestin itself to mitochondrial structure or function; the only progestin-mitochondria literature located anywhere concerns endogenous progesterone's role in steroidogenic mitochondria (ovarian/testicular steroid synthesis), which is not a contraceptive-effect finding. No progestin-specific mechanism or evidence therefore supports this category at any tier either.

  • Copper (elevation claim)

    Where it comes from: This database's own companion dossier for the drospirenone/ethinyl estradiol combination pill documents a real, Tier A, roughly two-fold serum copper elevation (De Groote et al. 2009), attributed by that study to estrogen-driven hepatic ceruloplasmin synthesis. A reader could reasonably, but incorrectly, extend that finding to any product containing the word "drospirenone."

    Why it fails: Single-agent SLYND contains no ethinyl estradiol or any other exogenous estrogen (confirmed directly from the DailyMed label, Section 12.3, this session). The proposed mechanism for the combination product's copper finding is specifically estrogen-driven carrier-protein synthesis, not a drospirenone effect; two independent Crossref searches this session for progestogen-only contraceptives and copper/trace elements returned no supporting studies at any tier for an estrogen-free product.

  • Vitamin D (total 25(OH)D elevation claim)

    Where it comes from: Same origin risk as copper: the combination-pill literature this database is aware of (from the companion dossier) attributes a total-25(OH)D rise in estrogen-containing contraceptive users to estrogen-driven vitamin-D-binding-globulin synthesis, a mechanism this review did not reopen or reverify this session and does not cite directly.

    Why it fails: The mechanism, as understood in general endocrine physiology, requires estrogen exposure to drive hepatic binding-protein synthesis; single-agent drospirenone provides no such exposure (it lowers, rather than adds, circulating estradiol, per Section 5.3 of its own label). No drospirenone-only or progestin-only vitamin D study was located to support this claim at any tier.

  • Folate

    Where it comes from: A long-standing, generic "oral contraceptives deplete folate" consumer and older-literature claim, historically attributed to high-dose-estrogen-driven hepatic enzyme induction accelerating folate catabolism.

    Why it fails: Single-agent drospirenone is confirmed, directly from its own label (Section 12.3), to have no described CYP450 induction activity at all; it is a CYP3A4 substrate only. The proposed mechanism (mechanism class B, hepatic enzyme induction) is absent by this drug's own pharmacokinetics, and no drospirenone-only-specific folate study was located to support the claim independent of that mechanism.

  • Vitamin B6

    Where it comes from: A long-standing, generic "oral contraceptives deplete B6" consumer and older-literature claim, historically attributed to ethinyl estradiol metabolites competitively inhibiting pyridoxal kinase.

    Why it fails: Single-agent drospirenone contains no ethinyl estradiol or any estrogen metabolite; the proposed mechanism requires a molecule this product does not contain. No drospirenone-only-specific vitamin B6 study was located to support the claim independent of that mechanism.

  • Vitamin B12

    Where it comes from: A generic "oral contraceptives deplete B12" consumer claim.

    Why it fails: This claim is contested even for combination, estrogen-containing oral contraceptives in more rigorous recent reviews (per this database's own companion dossier, which grades it fails-verification for that product too); with no estrogen component and no drospirenone-only evidence located at any tier this session, it fails a fortiori for this estrogen-free product.

All references used above
  1. DailyMed. SLYND (drospirenone) tablets, prescribing information. — Exeltis USA, Inc. Structured Product Label, setid db32bc55-f295-4d87-9dbb-0a2f45573dcf, labeling last updated 2026-08-27. Sections used: 4 (Contraindications), 5.1 (Hyperkalemia), 5.3 (Bone loss), 7 (Drug interactions), 8.1 (Pregnancy), 8.2 (Lactation), 8.4 (Pediatric use), 12.1-12.3 (Pharmacology/PK).
  2. Kimble T, Burke AE, Barnhart KT, Archer DF, Colli E, Westhoff CL. A 1-year prospective, open-label, single-arm, multicenter, phase 3 trial of the contraceptive efficacy and safety of the oral progestin-only pill drospirenone 4 mg using a 24/4-day regimen. — Contraception: X. 2020;2:100020. N=1,006. Directly measured hyperkalemia incidence (0.5%) and adverse-event profile used in the Potassium entry.
  3. Palacios S, Colli E, Regidor PA. Multicenter, phase III trials on the contraceptive efficacy, tolerability and safety of a new drospirenone-only pill. — Acta Obstet Gynecol Scand. 2019;98(12):1549-1557. DOI 10.1111/aogs.13688. PMC7186823.Full text blocked this session (Wiley 403; PMC bot-verification page). Bibliographic record only; not cited as evidentiary support.
  4. Archer DF, Ahrendt HJ, Drouin D. Drospirenone-only oral contraceptive: results from a multicenter noncomparative trial of efficacy, safety and tolerability. — Contraception. 2015;92(5):439-444. DOI 10.1016/j.contraception.2015.07.014.No open-access copy (confirmed via Unpaywall); PubMed abstract page blocked by bot-verification this session. Bibliographic record only; not cited as evidentiary support.
  5. Ismiyati A, Wiyasa IW, Hidayati DY. Protective Effect of Vitamins C and E on Depot-Medroxyprogesterone Acetate-Induced Ovarian Oxidative Stress In Vivo. — Journal of Toxicology. 2016;2016:3134105. PMID 26966434. Rat model; a different progestin (medroxyprogesterone acetate) from drospirenone.Full text blocked this session (Hindawi 403). Species, drug, and general finding direction confirmed via Crossref bibliographic metadata only; specific marker values not verified and not asserted.
  6. De Groote D, et al. Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old. — Contraception. 2009. PMID 19631796. Combination formulation (0.03 mg ethinylestradiol + 3 mg drospirenone).Cohort excludes this single-agent product by the study's own title; used only to confirm this is combination-formulation evidence, not reopened for its numeric findings this session.
  7. Hua X, et al. [Oral contraceptive use and gut microbiome, longitudinal study]. — Journal of Medical Microbiology. 2022. DOI 10.1099/jmm.0.001512. N=10, formulation not specified. Verbatim finding: "We observed no changes in the diversity or composition of the gut microbiome following OC initiation."
  8. Jonderko K, Skalba P, Kaminska M, Kasicka-Jonderko A, Galas E, Bialy A. Combined oral contraceptives affect liver mitochondrial activity. — Eur J Contracept Reprod Health Care. 2013;18(5):401-409. DOI 10.3109/13625187.2013.819847. N not stated in the retrieved abstract; ¹³C-alpha-ketoisocaproic-acid/L-leucine breath test comparing active combined-pill use, pill-free withdrawal bleeding, and a regularly-menstruating control group. Cited by 2 other works per OpenAlex.Full text remains paywalled this session (publisher page 403; no open-access copy per Unpaywall; PubMed abstract page bot-blocked). On revision, its abstract was retrieved via OpenAlex abstract-index reconstruction and its bibliographic detail via Crossref, confirming the studied cohort was combined oral contraceptives containing ethinylestradiol, not drospirenone or any progestin-only product, and that the reported effect is attributed by the authors to ethinylestradiol metabolism specifically. Cited here only to support the Mitochondrial burden fails-verification rebuttal; not cited as evidence of any drospirenone-specific effect.
  9. Prema K, et al. Serum Copper and Zinc in Hormonal Contraceptive Users. — 1980. Identified via Crossref bibliographic search only.Not opened this session; predates drospirenone's 2001 FDA approval, so this drug could not have been in the studied cohort; formulation otherwise unconfirmed. Not cited as evidentiary support.
  10. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index: G03AC10, drospirenone. — Anatomical Therapeutic Chemical classification, progestogens (G03AC) category.