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Vaginal DHEA (Prasterone)

Vaginal DHEA (prasterone / Intrarosa) is an FDA-approved intravaginal steroid for moderate-to-severe dyspareunia due to menopause. Unlike vaginal estrogen, prasterone is converted within vaginal tissue to both androgens and estrogens; the clinical contribution of each pathway is not fully established, and systemic estradiol and testosterone exposure is low but measurable.[1][2][3] A placebo-controlled analysis reported improvement across all six FSFI domains, including desire and arousal; vaginal estrogen was not the comparator.[4]

For related agents, see Vaginal and topical estrogen, Ospemifene, and Preoperative hormonal priming. For the clinical framework, see GSM.

Mechanism — the science of intracrinology​

Prasterone (synthetic DHEA) undergoes intracrine conversion from an inactive precursor to active androgens and estrogens within vaginal cells, followed in part by local inactivation; small rises in circulating estradiol and testosterone are measured after dosing.[2][3]

Enzymatic cascade within vaginal tissue:[5][2]

  1. DHEA to androstenedione (3β-HSD1/HSD2)
  2. Androstenedione to testosterone (17β-HSD3/HSD5)
  3. Testosterone to DHT (5α-reductase isoforms)
  4. Androstenedione to estrone to estradiol (aromatase and 17β-HSD)
  5. Active steroids to glucuronide or sulfate conjugates (UGT and SULT), released as inactive metabolites

Cellai 2021 confirmed the human vagina as an androgen-target organ: DHEA supplementation of human vaginal smooth-muscle cells increased androstenedione, testosterone, and DHT secretion and activated AR-dependent gene expression.[5]

Clinical consequence: after menopause, ovarian estrogen production ceases, and DHEA (the remaining endogenous androgen-estrogen precursor) declines progressively from about age 30. Placebo-controlled trials found improvements in vaginal epithelial maturation, pH, dyspareunia and sexual-function questionnaire scores, including lubrication with intravaginal DHEA.[1][4] Clinical muscularis support and increased vaginal blood flow were not measured; the cited mechanistic and sexual-function studies did not compare clinical outcomes with vaginal estrogen.[2][5][6]

FDA-approved indication and dosing​

ElementDetails
BrandIntrarosa[3]
US indicationModerate-to-severe dyspareunia — a symptom of vulvar and vaginal atrophy due to menopause
EU indicationTreatment of VVA in postmenopausal women with moderate-to-severe symptoms (broader than US)[8]
DoseOne vaginal insert (6.5 mg prasterone) once daily at bedtime via the provided applicator[3]
Loading / taperNone
ProgestogenNot required for endometrial protection; endometrial data extend to about 1 year[7]
US contraindicationUndiagnosed abnormal genital bleeding.[3]
EU contraindicationsHypersensitivity; undiagnosed genital bleeding; known, past, or suspected breast cancer; known or suspected estrogen-dependent malignancy; untreated endometrial hyperplasia; acute liver disease or prior liver disease with tests not normalized; current or previous VTE or thrombophilia; active or recent arterial thromboembolic disease; porphyria.[29]
Label warningEstrogen is a metabolite of prasterone; exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer; Intrarosa has not been studied in women with a history of breast cancer[3]
PediatricSafety not established
Hepatic / renal impairmentEffect on PK not studied; 19% of prasterone-treated participants in four 12-week trials and 11% in the 52-week open-label trial were ≥65 y[3]

Pivotal clinical trials​

Approval rested on two Phase III placebo-controlled RCTs (ERC-231, ERC-238) plus the 52-week open-label safety trial ERC-230.[3][8] Both RCTs met all four coprimary endpoints.

ERC-238 coprimary endpoints (n = 482 ITT, 12 weeks)[1]​

EndpointEffect over placebop
Parabasal cells (%)↓ 27.7%<0.0001
Superficial cells (%)↑ 8.44%<0.0001
Vaginal pH↓ 0.66 units<0.0001
Dyspareunia severity↓ 0.36 units over placebo (−1.42 from baseline)0.0002
Vaginal dryness (key secondary)↓ 0.27 units over placebo (−1.44 from baseline)0.004

On gynecologic evaluation, vaginal secretions, epithelial integrity, surface thickness, and color all improved 86–121% over the placebo effect (p < 0.0001).[1]

ERC-231 (Archer 2015, 12 weeks) was smaller and showed a different effect profile: parabasal cells ↓45.8%, superficial cells ↑4.7%, pH ↓0.83, dyspareunia severity ↓46% over placebo (p = 0.013), dryness ↓0.43 units (p = 0.013).[23]

2026 meta-analysis — Lemos​

Systematic review and meta-analysis of 6 RCTs (5 unique; n = 1,611):[9]

  • Vaginal dryness: MD −0.23 (95% CI −0.35 to −0.11) versus placebo[9]
  • Dyspareunia: MD −0.40 (95% CI −0.66 to −0.15) versus placebo[9]
  • In the short-term RCTs reviewed, reported AEs were generally mild and infrequent, with no major safety signal detected; the trials were too short and underpowered to assess infrequent serious harms.[9][15]
  • Low-to-moderate heterogeneity

Sexual function — placebo-controlled FSFI findings​

The ERC-238 cohort underwent a secondary FSFI analysis at 12 weeks: all six domain comparisons nominally favored prasterone over placebo, but the P values were not adjusted for multiplicity. Total-score and satisfaction analyses included 300 prasterone and 149 placebo participants; the other domains included 325 and 157, respectively.[4][35]

FSFI domainImprovement vs placebop
Desire+49.0%0.0105
Arousal+56.8%0.0022
Lubrication+36.1%0.0005
Orgasm+33.0%0.047
Satisfaction+48.3%0.0012
Pain+39.2%0.001
Total FSFI+41.3%0.0006

An earlier dose-finding Phase III (Labrie 2009, n = 216) showed dose-dependent improvements in arousal or sensation (+68%, p = 0.006), arousal or lubrication (+39%, p = 0.0014), orgasm (+75%, p = 0.047), and dryness during intercourse (−57%, p = 0.0001) with the 1.0% DHEA dose.[6]

Local androgenic activity is a proposed explanation for the desire and arousal findings.[4][6] The trials do not isolate that mechanism.[4][6]

Systemic exposure and its limits​

LC-MS/MS serum steroid analyses after 12 weeks of 6.5 mg daily (Ke 2015, one trial; Martel 2016, integrated n = 723 DHEA + n = 266 placebo):[10][11]

Steroid12-wk level on DHEANormal postmenopausal valueInterpretation
Estradiol (E2)3.26 pg/mL (single trial)[10]; 3.36 pg/mL (integrated analysis)[11]4.17 pg/mL (postmenopausal reference mean)22% and 19% below that mean, respectively, at week 12; within the reported reference range
Estrone sulfate (E1-S)209–219 pg/mL220 pg/mLSuperimposable
TestosteroneSlightly ↑Within postmenopausal rangeLowest half of the range
DHEA-S↑ (dose-dependent)Within postmenopausal range—
ADT-G (androgen metabolite)Within rangeNormal postmenopausalNo excess androgenic activity

The current label reports mean trough increases from baseline of 47% for prasterone, 21% for testosterone and 19% for estradiol after 12 weeks; it cautions that trough comparisons may underestimate total exposure because they omit the concentration–time profile.[3]

In cancer survivors — NCCTG N10C1 (Alliance)​

Barton 2018 studied an investigational compounded vaginal DHEA gel, not the marketed prasterone insert, against its plain-gel moisturizer vehicle in women with a breast or gynecologic cancer history (n = 345 with evaluable blood samples; 12 weeks): 3.25 mg versus 6.5 mg DHEA versus vehicle.[12]

  • DHEA-S and testosterone rose dose-dependently but stayed in the lowest half or quartile of the postmenopausal range
  • Estradiol increased with 6.5 mg (p < 0.05) but not with 3.25 mg (p = 0.05).[12]
  • Estrogen concentrations did not change in the aromatase-inhibitor subgroup during this study; long-term breast-cancer safety was not assessed
  • Biomarkers of bone formation unchanged in all arms
  • In the evaluable cytology subset (n = 46; 14, 17, and 15 women by arm), conversion from no intermediate/superficial cells at baseline to some at 12 weeks was reported in 100% (3.25 mg), 86% (6.5 mg), and 64% (vehicle); exact eligible denominators for these conditional percentages were not supplied, and between-arm differences were not statistically tested.[12]

Among 464 women randomized in NCCTG N10C1, neither dose of investigational compounded vaginal DHEA gel differed significantly from plain-gel moisturizer on the prespecified most-bothersome dryness-or-dyspareunia score at 12 weeks; the 6.5 mg dose improved FSFI sexual-health scores. Among 353 self-report adverse-effect respondents, small worsening of voice changes occurred in both DHEA groups and of headache in the 3.25 mg group, while clinician-graded toxicities did not differ.[32] These findings do not override the Intrarosa label warning or establish efficacy of the marketed insert or breast-cancer recurrence safety in AI users.

Comparison with vaginal estrogen​

Archer 2017 indirect cross-trial comparison of prasterone 6.5 mg versus CEE 0.3 mg versus estradiol 10 µg:[13]

OutcomePrasterone 6.5 mgCEE 0.3 mgEstradiol 10 µg
Dyspareunia — total Δ from baseline1.27–1.631.41.23
Dyspareunia — Δ over placebo0.35–1.210.7–1.00.33
Dryness — total Δ from baseline1.44–1.581.11.23
Dryness — Δ over placebo0.30–0.430.400.33

Authors: prasterone "appears to be at least as efficacious as 0.3 mg CEE or 10 µg estradiol" for VVA symptoms.[13] A 2023 JAMA review estimated subjective GSM symptom severity improvements of 60–80% with vaginal estrogen, 40–80% with prasterone, and 30–50% with oral ospemifene.[14]

Features to discuss when choosing between treatments​

  • All six FSFI domains improve including desire and arousal[4]
  • Vaginal smooth-muscle cells convert DHEA to androgens in vitro.[5][6]
  • In the steroid-analysis subset excluding participants with a serum signature of exogenous estrogen use, mean serum E2 rose from 2.72 pg/mL at baseline to 3.26 pg/mL at 12 weeks; the latter was below the untreated postmenopausal reference mean of 4.17 pg/mL and within its 1.0–9.27 pg/mL 5th–95th-percentile range.[10]
  • Comparative safety in AI users is unproven[12]

Disadvantages vs vaginal estrogen​

  • Daily dosing (versus 2×/wk inserts or 90-day ring)
  • Vaginal discharge from melting vehicle: 5.71% (38/665) across four 12-week trials and 14.2% (74/521) in a 52-week open-label trial[1][3]
  • More expensive; no generic
  • UTI-prevention efficacy is unproven. A matched retrospective claims cohort associated prasterone exposure for at least 12 weeks with fewer coded UTIs than no prescribed VVA treatment.[25] Vaginal estrogen reduced rUTIs in a meta-analysis of randomized trials (RR 0.42; 95% CI 0.30–0.59) and has a 2025 AUA/SUFU/AUGS Moderate Recommendation (Grade B) for patients with GSM and rUTI.[21][22]
  • Direct comparative evidence is limited.[15] In one open-label, 12-week RCT (n = 172), at least one-point dyspareunia improvement was 92% with DHEA versus 82% with 10 µg estradiol (overall p = 0.051); vaginal pH and maturation favored estradiol.[24] DHEA was reduced to twice weekly after four weeks, unlike the US-label nightly schedule.[3][24]

See Vaginal and topical estrogen for the rUTI data.

Adverse effects and safety​

Short-term (pooled 4 RCTs, n = 665 DHEA + n = 464 placebo)[3]​

Only AE with ≥2% incidence and greater than placebo: vaginal discharge 5.71% (DHEA) versus 3.66% (placebo); trial authors attributed application-site discharge to melting of the suppository vehicle at body temperature.[1][3]

Long-term (52-wk open-label ERC-230, n = 521)[8][3]​

  • Vaginal discharge: 14.2% (74/521)[3]
  • Abnormal Pap: 2.1% (11/521); 10 ASCUS, 1 LSIL[3]
  • No endometrial hyperplasia or carcinoma was reported in the 52-week open-label trial. In the FDA review of 422 end-of-trial biopsy assessments, one showed disordered proliferative endometrium; the reviewer did not consider this a safety concern. Endometrial safety beyond one year remains unstudied.[7][26]
  • In ERC-230, mean serum DHEA, testosterone, estrone and estrone sulfate increased from baseline at weeks 26 and 52, while estradiol decreased; the FDA reviewer called the systemic changes minimal and the measured concentrations remained within reported postmenopausal reference ranges.[26]
  • In ERC-230, one invasive breast carcinoma was considered possibly treatment-related by the investigator; the FDA reviewer could not rule out a contribution but found no overall serious-adverse-event safety signal across the 6.5 mg development program.[26]

Androgenic side effects​

Cochrane review of DHEA (all routes) found an association with androgenic AEs, mainly acne (OR 3.77; 95% CI 1.36–10.4; p = 0.01), but the pooled trials used oral or transdermal DHEA; none tested the intravaginal insert, and the label lists no androgenic adverse reaction for it.[16][3]

Endometrial safety​

No progestogen required; no hyperplasia in 52-wk data. The cited 52-week safety study was open-label, and long-term safety beyond this window is not established. Patients must be counseled to report any vaginal bleeding promptly.[14]

Use in breast cancer survivors​

The most nuanced clinical question. The US label warns about breast-cancer history, AUA/SUFU/AUGS 2025 allows multidisciplinary shared decision-making for survivors, and a 2026 Dana-Farber breast-oncology consensus finds safety data insufficient to recommend vaginal DHEA in this population.[3][22][36]

SourcePosition
FDA labelEstrogen is a metabolite; use of exogenous estrogen is contraindicated in women with known/suspected breast cancer; Intrarosa has not been studied in this population[3]
ACOG 2021 clinical consensusDHEA or vaginal testosterone may be considered when vaginal estrogen is not an option[17]
AUA/SUFU/AUGS 2025Clinicians should counsel that vaginal DHEA does not increase breast-cancer risk . The guideline text says clinicians may recommend vaginal DHEA in multidisciplinary shared decision-making for patients with a breast-cancer history, noting little data in this group; its discussion reports a small serum estradiol increase within the menopausal range but also says DHEA is not associated with increased circulating estradiol; the US label reports a 19% rise in mean trough estradiol after 12 weeks[22][3]
NAMS 2020Vaginal DHEA is not contraindicated in breast-cancer survivors, but US labeling advises caution because estrogen is a metabolite; it has not been studied in this group, and estradiol and testosterone stay within postmenopausal ranges. Vaginal estrogen or DHEA may be considered when GSM persists after nonhormonal trials (Level C)[7]
NCCN Survivorship 2026Listed among "other topical hormones" for vaginal dryness; "limited data regarding the use of androgen therapy in survivors of hormonally mediated cancers"; "more information needed … particularly for breast cancer survivors on AIs"[18]
NCCN Breast Cancer Risk Reduction 2026"Consider avoiding bioidentical hormones or DHEA" in women on risk-reducing agents[19]

VIBRA pilot — Mension 2022​

10 breast cancer survivors on AIs, 6 months of vaginal prasterone (nightly for month 1, then every second night):[20]

  • Mean serum E2 3.4 to 4.3 pg/mL (p = 0.91, not significant)
  • Dyspareunia VAS 8.5 to 0.4 (p = 0.018)
  • VHI 9.75 to 15.8 (p = 0.028)
  • FSFI 11.2 to 20.6 (p = 0.028)
  • Vaginal pH 8.1 to 6.5 (p = 0.033)

Pharmacologic rationale in AI users​

Aromatase inhibition offers a mechanistic rationale for lower estrogen conversion. NCCTG and the 10-patient VIBRA pilot provide short-term biochemical and symptom observations, not breast-cancer recurrence endpoints.[12][20]

Clinical implication​

The 2025 AUA/SUFU/AUGS GSM guideline finds local low-dose vaginal estrogen has the strongest evidence, but too little evidence to favor one hormonal therapy over another and does not support a required stepwise sequence; AUA/SUFU/AUGS 2025 recommends that clinicians offer vaginal DHEA to patients with GSM for dryness and/or dyspareunia ; the 2020 NAMS position statement lists vaginal DHEA among effective treatments for moderate-to-severe GSM (Level A).[22][7] For individuals with a history of estrogen-dependent breast cancer whose symptoms persist after nonhormonal treatment, ACOG considers vaginal DHEA when vaginal estrogen is not an option.[17] Explain the FDA warning, limited long-term cancer data and lack of proven comparative safety in AI users; involve oncology in the decision.[3][17]

Practical prescribing​

ParameterRecommendation
Ideal candidatePostmenopausal woman with moderate-to-severe dyspareunia who prefers a daily vaginal option; prasterone is a hormone precursor that forms estrogen and androgen metabolites[1]
Dose6.5 mg vaginal insert nightly at bedtime[3]
OnsetImprovement was observed by 6 weeks in the placebo-controlled trial; assess response at 12 weeks. In the open-label study, women with moderate-to-severe dyspareunia as their most bothersome symptom at baseline (n = 183) had a further 0.33-unit reduction in dyspareunia severity from weeks 12 to 52.[1][27]
DurationNo fixed US-label course; GSM is chronic and symptoms may recur after treatment stops. Reassess response, tolerability, and bleeding during continued use; EU labeling calls for benefit/risk reassessment at least every 6 months. Endometrial data extend to about 1 year.[3][7][22][29]
ProgestogenNot required[7]
MonitoringThe Intrarosa label does not specify routine serum hormone monitoring.[3] AUA/SUFU/AUGS advises no endometrial surveillance solely for vaginal DHEA use ; evaluate any postmenopausal bleeding.[14][22]
Patient counselingVaginal discharge attributed to the melting vehicle occurred in 5.71% (38/665) across four 12-week trials and 14.2% (74/521) in a 52-week open-label trial; a panty liner may help if bothersome.[1][3]
Breast cancer survivorsMay be discussed when vaginal estrogen is not an option; oncology involvement and explicit cancer-safety uncertainty[17][20]
CostBrand-name only (~$200–300/month without insurance); no generic
StorageStore at 5–30 °C; room temperature or refrigeration are permitted[3]

Comparative summary — DHEA vs vaginal estrogen vs ospemifene​

FeatureVaginal DHEA (prasterone)Vaginal estrogenOspemifene (oral SERM)
Regulatory indicationsUS: moderate-to-severe dyspareunia due to menopause; EU: VVA in postmenopausal women with moderate-to-severe symptoms[3][29]Product-specific, e.g., atrophic vaginitis (Vagifem) or moderate-to-severe dyspareunia (Imvexxy)[30][31]Moderate-to-severe dyspareunia or vaginal dryness due to menopause[28]
MechanismIntracrine → androgens + estrogensDirect estrogenicOral SERM (vaginal agonist)
Dosing frequencyDaily2×/wk or 90-day ringDaily oral
FSFI findings at 12 weeksAll six domains favored prasterone versus placebo in a secondary analysis[4]Estradiol softgel improved pain and lubrication at 10 and 25 µg, and arousal and satisfaction at 25 µg, versus placebo[33]All six domains improved versus placebo in one ospemifene trial[34]
UTI preventionMatched claims association only; no randomized prevention trial[25]Strong evidence (RR 0.42)[21]Not studied
Systemic exposureLow, but estrogen/testosterone metabolites can increaseUsually low with local low-dose products; formulation-dependentSystemic SERM; not an estradiol preparation
Progestogen neededNoNo (low dose)No
Breast cancer survivorsUS: label warning, limited data, and oncology discussion; EU: known, past, or suspected breast cancer is a contraindication[3][29]Consider local low-dose therapy after nonhormonal options through shared decision-makingUS label advises against use with known/suspected or prior breast cancer[28]
Main AEVaginal discharge: 5.71% at 12 weeks (38/665); 14.2% in a 52-week open-label trial (74/521)[3]Discharge / irritationHot flush: 6.5% at 12 weeks; 12.2% in trials up to 52 weeks[28]
Generic?NoYes (most)FDA-approved 60 mg equivalent (2024)[37]
Subjective GSM symptom severity improvement40–80%[14]60–80%30–50%

Evidence Summary​

DomainEvidence levelKey source
Dyspareunia efficacyShort-term placebo-controlled RCTs; low certainty in the 2024 systematic review[15]Labrie 2018 pivotal[1]; Lemos 2026 meta[9]
All-FSFI-domain sexual functionERC-238 secondary analysis at 12 weeks; nominal domain P valuesLabrie 2015[4]; earlier sexual-function dose-finding trial, Labrie 2009[6]; CADTH ERC-238 review[35]
Systemic absorption / safetyLevel 1 (pharmacology studies)Ke 2015[10]; Martel 2016[11]
Safety through 52 weeksOpen-label ERC-230 cohort (n = 521 treated)Heo 2019 review[8]; FDA clinical review[26]
Breast cancer survivors — pharmacologyLevel 2NCCTG Barton 2018[12]; VIBRA 2022[20]
Indirect comparison vs vaginal estrogenLevel 3Archer 2017[13]
UTI preventionRetrospective claims association only; no randomized prevention trialRubin 2025[25]

Clinical Positioning​

  • Vaginal DHEA 6.5 mg nightly is FDA-approved for moderate-to-severe dyspareunia due to menopause and is supported by two Phase III placebo-controlled RCTs meeting all four coprimary endpoints.[1][3]
  • FSFI improvement is supported by placebo-controlled data; superiority over vaginal estrogen or a specific androgen-mediated clinical mechanism has not been established.[4]
  • Systemic exposure is low, not absent.[10][11]
  • No progestogen is required and no endometrial hyperplasia was seen at 52 weeks; long-term (>1 y) endometrial data are absent. Evaluate any postmenopausal bleeding.[3][8][14]
  • Prasterone is not an established UTI-prevention treatment. For patients with GSM and rUTI, the AUA/SUFU/AUGS guideline recommends local low-dose vaginal estrogen ; a randomized-trial meta-analysis found RR 0.42 versus placebo.[21][22]
  • In breast cancer survivors, DHEA may be discussed when vaginal estrogen is not an option; ACOG does not require an estrogen trial first.[17][20]
  • Counsel about vaginal discharge: melting of the insert vehicle may contribute; discharge was reported in 38/665 (5.71%) prasterone recipients over 12 weeks and 74/521 (14.2%) in a 52-week open-label trial.[3] A panty liner may help if bothersome.[1][3]
  • Cost and daily dosing are the practical downsides: no generic, approximately $200–300/month; nightly application compared to 2×/wk or 90-day estrogen-ring alternatives.
  • Onset is gradual. Improvement was observed by 6 weeks and measured at 12 weeks in the placebo-controlled trial; in the open-label study, women with moderate-to-severe dyspareunia as their most bothersome symptom at baseline (n = 183) had a further 0.33-unit reduction in dyspareunia severity from weeks 12 to 52.[1][27]
  • Storage is 5–30 °C, at room temperature or refrigerated; the current US label does not impose the former seven-day room-temperature rule.[3]

See Also​

References​

1. Labrie F, Archer DF, Koltun W, et al. "Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause." Menopause. 2018;25(11):1339–1353. doi:10.1097/GME.0000000000001238

2. Labrie F, Bélanger A, Pelletier G, et al. "Science of intracrinology in postmenopausal women." Menopause. 2017;24(6):702–712. doi:10.1097/GME.0000000000000808

3. INTRAROSA (prasterone) prescribing information. Revised January 2026; DailyMed updated July 17, 2026.

4. Labrie F, Derogatis L, Archer DF, et al. "Effect of intravaginal prasterone on sexual dysfunction in postmenopausal women with vulvovaginal atrophy." J Sex Med. 2015;12(12):2401–2412. doi:10.1111/jsm.13045

5. Cellai I, Di Stasi V, Comeglio P, et al. "Insight on the intracrinology of menopause: androgen production within the human vagina." Endocrinology. 2021;162(2):bqaa219. doi:10.1210/endocr/bqaa219

6. Labrie F, Archer D, Bouchard C, et al. "Effect of intravaginal dehydroepiandrosterone (prasterone) on libido and sexual dysfunction in postmenopausal women." Menopause. 2009;16(5):923–931. doi:10.1097/gme.0b013e31819e85c6

7. The NAMS 2020 GSM Position Statement Editorial Panel. "The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society." Menopause. 2020;27(9):976–992. doi:10.1097/GME.0000000000001609

8. Heo YA. "Prasterone: a review in vulvovaginal atrophy." Drugs Aging. 2019;36(8):781–788. doi:10.1007/s40266-019-00693-6

9. Lemos MJ, Queiroz LF, Diniz AF, et al. "Intravaginal dehydroepiandrosterone for the treatment of vulvovaginal atrophy: a systematic review and meta-analysis." Menopause. 2026. doi:10.1097/GME.0000000000002736

10. Ke Y, Labrie F, Gonthier R, et al. "Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration." J Steroid Biochem Mol Biol. 2015;154:186–196. doi:10.1016/j.jsbmb.2015.08.016

11. Martel C, Labrie F, Archer DF, et al. "Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5 mg intravaginal prasterone for 12 weeks." J Steroid Biochem Mol Biol. 2016;159:142–153. doi:10.1016/j.jsbmb.2016.03.016

12. Barton DL, Shuster LT, Dockter T, et al. "Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance)." Support Care Cancer. 2018;26(4):1335–1343. doi:10.1007/s00520-017-3960-9

13. Archer DF, Labrie F, Montesino M, Martel C. "Comparison of intravaginal 6.5 mg (0.50%) prasterone, 0.3 mg conjugated estrogens and 10 µg estradiol on symptoms of vulvovaginal atrophy." J Steroid Biochem Mol Biol. 2017;174:1–8. doi:10.1016/j.jsbmb.2017.03.014

14. Crandall CJ, Mehta JM, Manson JE. "Management of menopausal symptoms: a review." JAMA. 2023;329(5):405–420. doi:10.1001/jama.2022.24140

15. Danan ER, Sowerby C, Ullman KE, et al. "Hormonal treatments and vaginal moisturizers for genitourinary syndrome of menopause: a systematic review." Ann Intern Med. 2024;177(10):1400–1414. doi:10.7326/ANNALS-24-00610

16. Scheffers CS, Armstrong S, Cantineau AE, Farquhar C, Jordan V. "Dehydroepiandrosterone for women in the peri- or postmenopausal phase." Cochrane Database Syst Rev. 2015;1:CD011066. doi:10.1002/14651858.CD011066.pub2

17. American College of Obstetricians and Gynecologists. "Treatment of urogenital symptoms in individuals with a history of estrogen-dependent breast cancer: clinical consensus." Obstet Gynecol. 2021;138(6):950–960. doi:10.1097/AOG.0000000000004601

18. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: survivorship. Updated 2026-04-08.

19. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction. Updated 2025-08-29.

20. Mension E, Alonso I, Cebrecos I, et al. "Safety of prasterone in breast cancer survivors treated with aromatase inhibitors: the VIBRA pilot study." Climacteric. 2022;25(5):476–482. doi:10.1080/13697137.2022.2050208

21. Chen YY, Su TH, Lau HH. "Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: a meta-analysis of randomized controlled trials." Int Urogynecol J. 2021;32(1):17–25. doi:10.1007/s00192-020-04397-z

22. Kaufman MR, Ackerman AL, Amin KA, et al. "The AUA/SUFU/AUGS Guideline on Genitourinary Syndrome of Menopause." J Urol. 2025;214(3):242–250. doi:10.1097/JU.0000000000004589

23. Archer DF, Labrie F, Bouchard C, et al. "Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone)." Menopause. 2015;22(9):950–963. doi:10.1097/GME.0000000000000428

24. Strandberg M, Cockin A, Lindén Hirschberg A. "Effects of vaginal dehydroepiandrosterone and estradiol on dyspareunia, a symptom of vulvovaginal atrophy in postmenopausal women - a randomized controlled trial." Maturitas. 2026;208:108924. doi:10.1016/j.maturitas.2026.108924

25. Rubin R, Sanaee M, Yee A, Moyneur E, Dea K, Dury AY. "Prevalence of urinary tract infections in women with vulvovaginal atrophy and the impact of vaginal prasterone on the rate of urinary tract infections." Menopause. 2025;32(3):217–227. doi:10.1097/GME.0000000000002485

26. U.S. Food and Drug Administration. Intrarosa (prasterone) NDA 208470 clinical review. 2016. FDA review.

27. Labrie F, Archer DF, Bouchard C, et al. "Prasterone has parallel beneficial effects on the main symptoms of vulvovaginal atrophy: 52-week open-label study." Maturitas. 2015;81(1):46–56. doi:10.1016/j.maturitas.2015.02.005

28. DailyMed. "OSPHENA (ospemifene) tablets, prescribing information." Revised February 2025. Full label, section 6.1.

29. European Medicines Agency. Intrarosa: European public assessment report. EMA product page. Accessed October 5, 2026.

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