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Vaginal and Topical Estrogen

Vaginal and topical estrogen is a cornerstone of genitourinary syndrome of menopause (GSM) management, with its most evidence-based urologic applications being prevention of recurrent UTIs (AUA Moderate Recommendation; Grade B) and treatment of vulvovaginal symptoms. For coexisting OAB, local estrogen is an optional adjunct under AUA/SUFU/AUGS 2025 expert opinion[31].[1][2] FDA labeling revisions began with a November 2025 request and the first six product approvals on February 12,2026; check the current label of the prescribed product.[4]

For related topics, see Vaginal DHEA (prasterone), Ospemifene, Preoperative hormonal priming, the clinical GSM article, Urethral Bulking Agents, and UTI suppressive & prophylactic therapy.

Why vaginal estrogen matters in urology​

The vagina and lower urinary tract are estrogen-responsive tissues; their embryologic origins are not identical. ERα and ERβ are expressed in vaginal epithelium, urethra, trigone, detrusor, pelvic-floor musculature, and endopelvic fascia.[5][6]

Menopausal hypoestrogenism is associated with:

  • Vaginal epithelial thinning (loss of superficial cells, rise in parabasal cells)
  • Vaginal pH 3.5–4.5 → 5.0–7.0 with loss of Lactobacillus dominance → uropathogen colonization (E. coli, Enterobacteriaceae)
  • Urethral mucosal atrophy, which may contribute to urinary symptoms; SUI remains multifactorial
  • Decreased periurethral blood flow and mucosal-barrier impairment
  • Urgency, frequency, and nocturia, which require assessment for other causes
  • Increased susceptibility to UTI[5][7][8]

Vaginal estrogen can improve local estrogenization — restoring epithelial thickness, normalizing pH, re-establishing Lactobacillus dominance, and improving periurethral tissue quality.[9][10]

Formulations and dosing​

All FDA-approved formulations; systemic absorption varies substantially by product and dose.

FormulationBrandActiveDoseScheduleSystemic absorption
Vaginal creamEstraceEstradiol 0.01%0.1 mg/g2–4 g daily × 1–2 wk → 1 g 1–3×/wkModerate (dose-dependent)
Vaginal creamPremarinConjugated estrogen 0.625 mg/g0.5–2 g for atrophic vaginitis (dose individualized)Daily21 days, then 7 days off; dyspareunia: 0.5 g twice weekly or 21 days on/7 off[36]Dose-dependent
Vaginal insert / tabletVagifem / YuvafemEstradiol10 µgDaily × 2 wk → 2×/wkVery low
Vaginal insertImvexxyEstradiol4 µg or 10 µgDaily × 2 wk → 2×/wkUltra-low (4 µg — lowest of all formulations)
Vaginal ringEstringEstradiol 2 mg ring releasing 7.5 µg/day—Insert; replace every 90 daysVery low
Vaginal insertIntrarosaPrasterone (DHEA) 6.5 mg—NightlyMinimal (intracrine) — see Vaginal DHEA
Oral SERMOsphenaOspemifene 60 mg—Daily with foodSystemic (oral) — see Ospemifene

Systemic absorption principles:[10][11]

  • Formulations associated with serum estradiol <10 pg/mL (within the postmenopausal range) include 10 µg tablets, 4 µg / 10 µg inserts, and the 7.5 µg/day ring
  • Circulating estrogen rises transiently with the first application on atrophic tissues, then normalizes within 2–12 weeks as epithelium thickens and absorption decreases
  • Creams produce the highest variability in systemic absorption due to dose-volume imprecision; inserts and rings give the most predictable low-dose exposure

Recurrent UTI prevention — the strongest urologic indication​

Guidelines​

  • AUA/CUA/SUFU 2025 (Moderate Recommendation; Grade B): recommend vaginal estrogen for peri- and postmenopausal patients with recurrent UTI when appropriate and without a contraindication.[1]
  • AGS Beers Criteria 2023: "First-line preventive therapy for recurrent UTIs in most older women is vaginal estrogen" — while explicitly recommending against systemic estrogen for this indication.[12]
  • NAMS 2020 GSM Position Statement — vaginal estrogen is effective for preventing recurrent UTIs.[13]

Evidence​

StudynDesignFinding
Chen 2021 meta-analysis1,936 (vaginal E)5 RCTsRR 0.42 (95% CI 0.30–0.59) for rUTI reduction with vaginal estrogen; oral estrogen showed no benefit (RR 1.11; 95% CI 0.92–1.35)[14]
Historical AUA 2022 guideline pool5 RCTsEarlier metaRR 0.58 (95% CI 0.39–0.87); SOE low[1]
Tan-Kim 20235,638Retrospective, Kaiser PermanenteUTI frequency 3.9 → 1.8/year (51.9% reduction, p <0.001); 31.4% had zero UTIs in the following year[15]

Predictors of persistent UTIs despite vaginal estrogen (Tan-Kim 2023): age ≥75, higher baseline UTI frequency, urinary incontinence, urinary retention, diabetes.[15]

TAPER trial (July 2026). In 114 postmenopausal participants, twice-weekly periurethral estradiol cream (0.5 g) was noninferior to intravaginal applicator delivery (1 g) for six-month UTI-free status: 50.9% versus 52.6% (difference −1.75 percentage points, 95% CI −20.0 to 17.0). This single-center, unblinded trial used a 25-percentage-point noninferiority margin. It supports discussing an application alternative when applicator use is difficult, but does not establish precise equivalence, long-term benefit, or applicability to other formulations.[35]

Mechanism — microbiome restoration​

Srinivasan 2022 secondary analysis of an RCT (JAMA Netw Open) — after 12 weeks of vaginal estradiol, 80% of women had Lactobacillus / Bifidobacterium-dominant vaginal communities vs 26% with placebo (p <0.001), with accompanying drops in vaginal pH.[10]

Shen 2016 and Moore 2024 — women with Lactobacillus-deficient baseline microbiomes show the greatest improvement; pH decreases by ~1.3 points and community state types transition to healthier profiles (p = 0.004); already-Lactobacillus-dominant women show stable microbiota.[8][16]

See UTI suppressive & prophylactic therapy and Non-antibiotic UTI prevention for the broader rUTI framework.

Urgency / urge urinary incontinence​

Vaginal estrogen may improve some urinary symptoms when GSM coexists, but benefit is inconsistent across outcomes. It is not a replacement for standard OAB or SUI care. Systemic estrogen can worsen incontinence.[31][11][17]

  • Christmas 2023 systematic review — vaginal estrogen improves dysuria, frequency, urge incontinence, and SUI; systemic HT may cause or worsen UI.[17]
  • IUGA Committee Opinion — vaginal estrogen has beneficial effects on UI symptoms vs placebo (evidence level 2C).[6]
  • Harncharoenkul 2026 RCT (n = 86, 17β-estradiol 10 µg vs placebo) — overall storage symptoms did not differ at 12 wk, but UUI showed sustained significant improvement at 4 and 12 wk (p = 0.013); urethral maturation index and vaginal pH improved significantly.[18]

The WHI vs vaginal contrast: WHI oral CEE increased incontinence. Systemic and local routes have fundamentally different effects on the lower urinary tract — systemic appears to act via counter-productive effects on collagen metabolism and vascular tone.[11][17]

Stress urinary incontinence​

Evidence for vaginal estrogen in SUI is less robust than for urgency symptoms.[19] Weber 2015 systematic review: topical estrogen appears to decrease both OAB and UI complaints, but signal is stronger for urgency-type symptoms. Rahn 2023 preoperative RCT in prolapse patients showed trends toward SUI improvement with preop vaginal estrogen (50% vs 43%; p = 0.78 — not statistically significant).[20]

Pelvic organ prolapse​

Vaginal estrogen has not established improved anatomical repair durability. The 2026 EVA multicenter trial adds a patient-reported recovery benefit; see the priming hub for results and limitations.

  • Taithongchai 2023 Cochrane review — little to no difference in subjective or objective POP improvement when estrogen was added to surgery; possible fewer postoperative UTIs, with heterogeneous contributing studies and uncertain overall conclusions.[21]
  • IUGA Committee Opinion — definitive evidence on local estrogen and POP prevention or treatment is lacking.[6]

Perioperative use is covered in Preoperative hormonal priming. The IMPROVE trial (Rahn 2023) showed 7 weeks of preop vaginal estrogen improved objective estrogenization signs but subjective symptom improvement was inconclusive.[20]

Perioperative use in urologic / gynecologic surgery​

Commonly prescribed preoperatively before:

  • Pelvic reconstructive surgery (prolapse repair, slings)
  • Vaginal hysterectomy
  • Anti-incontinence procedures

Rationale: improve tissue quality, vascularity, and wound healing — though high-quality evidence for improved surgical outcomes is limited.[20][21] See Preoperative hormonal priming.

Non-estrogen hormonal alternatives​

For detail, see the dedicated articles — Vaginal DHEA and Ospemifene. In brief:

AgentRouteKey features
Prasterone (Intrarosa)Vaginal 6.5 mg nightlyConverted to estrogens and androgens; small serum increases occur. FDA-approved for menopausal VVA-related moderate-to-severe dyspareunia[37][11][22]
Ospemifene (Osphena)Oral 60 mg daily with foodSERM with endometrial agonist activity and boxed endometrial/cardiovascular warnings;[38] FDA-approved for moderate-to-severe dyspareunia and vaginal dryness; ACOG Level A alternative to vaginal estrogen for GSM dyspareunia[22][23][24]

Safety​

Endometrial safety​

  • Low-dose vaginal estrogen generally does not require added progestogen, but this differs from systemic unopposed estrogen and does not establish lifetime absence of endometrial risk. AUA 2025 advises against surveillance solely because of local low-dose estrogen, DHEA, or ospemifene use; symptoms and other risk factors still require evaluation.[11][31]
  • Long-term (>1 year) endometrial safety data are limited for vaginal estrogen, vaginal DHEA, and ospemifene
  • Postmenopausal bleeding always warrants evaluation with endometrial biopsy and/or TVUS[11]

Breast cancer safety — reassuring observational data with remaining uncertainty​

SourcenFinding
Beste 2025 meta-analysis24,060Vaginal estrogen not associated with increased breast cancer recurrence (OR 0.48; 95% CI 0.23–0.98), BC mortality (OR 0.60), or overall mortality (OR 0.46)[26]
McVicker 2024 JAMA Oncology49,237No increase in breast-cancer-specific mortality (HR 0.77; 95% CI 0.63–0.94)[27]
Agrawal 2023 US claims analysis42,113Comparable recurrence risk (RR 1.03; 95% CI 0.91–1.18); also comparable in ER-positive disease (RR 0.94; 95% CI 0.77–1.15)[28]
Cold 2022 Danish cohortEarly breast cancerSmall increased recurrence risk in the aromatase-inhibitor subgroup (RR 1.39; 95% CI 1.04–1.85); survival not worse[29]

For the July 2026 VEMORA randomized symptom study and its limitations, see GSM in breast cancer survivors. Symptom improvement and serum estradiol measurements do not establish long-term recurrence safety.

Guideline positions in breast cancer survivors:

  • ACOG 2021 clinical consensus — low-dose vaginal estrogen may be used in breast cancer survivors, including those on tamoxifen; shared decision-making with oncology for AI users[30]
  • AUA/SUFU/AUGS 2025 — low-dose vaginal estrogen may be considered after multidisciplinary shared decision-making, including oncology; consider formulation-specific absorption[31]
  • Product labeling — FDA warnings changed through product-specific approvals; these do not replace individualized breast-cancer counseling.[4]

Cardiovascular and thromboembolic safety​

No evidence that low-dose vaginal estrogen increases CHD, stroke, or VTE. The WHI findings of increased CV risk applied to oral systemic CEE, not to vaginal preparations.[11][32]

FDA regulatory update — November 2025 to February 2026​

FDA requested changes in November 2025, then approved the first six products on February 12,2026, removing cardiovascular disease, breast cancer, and probable dementia statements from their boxed warnings. This was not simultaneous removal of every warning from every estrogen product. Use the actual product label for contraindications and counseling.[4]

Contemporary commentaries discuss how these changes may improve prescribing, but they are interpretations of the regulatory action, not substitutes for product labeling or individualized assessment.[3][33][34]

Practical prescribing​

Choosing a formulation​

SituationPreferred
UTI prevention (general)Any low-dose vaginal estrogen formulation; AUA does not specify a preferred product[1]
Patient convenience / adherenceVaginal ring (Estring) — 90-day replacement; RCT data favor comfort, ease, and satisfaction over cream
Lowest systemic absorption4 µg insert (Imvexxy) or 7.5 µg/day ring (Estring)[11]
Breast cancer survivor (on AI)Individualized low-dose product and shared decision with oncology; no universal safety ranking[29][31]
Prefers oral therapyOspemifene 60 mg daily[24]
Prefers non-estrogen vaginal therapyPrasterone 6.5 mg nightly[30]

Duration of therapy​

GSM is a chronic progressive condition — symptoms recur on discontinuation. NAMS and contemporary guidance support indefinite use of low-dose vaginal estrogen as long as symptoms persist and the patient benefits. Reassess benefit and tolerability periodically and follow the product-specific labeling.[13][4]

Monitoring​

  • No routine endometrial surveillance is required with low-dose vaginal estrogen[11][25]
  • Evaluate any postmenopausal bleeding with endometrial biopsy and/or TVUS[11]
  • No routine serum estradiol monitoring is needed[13]
  • Reassess symptoms periodically to confirm ongoing benefit[22]

Systemic estrogen — what NOT to do​

  • Systemic estrogen does NOT prevent UTIs (RR 1.11; 95% CI 0.92–1.35 vs placebo)[14]
  • Systemic estrogen WORSENS urinary incontinence (WHI data)[11][17]
  • AGS Beers Criteria explicitly state: "Do not initiate systemic estrogen; do not use systemic estrogen to manage incontinence (all types)"[12]
  • Women on systemic HT for vasomotor symptoms may still need additional vaginal estrogen for GSM symptoms[22]

Comparative summary​

IndicationVaginal estrogenSystemic estrogenOspemifenePrasterone (DHEA)
rUTI preventionEffective (RR 0.42); AUA Moderate Rec[1][14]NOT effective (RR 1.11)[14]Not studiedNot studied
Vaginal dryness / dyspareuniaEffective (Level A)Effective, more systemic riskEffective (ACOG Level A)[24]Effective (Level B)[22]
Urgency / UUIPossible benefit with coexisting GSM[31][17][18]Worsens UINot studiedNot studied
SUIModest / inconsistent[19][20]Worsens UINot studiedNot studied
POPInsufficient evidence[21]Not beneficialNot studiedNot studied
Endometrial safetyReassuring short-term data; long-term limits[25]Progestogen requiredEndometrial agonist; boxed warning[38]Long-term data limited
Breast cancer safetyReassuring observational data; AI subgroup uncertainty[26][27]Contraindicated (ER+)US label advises against use with known/suspected/history of breast cancer[38]Breast-cancer warning; not established safe[37]
Progestogen needed?No (low-dose formulations)[11]Yes (if uterus intact)NoNo

Evidence Summary​

IndicationEvidence levelKey source
rUTI preventionLevel 1 (meta-analysis)Chen 2021[14]; Tan-Kim 2023[15]; AUA/CUA/SUFU 2025[1]
Microbiome restoration mechanismLevel 1 (RCT secondary analysis)Srinivasan 2022[10]; Moore 2024[8]
Urgency / UUI improvementLevel 1Christmas 2023 SR[17]; Harncharoenkul 2026 RCT[18]
SUILevel 2–3 (inconsistent)Weber 2015[19]; Rahn 2023[20]
POPLevel 1 (Cochrane)Taithongchai 2023[21]
Endometrial safetyShort-term trials/observational evidence; long-term limitationsAUA 2025[31]; ACOG141[25]
Breast cancer safetyLevel 2 (meta-analyses, cohorts)Beste 2025[26]; McVicker 2024[27]; Agrawal 2023[28]; Cold 2022[29]
FDA labeling revisionsProduct-specific regulatory actionNovember 2025 request; first six approvals February 2026[4]

Clinical Positioning​

  • Vaginal estrogen is first-line for rUTI prevention in postmenopausal women per the AUA/CUA/SUFU 2025 guideline — RR 0.42 in meta-analysis and 51.9% reduction in the Tan-Kim Kaiser Permanente cohort.[1][14][15]
  • Route matters — vaginal works, oral does not. Oral estrogen has RR 1.11 for rUTI (no benefit) and worsens incontinence per WHI. Do not substitute.[14][17]
  • Check the current product label. FDA revisions were product-specific.[4]
  • Formulation choice follows patient preference and clinical context. Inserts and rings offer more predictable low-dose exposure; consider dexterity, cost, local symptoms, and oncology input when relevant.[13][31]
  • In breast cancer survivors, vaginal estrogen is no longer reflexively contraindicated. Recurrence studies and mortality studies address different outcomes: McVicker evaluated breast-cancer mortality, not recurrence. Observational associations do not prove protection. Shared decision-making with oncology is appropriate — particularly in AI users, where the Cold 2022 Danish cohort showed a small RR 1.39 recurrence signal without survival difference.[26][27][28][29]
  • No progestogen is needed for endometrial protection with low-dose vaginal estrogen at 1-year data; long-term data remain limited. Always evaluate postmenopausal bleeding.[11][25]
  • Microbiome restoration is the mechanism — vaginal estrogen converts 26% → 80% Lactobacillus-dominant microbiota per Srinivasan 2022 RCT. Women with baseline Lactobacillus-deficient microbiomes show the greatest benefit.[8][10]
  • For GSM with OAB, consider vaginal estrogen as an adjunct. Do not delay appropriate bladder training, pelvic-floor therapy, or OAB medication solely to complete an estrogen trial.[31]
  • SUI evidence is weaker. Vaginal estrogen may modestly improve SUI as part of GSM management but should not substitute for pelvic-floor PT, pessary, or surgical therapy.[19][20]
  • Counsel predictors of non-response — age ≥75, higher baseline UTI frequency, incontinence, retention, and diabetes predict persistent UTIs despite vaginal estrogen.[15]

See Also​

References​

1. AUA/CUA/SUFU. Recurrent Uncomplicated Urinary Tract Infections in Women Guideline. Amended 2025. Official guideline.

2. Mainar LB, Nieto-Pascual L, Bravo EI, et al. "Safety of vaginal estrogen in breast cancer survivors: current evidence on systemic absorption and oncologic outcomes." Maturitas. 2026;208:108914. doi:10.1016/j.maturitas.2026.108914

3. Sriprasert I, Hodis HN, Mack WJ, et al. "Elimination of the black box warning on menopausal hormone therapy." Obstet Gynecol. 2026;147(5):642–646. doi:10.1097/AOG.0000000000006226

4. US Food and Drug Administration. "FDA Approves Labeling Changes to Menopausal Hormone Therapy Products." February 12,2026. Official announcement.

5. Buck ES, Lukas VA, Rubin RS. "Effective prevention of recurrent UTIs with vaginal estrogen: pearls for a urological approach to genitourinary syndrome of menopause." Urology. 2021;151:31–36. doi:10.1016/j.urology.2020.05.058

6. Bodner-Adler B, Alarab M, Ruiz-Zapata AM, Latthe P. "Effectiveness of hormones in postmenopausal pelvic floor dysfunction — International Urogynecological Association Research and Development Committee Opinion." Int Urogynecol J. 2020;31(8):1577–1582. doi:10.1007/s00192-019-04070-0

7. Hirschberg AL. "Enhancing quality of life: addressing vulvovaginal atrophy and urinary tract symptoms." Climacteric. 2025. doi:10.1080/13697137.2025.2514029

8. Moore KH, Ognenovska S, Chua XY, et al. "Change in microbiota profile after vaginal estriol cream in postmenopausal women with stress incontinence." Front Microbiol. 2024;15:1302819. doi:10.3389/fmicb.2024.1302819

9. Chang JG, Lewis MN, Wertz MC. "Managing menopausal symptoms: common questions and answers." Am Fam Physician. 2023;108(1):28–39.

10. Srinivasan S, Hua X, Wu MC, et al. "Impact of topical interventions on the vaginal microbiota and metabolome in postmenopausal women: a secondary analysis of a randomized clinical trial." JAMA Netw Open. 2022;5(3):e225032. doi:10.1001/jamanetworkopen.2022.5032

11. Pinkerton JV. "Hormone therapy for postmenopausal women." N Engl J Med. 2020;382(5):446–455. doi:10.1056/NEJMcp1714787

12. Steinman MA. "Alternative treatments to selected medications in the 2023 American Geriatrics Society Beers Criteria." J Am Geriatr Soc. 2025;73(9):2657–2677. doi:10.1111/jgs.19500

13. North American Menopause Society. "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

14. 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

15. Tan-Kim J, Shah NM, Do D, Menefee SA. "Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women." Am J Obstet Gynecol. 2023;229(2):143.e1–143.e9. doi:10.1016/j.ajog.2023.05.002

16. Shen J, Song N, Williams CJ, et al. "Effects of low-dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis." Sci Rep. 2016;6:24380. doi:10.1038/srep24380

17. Christmas MM, Iyer S, Daisy C, et al. "Menopause hormone therapy and urinary symptoms: a systematic review." Menopause. 2023;30(6):672–685. doi:10.1097/GME.0000000000002187

18. Harncharoenkul P, Wattanayingcharoenchai R, Pongchaikul P, et al. "Efficacy of vaginal 17β-estradiol on the urinary storage symptoms in postmenopausal women: a randomized double-blind, placebo-controlled study." Sci Rep. 2026;16(1):12685. doi:10.1038/s41598-026-43359-1

19. Weber MA, Kleijn MH, Langendam M, et al. "Local oestrogen for pelvic floor disorders: a systematic review." PLoS One. 2015;10(9):e0136265. doi:10.1371/journal.pone.0136265

20. Rahn DD, Richter HE, Sung VW, Hynan LS, Pruszynski JE. "Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse." Am J Obstet Gynecol. 2023;229(3):309.e1–309.e10. doi:10.1016/j.ajog.2023.05.023

21. Taithongchai A, Johnson EE, Ismail SI, et al. "Oestrogen therapy for treating pelvic organ prolapse in postmenopausal women." Cochrane Database Syst Rev. 2023;7:CD014592. doi:10.1002/14651858.CD014592.pub2

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

23. 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

24. American College of Obstetricians and Gynecologists. "Female sexual dysfunction: ACOG Practice Bulletin No. 213." Obstet Gynecol. 2019;134(1):e1–e18. doi:10.1097/AOG.0000000000003324

25. American College of Obstetricians and Gynecologists. "ACOG Practice Bulletin No. 141: management of menopausal symptoms." Obstet Gynecol. 2014;123(1):202–216. doi:10.1097/01.AOG.0000441353.20693.78

26. Beste ME, Kaunitz AM, McKinney JA, Sanchez-Ramos L. "Vaginal estrogen use in breast cancer survivors: a systematic review and meta-analysis of recurrence and mortality risks." Am J Obstet Gynecol. 2025;232(3):262–270.e1. doi:10.1016/j.ajog.2024.10.054

27. McVicker L, Labeit AM, Coupland CAC, et al. "Vaginal estrogen therapy use and survival in females with breast cancer." JAMA Oncol. 2024;10(1):103–108. doi:10.1001/jamaoncol.2023.4508

28. Agrawal P, Singh SM, Able C, et al. "Safety of vaginal estrogen therapy for genitourinary syndrome of menopause in women with a history of breast cancer." Obstet Gynecol. 2023;142(3):660–668. doi:10.1097/AOG.0000000000005294

29. Cold S, Cold F, Jensen MB, et al. "Systemic or vaginal hormone therapy after early breast cancer: a Danish observational cohort study." J Natl Cancer Inst. 2022;114(10):1347–1354. doi:10.1093/jnci/djac112

30. 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

31. AUA/SUFU/AUGS. Genitourinary Syndrome of Menopause Guideline. 2025. Official guideline.

32. Laing AJ, Newson L, Simon JA. "Individual benefits and risks of intravaginal estrogen and systemic testosterone in the management of women in the menopause, with a discussion of any associated risks for cancer development." Cancer J. 2022;28(3):196–203. doi:10.1097/PPO.0000000000000598

33. Buchanan LA, Calkins MW, Kirk JK. "The Food and Drug Administration boxed warning on menopausal hormone therapy: history, impact, and a regulatory inflection point in women's health." Menopause. 2026. doi:10.1097/GME.0000000000002793

34. Bartz D, Tadikonda A, Manson JE. "Opportunity for improved menopausal hormone therapy prescribing." JAMA. 2026. doi:10.1001/jama.2026.1891

35. Zuo SW, Mowers EE, Hem S, et al. "Vaginal Estrogen Application Techniques for Prevention of Urinary Tract Infection: A Randomized Trial." Obstet Gynecol. Published online July 27,2026. doi:10.1097/AOG.0000000000006376

36. Pfizer. Premarin Vaginal Cream US prescribing information. Label.

37. INTRAROSA prescribing information. DailyMed.

38. OSPHENA prescribing information. DailyMed.