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Ospemifene

Ospemifene (Osphena) is an oral, non-estrogen FDA-approved treatment for moderate-to-severe dyspareunia and vaginal dryness due to menopause. As a third-generation selective estrogen receptor modulator (SERM), it exerts tissue-specific effects: agonist on vaginal and bone tissue, neutral to antagonist on breast tissue, and weak agonist on endometrium, making it an oral option for selected GSM patients who prefer or have difficulty using vaginal preparations, subject to the contraindications and warnings below.[1][2][3] Small observational studies have explored bladder symptoms in women with VVA, but OAB and UUI are not approved indications or established treatment roles.[4][5][6]

For related classes, see Vaginal and topical estrogen, Vaginal DHEA, Preoperative hormonal priming, and the clinical GSM article.

Mechanism and tissue-selective SERM profile​

Ospemifene is a triphenylethylene derivative (structurally related to tamoxifen and toremifene) with tissue-selective ER modulation:[3]

TissueER effectClinical implication
Vaginal epitheliumAgonistEpithelial maturation, ↑ superficial cells, ↓ pH, lubrication[3]
BoneAgonist↓ bone-turnover markers; bone-biomarker profile comparable to raloxifene[7][8]
BreastAntagonistPreclinical anti-proliferative on breast tissue[9]
EndometriumWeak agonistEndometrial thickening; one simple hyperplasia without atypia and no endometrial cancer in trials up to 52 weeks[10]
Cardiovascular / lipidsMixed↑ HDL, ↓ LDL; neutral on triglycerides[11]

Pharmacokinetics[12]​

  • Absorption. Must be taken with food; a high-fat meal increases Cmax and AUC 2.3× and 1.7× versus fasting
  • Protein binding >99% (clinically relevant for drug interactions)[12]
  • Volume of distribution 448 L
  • Metabolism. Primarily CYP3A4 and CYP2C9 (CYP2C19 minor); major metabolite 4-hydroxyospemifene
  • Half-life approximately 26 hours; steady state after about 9 days
  • Elimination approximately 75% fecal, approximately 7% urinary[12]

FDA-approved indications and dosing​

ElementDetails
BrandOsphena[12]
FDA indications(1) Moderate-to-severe dyspareunia of menopause; (2) moderate-to-severe vaginal dryness of menopause
Dose60 mg PO once daily with food[12]
GenericFDA approved a therapeutically equivalent 60-mg ospemifene tablet in 2024 (ANDA 215574); current dispensing availability requires verification[1]

Contraindications and boxed warning​

FDA boxed warning[12]​

  • Endometrial cancer. Estrogen-agonist effect on the endometrium; increased risk of endometrial cancer with unopposed estrogens; evaluate any undiagnosed persistent or recurring abnormal genital bleeding
  • Cardiovascular disorders. In ospemifene trials (up to 15 months), the label reports:
    • Thromboembolic stroke: 1.13 per 1,000 woman-years (versus 3.15 placebo)
    • Hemorrhagic stroke: 3.39 per 1,000 woman-years (versus 0 placebo)
    • DVT: 2.26 per 1,000 woman-years (2 cases) versus 3.15 per 1,000 woman-years (1 case) placebo

Contraindications[12]​

  • Undiagnosed abnormal genital bleeding
  • Estrogen-dependent neoplasia
  • Active DVT / PE or history of these
  • Active arterial thromboembolic disease (stroke, MI) or history
  • Hypersensitivity to ospemifene
  • Known or suspected pregnancy

The label also states that ospemifene should not be used in severe hepatic impairment; no dose adjustment is needed for mild or moderate (Child-Pugh A or B) impairment.[12]

Drug interactions​

Interacting drugMechanismEffectClinical action
FluconazoleModerate CYP3A / strong CYP2C9 / moderate CYP2C19 inhibitor↑ AUC 2.7×, ↑ Cmax 1.7×Do not co-administer[12]
RifampinStrong CYP3A / moderate CYP2C9-2C19 inducer↓ AUC 58%, ↓ Cmax 51%Do not co-administer (label prescribing highlights); reduced exposure may reduce clinical effect (section 7.3)[12]
KetoconazoleStrong CYP3A inhibitor↑ AUC 1.4×, ↑ Cmax 1.5×Use with caution
OmeprazoleModerate CYP2C19 inhibitor↑ AUC 1.17×, ↑ Cmax 1.20×No dose adjustment needed
WarfarinPossible protein-binding interaction; displacement unprovenRepeated ospemifene did not alter single-dose warfarin PK; repeated warfarin dosing and INR/PT effects were not studied[12]Monitor if co-administered
Estrogens / other SERMsPharmacodynamicSafety not studiedDo not co-administer
Highly protein-bound drugsDisplacementMay alter exposure of either drugUse with caution

The fluconazole interaction is particularly relevant in urogynecologic practice, as fluconazole is commonly prescribed for VVC in the same patient population.[2]

Pivotal efficacy data​

Approval rested on three 12-week efficacy trials and one 52-week safety trial, total 2,516 postmenopausal women (1,416 ospemifene / 1,100 placebo).[12] Vaginal cytology and pH improved; most-bothersome dyspareunia improved in Trials 1 and 2, and most-bothersome dryness improved in Trials 1 and 3. Trial 2 did not show a statistically significant dryness benefit.[12]

Di Donato 2019 meta-analysis (6 RCTs)[13]​

Ospemifene 60 mg versus placebo at 12 weeks[13]:

  • Vaginal pH: SMD −0.96 (95% CI −1.12 to −0.81; p < 0.0001)[13]
  • Parabasal cells: SMD −36.84 (95% CI −46.95 to −26.72; p < 0.0001)[13]
  • Superficial cells: SMD 8.23 (95% CI 3.73 to 12.74; p < 0.0003)[13]
  • Dyspareunia: SMD −2.70 (95% CI −2.88 to −2.52; p < 0.0001)[13]

The abstract reports standardized mean differences on differing scales; direction and consistency across trials are the dependable message.

Portman 2013 phase 3 trial[30]​

605 women aged 40–80 with dyspareunia as the most bothersome symptom were randomized to ospemifene 60 mg (n = 303) or placebo (n = 302) for 12 weeks.[30] Ospemifene was superior on all coprimary endpoints (parabasal and superficial cells, vaginal pH, dyspareunia severity; p < 0.0001 except dyspareunia p = 0.0001). Hot flushes were the most frequent treatment-related adverse event (6.6% versus 3.6%); one participant per arm discontinued.[30]

Simon 2023 network meta-analysis[14]​

The FDA label reports endometrial thickening ≥5 mm and one simple hyperplasia without atypia, with no endometrial cancer during trials through 52 weeks.[12]

Urogynecologic applications beyond dyspareunia​

Overactive bladder and urge urinary incontinence — exploratory evidence​

StudynDesignFinding
Schiavi 201746Retrospective 12 wkDetrusor overactivity 39% → 13% (p = 0.04); voids/day 9.57 → 6.63; urgency episodes 5.63 → 1.44; nocturia 3.17 → 1.11; UUI 0.85 → 0.33 (all p ≤ 0.003)[4]
Schiavi 2018105Single-arm, 12 wkOAB-Q symptom score 55.34 → 23.22 (p < 0.0001); total FSFI improved; study-defined PGI-I success was 90.5% without a comparator[5]
Novara 202025Prospective 12 wk (first-line-refractory OAB)Significant reduction in micturition, nocturia, urgency, incontinence; bladder-wall thickness decreased; UDI-6 and OAB-Q improved[6]
Russo 202340Prospective 12 wk with urodynamicsCystometric capacity, compliance, and verbal sensory threshold improved; daily voids, UUI, and nocturia decreased; ICIQ-UI SF and ICIQ-OAB improved[15]

Proposed mechanism: estrogen-receptor activity in lower urinary tract tissues may affect bladder symptoms.[4][15]

Recurrent UTI prevention — not a primary indication​

In a pooled analysis of six phase 2/3 trials, UTI was recorded as a treatment-emergent adverse event in 81/1,242 (6.5%) ospemifene recipients and 46/958 (4.8%) placebo recipients; these trials did not test rUTI prevention.[21]

Evidence is insufficient to establish ospemifene as rUTI prophylaxis, despite observational urinary-symptom signals.[16] The 2023 JAMA review notes that none of the FDA-approved GSM therapies (including ospemifene) are approved for reducing rUTI frequency.[2]

PEONY observational signal (64 breast-cancer survivors, 6 months): the modeled probability of self-reported moderate/severe recurring-UTI symptoms fell from 22.5% to 4.3%, and postcoital-cystitis symptoms from 27.3% to 1.9% (within-group ORs 0.2 and 0.1).[16]

Sexual function​

Schiavi 2018 showed significant improvement in total FSFI and decreased sexual distress in women with VVA and OAB/UUI.[5] The 12-month PEONY study confirmed sustained improvements in lubrication and pain domains; overall FSFI total did not reach significance.[17]

Guideline positioning​

  • AUA/SUFU/AUGS 2025 GSM guideline: ospemifene may be offered for vulvovaginal dryness and/or dyspareunia .[29]

    • Patients can be counseled that neither vaginal DHEA nor ospemifene increases breast cancer risk or the risk of atypical hyperplasia or endometrial cancer .[29] No endometrial surveillance is needed solely because of ospemifene use (statement 24).[29] For OAB with GSM, the guideline names local low-dose vaginal estrogen, not ospemifene (statement 12).[29] The FDA label still advises against ospemifene in women with a history of breast cancer.[12]

  • Menopause Society (NAMS) 2020 GSM position statement. Oral ospemifene is one of the effective prescription options for moderate-to-severe GSM, alongside low-dose vaginal estrogen and vaginal DHEA.[31]

  • ACOG 2021 clinical consensus addresses hormonal and nonhormonal therapy for urogenital symptoms in breast cancer survivors (see below).[18]

  • AGS 2025 companion alternatives list to the 2023 Beers Criteria includes ospemifene for GSM-associated vaginal atrophy or dyspareunia alongside vaginal estrogen, DHEA, and hyaluronic acid.[19]

  • AAFP 2023 lists it as an FDA-approved non-estrogen therapy for vaginal atrophy and dyspareunia[20]

Adverse effects and safety​

Pooled safety (6 Phase 2/3 trials; n = 1,242 ospemifene versus n = 958 placebo):[12][21]

AEOspemifene 60 mgPlacebo
Hot flush (treatment-emergent)8.5%3.3%[21]
UTI (treatment-emergent)6.5%4.8%[21]
Vulvovaginal candidiasis (treatment-emergent)4.3% (53/1,242)0.5% (5/958)[21]
Vaginal discharge (treatment-related)3.8%0.3%[21]
Muscle spasms (treatment-related)3.2%0.9%[21]
Headache (treatment-related)2.4%2.4%[21]
Hyperhidrosis (label 12-week trials; n=1,459 vs 1,136)1.1%0.2%[12]
Vaginal hemorrhage (label trials up to 52 weeks; n=847 vs 165)1.3%0.0%[12]
Night sweats (label trials up to 52 weeks; n=847 vs 165)1.2%0.0%[12]
Discontinuation for treatment-emergent AEs7.6%3.8%[21]
Serious AEs2.6%1.8%[21]

Hot flashes (approximately 8.5%) were the most commonly reported treatment-emergent AE in the pooled trials.[21] Counsel that hot flushes may emerge during treatment.[2][21] A six-week placebo-controlled trial of 198 women with existing moderate-to-severe hot flashes did not find worsening of their frequency or severity.[35]

Endometrial safety​

Constantine 2015 Phase 2/3 pooled analysis (n = 1,242 ospemifene / n = 924 placebo):[10] The proliferative-endometrium and uterine-polyp rates below are from the OSPHENA label (up to 52 weeks).[12]

  • No endometrial cancer in any ospemifene trial
  • Endometrial hyperplasia: <1% of ospemifene-treated women over up to 52 weeks[10]
  • Proliferative endometrium: 26.3 per 1,000 women (ospemifene) versus 0 (placebo)
  • Uterine polyps: 19.6 versus 8.3 per 1,000 women

Endometrial thickening of 5 mm or more occurred in 101.4 per 1,000 women on ospemifene versus 20.9 per 1,000 on placebo (label, up to 52 weeks).[12] Progestogen co-administration was not evaluated in trials; the FDA label does not mandate it.[10][12] Long-term (>1 y) endometrial data are limited; counsel patients to report any postmenopausal bleeding. The current label also lists postmarketing reports of endometrial cancer/hyperplasia and DVT/PE, without an estimable frequency or established causal relationship.[10][12]

VTE risk — real-world signal favorable​

SourcenVTE signal
Clinical trials (up to 15 mo)PooledDVT 2.26 / 1,000 woman-y (2 cases) vs 3.15 / 1,000 (1 case) placebo — trials not powered for VTE[12]
Nordstrom 2020 MarketScan 2013–20178,188 ospemifene3.7 per 1,000 person-years VTE
Other SERMs11,77711.5 per 1,000 person-years
Untreated VVA220,24211.3 per 1,000 person-years

In the final 2013–2018 MarketScan claims cohort (8,977 ospemifene users), VTE incidence during the first continuous treatment episode was 3.39 per 1,000 person-years; among women aged 54–72 years, adjusted hazard ratios were 0.40 (95% CI 0.19–0.82) versus other SERMs and 0.47 (0.24–0.91) versus untreated VVA, with treatment selection and residual confounding possible.[44] Despite the observational VTE findings,[22] the FDA contraindication for active or prior DVT/PE/stroke/MI remains.[12]

Perioperative​

Per FDA label, if feasible, discontinue at least 4–6 weeks before high-VTE-risk surgery or during prolonged immobilization.[12]

Bone and lipid effects​

Bone​

  • In a 12-week phase 3 vaginal-dryness trial, 7 of 9 bone biomarkers decreased more with ospemifene than placebo; separate early-phase studies found bone-turnover marker effects comparable to raloxifene[7][8]
  • Maffei 2022 observational 12-month study (n = 128; 61 ospemifene, 67 controls): total-femur and lumbar-spine BMD were stable in the ospemifene group, while femoral-neck BMD declined; control-group BMD declined at all three sites; bone alkaline phosphatase decreased in the ospemifene group[23]
  • AYSEX real-world 12-month study (n = 100): no significant change in DXA or bone-resorption markers[24]
  • Ospemifene is not FDA-approved for osteoporosis.[12] Randomized evidence reports bone-turnover markers, while 12-month observational cohorts report DXA findings; fracture-outcome data are unavailable.[7][23][24]

Lipids​

Archer 2017 post-hoc analysis (n = 2,166):[11]

  • HDL ↑ 4.4% at 3 mo versus 0.2% placebo (p < 0.0001), and 5.1% at 6 mo versus 1.5% placebo (p = 0.0359)[11]
  • LDL decrease (p < 0.05)
  • Triglycerides neutral (unlike oral estrogens)

Use in breast cancer survivors — regulatory divergence​

SourcePosition
FDA labelAdvises against use with known/suspected or a history of breast cancer; estrogen-dependent neoplasia is contraindicated[12]
EMA (Europe)European labeling permits consideration for VVA only after all breast-cancer treatment, including adjuvant therapy, is completed[28]
AUA/SUFU/AUGS 2025Ospemifene is not known to increase breast-cancer risk (statement 21), but few studies address breast-cancer survivors; the guideline text notes the FDA warning and says clinicians may recommend it in a patient with a breast-cancer history using informed shared decision-making with the treating oncologist[29]
NAMS 2020Not recommended for GSM in women with known or suspected breast cancer because of the label[31]
NCCN Survivorship 2026"Currently ospemifene is contraindicated in survivors with a history of estrogen-dependent cancers"[25]
ACOG 2021 clinical consensusFDA warning is "controversial"; post-approval data have not demonstrated increased recurrence; long-term safety data are limited; clinicians should discuss the label warning with the patient and use clinical judgment (2021 consensus lists ospemifene as an option to consider in survivors)[18]

Supporting clinical data​

  • Preclinical: antagonist activity in breast tissue; anti-proliferative effects[18][26]
  • PEONY 6-month (n = 64 breast cancer survivors without ongoing oncologic treatment): in this observational cohort, VVA symptoms and treatment satisfaction improved; fewer women reported moderate/severe recurring-UTI and postcoital-cystitis symptoms; no severe adverse events or cancer recurrence were observed during follow-up[16]
  • PEONY 12-month (n = 385 overall; 145 ospemifene including breast cancer survivors): sustained efficacy; ospemifene users had approximately 3× higher odds of clinically relevant satisfaction improvement versus local estrogen (OR 2.85; 95% CI 1.33–6.11)[17]

The US label advises against use in women with known or suspected or prior breast cancer. European labeling differs after completion of cancer treatment. Any discussion requires oncology involvement.[16][18][27]

Long-term efficacy and adherence​

AYSEX 12-month real-world (n = 100)[24]​

  • Significant improvement in all VHI domains sustained at 12 months
  • Only 1 patient remained with vaginal atrophy at 12 months (versus 100% at baseline)[24]
  • Significant improvement in sexual function and QoL
  • No significant change in endometrial thickness, mammography, or bone health

PEONY 12-month (n = 385; 145 ospemifene / 240 local estrogen)[17]​

  • 75.9% of ospemifene participants completed 12-month follow-up (versus 78.7% of local-estrogen participants); these are follow-up completion rates[17]
  • Treatment satisfaction 7.02 at 3 mo, then 8.32 at 12 mo (p < 0.001)
  • Ospemifene was associated with greater odds of clinically relevant improvement in treatment satisfaction versus local estrogen at 12 months (adjusted OR 2.85; 95% CI 1.33–6.11)[17]

Practical prescribing​

ParameterRecommendation
Ideal candidatePostmenopausal woman with moderate-to-severe dyspareunia or dryness who prefers oral therapy over vaginal application[12]
Dose60 mg PO daily with food (absorption is food-dependent)[12]
OnsetVaginal dryness differed from placebo by week 4 in one RCT; coprimary outcomes were assessed at week 12[2][34]
DurationShortest duration consistent with treatment goals and risks; reassess periodically whether treatment is still needed[12]
ProgestogenNot mandated; one simple hyperplasia without atypia and no cancer in trials through 52 weeks; evaluate abnormal bleeding[12]
MonitoringEvaluate postmenopausal bleeding per label; do not perform endometrial surveillance solely because of ospemifene use [12][29]
Avoid inUndiagnosed abnormal genital bleeding; estrogen-dependent neoplasia; active or prior DVT, PE, stroke, or MI; hypersensitivity; pregnancy; known/suspected or prior breast cancer; severe hepatic impairment; concurrent fluconazole or rifampin[12]
PerioperativeIf feasible, discontinue at least 4–6 weeks before surgery associated with increased thromboembolic risk or during prolonged immobilization.[12]
Suspected VTE or strokeDiscontinue ospemifene immediately if VTE, thromboembolic stroke, or hemorrhagic stroke occurs or is suspected.[12]
Counsel aboutHot flashes ~8.5%; vaginal discharge ~4%; take with food[21]
Breast cancer survivorsUS label advises against use; European restrictions differ after completion of all cancer treatment; oncology discussion[18]
CostBrand-name only; ~$200–300/month uninsured

Comparative summary — ospemifene vs vaginal estrogen vs vaginal DHEA​

FeatureOspemifene (oral SERM)Vaginal estrogenVaginal DHEA (prasterone)
RouteOralVaginal (cream, insert, ring)Vaginal insert
Dosing frequencyDaily with foodEstradiol inserts and cream: daily for 2 weeks, then maintenance (inserts twice weekly; cream 1–3×/wk); Premarin cream: twice weekly or daily for 21 days then 7 days off, depending on indication; Estring: every 3 months[29][33]Daily at bedtime
FDA indicationsModerate-to-severe dyspareunia or vaginal dryness due to menopause[12]Product-specific; for example, atrophic vaginitis, kraurosis vulvae, or moderate-to-severe dyspareunia due to menopause for Premarin vaginal cream[33]Dyspareunia (US)
OAB improvementExploratory small observational studies; not established therapy[4][5][6][15]May be offered when GSM coexists with OAB [29]Two uncontrolled 12-week GSM cohorts reported improved OAB or urgency scores (n = 32 and 21)[40][41]
UTI preventionObservational urinary-symptom signal; prophylactic efficacy unestablished[16]Five-trial meta-analysis in postmenopausal women: vaginal estrogen versus placebo, rUTI RR 0.42 (95% CI 0.30–0.59)[32]; AUA/SUFU/AUGS 2025 recommends local low-dose vaginal estrogen [29]Not established
FSFI sexual-function domainsAll six domains improved versus placebo at 12 wk in one RCT secondary analysis[36]In a 12-week RCT, 10 and 25 µg estradiol softgel inserts improved pain and lubrication versus placebo; 25 µg also improved arousal and satisfaction[42]All six domains including desire / arousal
Systemic exposureSystemic SERMLow with local low-dose formulationsLow, but estrogen/androgen metabolites can increase
Hot flashesHot flushes reported in 8.5% versus 3.3% placebo (treatment-emergent, pooled trials)[21]Premarin vaginal cream has no vasomotor indication[33]Intrarosa has no vasomotor indication[43]
Bone effectsFavorable biomarkers (not FDA-approved)[7]In a randomized trial of 30 women aged at least 60, a 7.5 µg/day estradiol vaginal ring showed a 2.1% increase in forearm bone density versus a 2.7% decrease without treatment at 6 months; fractures were not assessed[37]None demonstrated
Lipid effects↑HDL, ↓LDL, neutral TGNoneNone
VTE considerationsActive/prior DVT/PE contraindication and boxed warning[12]Local low-dose observational evidence is reassuring[29]; Premarin cream and Estring labels contraindicate active or prior DVT/PE[33][39]Rare-event comparative safety not established
Endometrial safetyThickening and one simple hyperplasia without atypia; no cancer in 52-week trialsVagifem 10 µg: one complex hyperplasia without atypia and one adenocarcinoma among 172 end-of-study biopsies after 12 months; a separate 12-month study found one complex hyperplasia among 297 biopsies[38]No hyperplasia (52 wk)
Breast cancer survivorsUS label advises against useLocal low-dose therapy may be discussed after nonhormonal optionsLabel warning; limited evidence; oncology discussion when estrogen is not an option
Progestogen neededNot mandated; coadministration unstudied[12]No (low dose)No
Generic60-mg equivalent FDA-approved in 2024; listed discontinued in April 2025, so verify current supply[1]Yes (most)No

Evidence Summary​

IndicationEvidence levelKey source
Dyspareunia + vaginal drynessPhase III trials and meta-analysis; AUA/SUFU/AUGS 2025 recommendation is Conditional (Grade C)Di Donato 2019[13]; FDA label[12]; AUA guideline[29]
Endometrial findings through 52 wkPooled trial safety observations; longer-term cancer risk uncertainConstantine 2015[10]; Simon 2023 NMA[14]
OAB / UUI improvementSmall uncontrolled 12-week studies, including one retrospective seriesSchiavi 2017[4] / 2018[5]; Novara 2020[6]; Russo 2023[15]
Bone biomarkersLevel 2–3de Villiers 2019[7]; Maffei 2022[23]
Lipid effectsLevel 2Archer 2017[11]
VTE in real-world useLevel 3 (PASS)Nordstrom 2020[22]
Long-term efficacy / adherence (12 mo)Level 3AYSEX[24]; PEONY[17]
Breast cancer survivorsLevel 3PEONY[16][17]; ACOG consensus[18]

Clinical Positioning​

  • Ospemifene, an oral estrogen agonist/antagonist, is FDA-approved at 60 mg once daily with food for moderate-to-severe dyspareunia and vaginal dryness due to menopause. Absorption nearly doubles with a fatty meal.[12]
  • Avoid with fluconazole (2.7× AUC) and rifampin (58% AUC loss). The fluconazole interaction collides with common VVC management in the same patient population.[2][12]
  • Ospemifene is not an established OAB/UUI treatment.[6]
  • Ospemifene is not established for rUTI prevention. The 2025 AUA/SUFU/AUGS GSM guideline recommends local low-dose vaginal estrogen for GSM with rUTI .[29] PEONY's self-reported urinary-symptom signal is hypothesis-generating only.[16]
  • Hot flushes were the most common treatment-emergent event (8.5%), and led to discontinuation in 1.0% of ospemifene recipients in the pooled trials.[21] Counsel preemptively, particularly in women with pre-existing vasomotor symptoms.[2][21]
  • In pooled trials through 52 weeks, no endometrial cancer was observed and <1% of ospemifene recipients had hyperplasia; some patients developed thickening ≥5 mm.[10] Long-term (>1 y) endometrial data remain limited; evaluate any postmenopausal bleeding.[10][14]
  • Observational VTE comparisons do not establish protection or comparative safety.[22] The FDA contraindications for active or prior DVT, PE, stroke, and MI remain.[12]
  • If feasible, discontinue at least 4–6 weeks before high-VTE-risk surgery or during prolonged immobilization per label.[12]
  • Breast-cancer recommendations differ by jurisdiction. The US label advises against use with known, suspected or prior breast cancer; European labeling permits consideration only after all treatment is complete.[18][17]
  • Bone and lipid effects are favorable but off-label.[7][11]
  • Counsel that, in a randomized trial of 631 postmenopausal women, vaginal dryness improved versus placebo by week 4; coprimary outcomes were assessed at week 12.[2][34]

See Also​

References​

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4. Schiavi MC, Zullo MA, Faiano P, et al. "Retrospective analysis in 46 women with vulvovaginal atrophy treated with ospemifene for 12 weeks: improvement in overactive bladder symptoms." Gynecol Endocrinol. 2017;33(12):942–945. doi:10.1080/09513590.2017.1323859

5. Schiavi MC, Sciuga V, Giannini A, et al. "Overactive bladder syndrome treatment with ospemifene in menopausal patients with vulvovaginal atrophy: improvement of sexuality?" Gynecol Endocrinol. 2018;34(8):666–669. doi:10.1080/09513590.2018.1441398

6. Novara L, Sgro LG, Mancarella M, et al. "Potential effectiveness of ospemifene on detrusor overactivity in patients with vaginal atrophy." Maturitas. 2020;138:58–61. doi:10.1016/j.maturitas.2020.05.001

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10. Constantine GD, Goldstein SR, Archer DF. "Endometrial safety of ospemifene: results of the Phase 2/3 clinical development program." Menopause. 2015;22(1):36–43. doi:10.1097/GME.0000000000000275

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12. OSPHENA (ospemifene) prescribing information. DailyMed, accessed September 11, 2026.

13. Di Donato V, Schiavi MC, Iacobelli V, et al. "Ospemifene for the treatment of vulvar and vaginal atrophy: a meta-analysis of randomized trials. Part I: evaluation of efficacy." Maturitas. 2019;121:86–92. doi:10.1016/j.maturitas.2018.11.016

14. Simon JA, Ferenczy A, Black D, et al. "Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis." Menopause. 2023;30(8):855–866. doi:10.1097/GME.0000000000002211

15. Russo E, Misasi G, Montt-Guevara MM, Giannini A, Simoncini T. "Effects of ospemifene on overactive bladder in postmenopausal women with vulvovaginal atrophy." Climacteric. 2023;26(3):284–288. doi:10.1080/13697137.2023.2184251

16. Villa P, Cassani C, Nappi RE, et al. "Quality of life and satisfaction with ospemifene for treating vulvovaginal atrophy in breast cancer survivors: six-month results from the PatiEnt SatisfactiON studY (PEONY)." Clin Breast Cancer. 2025. doi:10.1016/j.clbc.2025.08.001

17. Meriggiola MC, Villa P, Cagnacci A, et al. "Treatment of vulvovaginal atrophy is associated with high levels of satisfaction and improves symptom severity and patient-reported outcomes: 12-month results of the PatiEnt SatisfactiON studY (PEONY)." Menopause. 2026. doi:10.1097/GME.0000000000002737

18. 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

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