Trial reportMenopause (New York, N.Y.)2017
TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol.
Trial report in Menopause (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Systemic estradiol levels with low-dose vaginal estrogens.Menopause (New York, N.Y.) · 2020Pooled it
- Association of Vaginal Estradiol Tablet With Serum Estrogen Levels in Women Who Are Postmenopausal: Secondary Analysis of a Randomized Clinical Trial.JAMA network open · 2022Trial
- Physical characteristics and properties of estradiol softgel vaginal inserts.Menopause (New York, N.Y.) · 2020Trial
- Patient acceptability and satisfaction with a low-dose solubilized vaginal estradiol softgel capsule, TX-004HR.Menopause (New York, N.Y.) · 2017Trial
- Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women.Journal of women's health (2002) · 2017Trial
- Establishment of harmonized international reference ranges for plasma estradiol concentrations in postmenopausal women.The Journal of clinical endocrinology and metabolism · 2026Article
- Survival Outcomes in Breast Cancer Patients With Use of Vaginal Estrogen Therapy: A SEER Analysis.JCO oncology practice · 2026Article
- Addressing Sexual Health in Breast Cancer Survivors: Evidence-Based Practices and Clinical Considerations.Current treatment options in oncology · 2025Review
- WISDOM survey: attitudes and behaviors of physicians toward vulvar and vaginal atrophy (VVA) treatment in women including those with breast cancer history.Menopause (New York, N.Y.) · 2019Article
Corrections and comments
- Commented on byTo the Editor.2017
- Commented on byIn Reply.2017
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo evaluate the pharmacokinetics of TX-004HR vaginal estradiol softgel capsules when used for treating moderate-to-severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy.
methodsA substudy of the REJOICE trial (multicenter, double-blind, placebo-controlled, phase 3) evaluated the pharmacokinetics of 4, 10, and 25-μg TX-004HR doses once/d for 2 weeks, followed by twice/wk for 10 weeks. Serum samples obtained at 2, 4, 6, 10, and 24 hours postdose on days 1 and 14, and once on day 84, were analyzed for area under the serum concentration-time curve, tmax, Cmin, Cavg, and Cmax for estradiol, estrone, and estrone conjugates.
resultsSeventy-two women (mean 59 y) participated. TX-004HR 4 μg showed no statistical differences from placebo in estradiol pharmacokinetic (PK) parameters. At 10 μg, estradiol Cmax was statistically higher than placebo on day 1, but was not different from placebo on day 14. With 25 μg, estradiol PK parameters were statistically higher than placebo. Estradiol Cavg values for 25 μg were 9.1 pg/mL on day 1 and 7.1 pg/mL on day 14. Estrone and estrone conjugate PK parameters with TX-004HR were lower than or similar to placebo across all doses. No drug accumulation was observed.
conclusionsVaginal TX-004HR resulted in negligible to very low systemic absorption of estradiol. No statistical differences in estradiol PK parameters were observed on day 14 with 4 and 10 μg, and only minor increases were observed with 25 μg (within the normal postmenopausal range). This PK substudy, in conjunction with the primary efficacy results, demonstrated that TX-004HR provided local benefits of estradiol with limited systemic exposure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.