SynthesisMenopause (New York, N.Y.)2020
Systemic estradiol levels with low-dose vaginal estrogens.
Synthesis in Menopause (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- A systematic review of randomised clinical trials - The safety of vaginal hormones and selective estrogen receptor modulators for the treatment of genitourinary menopausal symptoms in breast cancer survivors.Post reproductive health · 2023Pooled it
- Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: a meta-analysis of randomized controlled trials.International urogynecology journal · 2021Pooled it
- Report of the FDA's expert panel on hormone therapy.Menopause (New York, N.Y.) · 2026Review
- Establishment of harmonized international reference ranges for plasma estradiol concentrations in postmenopausal women.The Journal of clinical endocrinology and metabolism · 2026Article
- Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology.Neurology · 2026Article
- Vaginal Estrogen for Urinary Tract Infection Prevention: A Narrative Review of Evidence, Guidelines, and Regulatory Gaps.Gynecologic and obstetric investigation · 2026Review
- Survival Outcomes in Breast Cancer Patients With Use of Vaginal Estrogen Therapy: A SEER Analysis.JCO oncology practice · 2026Article
- Does estradiol supplementation improve rotator cuff repair outcomes in postmenopausal women?JSES reviews, reports, and techniques · 2026Review
- Case-Based Perspectives on the Management of Genitourinary Syndrome of Menopause.Clinics and practice · 2026Review
- Electrospun poly-4-hydroxybuterate scaffolds enable local zero-order estradiol delivery and promote collagen maturation in a hypoestrogenic rat model for pelvic organ prolapse repair.Biomaterials and biosystems · 2026Article
- Treating Genitourinary Syndrome of Menopause in Postmenopausal Women with a History of Breast Cancer.Drugs & aging · 2026Review
- Menopausal hormone therapy and long term mortality: nationwide, register based cohort study.BMJ (Clinical research ed.) · 2026Article
- Association of Menopause and Hormonal Contraceptive Use With Chronic Rhinosinusitis: An "All of Us" Analysis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- [Russian eligibility criteria for prescription of menopausal hormone therapy to patients with cardiovascular and metabolic diseases. Agreement document of RKO, ROAG, RAE, EAT, AFR, RNMOT, RAGG].Problemy endokrinologii · 2026Article
- Reproductive Longevity: Innovative Approaches Beyond Hormone Replacement Therapy.Medicina (Kaunas, Lithuania) · 2026Review
- Urinary manifestations of genitourinary syndrome of menopause: a review of the pathophysiology, clinical presentation, and management.Gynecology and pelvic medicine · 2026Review
- Synthesizing the latest guideline-based recommendations for the management of female hypogonadism.Archives of endocrinology and metabolism · 2025Review
- Addressing the Needs of Breast Cancer Survivors.Current oncology reports · 2025Review
- Improving Cardiovascular Clinical Competencies for the Menopausal Transition: A Focus on Cardiometabolic Health in Midlife.JACC. Advances · 2025Article
- Addressing Sexual Health in Breast Cancer Survivors: Evidence-Based Practices and Clinical Considerations.Current treatment options in oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women.
methodsPubMed was searched for studies reporting systemic estradiol levels with lower-dose vaginal estrogens (≤25 μg estradiol or 0.3 mg conjugated equine estrogens). Estradiol levels at baseline and during treatment, area under the curve, and maximum estradiol concentrations were summarized by dose within assay type. A proposed range of systemic estradiol in normal, untreated, postmenopausal women was estimated by conservatively pooling means and standard deviations from published studies.
resultsMean basal estradiol levels were 3.1 to 4.9 pg/mL using liquid or gas chromatography/mass spectroscopy (LC or GC/MS/MS) with a range of undetectable to 10.5 pg/mL using radioimmunoassay. Systemic estradiol levels with vaginal estrogens reflected their doses as measured with LC or GC/MS/MS in different studies: 7.1 to 9.1 pg/mL and 16.7 to 22.7 pg/mL with a 25-μg softgel capsule insert and a tablet insert, respectively; 4.6 to 7.4 pg/mL and 6.6 to 14.8 pg/mL with a 10-μg softgel capsule and a tablet insert, respectively; and 3.6 to 3.9 pg/mL with a 4-μg softgel capsule insert. A mean systemic estradiol concentration ranging from undetectable to 10.7 pg/mL is proposed as an estimate for basal estradiol levels in normal, untreated, postmenopausal women. Systemic estradiol absorption may be influenced by the placement of estradiol higher (as with an applicator) versus lower (as without an applicator) in the vagina, as estradiol transport to the uterus would be more likely further away than closer to the introitus.
conclusionSerum estradiol concentrations were generally lower when measured with more specific and sensitive assays. Estradiol absorption was dose-dependent, and may be influenced by dose, formulation, and positioning in the vagina. Very low systemic estradiol absorption with low/ultralow-dose vaginal estrogens may potentially decrease any adverse events that may be associated with higher doses of vaginal estrogens used for treating moderate to severe VVA due to less estradiol exposure.
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What OpenQuestion holds
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.