Ultralow-Dose Micronized 17β-Estradiol and Bone Density and Bone Metabolism in Older Women: A Randomized Controlled Trial
Abstract
Context Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known. Objective To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17beta-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women. Design, setting, and participants Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment. Intervention Dosage of 0.25 mg/d of micronized 17beta-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. Main outcome measures The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment. Results Mean BMD increased at all sites for participants taking low-dose estrogen (17beta-estradiol) compared with placebo (P Conclusions In older women, a dosage of 0.25 mg/d of 17beta-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects.…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fracture risk rises as estrogen falls in postmenopausal women, and a quarter of the breast/uterus dose can lower resorption and raise bone mass in older women.
“Fracture risk is inversely related to estrogen levels in postmenopausal women, and as little as one-quarter of the dose of estrogen that stimulates the breast and uterus is sufficient to decrease bone resorption and increase bone mass in older women”
From Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005) · cites this paper as [13]
Much lower estrogen doses can prevent bone loss in postmenopausal women.
“The fact that much lower doses of estrogen can prevent bone loss in postmenopausal women (13) suggests that the cost/benefit ratio might be reversed with such therapy, but appropriate long-term studies have not yet been carried out.”
From Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005) · cites this paper as [13]
Cites
Flagged first, then by citations
Cited by
Sorted by citations
Studenski, S. A., Peters, K. W., Alley, D. E., Cawthon, P. M., McLean, R. R., Harris, T. B., Ferrucci, L., Guralnik, J. M., Fragala, M. S., Kenny, A. M., et al. (2014) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glu010 · Cited by 2,545 · see citing works
Self-citationPathogenesis of osteoporosis: concepts, conflicts, and prospects
Raisz, L. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27071 · Cited by 1,779 · see citing works
DHEA in elderly women and DHEA or testosterone in elderly men.
Nair, K. S., Rizza, R. A., O'Brien, P., Dhatariya, K., Short, K. R., Nehra, A., Vittone, J. L., Klee, G. G., Basu, A., Basu, R., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054629 · Cited by 566 · see citing works
Grip Strength Cutpoints for the Identification of Clinically Relevant Weakness
Alley, D. E., Shardell, M. D., Peters, K. W., McLean, R. R., Dam, T.-T. L., Kenny, A. M., Fragala, M. S., Harris, T. B., Kiel, D. P., Guralnik, J. M., et al. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu011 · Cited by 535 · see citing works
Self-citationCawthon, P. M., Peters, K. W., Shardell, M. D., McLean, R. R., Dam, T.-T. L., Kenny, A. M., Fragala, M. S., Harris, T. B., Kiel, D. P., Guralnik, J. M., et al. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu023 · Cited by 388 · see citing works
Self-citationAn evidence-based comparison of operational criteria for the presence of sarcopenia
Dam, T.-T., Peters, K. W., Fragala, M., Cawthon, P. M., Harris, T. B., McLean, R., Shardell, M., Alley, D. E., Kenny, A., Ferrucci, L., et al. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu013 · Cited by 363 · see citing works
Self-citationStanczyk, F. Z., Archer, D. F., & Bhavnani, B. R. (2013) · Contraception · doi:10.1016/j.contraception.2012.12.011 · Cited by 201 · see citing works
Kenny, A. M., Boxer, R. S., Kleppinger, A., Brindisi, J., Feinn, R., & Burleson, J. A. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.03019.x · Cited by 125 · see citing works
Self-citationThe impact of micronized progesterone on the endometrium: a systematic review
Stute, P., Neulen, J., & Wildt, L. (2016) · Climacteric · doi:10.1080/13697137.2016.1187123 · Cited by 109 · see citing works
- Authors
- Prestwood, K. M., Kenny, A. M., Kleppinger, A., & Kulldorff, M.
- Affiliations
- UConn Health (US)
- ORCID
- Kulldorff, Martin
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2003-08-27
- Volume
- 290
- Issue
- 8
- Pages
- 1042
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2109076870
- Cited by
- 200
- References
- 1
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 8 · 2013: 10 · 2012: 3
- FWCI
- 10.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p60ag013631-05)
- National Institute on Aging (5P60AG13631)
- National Center for Research Resources (M01RR006192)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- low-dose estrogen therapy, bone mineral density, bone turnover markers, postmenopausal women, osteoporosis prevention, bone resorption, bone-specific alkaline phosphatase, progesterone, mammography, older women, sex hormone levels, sex hormone-binding globulin
- MeSH terms
- Aged, Double-Blind Method, Estradiol, Female, Humans, Biomarkers, Absorptiometry, Photon, Bone Density, Osteoporosis, Postmenopausal, Bone Remodeling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
