Evidence map›Paper›PMID 40576264›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2026

Sex Hormones Mediate Intensive Lifestyle Intervention-Induced Bone Mineral Density Changes: Look AHEAD Sex Hormone Study.

Jiahuan Helen He, Wendy L Bennett, Jianqiao Ma, Chigolum P Oyeka, Lakshmi Spurthi Kodali, Nityasree Srialluri, Teresa Gisinger, Mark Woodward, Erin D Michos, Karen C Johnson and 1 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Jiahuan Helen HeDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.ORCID 0009-0006-7769-4444
Wendy L BennettDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Jianqiao MaDepartment of Pediatrics, Division of General Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chigolum P OyekaDepartment of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lakshmi Spurthi KodaliDivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nityasree SrialluriDivision of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Teresa GisingerDivision of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria.
Mark WoodwardThe George Institute for Global Health, School of Public Health, Imperial College London, London SW7 2BX, UK.ORCID 0000-0001-9800-5296
Erin D MichosDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Karen C JohnsonDepartment of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Dhananjay VaidyaDepartment of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0002-7164-1601

Funding

The Effect of Sex Hormones on Cardiometabolic Outcomes in Men and Women with Diabetes: The Look AHEAD (Action for Health in Diabetes) StudyR01DK127222 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BENNETT, WENDY LYNET, VAIDYA, DHANANJAY MADHUKAR · 2020 to 2024
$2.5M
National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases R01DK127222National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases U01DK57149NIDDK NIH HHS R01 DK127222
6 · The paper itself

Abstract

contextThe Look AHEAD (Action in Health for Diabetes) randomized controlled trial, which compared an Intensive Lifestyle Intervention (ILI) to Diabetes Support and Education (DSE) in people with overweight/obesity and type 2 diabetes (T2D), showed a greater decline in bone mineral density (BMD) along with greater weight loss in the ILI group. Because weight loss interventions change sex hormones and also affect BMD, understanding the role of sex hormones on these changes has implications for bone health in people with diabetes.

objectiveWe assessed sex hormone mediation on BMD changes due to ILI, by sex, among postmenopausal women and older men over 4 years of follow-up.

methodsIn the Look AHEAD Sex Hormone Ancillary Study, we applied structural equation models to estimate the effects of ILI (vs DSE) on hip, femoral neck, and whole-body BMD after 4 years of follow-up, temporally mediated by sex hormones estradiol (E2), total testosterone, bioavailable testosterone, and sex hormone binding globulin (SHBG) measured at 1 year after baseline (nadir of weight loss).

resultsIn women, an ILI-associated decrease in estradiol of 14% from baseline to year 1 mediated a decline in whole-body BMD (-1.15 mg/cm2, 95% CI: -2.54, -0.21). In men, an ILI-associated increase of 11% in total testosterone mediated a decline of hip BMD (-1.18 mg/cm2, 95% CI: -2.68, -0.13).

conclusionILI-associated changes in estradiol and total testosterone resulted in whole-body and hip bone loss, providing insights in the potential role of sex hormones in bone loss accompanying weight loss in older adults with T2D who are at a higher risk of bone fractures.

Indexed as

Bone DensityDiabetes Mellitus, Type 2Gonadal Steroid HormonesLife StyleObesityAgedEstradiolFemaleFollow-Up StudiesHumansMaleMiddle AgedOverweightSex Hormone-Binding GlobulinTestosteroneWeight LossEstradiolGonadal Steroid HormonesSex Hormone-Binding GlobulinTestosteronebone mineral densitiesdiabeteslifestyle interventionsmediationsex hormones

Identifiers

PMID40576264
PMCPMC12819871

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.