Evidence map›Paper›PMID 42678760›Full record

ArticleEndocrinology2026

Targeting estrogen to the brain via DHED does not seem to protect against metabolic dysfunction in obese OVX mice.

Celine Camon, Elodie Kip, Rebecca Lord, Caroline Decourt, Mel Prescott, Jenny Clarkson, Norma P Sandoval, Paul B Vander, J Edward Van Veen, Katalin Prokai-Tatrai and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Celine CamonCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.ORCID 0009-0009-6707-5975
Elodie KipCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.
Rebecca LordCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.
Caroline DecourtCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.
Mel PrescottCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.
Jenny ClarksonCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.
Norma P SandovalDepartment of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Paul B VanderDepartment of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-4348-6103
J Edward Van VeenDepartment of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Katalin Prokai-TatraiDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Stephanie M CorreaDepartment of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Rebecca E CampbellCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.ORCID 0000-0002-0309-532X
Michael GarrattCentre for Neuroendocrinology, University of Otago, Dunedin 9016, New Zealand.

Funding

British Society for NeuroendocrinologyElman Poole FoundationHope Foundation for Research on AgeingUniversity of Otago's Doctoral Scholarship
6 · The paper itself

Abstract

Menopausal hormone therapy (MHT), prescribed for climacteric symptoms including hot flushes and weight gain, contains estrogens such as 17 beta-estradiol (17βE2). However, estrogen receptor activation by MHT may increase reproductive cancers in some people. As the protective metabolic effects of 17βE2 are partly mediated through the arcuate nucleus (ARC) of the hypothalamus, restricting 17βE2 actions to the brain could serve as a safer method for MHT. The prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) is enzymatically converted into 17βE2 exclusively within the brain. DHED has already demonstrated positive benefit in rodent models of hot flushes and cognitive decline, while avoiding peripheral hormonal burden. Therefore, we hypothesized that DHED treatment in obese female mice would act within the hypothalamus to provide the same beneficial metabolic effects as 17βE2. Female mice were ovariectomized, placed on a high fat diet and split into control, 17βE2, or DHED treatment groups. Body weight, uterine weight, glucose tolerance and peripheral concentrations of luteinizing hormone were recorded, along with the expression of the progesterone receptor and kisspeptin mRNA within the ARC. Delivery of DHED at a similar dose as 17βE2 failed to improve metabolic parameters or recapitulate the hypothalamic responses induced by 17βE2. Our findings subsequently show that delivery of DHED at higher doses elicited estrogen-like actions within the brain but still failed to improve metabolic health. Additional investigations surrounding DHED's conversion to 17βE2 within the hypothalamus are warranted to conclude whether estradiol actions exclusively within the central nervous system can independently regulate protective effects on metabolism.

Indexed as

BrainEstrogensObesityAnimalsArcuate Nucleus of HypothalamusBody WeightDiet, High-FatEstradiolFemaleMiceMice, Inbred C57BLMice, ObeseOvariectomyEstradiolEstrogensDHEDestrogenhypothalamusmenopausemetabolic health

Identifiers

PMID42678760
PMCPMC13627730

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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.