Trial reportClimacteric : the journal of the International Menopause Society2016
Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS.
Trial report in Climacteric : the journal of the International Menopause Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Maternal excessive gestational weight gain as a risk factor for autism spectrum disorder in offspring: a systematic review.BMC pregnancy and childbirth · 2020Pooled it
- Lessons from KEEPS: the Kronos Early Estrogen Prevention Study.Climacteric : the journal of the International Menopause Society · 2021Trial
- Effect of menopausal hormone therapy on proteins associated with senescence and inflammation.Physiological reports · 2020Trial
- Menopausal hormone therapy, blood thrombogenicity, and development of white matter hyperintensities in women of the Kronos Early Estrogen Prevention Study.Menopause (New York, N.Y.) · 2020Trial
- Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy.Maturitas · 2017Trial
- The effects of menopausal hormone therapy on cardiovascular disease, cancer, cognition and depression in younger women: A systematic review.JRSM open · 2026Review
- Depression, Anxiety, and Bipolar Disorder and Atherosclerosis.Current atherosclerosis reports · 2026Review
- Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause.Nature aging · 2024Review
- The effect of hormone replacement therapy on cognition and mood.Clinical endocrinology · 2023Review
- The Kronos Early Estrogen Prevention Study (KEEPS): what have we learned?Menopause (New York, N.Y.) · 2019Review
- Effects of Estrogens on Platelets and Megakaryocytes.International journal of molecular sciences · 2019Review
- Changes in carotid artery intima-media thickness 3 years after cessation of menopausal hormone therapy: follow-up from the Kronos Early Estrogen Prevention Study.Menopause (New York, N.Y.) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundSerotonin (5-hydroxytryptamine, 5-HT) is modulated by sex steroid hormones and affects vascular function and mood. In the Kronos Early Estrogen Prevention Cognitive and Affective Ancillary Study (KEEPS-Cog), women randomized to oral conjugated equine estrogens (oCEE) showed greater benefit on affective mood states than women randomized to transdermal 17β-estradiol (tE2) or placebo (PL). This study examined the effect of these treatments on the platelet content of 5-HT as a surrogate measure of 5-HT synthesis and uptake in the brain.
methodsThe following were measured in a subset (n = 79) of women enrolled in KEEPS-Cog: 5-HT by ELISA, carotid intima-medial thickness (CIMT) by ultrasound, endothelial function by reactive hyperemic index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire.
resultsMean platelet content of 5-HT increased by 107.0%, 84.5% and 39.8%, in tE2, oCEE and PL groups, respectively. Platelet 5-HT positively correlated with estrone in the oCEE group and with 17β- estradiol in the tE2 group. Platelet 5-HT showed a positive association with RHI, but not CIMT, in the PL and oCEE groups. Reduction in mood scores for depression-dejection and anger-hostility was associated with elevations in platelet 5-HT only in the oCEE group (r = -0.5, p = 0.02).
conclusionsEffects of oCEE compared to tE2 on RHI and mood may be related to mechanisms involving platelet, and perhaps neuronal, uptake and release of 5-HT and reflect conversion of estrone to bioavailable 17β-estradiol in platelets and the brain.
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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.