Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS

Abstract

Background Serotonin (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. Methods The 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 hyperemia index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire. Results Mean 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 associated with elevations in platelet 5-HT only in the oCEE group (r = −0.5, p = 0.02). Conclusions Effects 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.

Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy

“…This is an important issue to consider, as studies have reported a greater frequency of sleep problems associated with age at discontinuation, type and duration of MHT [26,27]. Differences in various physiological parameters between o-CEE and t-E2 have been observed in women participating in KEEPS including differences in effects on lipids, glucose metabolism [28], contents of vasoactive agents in circulating platelets [15], mood [29] and brain volumes [30]. Therefore, our results add to the accumulating evidence that various types of MHT are not equal and precision is required in discussing their efficacy relative to target outcome, mode of delivery, composition and dose.…”

“…This study evaluated a subgroup of white participants (n = 74) from the Kronos Early Estrogen Prevention Study (KEEPS; NCT00154180) Cognitive and Affective Ancillary study (KEEPS-Cog) at Mayo Clinic, Rochester MN [15]. KEEPS was a randomized, double-blind, placebo-controlled trial studying the effects of MHT, started within 3 years of menopause, on progression of cardiovascular disease.…”

Hemostasis and female sex hormones

“…На сегодняшний день последние клинические исследования (ELITE 2016 и KEEPS 2016) подтверждают пользу раннего применения эстроген-гестагенной менопаузальной терапии с целью замедления темпов развития атеросклероза и первичной профилактики сердечно-сосудистой патологии у женщин в ранней менопаузе. При этом исследователи выдвигают временную теорию применения МГТ (раннее начало применения МГТ от возникновения менопаузы обеспечивает наилучшее протекторное действие гормонов на сосудистую стенку) как залог успешной профилактики ССЗ [17,18].…”

Effects of Vitamin D Supplementation on Depression Status, Selected Pro-inflammatory Biomarkers and Neurotransmitters in Depressive Patients: A Study Protocol

“…vitamin D) are contradictory (12). Several studies have reported that insufficient levels of serotonin, as a neurotransmitter involved in mood and behavior, may result in depression (13)(14)(15). However, most of these reports are based on serum serotonin measurements in depressive patients (16)(17)(18), while platelet serotonin measurement is a further accurate alternative of brain serotonin (15,19).…”

“…Several studies have reported that insufficient levels of serotonin, as a neurotransmitter involved in mood and behavior, may result in depression (13)(14)(15). However, most of these reports are based on serum serotonin measurements in depressive patients (16)(17)(18), while platelet serotonin measurement is a further accurate alternative of brain serotonin (15,19). It is broadly accepted that dysfunction of oxytocin, another neurotransmitter, includes important roles in mood, behavior, brain development and sociality (21)(22)(23)(24).…”