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? Agonists as a novel therapy for menopausal hot flashes.

ABSTRACT: The etiology of postmenopausal hot flashes is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing kisspeptin, neurokinin B and dynorphin-called KNDy neurons-are located adjacent to the thermoregulatory center. KNDy neurons regulate pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Dynorphin may inhibit this system by binding ? opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation.A double-blind, cross-over, placebo-controlled pilot study evaluated the effects of a ? agonist. Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate to severe hot flashes (aged 48-60 y) were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all three interventions: placebo, standard-dose pentazocine/naloxone (50/0.5?mg), or low-dose pentazocine/naloxone (25/0.25?mg). In an inpatient research setting, each participant received the three interventions, in randomized order, on three separate days. On each day, an intravenous catheter was inserted for LH blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded.The mean (SEM) hot flash frequency 2 to 7?hours after therapy initiation was lower than that for placebo (standard-dose ? agonist, 4.75 [0.67] hot flashes per 5?h; low-dose ? agonist, 4.50 [0.57] hot flashes per 5?h; placebo, 5.94 [0.78] hot flashes per 5?h; P?=?0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some--but not all--women.This pilot study suggests that ? agonists may affect menopausal vasomotor symptoms.

SUBMITTER: Oakley AE

PROVIDER: S-EPMC4651855 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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κ Agonists as a novel therapy for menopausal hot flashes.

Oakley Amy E AE Steiner Robert A RA Chavkin Charles C Clifton Donald K DK Ferrara Laura K LK Reed Susan D SD

Menopause (New York, N.Y.) 20151201 12

<h4>Objective</h4>The etiology of postmenopausal hot flashes is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing kisspeptin, neurokinin B and dynorphin-called KNDy neurons-are located adjacent to the thermoregulatory center. KNDy neurons regulate pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Dynorphin may inhibit this system by binding κ opioid receptors within ...[more]

PMID: 25988798

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Project description:BackgroundEvidence on the impact of expectancy on acupuncture treatment response is conflicting.ObjectivesThis secondary analysis of a randomized sham-controlled trial on acupuncture for menopausal hot flashes investigated whether treatment expectancy score was associated with hot flash score at end-of-treatment. Secondary analyses investigated whether there were associations between other pre-specified factors and hot flash score.Study designWomen experiencing moderately-severe hot flashes were randomized to receive 10 sessions of real or sham acupuncture over eight weeks. Hot flash score was collected using a seven-day hot flash diary, and expectancy using the modified Credibility and Expectancy Questionnaire immediately after the first treatment. Linear mixed-effects models with random intercepts were used to identify associations between expectancy score and hot flash score at end-of-treatment. Regression was also used to identify associations between pre-specified factors of interest and hot flash score. Because there was no difference between real and sham acupuncture for the primary outcome of hot flash score, both arms were combined in the analysis.Results285 women returned the Credibility and Expectancy Questionnaire, and 283 women completed both expectancy measures. We found no evidence for an association between expectancy and hot flash score at end-of-treatment for individual cases in either acupuncture or sham group. Hot flash scores at end-of-treatment were 8.1 (95%CI, 3.0 to 13.2; P = 0.002) points lower in regular smokers compared to those who had never smoked, equivalent to four fewer moderate hot flashes a day.ConclusionIn our study of acupuncture for menopausal hot flashes, higher expectancy after the first treatment did not predict better treatment outcomes. Future research may focus on other determinants of outcomes in acupuncture such as therapist attention. The relationship between smoking and hot flashes is poorly understood and needs further exploration.

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? Agonists as a novel therapy for menopausal hot flashes.

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κ Agonists as a novel therapy for menopausal hot flashes.

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