Evidence-Based Hormone Therapies

Oxytocin

Oxytocin activity declines with advancing age, making the need for oxytocin supplementation progressively greater with age. While the decrease in number of cells producing oxytocin has not been confirmed in humans, it has been repeatedly reported in rats. Other indications confirm the age-related decline in oxytocin activity.

Firstly, the cells that produce oxytocin become less and less responsive to stimuli, resulting in insufficient production of oxytocin when additional amounts are necessary such as in social and familial encounters and sexual activities for example.

Secondly, the levels of oxytocin decrease in central areas of the brain that are important for emotions such as the septum and hippocampus. Levels of oxytocin have not been reported to decline significantly with age in the blood, nor in the pituitary gland or hypothalamus.

Thirdly, the oxytocin receptors on the target cells, necessary for oxytocin action, decrease in number with age, making it necessary for elderly people to have higher than normal oxytocin levels to saturate the receptors and benefit from sufficient oxytocin action, a compensation that does not spontaneously occur in elderly persons.

Healthy adults

 

Pharmacokinetics

 

Placebo-controlled trials: salivary oxytocin levels
Salivary levels of oxytocin: the persistence of higher levels more than 7 h after a single dose (24 IU) of intranasal oxytocin in healthy women (1 reference)
  1. Van Ijzendoorn MH, Bhandari R, van der Veen R, Grewen KM, Bakermans-Kranenburg MJ. Elevated salivary levels of oxytocin persist more than 7 h after intranasal administration. Front Neurosci. 2012 Dec 7;6:174.
Salivary levels of oxytocin: the persistence of higher levels more than 2 h after a single dose (16 IU) of intranasal oxytocin in healthy women (1 reference)
  1. Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, Ijzendoorn MH. Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration. Neuro Endocrinol Lett. 2012;33(1):21-5. Centre for Child and Family Studies, Leiden University, Leiden, the Netherlands.
Salivary oxytocin level: the dramatic (up to 200x) increase (peak 15 min. after) after a single dose of intranasal oxytocin treatment in healthy adults (with increased levels up to more than 4 hours later) (1 reference)
  1. Weisman O, Zagoory-Sharon O, Feldman R. Intranasal oxytocin administration is reflected in human saliva. Psychoneuroendocrinology. 2012 Sep;37(9):1582-6. Bar-Ilan University, Ramat-Gan, Israel.

 

Plasma oxytocin levels
Plasma oxytocin: Similar oxytocin systemic exposure can be achieved with intramuscular and inhaled oxytocin administration routes, and no safety concerns were identified with either route (1 reference)
  1. Fernando D, Siederer S, Singh S, Schneider I, Gupta A, Powell M, Richards D, McIntosh MP, Lambert P, Fowles S. Safety, Tolerability and pharmacokinetics of single doses of oxytocin administered via an inhaled route in healthy females: Randomized, single-blind, Phase 1 Study. EBioMedicine. 2017 Aug;22:249-255.
Plasma oxytocin levels: the increase in serum oxytocin (peak at 30 min.) after a single dose of intranasal oxytocin in healthy men (1 reference)
  1. Daughters K, Manstead AS, Hubble K, Rees A, Thapar A, van Goozen SH. Salivary Oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study. PLoS One. 2015 Dec 15;10(12):e0145104.
Plasma oxytocin levels: the increase (30-40 min.) after a single dose of intranasal oxytocin alone, and even greater increase after intake of ectacy (MDMA = 3,4-methylenedioxymethamphetamine) in healthy adults (1 reference)
  1. Kirkpatrick MG, Francis SM, Lee R, de Wit H, Jacob S. Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans. Psychoneuroendocrinology. 2014 Aug;46:23-31.

 

Cerebrospinal fluid and plasma levels of oxytocin
Cerebrospinal fluid and plasma levels of oxytocin: the increase (plasma levels peaked after 15 min., while CSF levels peaked after 75 min.) with a single dose of intranasal oxytocin in healthy adults (1 reference)
  1. Striepens N, Kendrick KM, Hanking V, Landgraf R, Wüllner U, Maier W, Hurlemann R. Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans. Sci Rep. 2013 Dec 6;3:3440.

 

Brain oxytocin levels
Brain oxytocin levels: the increase of oxytocin in the brain (with peak response at 39-51 min and its distribution (in core regions of the brain circuitry underpinning social cognition and emotion processing) with a single dose of intranasal oxytocin in healthy men (1 reference)
  1. Paloyelis Y, Doyle OM, Zelaya FO, Maltezos S, Williams SC, Fotopoulou A, Howard MA. A Spatiotemporal profile of in vivo cerebral blood flow changes following intranasal oxytocin in humans. Biol Psychiatry. 2016 Apr 15;79(8):693-705.

 

Oxytocin has significant Influence
Salivary vasopressin level: the +53% increase after a single dose of intranasal oxytocin administration in healthy men and women (1 reference)
  1. Weisman O, Schneiderman I, Zagoory-Sharon O, Feldman R. Salivary vasopressin increases following intranasal oxytocin administration. Peptides. 2013 Feb;40:99-103.
Ghrelin levels: the reduction of basal and lipopolysaccharide-induced ghrelin levels with intravenous oxytocin treatment in healthy men (1 reference)
  1. Vila G, Riedl M, Resl M, van der Lely AJ, Hofland LJ, Clodi M, Luger A. Systemic administration of oxytocin reduces basal and lipopolysaccharide-induced ghrelin levels in healthy men. J Endocrinol. 2009 Oct;203(1):175-9.
ACTH and cortisol secretion during labor: the reduction with intravenous oxytocin in women at delivery (1 reference)
  1. Izzo A, Rotondi M, Perone C, Lauro C, Manzo E, Casilli B, Rasile M, Amato G. Inhibitory effect of exogenous oxytocin on ACTH and cortisol secretion during labour. Clin Exp Obstet Gynecol. 1999;26(3-4):221-4.

 

Oxytocin has no significant influence
ACTH-secretion: no beneficial effects of single doses of intravenous oxytocin perfusion in healthy men (1 reference)
  1. Lewis DA, Sherman BM. Oxytocin does not influence adrenocorticotropin secretion in man. J Clin Endocrinol Metab. 1985 Jan;60(1):53-6.
LH secretion: no effect of intravenous oxytocin in fertile and amenorrheic women (1 reference)
  1. Monzani A, Petraglia F, De Leo V, Fabbri G, D’Ambrogio G, Volpe A, Genazzani AR. Glucocorticoids but not vasopressin or oxytocin inhibit luteinizing hormone secretion in patients with psychogenic amenorrhea. Gynecol Endocrinol. 1989;3(1):55-62.
Serum testosterone, progesterone, or cortisol: no influence of intranasal oxytocin treatment in healthy men and women (1 reference)
  1. Wirth MM, Gaffey AE, Martinez BS. Effects of intranasal oxytocin on steroid hormones in men and women. Neuropsychobiology. 2015;71(4):202-11.

 

Oxytocin influence on neurotransmitters and other hormones
Epinephrine plasma levels during sexual activity: the increase with a single dose of intranasal oxytocin but no effect of oxytocin on cortisol levels, prolactin levels or heart rate in healthy men (1 reference)
  1. Burri A, Heinrichs M, Schedlowski M, Kruger TH. The acute effects of intranasal oxytocin administration on endocrine and sexual function in males. Psychoneuroendocrinology. 2008 Jun;33(5):591-600.

 

Oxytocin influence on other neurotransmitters
Serotonin signaling: the inhibition of serotonin signaling with oxytocin treatment in healthy adults (1 reference)
  1. Mottolese R, Redouté J, Costes N, Le Bars D, Sirigu A. Switching brain serotonin with oxytocin. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8637-42.;
Serum neuropeptide Y increase after insulin-induced hypoglycemia: the reduction with intravenous oxytocin treatment in healthy men (1 reference)
  1. Coiro V, Volpi R, Volta E, Magotti MG, Cataldo S, Stella A, Chiodera P. Systemic oxytocin administration modulates NPY response to insulin-induced hypoglycemia in man. Horm Metab Res. 2011 Feb;43(2):146-7.

 

EMOTIONS

 

Emotion recognition
Neutral and emotional face stimuli: the switching of attention away from neutral and emotional face stimuli towards external salient social cues with a single dose of intranasal oxytocin treatment by enhancing right anterior insula responses and its control over the left posterior insula in healthy adults (1 reference)
  1. Yao S, Becker B, Zhao W, Zhao Z, Kou J, Ma X, Geng Y, Ren P, Kendrick KM. Oxytocin Modulates Attention Switching Between Interoceptive Signals and External Social Cues. Neuropsychopharmacology. 2018 Jan;43(2):294-301
Recognition of emotional facial expressions: the improvement (faster recognition of emotional facial expressions) with a single dose of intranasal oxytocin in healthy adult men (1 reference)
  1. Hubble K, Daughters K, Manstead AS, Rees A, Thapar A, van Goozen SH. Oxytocin reduces face processing time but leaves recognition accuracy and eye-gaze unaffected. J Int Neuropsychol Soc. 2017 Jan;23(1):23-33.
Facial emotion recognition: the improvement (increase) with intranasal oxytocin in healthy men (1 reference)
  1. Hubble K, Daughters K, Manstead AS, Rees A, Thapar A, van Goozen SH. Oxytocin reduces face processing time but leaves recognition accuracy and eye-gaze unaffected. J Int Neuropsychol Soc.. 2017 Jan;23(1):23-33.
Emotion recognition from body language: the improvement (increase in emotion recognition) with a single dose of intranasal oxytocin in healthy adult men (1 reference)
  1. Bernaerts S, Berra E, Wenderoth N, Alaerts K. Influence of oxytocin on emotion recognition from body language: A randomized placebo-controlled trial. Psychoneuroendocrinology. 2016 Oct;72:182-9.
Response of the amygdala to emotional stimuli: the improvement (reduction) with a single dose of intranasal oxytocin in healthy adults (1 reference)
  1. Quintana DS, Westlye LT, Alnæs D, Rustan ØG, Kaufmann T, Smerud KT, Mahmoud RA, Djupesland PG, Andreassen OA. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled cross-over study randomized dose-response fMRI trial. Psychoneuroendocrinology. 2016 Jul;69:180-8.
Attentional control and interpretation of facial expressions: no significant effect (no decrease in the hostility detection ratio, nor any effect on attentional-inhibitory control) with a single dose of intranasal oxytocin treatment in healthy men (1 reference)
  1. Hirosawa T, Kikuchi M, Okumura E, Yoshimura Y, Hiraishi H, Munesue T, Takesaki N, Furutani N, Ono Y, Higashida H, Minabe Y. Attentional control and interpretation of facial expression after oxytocin administration to typically developed male adults. PLoS One. 2015 Feb 6;10(2):e0116918.
Ability to recognize avoidance-related facial emotion (emotions that reveal avoidance): the improvement (increase) with a single dose of intranasal oxytocin in healthy men with lower early life stress, (men with higher early life stress had already without oxytocin a high ability to recognize avoidance-related facial emotion) as compared to approach-related emotional faces (emotions that reveal approach) (1 reference)
  1. Feeser M, Fan Y, Weigand A, Hahn A, Gärtner M, Aust S, Böker H, Bajbouj M, Grimm S. The beneficial effect of oxytocin on avoidance-related facial emotion recognition depends on early life stress experience. Psychopharmacology (Berl). 2014 Dec;231(24):4735-44.
Men tend to have lower levels of oxytocin than women and older men tend to have worse emotion recognition than older women (1 reference)
  1. Campbell A, Ruffman T, Murray JE, Glue P. Oxytocin improves emotion recognition for older males. Neurobiol Aging. 2014 Oct;35(10):2246-8. University of Otago, Dunedin, New Zealand. (68 older and 68 young adults, oxytocin nasal spray (20 IU) or placebo)
Emotion in facial stimuli: the improvement (detecting greater emotional intensity in emotions expressed in face images) with a single dose of intranasal oxytocin in healthy adults (1 reference)
  1. Cardoso C, Ellenbogen MA, Linnen AM. The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Emotion. 2014 Feb;14(1):43-50.
Processing of negative emotional faces: the improvement (lower trustworthiness scores for previously negative faces, than for faces previously seen as emotionally neutral or positive) with a single dose of intranasal oxytocin in healthy men, similar to the effects of social pretreatment (unlike in control groups) (1 reference)
  1. Kis A, Kemerle K, Hernádi A, Topál J. Oxytocin and social pretreatment have similar effects on processing of negative emotional faces in healthy adult males. Front Psychol. 2013 Aug 14;4:532.
Attention for socio-affective stimuli: the improvement (increase in recognition of facial expressions at lower intensity levels, increased pupil dilatation for male faces) with a single dose of intranasal oxytocin in healthy men – otherwise without oxytocin, the men experienced increased pupil dilatation only for female faces) (1 reference)
  1. Prehn K, Kazzer P, Lischke A, Heinrichs M, Herpertz SC, Domes G. Effects of intranasal oxytocin on pupil dilation indicate increased salience of socioaffective stimuli. Psychophysiology. 2013 Jun;50(6):528-37.
Event-related potential (ERP) responses to emotional faces with performance feedback: the improvement (vertex positive potential (VPP) and late positive potential (LPP) amplitudes were more positive) with a single dose of intranasal oxytocin in healthy young women (1 reference)
  1. Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, van Ijzendoorn MH. The impact of oxytocin administration and maternal love withdrawal on event-related potential (ERP) responses to emotional faces with performance feedback. Horm Behav. 2013 Mar;63(3):399-410.
Processing of socially relevant cues (ventral tegmental area activation in response to cues signaling social reward (friendly face) or social punishment (angry face) in the ventral tegmental area of the human brain: the improvement (increase) with a single dose of intranasal oxytocin in healthy nulliparous women (1 reference)
  1. Groppe SE, Gossen A, Rademacher L, Hahn A, Westphal L, Gründer G, Spreckelmeyer KN. Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain. Biol Psychiatry. 2013 Aug 1;74(3):172-9.
Evaluative processing of others’ positive and negative facial expression for both explicit and hidden emotional information: the improvement (increase, sharpening) with a single dose of intranasal oxytocin in healthy adults (1 reference)
  1. Leknes S, Wessberg J, Ellingsen DM, Chelnokova O, Olausson H, Laeng B. Oxytocin enhances pupil dilation and sensitivity to ‘hidden’ emotional expressions. Soc Cogn Affect Neurosci. 2013 Oct;8(7):741-9.
Automatic and effortful attentional shifting to emotional faces: the improvement (speed reduction of shifting to sad faces and accelerates disengagement from right hemifield sad and angry faces) with a single dose of intranasal oxytocin in healthy adults (1 reference)
  1. Ellenbogen MA, Linnen AM, Grumet R, Cardoso C, Joober R. The acute effects of intranasal oxytocin on automatic and effortful attentional shifting to emotional faces. Psychophysiology. 2012 Jan;49(1):128-37.
Recognition of emotional expressions at lower intensity: the improvement (increase) with a single dose of intranasal oxytocin in healthy adults (1 reference)
  1. Lischke A, Berger C, Prehn K, Heinrichs M, Herpertz SC, Domes G. Intranasal oxytocin enhances emotion recognition from dynamic facial expressions and leaves eye-gaze unaffected. Psychoneuroendocrinology. 2012 Apr;37(4):475-81.
Differential heart rate responses to facial expressions as a function of the emotional valence the improvement (increase) with a single dose of intranasal oxytocin in healthy men (1 reference)
  1. Gamer M, Büchel C. Oxytocin specifically enhances valence-dependent parasympathetic responses. Psychoneuroendocrinology. 2012 Jan;37(1):87-93.
Detection accuracy of emotional stimuli (on faces): the improvement (increase) with oxytocin treatment in healthy adults, especially more pronounced for the recognition of happy faces.) (1 reference)
  1. Schulze L, Lischke A, Greif J, Herpertz SC, Heinrichs M, Domes G. Oxytocin increases recognition of masked emotional faces. Psychoneuroendocrinology. 2011 Oct;36(9):1378-82.
Identification of positive emotional (happy facial) facial expressions: the improvement with a single dose of intranasal oxytocin in healthy adults but not of other emotional expressions such as anger, disgust, fear, sadness, and surprise (1 reference)
  1. Marsh AA, Yu HH, Pine DS, Blair RJ. Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology (Berl). 2010 Apr;209(3):225-32.
Fear recognition: the improvement with a single dose of intranasal oxytocin in healthy men but no influence on other emotions (1 reference)
  1. Fischer-Shofty M, Shamay-Tsoory SG, Harari H, Levkovitz Y. The effect of intranasal administration of oxytocin on fear recognition. Neuropsychologia. 2010 Jan;48(1):179-84
Emotional face processing: the improvement with a single dose of intranasal oxytocin in women (1 reference)
  1. Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC. Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology. 2010 Jan;35(1):83-93.
Discrimination between positive (happiness) and negative (anger) emotions: no effect of intranasal oxytocin treatment in healthy adults (1 reference)
  1. Guastella AJ, Carson DS, Dadds MR, Mitchell PB, Cox RE. Does oxytocin influence the early detection of angry and happy faces? Psychoneuroendocrinology. 2009 Feb;34(2):220-5.
Discrimination between positive and negative emotions: the improvement (reduction of misclassification) with a single dose of intranasal oxytocin in healthy men but increase of reaction time to correctly identify fear (fearful facial expressions) (1 reference)
  1. Di Simplicio M, Massey-Chase R, Cowen PJ, Harmer CJ. Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. J Psychopharmacol. 2009 May;23(3):241-8.
Reactions to positive (happy) and negative (fearful, angry) stimuli from facial expressions: the reduction of right-sided amygdala responses with a single dose of intranasal oxytocin (1 reference)
  1. Domes G, Heinrichs M, Gläscher J, Büchel C, Braus DF, Herpertz SC. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry. 2007 Nov 15;62(10):1187-90.

 

Emotion recognition and diverting attention from angry to happy faces
Attention to angry and happy faces: the improvement (reduced attention towards angry facial expressions, and increased and sustained attention towards happy faces, specifically under conditions of heightened awareness) with a single dose of intranasal oxytocin in adults with chronic depression (1 reference)
  1. Domes G, Normann C, Heinrichs M. The effect of oxytocin on attention to angry and happy faces in chronic depression. BMC Psychiatry. 2016 Apr 6;16:92.
Social recognition of emotions: the improvement (reduction of anger ratings of emotionally ambiguous faces (facial images)) with single doses of intranasal and intravenous in healthy men (1 reference)
  1. Quintana DS, Westlye LT, Rustan ØG, Tesli N, Poppy CL, Smevik H, Tesli M, Røine M, Mahmoud RA, Smerud KT, Djupesland PG, Andreassen OA. Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment. Transl Psychiatry. 2015 Jul 14;5:e602.
Shift of attention towards happy facial expressions presented for 100 ms, not 500 ms, after OT administration (covert (clandestine) attention to positive social cues: the improvement (increase) with a single dose of intranasal oxytocin in healthy men (1 reference)
  1. Domes G, Sibold M, Schulze L, Lischke A, Herpertz SC, Heinrichs M. Intranasal oxytocin increases covert attention to positive social cues. Psychol Med. 2013 Aug;43(8):1747-53.

 

Emotion recognition: effects of oxytocin differ following the genetic polymorphism
Emotion recognition (performance): the improvement (increase) with a single dose of intranasal oxytocin in men with the oxytocin receptor gene variation TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917-rs2268498-rs4564970-rs237897-rs2268495-rs53576but the worsening (reduction of emotion recognition performance) with oxytocin in men with the oxytocin receptor gene variation CCGAGA haplotype (1 reference)
  1. Chen FS, Kumsta R, Dvorak F, Domes G, Yim OS, Ebstein RP, Heinrichs M. Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach. Transl Psychiatry. 2015 Oct 27;5:e664.

 

Attention to feelings
Components of meta-mood (attending to and understanding one’s own feelings):  the improvement (increase) with a single dose of intranasal oxytocin in young women but its reduction with oxytocin in older women (1 reference)
  1. Ebner NC, Horta M, Lin T, Feifel D, Fischer H, Cohen RA. Oxytocin modulates meta-mood as a function of age and sex. Front Aging Neurosci. 2015 Sep 10;7:175.

 

Willingness to share one’s emotions
Willingness to socially share one’s emotions: the improvement (increase) with a single dose of intranasal oxytocin in young healthy men (1 reference)
  1. Lane A, Luminet O, Rimé B, Gross JJ, de Timary P, Mikolajczak M. Oxytocin increases willingness to socially share one’s emotions. Int J Psychol. 2013;48(4):676-81.

 

Physical expression of emotions
Facial and vocal expressiveness of fear and happiness: the enhancement after oxytocin treatment (1 reference)
  1. Spengler FB, Scheele D, Marsh N, Kofferath C, Flach A, Schwarz S, Stoffel-Wagner B, Maier W, Hurlemann R. Oxytocin facilitates reciprocity in social communication. Soc Cogn Affect Neurosci. 2017 Aug 1;12(8):1325-1333.
Contagious yawning from one person to the other (a basic form of empathy): the reduction of contagious yawning (by increasing the likelihood to conceal one’s yawns and reducing the likelihood to display overt cues associated with yawning) with a single dose of intranasal oxytocin in healthy men (1 reference)
  1. Gallup AC, Church AM. The effects of intranasal oxytocin on contagious yawning. Neurosci Lett. 2015 Oct 21;607:13-6

 

Positive feelings
Positive emotional states: the improvement (with an increase in blood oxygenation in the midbrain) when a single dose of intranasal oxytocin is administered in healthy men (1 reference)
  1. Mickey BJ, Heffernan J, Heisel C, Peciña M, Hsu DT, Zubieta JK, Love TM. Oxytocin modulates hemodynamic responses to monetary incentives in humans. Psychopharmacology (Berl). 2016 Dec;233(23-24):3905-3919

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Quality of life, energy: the association with higher oxytocin levels (5 references)
  1. Niwayama R, Nishitani S, Takamura T, Shinohara K, Honda S, Miyamura T, Nakao Y, Oishi K, Araki-Nagahashi M. Oxytocin mediates a calming effect on postpartum mood in primiparous mothers. Breastfeed Med. 2017 Mar;12:103-109.
  2. Lipschitz DL, Kuhn R, Kinney AY, Grewen K, Donaldson GW, Nakamura Y. An Exploratory Study of the Effects of Mind-Body Interventions Targeting Sleep on Salivary Oxytocin Levels in Cancer Survivors. Integr Cancer Ther. 2015 Jul;14(4):366-80.
  3. Burri A, Heinrichs M, Schedlowski M, Kruger TH.The acute effects of intranasal oxytocin administration on endocrine and sexual function in males. Psychoneuroendocrinology. 2008 Jun;33(5):591-600
  4. Uvnas-Moberg K, Petersson M. Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing. Z Psychosom Med Psychother. 2005;51(1):57-80
  5. Anderberg UM, Uvnäs-Moberg K. Plasma oxytocin levels in female fibromyalgia syndrome patients. Z Rheumatol. 2000 Dec;59(6):373-9
Low quality of life, fatigue: the improvement with oxytocin treatment (4 references)
  1. Miller JL, Tamura R, Butler MG, Kimonis V, Sulsona C, Gold JA, Driscoll DJ. Oxytocin treatment in children with Prader-Willi syndrome: a double-blind, placebo-controlled, crossover study. Am J Med Genet A. 2017 May;173(5):1243-1250.
  2. Bernaerts S, Prinsen J, Berra E, Bosmans G, Steyaert J, Alaerts K. Long-term oxytocin administration enhances the experience of attachment. 2017 Apr;78:1-9.
  3. Barraza JA, Grewal NS, Ropacki S, Perez P, Gonzalez A, Zak PJ. Effects of a 10-day oxytocin trial in older adults on health and well-being. Exp Clin Psychopharmacol. 2013 Apr;21(2):85-92.
  4. Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, Wang AT, Pepa L, Tanel N, Kushki A, Hollander E. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism. 2012 Dec 5;3(1):16.
High sociability: the association with higher oxytocin levels (4 references)
  1. Carter CS, DeVries AC, Getz LL. Physiological substrates of mammalian monogamy: the prairie vole model. Neurosci Biobehavioral Rev. 1995;19:303–314
  2. Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD. Early experience in humans is associated with changes in neuropeptides critical for regulating socialbehavior. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17237-40
  3. Insel TR. A neurobiological basis of social attachment. Am J Psychiatry. 1997;154:726–735
  4. Wallner B, Dittami J, Machatschke I. Social stimuli cause changes of plasma oxytocin and behavior in guinea pigs. Biol Res. 2006;39(2):251-8
Sociability: the improvement with oxytocin treatment (7 references)
  1. Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M. Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry. 2009 May 1;65(9):728-31
  2. Insel TR. A neurobiological basis of social attachment. Am J Psychiatry. 1997;154:726–735
  3. Lee PR, Brady DL, Shapiro RA, Dorsa DM, Koenig JI. Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin Neuropsychopharmacology 2005. 30:1883–94
  4. Young LJ. Frank A. Beach Award. Oxytocin and vasopressin receptors and species-typical social behaviors. Horm Behav. 1999;36:212–221
  5. Uvnäs-Moberg K. Neuroendocrinology of the mother-child interaction. Trends Endocrinol Metab. 1996 May-Jun;7(4):126-31

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Higher mood, less risk of depression: the association with higher oxytocin levels (9 references)
  1. Lara-Cinisomo S, McKenney K, Di Florio A, Meltzer-Brody S. Associations between postpartum depression, breastfeeding, and oxytocin levels in latina mothers. Breastfeed Med. 2017 Sep;12(7):436-442.
  2. Jobst A, Krause D, Maiwald C, Härtl K, Myint AM, Kästner R, Obermeier M, Padberg F, Brücklmeier B, Weidinger E, Kieper S, Schwarz M, Zill P, Müller N. Oxytocin course over pregnancy and postpartum period and the association with postpartum depressive symptoms. Arch Womens Ment Health. 2016 Aug;19(4):571-9.
  3. Mohiyeddini C, Opacka-Juffry J. Disentangling the link between depressive symptoms and plasma oxytocin in men: The role of brooding rumination. Horm Behav. 2015 Sep;75:142-9.
  4. Lipschitz DL, Kuhn R, Kinney AY, Grewen K, Donaldson GW, Nakamura Y. An Exploratory Study of the Effects of Mind-Body Interventions Targeting Sleep on Salivary Oxytocin Levels in Cancer Survivors. Integr Cancer Ther. 2015 Jul;14(4):366-80.
  5. Garfield L, Giurgescu C, Carter CS, Holditch-Davis D, McFarlin BL, Schwertz D, Seng JS, White-Traut R. Depressive symptoms in the second trimester relate to low oxytocin levels in African-American women: a pilot study. Arch Womens Ment Health. 2015 Feb;18(1):123-9.

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Depression: the improvement with oxytocin treatment (2 references)
  1. Scantamburlo G, Hansenne M, Geenen V, Legros JJ, Ansseau M. Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: an open trial. Eur Psychiatry. 2015 Jan;30(1):65-8.
  2. MacDonald K, MacDonald TM, Brüne M, Lamb K, Wilson MP, Golshan S, Feifel D. Oxytocin and psychotherapy: a pilot study of its physiological, behavioral and subjective effects in males with depression. Psychoneuroendocrinology.2013Dec;38(12):2831-43.
Depression (antidepressant-resistant): the improvement with oxytocin treatment (1 reference)
  1. Scantamburlo G, Hansenne M, Geenen V, Legros JJ, Ansseau M. Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: an open trial. Eur Psychiatry. 2015 Jan;30(1):65-8.
Calmness, serenity: the association with higher oxytocin levels (11 references)
  1. Niwayama R, Nishitani S, Takamura T, Shinohara K, Honda S, Miyamura T, Nakao Y, Oishi K, Araki-Nagahashi M. Oxytocin mediates a calming effect on postpartum mood in primiparous mothers. Breastfeed Med. 2017 Mar;12:103-109.
  2. Scheel T, Hoeppner D, Grotevendt A, Barthlen W. Clowns in paediatric surgery: less anxiety and more oxytocin? a pilot study. Klin Padiatr. 2017 Sep;229(5):274-280.
  3. Lebowitz ER, Leckman JF, Feldman R, Zagoory-Sharon O, McDonald N, Silverman WK. Salivary oxytocin in clinically anxious youth: Associations with separation anxiety and family accommodation. Psychoneuroendocrinology. 2016 Mar;65:35-43.
  4. Carson DS, Berquist,SW, Trujillo TH, Garner JP, Hannah SL, Hyde SA, Sumiyoshi RD, Jackson LP, Moss JK, Strehlow MC, Cheshier SH, Partap S, Hardan AY, Parker KJ. Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children. Mol Psychiatry. 2015 Sep;20(9):1085-90.
  5. Eapen V, Dadds M, Barnett B, Kohlhoff J, Khan F, Radom N, Silove DM. Separation anxiety, attachment and inter-personal representations: disentangling the role of oxytocin in the perinatal period. PLoS One. 2014 Sep 17;9(9):e107745.

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Anxiety: the improvement with oxytocin treatment (12 references)
  1. Fang A, Treadway MT, Hofmann SG. Working hard for oneself or others: effects of oxytocin on reward motivation in social anxiety disorder. Biol Psychol. 2017 Jul;127:157-162.
  2. Chen X, Hackett PD, DeMarco AC, Feng C, Stair S, Haroon E, Ditzen B, Pagnoni G, Rilling JK. Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women. Brain Imaging Behav. 2016 Jun;10(2):581-93.
  3. Clark-Elford R, Nathan PJ, Auyeung B, Mogg K, Bradley BP, Sule A, Müller U, Dudas RB, Sahakian BJ, Baron-Cohen S. Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males. Int J Neuropsychopharmacol. 2014 Oct 31;18(2). pii: pyu012.
  4. Dodhia S, Hosanagar A, Fitzgerald DA, Labuschagne I, Wood AG, Nathan PJ, Phan KL. Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder. Neuropsychopharmacology. 2014 Aug;39(9):2061-9.
  5. Radke S, Roelofs K, de Bruijn ER. Acting on anger: social anxiety modulates approach-avoidance tendencies after oxytocin administration. Psychol Sci. 2013 Aug;24(8):1573-8.

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Attachment anxiety, jealousy: the association with higher oxytocin levels (2 references)
  1. Tops M, van Peer JM, Korf J, Wijers AA, Tucker DM. Anxiety, cortisol, and attachment predict plasma oxytocin. Psychophysiology. 2007 May;44(3):444-9
  2. Marazziti D, Dell’Osso B, Baroni S, Mungai F, Catena M, Rucci P, Albanese F, Giannaccini G, Betti L, Fabbrini L, Italiani P, Del Debbio A, Lucacchini A, Dell’Osso L. A relationship between oxytocin and anxiety of romantic attachment. Clin Pract Epidemol Ment Health. 2006 Oct 11;2:28
Envy: the increase with oxytocin treatment (1 reference)
  1. Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y. Intranasal administration of oxytocin increases envy and schadenfreude (gloating). Biol Psychiatry. 2009 Nov 1;66(9):864-70
Somatization, obsessive-compulsive disorder: the association with low oxytocin levels (1 reference)
  1. Kontoangelos K, Raptis AE, Papageorgiou CC, Tsiotra PC, Papadimitriou GN, Rabavilas AD, Dimitriadis G, Raptis SA. Oxytocin and psychological factors affecting type 2 diabetes mellitus. Exp Diabetes Res. 2012;2012:560864.
Memory loss, cognitive impairment: the association with lower oxytocin levels (3 references)
  1. Tse WS, Siu AFY, Zhang Q, Chan HYE. Maternal oxytocin responsiveness improves specificity of positive social memory recall. 2018 Dec;98:148-152.
  2. Aydın O, Lysaker PH, Balıkçı K, Ünal-Aydın P, Esen-Danacı A. Associations of oxytocin and vasopressin plasma levels with neurocognitive, social cognitive and metacognitive function in schizophrenia. Psychiatry Res. 2018 Dec;270:1010-1016.
  3. Rubin LH, Wehring HJ, Demyanovich H, Sue Carter C, Pournajafi-Nazarloo H, Feldman SM, Earl AK, August S, Gold JM, Kelly DL. Peripheral oxytocin and vasopressin are associated with clinical symptom severity and cognitive functioning in midlife women with chronic schizophrenia. Schizophr Res. 2018 May;195:409-411  
Memory loss, cognitive impairment: the improvement with oxytocin treatment (17 references)
  1. Wagner U, Echterhoff G. When does oxytocin affect human memory encoding? the role of social context and individual attachment style. Front Hum Neurosci. 2018 Sep 20;12:349
  2. Flanagan JC, Hand A, Jarnecke AM, Moran-Santa Maria MM, Brady KT, Joseph JE. Effects of oxytocin on working memory and executive control system connectivity in posttraumatic stress disorder. Exp Clin Psychopharmacol. 2018 Aug;26(4):391-402.
  3. Yue T, Yue C, Liu G, Huang X. Effects of oxytocin on facial expression and identity working memory are found in females but not males. Front Neurosci. 2018 Apr 17;12:205.
  4. de Boer M, Kokal I, Blokpoel M, Liu R, Stolk A, Roelofs K, van Rooij I, Toni l. Oxytocin modulates human communication by enhancing cognitive exploration. 2017 Dec;86:64-72.
  5. Brambilla M, Manenti R, de Girolamo G, Adenzato M, Bocchio-Chiavetto L, Cotelli M. Effects of intranasal oxytocin on long-term memory in healthy humans: a systematic review. Drug Dev Res. 2016 Dec;77(8):479-488.

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Dementia: the improvement of social behavior with oxytocin treatment (1 reference)
  1. Jesso S, Morlog D, Ross S, Pell MD, Pasternak SH, Mitchell DG, Kertesz A, Finger EC. The effects of oxytocin on social cognition and behaviour in frontotemporal dementia. 2011 Sep;134(Pt 9):2493-501.
Dementia: the improvement of social behavior with oxytocin treatment (review study) (1 reference)
  1. Tampi RR, Maksimowski M, Ahmed M, Tampi DJ. Oxytocin for frontotemporal dementia: a systematic review. Ther Adv Psychopharmacol. 2017 Jan;7(1):48-53.
Dementia: no improvement of cognition with oxytocin treatment (1 reference)
  1. Finger EC, MacKinley J, Blair M, Oliver LD, Jesso S, Tartaglia MC, Borrie M, Wells J, Dziobek I, Pasternak S, Mitchell DG, Rankin K, Kertesz A, Boxer A. Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability. Neurology. 2015 Jan 13;84(2):174-81.  
Sleep disorders, insomnia: the association with low oxytocin levels (2 references)
  1. Lipschitz DL, Kuhn R, Kinney AY, Grewen K, Donaldson GW, Nakamura Y. An Exploratory Study of the Effects of Mind-Body Interventions Targeting Sleep on Salivary Oxytocin Levels in Cancer Survivors. Integr Cancer Ther. 2015 Jul;14(4):366-80.
  2. Fekete EM, Seay J, Antoni MH, Mendez AJ, Fletcher MA, Szeto A, Schneiderman N. Oxytocin, social support, and sleep quality in low-income minority women living with HIV. Behav Sleep Med. 2014;12(3):207-21.
Hypercholesterolemia: the association with lower oxytocin levels (1 reference)
  1. Qian W, Zhu T, Tang B, Yu S, Hu H, Sun W, Pan R, Wang J, Wang D, Yang L, Mao C, Zhou L, Yuan G. Decreased circulating levels of oxytocin in obesity and newly diagnosed type 2 diabetic patients. J Clin Endocrinol Metab. 2014 Dec;99(12):4683-9.
Hypercholesterolemia: no association with oxytocin treatment (animal studies) (2 references)
  1. Szeto A, Rossetti MA, Mendez AJ, Noller CM, Herderick EE, Gonzales JA, Schneiderman N, McCabe PM. Oxytocin administration attenuates atherosclerosis and inflammation in Watanabe Heritable Hyperlipidemic rabbits. Psychoneuroendocrinology. 2013 May;38(5):685-93.
  2. Nation DA, Szeto A, Mendez AJ, Brooks LG, Zaias J, Herderick EE, Gonzales J, Noller CM, Schneiderman N, McCabe PM. Oxytocin attenuates atherosclerosis and adipose tissue inflammation in socially isolated ApoE-/- mice. Psychosom Med.2010 May;72(4):376-82.
Arterial hypertension: the association with lower oxytocin (receptor) levels (11 references)
  1. Binay Ç, Paketçi C, Güzel S, Samancı N. Serum irisin and oxytocin levels as predictors of metabolic parameters in obese children. J Clin Res Pediatr Endocrinol. 2017 Jun 1;9(2):124-131.
  2. Amico JA, Corder CN, McDonald RH Jr, Robinson AG. Levels of the oxytocin-associated and vasopressin-associated neurophysins in plasma and their responses in essential hypertension. Clin Endocrinol (Oxf). 1984 Mar;20(3):289-97.
  3. Light KC, Grewen KM, Amico JA. More frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women. Biol Psychol. 2005 Apr;69(1):5-21
  4. Light KC, Grewen KM, Amico JA, Brownley KA, West SG, Hinderliter AL, Girdler SS. Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement. Horm Behav. 2005 May;47(5):540-8
  5. Light KC, Grewen KM, Amico JA. Higher baseline OT before partner contact was associated with lower BP a more frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women. Biol Psychol. 2005 Apr;69(1):5-21

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Hypertension: the improvement with oxytocin treatment (18 references)
  1. Alcorn JL 3rd, Green CE, Schmitz J, Lane SD. Effects of oxytocin on aggressive responding in healthy adult men. Behav Pharmacol. 2015 Dec;26(8 Spec No):798-804.
  2. Rosseland LA, Hauge TH, Grindheim G, Stubhaug A, Langesæter E. Changes in blood pressure and cardiac output during cesarean delivery: the effects of oxytocin and carbetocin compared with placebo. Anesthesiology. 2013 Sep;119(3):541-51.
  3. Moertl MG, Friedrich S, Kraschl J, Wadsack C, Lang U, Schlembach D. Haemodynamic effects of carbetocin and oxytocin given as intravenous bolus on women undergoing caesarean delivery: a randomised trial. BJOG. 2011 Oct;118(11):1349-56.
  4. Langesæter E, Rosseland LA, Stubhaug A. Haemodynamic effects of oxytocin in women with severe preeclampsia. Int J Obstet Anesth. 2011 Jan;20(1):26-9.
  5. Langesaeter E, Rosseland LA, Stubhaug A. Haemodynamic effects of repeated doses of oxytocin during Caesarean delivery in healthy parturients. Br J Anaesth. 2009 Aug;103(2):260-2.

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Coronary heart disease and other cardiac diseases: the improvement with oxytocin treatment (animal studies) (14 references)
  1. Bulut EC, Abueid L, Ercan F, Süleymanoğlu S, Ağırbaşlı M, Yeğen BÇ. Treatment with oestrogen-receptor agonists or oxytocin in conjunction with exercise protects against myocardial infarction in ovariectomized rats. Exp Physiol. 2016 May 1;101(5):612-27.
  2. Al-Amran FF, Shahkolahi M. Oxytocin ameliorates the immediate myocardial injury in heart transplant through downregulation of the neutrophil dependent myocardial apoptosis. Heart Views. 2014 Apr;15(2):37-45.
  3. Ondrejcakova M, Barancik M, Bartekova M, Ravingerova T, Jezova D. Prolonged oxytocin treatment in rats affects intracellular signaling and induces myocardial protection against infarction. Gen Physiol Biophys. 2012 Sep;31(3):261-70.
  4. Houshmand F, Faghihi M, Zahediasl S. Biphasic protective effect of oxytocin on cardiac ischemia/reperfusion injury in anesthetized rats. Peptides. 2009 Dec;30(12):2301-8.
  5. Ondrejcakova M, Ravingerova T, Bakos J, Pancza D, Jezova D. Oxytocin exerts protective effects on in vitro myocardial injury induced by ischemia and reperfusion. Can J Physiol Pharmacol. 2009 Feb;87(2):137-42.

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Obesity: the association with low oxytocin levels (6 references)
  1. Maestrini S, Mele C, Mai S, Vietti R, Di Blasio A, Castello L, Surico D, Aimaretti G, Scacchi M, Marzullo P. Plasma oxytocin concentration in pre- and postmenopausal women: Its relationship with obesity, body composition and metabolic variables. Obes Facts. 2018;11(5):429-439.
  2. Akour A, Kasabri V, Bulatova N, Al Muhaissen S, Naffa R, Fahmawi H, Momani M, Zayed A, Bustanji Y. Association of oxytocin with glucose intolerance and inflammation biomarkers in metabolic syndrome patients with and without prediabetes. Rev Diabet Stud. 2018 Winter;14(4):364-371.
  3. Eisenberg Y, Dugas LR, Akbar A, Reddivari B, Layden BT, Barengolts E. Oxytocin is lower in African American men with diabetes and associates with psycho-social and metabolic health factors. PLoS One. 2018 Jan 4;13(1):e0190301.
  4. Binay Ç, Paketçi C, Güzel S, Samancı N. Serum Irisin and Oxytocin Levels as Predictors of Metabolic Parameters in Obese Children. J Clin Res Pediatr Endocrinol. 2017 Jun 1;9(2):124-131.
  5. Yuan G, Qian W, Pan R, Jia J, Jiang D, Yang Q, Wang S, Liu Y, Yu S, Hu H, Sun W, Ye J, Mao C, Zhuang R, Zhou L. Reduced circulating oxytocin and High-Molecular-Weight adiponectin are risk factors for metabolic syndrome. Endocr J. 2016 Jul 30;63(7):655-62.

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Obesity: the improvement with oxytocin treatment (5 references)
  1. Plessow F, Marengi DA, Perry SK, Felicione JM, Franklin R, Holmes TM, Holsen LM, Makris N, Deckersbach T, Lawson EA. Effects of intranasal oxytocin on the blood oxygenation level-dependent signal in food motivation and cognitive control pathways in overweight and obese men. Neuropsychopharmacology. 2018 Feb;43(3):638-645.
  2. Striepens N, Schröter F, Stoffel-Wagner B, Maier W, Hurlemann R, Scheele D. Oxytocin enhances cognitive control of food craving in women. Hum Brain Mapp. 2016 Dec;37(12):4276-4285.
  3. Thienel M, Fritsche A, Heinrichs M, Peter A, Ewers M, Lehnert H, Born J, Hallschmid M. Oxytocin’s inhibitory effect on food intake is stronger in obese than normal-weight men. Int J Obes (Lond). 2016 Nov;40(11):1707-1714.
  4. Lawson EA, Marengi DA, DeSanti RL, Holmes TM, Schoenfeld DA, Tolley CJ. Oxytocin reduces caloric intake in men. Obesity (Silver Spring). 2015 May;23(5):950-6.
  5. Zhang H, Wu C, Chen Q, Chen X, Xu Z, Wu J, Cai D. Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models. PLoS One. 2013 May 20;8(5):e61477.

 

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