Evidence-Based Hormone Therapies

Healthy subjects

Emotions: the reduction of brain connectivity (in amygdala region) with pregnenolone treatment in healthy volunteers (1 reference)

1. Sripada RK, Welsh RC, Marx CE, Liberzon I. The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity. Hum Brain Mapp. 2014 Jul;35(7):3249-61.

Anxiety: the improvement (reduction) with pregnenolone treatment in healthy volunteers (1 reference)

2. Sripada RK, Marx CE, King AP, Rampton JC, Ho SS, Liberzon I. Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biol Psychiatry. 2013 Jun 1;73(11):1045-53.

Benzodiazepine-sedation: the sedation reduction with pregnenolone treatment (1 reference)

3. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology. 2004 May;29(4):486-500.

Patients with psychological disorders

Substance abuse: the different metabolism of pregnenolone treatment (pharmacology) (2 references)

4. Kashani L, Shams N, Moazen-Zadeh E, Karkhaneh-Yousefi MA, Sadighi G, Khodaie-Ardakani MR, Rezaei F, Rahiminejad F, Akhondzadeh S. Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial. J Psychiatr Res. 2017 Nov;94:70-77.
5. Mason BL, Van Enkevort E, Filbey F, Marx CE, Park J, Nakamura A, Sunderajan P, Brown ES. Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis Use Disorders. J Clin Psychopharmacol. 2017 Dec;37(6):684-688.

Obsessive-compulsive disorder: nonsignificant improvement with pregnenolone treatment (1 reference)

6. Kellner M, Nowack S, Wortmann V, Yassouridis A, Wiedemann K. Does pregnenolone enhance exposure therapy in obsessive-compulsive disorder? – A pilot, interim report of a randomized, placebo-controlled, double-blind study. Pharmacopsychiatry. 2016 Mar;49(2):79-81.

Bipolar disorder: the improvement of depression with pregnenolone treatment (3 references)

7. Daftary S, Yon JM, Choi EK, Kim YB, Bice C, Kulikova A, Park J, Sherwood Brown E. Microtubule associated protein 2 in bipolar depression: Impact of pregnenolone. J Affect Disord. 2017 Aug 15;218:49-52.
8. Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014 Nov;39(12):2867-73.
9. Osuji IJ, Vera-Bolaños E, Carmody TJ, Brown ES. Pregnenolone for cognition and mood in dual diagnosis patients. Psychiatry Res. 2010 Jul 30;178(2):309-12.

Schziophrenia: the improvement with pregnenolone treatment (5 references)

10. Marx CE, Lee J, Subramaniam M, Rapisarda A, Bautista DC, Chan E, Kilts JD, Buchanan RW, Wai EP, Verma S, Sim K, Hariram J, Jacob R, Keefe RS, Chong SA. Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. Psychopharmacology (Berl). 2014 Sep;231(17):3647-62.
11. Ritsner MS, Bawakny H, Kreinin A. Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial. Psychiatry Clin Neurosci. 2014 Jun;68(6):432-40.
12. Ritsner MS, Gibel A, Shleifer T, Boguslavsky I, Zayed A, Maayan R, Weizman A, Lerner V. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010 Oct;71(10):1351-62.
13. Marx CE, Keefe RS, Buchanan RW, Hamer RM, Kilts JD, Bradford DW, Strauss JL, Naylor JC, Payne VM, Lieberman JA, Savitz AJ, Leimone LA, Dunn L, Porcu P, Morrow AL, Shampine LJ. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology. 2009 Jul;34(8):1885-903.
14. Kreinin A, Bawakny N, Ritsner MS. Adjunctive pregnenolone ameliorates the cognitive deficits in recent-onset schizophrenia: An 8-week, randomized, double-blind, placebo-controlled trial. Clin Schizophr Relat Psychoses. Winter 2017;10(4):201-210.

Schizophrenia: the improvement with combined pregnenolone with L-theanine therapies (1 reference)

15. Kardashev A, Ratner Y, Ritsner MS. Add-on Pregnenolone with L-theanine to antipsychotic therapy relieves negative and anxiety symptoms of schizophrenia: An 8-week, randomized, double-blind, placebo-controlled trial. Clin Schizophr Relat Psychoses. 2015 Jul 28.

Fatigue and work performance: the improvement with pregnenolone (3 references)

1. Pincus G, Hoagland H. Effects on industrial production of the administration of 5 pregnenolone to factor workers, I. Psychosom Med. 1945;7:342-6
2. Pincus G, Hoagland H, Wilson CH, Fay NJ. Effects on industrial production of the administration of 5-pregnenolone to factory workers, II. Psychosom Med. 1945-7-347-352
3. Pincus G, Hoagland H. Effects of administered pregnenolone on fatigue and psychomotor performance. J Aviat Med. 1944;15:98-115,135

Benzodiazepine-sedation: the sedation reduction with pregnenolone treatment (1 reference)

1. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology. 2004 May;29(4):486-500

Depression: the improvement with pregnenolone treatment (3 references)

1. Daftary S, Yon JM, Choi EK, Kim YB, Bice C, Kulikova A, Park J, Sherwood Brown E. Microtubule-associated protein 2 in bipolar depression: Impact of pregnenolone. J Affect Disord. 2017 Aug 15;218:49-52.
2. Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. 2014 Nov;39(12):2867-73.
3. Osuji IJ, Vera-Bolaños E, Carmody TJ, Brown ES. Pregnenolone for cognition and mood in dual diagnosis patients. Psychiatry Res. 2010 Jul 30;178(2):309-12.

Anxiety: the association with lower pregnenolone levels (4 references)

1. Ritsner M, Maayan R, Gibel A, Weizman A. Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects. Eur Neuropsychopharmacol. 2007 Apr;17(5):358-65
2. Heydari B, Le Melledo JM. Low pregnenolone sulphate plasma concentrations in patients with generalized social phobia. Psychol Med. 2002 Jul;32(5):929-33
3. Semeniuk T, Jhangri GS, Le Melledo JM. Neuroactive steroid levels in patients with generalized anxiety disorder. J Neuropsychiatry Clin Neurosci. 2001 Summer;13(3):396-8
4. Serra M, Pisu MG, Littera M, Papi G, Sanna E, Tuveri F, Usala L, Purdy RH, Biggio G. Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor function in rat brain. J Neurochem. 2000 Aug;75(2):732-40

Anxiety: the improvement with pregnenolone treatment (5 references)

1. Sripada RK, Marx CE, King AP, Rampton JC, Ho SS, Liberzon I. Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biol Psychiatry. 2013 Jun 1;73(11):1045-53.
2. Reddy DS, Kulkarni SK. Neurosteroid coadministration prevents the development of tolerance and augments recovery from benzodiazepine withdrawal anxiety and hyperactivity in mice. Methods Find Exp Clin Pharmacol. 1997 Jul-Aug;19(6):395-405
3. Reddy DS, Kulkarni SK. Differential anxiolytic effects of neurosteroids in the mirrored chamber behavior test in mice. Brain Res. 1997 Mar 28;752(1-2):61-71
4. Jorge JC, Gonzalez L, Fortis A, Cruz ND. Sex-specific modulation of anxiety and locomotion after neonatal exposure to pregnenolone sulfate. Physiol Behav. 2005 Jan 17;83(5):779-86
5. Melchior CL, Ritzmann RF. Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze. Pharmacol Biochem Behav. 1994 Aug;48(4):893-7

Anxiety: the improvement with pregnenolone (and theanine) treatment in schizophrenia (1 reference)

1. Kardashev A, Ratner Y, Ritsner MS. Add-on pregnenolone with l-theanine to antipsychotic therapy relieves negative and anxiety symptoms of schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. Clin Schizophr Relat Psychoses. Spring 2018;12(1):31-41.

Memory loss: the association with lower pregnenolone levels (animal studies) (2 references)

1. Baulieu EE. The decrease in the hippocampus of the neurosteroid pregnenolone sulfate is involved in memory deficit in the aged animal. C R Acad Sci III. 1998 Feb-Mar;321(2-3):223-7
2. Vallee M, Mayo W, Darnaudery M, Corpechot C, Young J, Koehl M, Le Moal M, Baulieu EE, Robel P, Simon H. Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci USA. 1997 Dec 23;94(26):14865-70

Memory and attention: the improvement with pregnenolone treatment (1 reference)

1. Ritsner MS, Gibel A, Shleifer T, Boguslavsky I, Zayed A, Maayan R, Weizman A, Lerner V. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010 Oct;71(10):1351-62.

Memory loss: the improvement with pregnenolone treatment (animal studies) (15 references)

1. Martín-García E, Pallarès M. The neurosteroid pregnenolone sulfate neutralized the learning impairment induced by intrahippocampal nicotine in alcohol-drinking rats. Neuroscience. 2005;136(4):1109-19
2. Darnaudery M, Pallares M, Piazza PV, Le Moal M, Mayo W. The neurosteroid pregnenolone sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats. Brain Res. 2002 Oct 4;951(2):237-42
3. Vallee M, Shen W, Heinrichs SC, Zorumski CF, Covey DF, Koob GF, Purdy RH. Steroid structure and pharmacological properties determine the anti-amnesic effects of pregnenolone sulphate in the passive avoidance task in rats. Eur J Neurosci. 2001 Dec;14(12):2003-10
4. Vallee M, Mayo W, Le Moal M. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Brain Res Rev  2001 Nov;37(1-3):301-312
5. Mayo W, Le Moal M, Abrous DN. Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations. Horm Behav. 2001 Sep;40(2):215-7

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Attention deficit: the improvement with pregnenolone treatment (1 reference)

1. Morley JE, Kaiser F, Raum WJ, Perry HM 3rd, Flood JF, Jensen J, Silver AJ, Roberts E. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA. 1997 Jul 8;94(14):7537-42

Alzheimer’s disease: the association with lower pregnenolone levels (1 reference)

1. Weill-Engerer S, David JP, Sazdovitch V, Liere P, Eychenne B, Pianos A, Schumacher M, Delacourte A, Baulieu EE, Akwa Y. Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients. J Clin Endocrinol Metab. 2002 Nov;87(11):5138-43

Alzheimer’s disease/amyloid beta toxicity: the improvement with pregnenolone treatment in vitro (1 reference)

3. Akan P, Kizildag S, Ormen M, Genc S, Oktem MA, Fadiloglu M. Pregnenolone protects the PC-12 cell line against amyloid beta peptide toxicity but its sulfate ester does not. Chem Biol Interact. 2009 Jan 15;177(1):65-70

Autism spectrum disorder: the improvement of irritability with pregnenolone treatment (1 reference)

1. Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY. Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord. 2014 Nov;44(11):2971-7. (reduction of irritability)

Schizophrenia: the associations with low pregnenolone levels (1 reference)

4. Ritsner M, Maayan R, Gibel A, Weizman A. Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects. Eur Neuropsychopharmacol. 2007 Apr;17(5):358-65

Schizophrenia (negative symptoms): the improvement with pregnenolone treatment (6 references)

1. Kardashev A, Ratner Y, Ritsner MS. Add-on pregnenolone with l-theanine to antipsychotic therapy relieves negative and anxiety symptoms of schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. Clin Schizophr Relat Psychoses. Spring 2018;12(1):31-41
2. Kashani L, Shams N, Moazen-Zadeh E, Karkhaneh-Yousefi MA, Sadighi G, Khodaie-Ardakani MR, Rezaei F, Rahiminejad F, Akhondzadeh S. Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: a randomized double-blind placebo-controlled clinical trial. J Psychiatr Res. 2017 Nov;94:70-77.
3. Kreinin A, Bawakny N, Ritsner MS. Adjunctive pregnenolone ameliorates the cognitive deficits in recent-onset schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. Clin Schizophr Relat Psychoses. Winter 2017;10(4):201-210
4. Marx CE, Lee J, Subramaniam M, Rapisarda A, Bautista DC, Chan E, Kilts JD, Buchanan RW, Wai EP, Verma S, Sim K, Hariram J, Jacob R, Keefe RS, Chong SA. Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. psychopharmacology (berl). 2014 Sep;231(17):3647-62.
5. Ritsner MS, Bawakny H, Kreinin A. Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial. Psychiatry Clin Neurosci. 2014 Jun;68(6):432-40.

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Schizophrenia (positive symptoms): the improvement with pregnenolone treatment (1 reference)

1. Ritsner MS, Gibel A, Shleifer T, Boguslavsky I, Zayed A, Maayan R, Weizman A, Lerner V. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010 Oct;71(10):1351-62.

Pain: reduction with pregnenolone in animals (1 reference)

1. Chen SC, Liu BC, Chen CW, Wu FS. Intradermal pregnenolone sulfate attenuates capsaicin-induced nociception in rats. Biochem Biophys Res Commun. 2006 Oct 20;349(2):626-33.

Sleep disorder, insomnia: the improvement) with pregnenolone treatment in humans (1 reference)

1. Steiger A, Trachsel L, Guldner J, Hemmeter U, Rothe B, Rupprecht R, Vedder H, Holsboer F. Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation. Brain Res. 1993 Jul 2;615(2):267-74.

Sleep disorder, insomnia: the improvement with pregnenolone treatment in rats (2 references)

1. Darnaudéry M, Bouyer JJ, Pallarés M, Le Moal M, Mayo W. The promnesic neurosteroid pregnenolone sulfate increases paradoxical sleep in rats. Brain Res. 1999 Feb 13;818(2):492-8.
2. Lancel M, Crönlein TA, Müller-Preuss P, Holsboer F. Pregnenolone enhances EEG delta activity during non-rapid eye movement sleep in the rat, in contrast to midazolam. Brain Res. 1994 May 16;646(1):85-94.

Rheumatoid arthritis: the association with lower pregnenolone levels (2 references)

1. Vogl D, Falk W, Dorner M, Schölmerich J, Straub RH. Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones. J Rheumatol. 2003 Feb;30(2):269-75.
2. Hedman M, Nilsson E, de la Torre B. Low blood and synovial fluid levels of sulpho-conjugated steroids in rheumatoid arthritis. Clin Exp Rheumatol. 1992 Jan-Feb;10(1):25-30

Lupus: the association with lower pregnenolone levels (1 reference)

1. Vogl D, Falk W, Dorner M, Schölmerich J, Straub RH. Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones. J Rheumatol. 2003 Feb;30(2):269-75.

Rheumatoid arthritis: the improvement with pregnenolone treatment (9 references)

1. McGavack TH. ACTH, cortisone and pregnenolone in arthritis and allied diseases. 1952 Mar-Apr;7(2):99-108
2. Mendell HE, Skelton JM, Moyer JH. An evaluation of pregnenolone and a combination of desoxycorticosterone acetate-sodium ascorbate in the treatment of arthritis. Am Pract Dig Treat. 1952 Oct;3(10):818-23
3. Schaposnik F, Gutierrez A. Inefficacy of pregnenolone in maintaining remission obtained with cortisone in rheumatoid arthritis. Prensa Med Argent. 1952 May 16;39(20):1049-51
4. Myers GN. Pregnenolone in the treatment of rheumatoid arthritis. Ann Rheum Dis. 1951 Mar;10(1):32-45.
5. Mattikow B. Pregnenolone in arthritis. N Y State J Med. 1951 Feb 1;51(3):395.

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