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Categories available are: Androgens; Estrogens; Progesterone; Bone: Brain; Breast; Cardiovascular; Formulations; Menopausal Symptoms; Premenopause; Progestin; Safety; Uterus.
1. - Effects of acute progesterone administration in healthy postmenopausal women and normally-cycling women. de Wit H, Schmitt L, Purdy R, Hauger R.
Psychoneuroendocrinology 2001;26(7):697-710.
This randomized controlled study investigated the effects of acute progesterone administration (25, 50, 100 mg, intramuscularly, 1 dose/wk) on mood. Contrary to the investigators’ expectations, very few unwanted behavioral effects were noted, and only in the highest dose (100 mg) did women slightly increase their self-rating of “sluggishness”.
Article on Pubmed
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2. - Progesterone as a neuroprotective factor in traumatic and ischemic Brain injury. Sayeed I, Stein DG.
Prog Brain Res. 2009;175:219-37.
This review describes the effectiveness of progesterone in the treatment of traumatic Brain injury, and then focuses on its potential role in the treatment of ischemic stroke. Progesterone and its natural metabolites act through numerous mechanisms to exert their neuroprotective activity, and these are described in the review. The authors recommend testing progesterone in clinical trials as a compelling natural treatment for nervous system injuries such as traumatic brain injury and stroke.
Article on Pubmed
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3. - Novel perspectives for progesterone in hormone replacement therapy, with special reference to the nervous system. Schumacher M, Guennoun R, Ghoumari A, Massaad C, Robert F, El-Etr M, Akwa Y, Rajkowski K, Baulieu EE.
Endocr Rev. 2007;28(4):387-439.
The authors describe in detail the neuroprotective effects of progesterone when used in postmenopausal hormone replacement therapy. They emphasize that natural progesterone has very different properties than synthetic progestins. Medroxyprogesterone acetate actually inhibits the beneficial effects of estradiol on the nervous system and also exerts damaging effects, whereas progesterone does neither. Progesterone is known to have neuroprotective, neurotrophic, and promyelinating effects.
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4. - ProTECT: a randomized clinical trial of progesterone for acute traumatic Brain injury. Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG.
Ann Emerg Med. 2007;49(4):391-402, 402.e1-2.
A neuroprotective effect of progesterone was observed in this randomized, placebo-controlled trial of very high dose, intravenous progesterone therapy given for 3 days after acute traumatic Brain injury. Only 13% of the patients died within 30 days after injury in the progesterone group, compared with 30% of the placebo group, and the progesterone group was more likely to have a moderate to good functional outcome after 30 days than the placebo group. Even at the extremely high dose used, no serious adverse events were seen with progesterone.
Article on Pubmed
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5. - Effects of progesterone on the inflammatory response to Brain injury in the rat. Grossman KJ, Goss CW, Stein DG.
Brain Res. 2004;1008(1):29-39.
Progesterone has a known anti-inflammatory effect. In this study, male rats treated with progesterone (4 mg/kg) and/or vehicle, were examined with respect to cellular inflammatory response to frontal cortex injury on postsurgical days 1, 3, 5, 7 and 9. The treated mice suffered significantly less edema than untreated mice, as well as showed an increase in the accumulation of activated microglia, demonstrating a neuroprotective effect on the rat Brain.
Article on Pubmed
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6. - Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination. Schumacher M, Guennoun R, Robert F, Carelli C, Gago N, Ghoumari A, Gonzalez Deniselle MC, Gonzalez SL, Ibanez C, Labombarda F, Coirini H, Baulieu EE, De Nicola AF.
Growth Horm IGF Res. 2004;14 Suppl A:S18-33.
This paper reviews of the effects of progesterone as an autocrine/paracrine hormone in the Brain. The brain, spinal cord and peripheral nerves all synthesize progesterone from the precursor, pregnenolone. Macroglial cells, including astrocytes, oligodendroglial cells and Schwann cells, also have the capacity to synthesize progesterone. This production is regulated by cellular interactions. Recent research has suggested the role progesterone plays in the brain is likely a significant one, supporting the viability of neurons and the formation of myelin sheaths. In mice and rat studies, progesterone also demonstrated a neuroprotective effect. These actions of progesterone suggest viable therapeutic possibilities for the prevention and treatment of neurodegenerative diseases, as well as for repair processes and for preserving cognitive functions with age.
Article on Pubmed
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7. - Progesterone enhances functional recovery after middle cerebral artery occlusion in male mice. Gibson CL, Murphy SP.
J Cereb Blood Flow Metab. 2004;24(7):805-13.
Differences in outcomes following ischemia have been noted between men and women, and this is thought to be attributed to sex steroids. This study investigated the potential benefits of progesterone administration after focal cerebral ischemia of the middle cerebral artery of male mice. Male mice undergoing 60-minute middle cerebral artery occlusion (MCAO) received either progesterone or vehicle following occlusion. The mice receiving progesterone had significantly reduced lesion volume (p< 0.05) when compared with the vehicle treated mice (control). Progesterone treatment also improved survival rate, weight recovery, and motor ability when compared to the control group. In addition, mice treated with progesterone demonstrated motor ability comparable to mice that did not undergo MCAO. The authors suggest the need to further investigate the mechanisms of progesterone action on recovery from cerebral injury.
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8. - Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women. Cummings JA, Brizendine L.
Menopause 2002;9(4):253-63.
Twenty-three early postmenopausal women were randomized to either medroxyprogesterone acetate (MPA) or oral micronized progesterone combined with conjugated equine estrogens (CEE) and followed for 91 days in a sequence of treatments. None of the hormone treatments had any noticeable effect on mood. Participants using MPA experienced more breast tenderness and bleeding than those using progesterone. This study debunks the belief that progesterone depresses mood in healthy individuals.
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9. - Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination. Baulieu E, Schumacher M.
Steroids 2000;65(10-11):605-12.
This paper reviews the effects of progesterone on the Brain, with special focus on its role in the formation of the myelin sheath surrounding nerve fibers. Other roles of progesterone in the brain include activating GABA receptors, which induces a calming effect.
Article on Pubmed
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10. - Progestogens used in menopause. Side effects, mood and quality of life. Sherwin BB.
J Reprod Med 1999;44(2 Suppl):227-32.
This review summarizes the effects of progesterone on mood and other Brain functions. Progesterone receptors are present in many of the same areas of the brain as estrogen receptors, including the limbic system and hypothalamus. The limbic system plays a prominent role in regulating mood and emotion. As a comparison, progesterone decreases brain excitability, while estrogens increase it. This relates to why women with epilepsy have a higher frequency of seizures during the part of the cycle when estrogen levels are high, and a reduced frequency when progesterone levels are high. Estrogen and progesterone may also have differing effects on MAO, thereby affecting concentration of serotonin (a mood elevator) in the brain.
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11. - Diverse modes of action of progesterone and its metabolites. Mahesh VB, Brann DW, Hendry LB.
Steroid Biochem Mol Biol 1996;56(1-6):209-19.
A review of the actions of progesterone and its metabolites demonstrates physiological significance in such biological activities as may have importance in the regulation of stress, post-partum depression, memory, cognition, PMS, and depression, to name a few.
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12. - Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites. Arafat ES, Hargrove JT, Maxson WS, Desiderio DM, Wentz AC, Andersen RN.
Am J Obstet Gynecol 1988;159(5):1203-9.
This small pilot study evaluated progesterone and its metabolites following administration of oral micronized progesterone in eight postmenopausal women. Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry. Evaluation of serial blood samples showed elevated levels of serum progesterone and its metabolites from baseline, reaching a peak between 2 and 6 hours after oral administration. The following compounds: progesterone, 5 beta-pregnan-3 alpha, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione, were identified. These compounds have reported anesthetic qualities, which may contribute to the sedative and hypnotic effects seen with oral administration of progesterone. The authors reported that, in one subject, 400 mg of oral micronized progesterone induced a hypnotic state lasting approximately 2 hours.
Article on Pubmed
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