پروژسترون

از ویکی‌پدیا، دانشنامهٔ آزاد
پرش به: ناوبری، جستجو
فارسی English
پروژسترون
سامانه‌شناسی نام (آیوپاک)
Pregn-4-ene-3,20-dione
داده‌های بالینی
نام تجاری Crinone, Endometrin
AHFS/Drugs.com monograph
مدلاین پلاس a604017
رده بارداری. B (USA)
وضعیت حقوقی  ?
Routes oral, implant
داده‌های فارماکوکینتیکی
فراهمی زیستی prolonged absorption, half-life approx 25-50 hours
پیوند پروتئینی 96%-99%
Metabolism hepatic to pregnanediols and pregnanolones
نیمه‌عمر 34.8-55.13 hours
دفع renal
شناسه
شماره سی‌ای‌اس 57-83-0 YesY
ATC code G03DA04
پاب‌کم CID 5994
IUPHAR ligand 2377
بانک‌دارو DB00396
کم‌اسپایدر 5773 YesY
UNII 4G7DS2Q64Y YesY
KEGG D00066 N
ChEBI CHEBI:17026 YesY
ChEMBL CHEMBL103 YesY
مترادفها 4-pregnene-3,20-dione
داده‌های شیمی
فرمول C21H30O2 
وزن مولکولی 314.46
SMILES eMolecules & PubChem
Physical data
دمای ذوب 126 °C (259 °F)
Spec. rot [α]D
 N(what is this?)  (verify)

پروژسترون [۱] (به انگلیسی: Progesterone)

یکی از هورمون‌های جنسی زنانه است. این هورمون یک استروئید بیست و یک کربنه است.

پروژسترون در طی چرخه تخمک گذاری طبیعی از جسم زرد ترشح می‌شود و قطع آن موجب شروع قاعدگی می‌شود. در زمان بارداری نیز این هورمون ترشح می‌شود . مقدار اندکی هم از غده فوق کلیوی آزاد می‌شود.

از پروژسترون در پزشکی در پیشگیری از حاملگی، سقط، درمان آمنوره، هورمون‌تراپی در زنان یائسه و ... استفاده می‌شود.


موارد و مقدار مصرف[ویرایش]

الف) آمنوره

بزرگسالان: مقدار mg/day 10-5 به مدت 8-6 روز تزريق عضلاني مي‌شود كه معمولاً 10-8 روز پيش از آغاز دوره قاعدگي قابل انتظار شروع مي‌شود. خونريزي 72-48 ساعت پس از قطع مصرف ممكن است رخ دهد.

ب) خونريزي ناشي از اختلال عملكرد رحم.

بزرگسالان: از راه تزريق عضلاني، مقدار mg/day 10-5 به مدت 6 روز مصرف مي‌شود يا مقدار 100-50 ميلي‌گرم به صورت مقدار واحد تزريق عضلاني مي‌شود.

موارد منع مصرف و احتياط[ویرایش]

تداخل دارويي

پروژسترون ممكن است موجب بروز آمنوره يا گالاكتوره شود و از اين رو، با اثر بروموكريپتين تداخل دارد؛ مصرف همزمان اين داروها توصيه نمي‌شود.

عوارض حانبي[ویرایش]

اعصاب مركزي : سردرد، افسردگي، خواب آلودگي‌، سكته.

قلبي ـ عروقي: ترومبوفلبيت، آمبولي ريوي، ادم، ترومبوآمبولي.

ادراري - تناسلي: لكه بيني، قاعدگي دردناك، آمنوره، ضايعات فرسايشي يا ترشحات غير طبيعي گردن رحم، دفع ادرار شبانه، خونريزي شديد.

كبد:يرقان انسدادي.

متابوليك: افزايش سطح آمينواسيدها.

ساير عوارض: حساسيت به لمس، بزرگي و ترشحات پستان.

توجه: در صورت بروز حساسيت مفرط، اختلالات ترومبوآمبوليك يا ترومبوتيك، اختلالات بينايي، سردرد ميگرني يا افسردگي شديد، بايد مصرف دارو قطع شود.

منابع[ویرایش]

  • ویکی‌پدیای انگلیسی
  • سایت دارونما

پانویس[ویرایش]

  1. نام دیگر فرتيژست است
Progesterone
Progesteron.svg
Progesterone molecule
Systematic (IUPAC) name
Pregn-4-ene-3,20-dione
Clinical data
Trade names Crinone, Endometrin
AHFS/Drugs.com monograph
MedlinePlus a604017
Pregnancy cat. B (USA)
Legal status ?
Routes oral, implant, transdermal
Pharmacokinetic data
Bioavailability prolonged absorption, half-life approx 25-50 hours
Protein binding 96%-99%
Metabolism hepatic to pregnanediols and pregnanolones
Half-life 34.8-55.13 hours
Excretion renal
Identifiers
CAS number 57-83-0 YesY
ATC code G03DA04
PubChem CID 5994
IUPHAR ligand 2377
DrugBank DB00396
ChemSpider 5773 YesY
UNII 4G7DS2Q64Y YesY
KEGG D00066 N
ChEBI CHEBI:17026 YesY
ChEMBL CHEMBL103 YesY
Synonyms 4-pregnene-3,20-dione
Chemical data
Formula C21H30O2 
Mol. mass 314.46
Physical data
Melt. point 126 °C (259 °F)
Spec. rot [α]D
 N (what is this?)  (verify)

Progesterone also known as P4 (pregn-4-ene-3,20-dione) is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species.[1] Progesterone belongs to a class of hormones called progestogens, and is the major naturally occurring human progestogen.

Chemistry

Progesterone was independently discovered by four research groups.[2][3][4][5]

Willard Myron Allen co-discovered progesterone with his anatomy professor George Washington Corner at the University of Rochester Medical School in 1933. Allen first determined its melting point, molecular weight, and partial molecular structure. He also gave it the name Progesterone derived from Progestational Steroidal ketone.[6]

Like other steroids, progesterone consists of four interconnected cyclic hydrocarbons. Progesterone contains ketone and oxygenated functional groups, as well as two methyl branches. Like all steroid hormones, it is hydrophobic.

Sources

Animal

Progesterone is produced in the ovaries (by the corpus luteum), the adrenal glands (near the kidney), and, during pregnancy, in the placenta. Progesterone is also stored in adipose (fat) tissue.

In humans, increasing amounts of progesterone are produced during pregnancy:

  • At first, the source is the corpus luteum that has been "rescued" by the presence of human chorionic gonadotropins (hCG) from the conceptus.
  • However, after the 8th week, production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal corticosteroids. At term the placenta produces about 250 mg progesterone per day.
  • An additional source of progesterone is milk products. After consumption of milk products the level of bioavailable progesterone goes up.[7]

Plants

In at least one plant, Juglans regia, progesterone has been detected.[8] In addition, progesterone-like steroids are found in Dioscorea mexicana. Dioscorea mexicana is a plant that is part of the yam family native to Mexico.[9] It contains a steroid called diosgenin that is taken from the plant and is converted into progesterone.[10] Diosgenin and progesterone are found in other Dioscorea species as well.

Another plant that contains substances readily convertible to progesterone is Dioscorea pseudojaponica native to Taiwan. Research has shown that the Taiwanese yam contains saponins — steroids that can be converted to diosgenin and thence to progesterone.[11]

Many other Dioscorea species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are Dioscorea villosa and Dioscorea polygonoides. One study showed that the Dioscorea villosa contains 3.5% diosgenin.[12] Dioscorea polygonoides has been found to contain 2.64% diosgenin as shown by gas chromatography-mass spectrometry.[13] Many of the Dioscorea species that originate from the yam family grow in countries that have tropical and subtropical climates.[14]

Synthesis

Biosynthesis

Top: Conversion of cholesterol (1) into pregnenolone (3) to progesterone (6).
Bottom: Progesterone is important for aldosterone (mineralocorticoid) synthesis, as 17-hydroxyprogesterone is for cortisol (glucocorticoid), and androstenedione for sex steroids.

In mammals, progesterone (6), like all other steroid hormones, is synthesized from pregnenolone (3), which in turn is derived from cholesterol (1) (see the upper half of the figure to the right).

Cholesterol (1) undergoes double oxidation to produce 20,22-dihydroxycholesterol (2). This vicinal diol is then further oxidized with loss of the side chain starting at position C-22 to produce pregnenolone (3). This reaction is catalyzed by cytochrome P450scc. The conversion of pregnenolone to progesterone takes place in two steps. First, the 3-hydroxyl group is oxidized to a keto group (4) and second, the double bond is moved to C-4, from C-5 through a keto/enol tautomerization reaction.[15] This reaction is catalyzed by 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase.

Progesterone in turn (see lower half of figure to the right) is the precursor of the mineralocorticoid aldosterone, and after conversion to 17-hydroxyprogesterone (another natural progestogen) of cortisol and androstenedione. Androstenedione can be converted to testosterone, estrone and estradiol.

Pregnenolone and progesterone can also be synthesized by yeast.[16]

Laboratory

The Marker semisynthesis of progesterone from diosgenin.[17]

An economical semisynthesis of progesterone from the plant steroid diosgenin isolated from yams was developed by Russell Marker in 1940 for the Parke-Davis pharmaceutical company (see figure to the right).[17] This synthesis is known as the Marker degradation. Additional semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, cortisone can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in chloroform to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.[18]

The Johnson total synthesis of progesterone.[19]

A total synthesis of progesterone was reported in 1971 by W.S. Johnson (see figure to the right).[19] The synthesis begins with reacting the phosphonium salt 7 with phenyl lithium to produce the phosphonium ylide 8. The ylide 8 is reacted with an aldehyde to produce the alkene 9. The ketal protecting groups of 9 are hydrolyzed to produce the diketone 10, which in turn is cyclized to form the cyclopentenone 11. The ketone of 11 is reacted with methyl lithium to yield the tertiary alcohol 12, which in turn is treated with acid to produce the tertiary cation 13. The key step of the synthesis is the π-cation cyclization of 13 in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce 14. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as biomimetic. In the next step the enol orthoester is hydrolyzed to produce the ketone 15. The cyclopentene A-ring is then opened by oxidizing with ozone to produce 16. Finally, the diketone 17 undergoes an intramolecular aldol condensation by treating with aqueous potassium hydroxide to produce progesterone.[19]

Levels

In women, progesterone levels are relatively low during the preovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase, as shown in diagram below. Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. If pregnancy occurs, human chorionic gonadotropin is released maintaining the corpus luteum allowing it to maintain levels of progesterone. At around 12 weeks the placenta begins to produce progesterone in place of the corpus luteum, this process is named the luteal-placental shift. After the luteal-placental shift progesterone levels start to rise further and may reach 100-200 ng/ml at term. Whether a decrease in progesterone levels is critical for the initiation of labor has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.

Progesterone levels are relatively low in children and postmenopausal women.[20] Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.

Blood test results should always be interpreted using the reference ranges provided by the laboratory that performed the results. Example reference ranges are listed below.

Person type Reference range for blood test
Lower limit Upper limit Unit
Female - menstrual cycle (see diagram below)
Female - postmenopausal <0.2[21] 1[21] ng/mL
<0,6[22] 3[22] nmol/L
Female on oral contraceptives 0.34[21] 0.92[21] ng/mL
1.1[22] 2.9[22] nmol/L
Males 16 years 0.27[21] 0.9[21] ng/mL
0.86[22] 2.9[22] nmol/L
Female or male 1–9 years 0.1[21] 4.1[21] or 4.5[21] ng/mL
0.3[22] 13[22] nmol/L
Progesterone levels during the menstrual cycle.
- The ranges denoted By biological stage may be used in closely monitored menstrual cycles in regard to other markers of its biological progression, with the time scale being compressed or stretched to how much faster or slower, respectively, the cycle progresses compared to an average cycle.
- The ranges denoted Inter-cycle variability are more appropriate to use in non-monitored cycles with only the beginning of menstruation known, but where the woman accurately knows her average cycle lengths and time of ovulation, and that they are somewhat averagely regular, with the time scale being compressed or stretched to how much a woman's average cycle length is shorter or longer, respectively, than the average of the population.
- The ranges denoted Inter-woman variability are more appropriate to use when the average cycle lengths and time of ovulation are unknown, but only the beginning of menstruation is given.

Effects

Micrograph showing changes to the endometrium due to progesterone (decidualization) H&E stain.

Progesterone exerts its primary action through the intracellular progesterone receptor although a distinct, membrane bound progesterone receptor has also been postulated.[23][24] In addition, progesterone is a highly potent antagonist of the mineralocorticoid receptor (MR, the receptor for aldosterone and other mineralocorticosteroids). It prevents MR activation by binding to this receptor with an affinity exceeding even those of aldosterone and other corticosteroids such as cortisol and corticosterone.[25]

Progesterone has a number of physiological effects that are amplified in the presence of estrogen. Estrogen through estrogen receptors upregulates the expression of progesterone receptors.[26] Also, elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.[27]

Effects of Progesterone on Nicotine and Cocaine Addiction

Progesterone inhibits the enzyme monoamine oxidase (MAO) which is responsible for breaking down serotonin, the “feel good” neurotransmitter. In addition, progesterone enhances the serotonin receptor function in the brain, so too much or too little progesterone can cause significant problems on brain chemistry. This explains why people resort to substances that enhance serotonin activity such as nicotine, alcohol, and marijuana when their progesterone levels fall below optimal levels.[28]

  • To examine the effects of progesterone on nicotine addiction specifically, one study researched the reinforcing effects of smoking in both men and women addicted to nicotine. Participants were either treated orally with a progesterone treatment, or treated with a placebo. When treated with progesterone, participants exhibited enhanced suppression of smoking urges, reported higher ratings of “bad effects” from IV nicotine, and reported lower ratings of “drug liking”. These results suggest that progesterone not only alters the subjective effects of nicotine, but reduces the urge to smoke cigarettes.[29]
  • Further studies demonstrated sex differences such that changes in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels.[30] Therefore, females have an increased biological vulnerability to nicotine’s reinforcing effects compared to men and progesterone may be used to counter this enhanced vulnerability. This information helps us to understand how the female hormones profoundly impact brain functioning, and, thus behavior.[28]
  • Furthermore, interestingly, past research suggests possible effects of progesterone on cocaine addiction. Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.[31]

Reproductive system

Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor(s) as yet remain unidentified.[32] Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes,[33] slow calcium oscillations,[34] now thought to possibly regulate motility.[35] Interestingly, progesterone has also been shown to demonstrate effects on octopus spermatozoa.[36]

Progesterone modulates the activity of CatSper (cation channels of sperm) voltage-gated Ca2+ channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs (chemotaxis). Hence substances that block the progesterone binding site on CatSper channels could potentially be used in male contraception.[37][38]

Progesterone is sometimes called the "hormone of pregnancy",[39] and it has many roles relating to the development of the fetus:

  • Progesterone converts the endometrium to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the vaginal epithelium and cervical mucus, making it thick and impenetrable to sperm. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to menstruation. Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the corpus luteum does not develop, levels of progesterone may be low, leading to anovulatory dysfunctional uterine bleeding.
  • During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy.
  • Progesterone decreases contractility of the uterine smooth muscle.[39]
  • In addition progesterone inhibits lactation during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production.
  • A drop in progesterone levels is possibly one step that facilitates the onset of labor.

The fetus metabolizes placental progesterone in the production of adrenal steroids.

Nervous system

Progesterone, like pregnenolone and dehydroepiandrosterone, belongs to the group of neurosteroids. It can be synthesized within the central nervous system and also serves as a precursor to another major neurosteroid, allopregnanolone.

Neurosteroids affect synaptic functioning, are neuroprotective, and affect myelination.[40] They are investigated for their potential to improve memory and cognitive ability. Progesterone affects regulation of apoptotic genes.

Its effect as a neurosteroid works predominantly through the GSK-3 beta pathway, as an inhibitor. (Other GSK-3 beta inhibitors include bipolar mood stabilizers, lithium and valproic acid.)

Other effects

  • It raises epidermal growth factor-1 levels, a factor often used to induce proliferation, and used to sustain cultures, of stem cells.
  • It increases core temperature (thermogenic function) during ovulation.[41]
  • It reduces spasm and relaxes smooth muscle. Bronchi are widened and mucus regulated. (Progesterone receptors are widely present in submucosal tissue.)
  • It acts as an antiinflammatory agent and regulates the immune response.
  • It reduces gall-bladder activity.[42]
  • It normalizes blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy.
  • It may affect gum health, increasing risk of gingivitis (gum inflammation) and tooth decay.[43]
  • It appears to prevent endometrial cancer (involving the uterine lining) by regulating the effects of estrogen.
  • Progesterone plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes or gestational diabetes.[44][45]
  • It is related with apoptosis theory <not just Abstract> and increase monocytes

Medical applications

Prometrium 100 mg Oral Capsule

The use of progesterone and its analogues have many medical applications, both to address acute situations and to address the long-term decline of natural progesterone levels. Because of the poor bioavailability of progesterone when taken orally, many synthetic progestins have been designed with improved oral bioavailability and have been used long before progesterone formulations became available.[46] Progesterone was approved by the United States Food and Drug Administration as vaginal gel on July 31, 1997,[47] an oral capsule on May 14, 1998[48] in an injection form on April 25, 2001[49] and as a vaginal insert on June 21, 2007.[50] In Italy and Spain, Progesterone is sold under the trademark Progeffik.

Bioavailability

The route of administration impacts the effect of the drug. Given orally, progesterone has a wide person-to-person variability in absorption and bioavailability while synthetic progestins are rapidly absorbed with a longer half-life than progesterone and maintain stable levels in the blood.[51]

Progesterone does not dissolve in water and is poorly absorbed when taken orally unless micronized in oil. Products are often sold as capsules containing micronised progesterone in oil. Progesterone can also be administered through vaginal or rectal suppositories or pessaries, transdermally through a gel or cream,[52] or via injection (though the latter has a short half-life requiring daily administration).

Transdermal "natural progesterone" products made with Progesterone USP do not require a prescription. Some of these products also contain "wild yam extract" derived from Dioscorea villosa, but there is no evidence that the human body can convert its active ingredient (diosgenin, the plant steroid that is chemically converted to produce progesterone industrially[17]) into progesterone.[53][54]

Prevention of preterm birth

Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. The initial study by Fonseca suggested that vaginal progesterone could prevent preterm birth in women with a history of preterm birth.[55] According to a recent study, women with a short cervix that received hormonal treatment with a progesterone gel had their risk of prematurely giving birth reduced. The hormone treatment was administered vaginally every day during the second half of a pregnancy.[56] A subsequent and larger study showed that vaginal progesterone was no better than placebo in preventing recurrent preterm birth in women with a history of a previous preterm birth,[57] but a planned secondary analysis of the data in this trial showed that women with a short cervix at baseline in the trial had benefit in two ways: a reduction in births less than 32 weeks and a reduction in both the frequency and the time their babies were in intensive care.[58] In another trial, vaginal progesterone was shown to be better than placebo in reducing preterm birth prior to 34 weeks in women with an extremely short cervix at baseline.[59] An editorial by Roberto Romero discusses the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment.[60] A meta-analysis published in 2011 found that vaginal progesterone cut the risk of premature births by 42 percent in women with short cervixes.[61] The meta-analysis, which pooled published results of five large clinical trials, also found that the treatment cut the rate of breathing problems and reduced the need for placing a baby on a ventilator.[62]

Other specific uses

Role in aging

Since most progesterone in males is created during testicular production of testosterone, and most in females by the ovaries, the shutting down (whether by natural or chemical means), or removal, of those inevitably causes a considerable reduction in progesterone levels. Previous concentration upon the role of progestogens (progesterone and molecules with similar effects) in female reproduction, when progesterone was simply considered a "female hormone", obscured the significance of progesterone elsewhere in both sexes.

The tendency for progesterone to have a regulatory effect, the presence of progesterone receptors in many types of body tissue, and the pattern of deterioration (or tumor formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females.

Role in brain damage

Studies as far back as 1987 show that female sex hormones have an effect on the recovery of traumatic brain injury.[66] In these studies, it was first observed that pseudopregnant female rats had reduced edema after traumatic brain injury. Recent clinical trials have shown that among patients that have suffered moderate traumatic brain injury, those that have been treated with progesterone are more likely to have a better outcome than those who have not.[67]

Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to traumatic brain injury and this protective effect has been hypothesized to be caused by increased circulating levels of estrogen and progesterone in females.[68] A number of additional animal studies have confirmed that progesterone has neuroprotective effects when administered shortly after traumatic brain injury.[69] Encouraging results have also been reported in human clinical trials.[70][71]

Proposed mechanism

The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma.[72]

Damage incurred by traumatic brain injury is believed to be caused in part by mass depolarization leading to excitotoxicity. One way in which progesterone helps to alleviate some of this excitotoxicity is by blocking the voltage-dependent calcium channels that trigger neurotransmitter release.[73] It does so by manipulating the signaling pathways of transcription factors involved in this release. Another method for reducing the excitotoxicity is by up-regulating the inhibitory neurotransmitter receptor, GABAA.[74]

Progesterone has also been shown to prevent apoptosis in neurons, a common consequence of brain injury.[66] It does so by inhibiting enzymes involved in the apoptosis pathway specifically concerning the mitochondria, such as activated caspase 3 and cytochrome c.

Not only does progesterone help prevent further damage, it has also been shown to aid in neuroregeneration. One of the serious effects of traumatic brain injury includes edema. Animal studies show that progesterone treatment leads to a decrease in edema levels by increasing the concentration of macrophages and microglia sent to the injured tissue.[73][75] This was observed in the form of reduced leakage from the blood brain barrier in secondary recovery in progesterone treated rats. In addition, progesterone was observed to have antioxidant properties, reducing the concentration of oxygen free radicals faster than without.[74] There is also evidence that the addition of progesterone can also help remyelinate damaged axons due to trauma, restoring some lost neural signal conduction.[74] Another way progesterone aids in regeneration includes increasing the circulation of endothelial progenitor cells in the brain.[76] This helps new vasculature to grow around scar tissue which helps repair the area of insult.

Combination treatments

Vitamin D and progesterone separately have neuroprotective effects after traumatic brain injury, but when combined their effects are synergistic.[77] When used at their optimal respective concentrations, the two combined have been shown to reduce cell death more than when alone.

One study looks at a combination of progesterone with estrogen. Both progesterone and estrogen are known to have antioxidant-like qualities and are shown to reduce edema without injuring the blood-brain barrier. In this study, when the two hormones are administered alone it does reduce edema, but the combination of the two increases the water content, thereby increasing edema.[78]

Clinical trials

The clinical trials for progesterone as a treatment for traumatic brain injury have only recently begun. ProTECT, a phase II trial conducted in Atlanta at Grady Memorial Hospital in 2007, the first to show that progesterone reduces edema in humans. Since then, trials have moved on to phase III. The National Institute of Health began conducting a nationwide phase III trial in 2011 led by Emory University.[67] A global phase III initiative called SyNAPSe®, initiated in June 2010, is run by a U.S.-based private pharmaceutical company, BHR Pharma, and is being conducted in the United States, Argentina, Europe, Israel and Asia.[79][80] Approximately 1,200 patients with severe (Glasgow Coma Scale scores of 3-8), closed-head TBI will be enrolled in the study at nearly 150 medical centers.

See also

References

  1. ^ "Metabocard for Hydroxyprogesterone". Human Metabolome Database. Retrieved 31 July 2013. 
  2. ^ Allen WM (1935). "The isolation of crystalline progestin". Science 82 (2118): 89–93. doi:10.1126/science.082.2118.89. PMID 17747122. 
  3. ^ Butenandt A, Westphal U (1934). "Zur Isolierung und Charakterisierung des Corpusluteum-Hormons". Berichte Deu0tsche chemische Gesellschaft 67 (8): 1440–1442. doi:10.1002/cber.19340670831. 
  4. ^ Hartmann M, Wettstein A (1934). "Ein krystallisiertes Hormon aus Corpus luteum". Helvetica Chimica Acta 17: 878–882. doi:10.1002/hlca.193401701111. 
  5. ^ Slotta KH, Ruschig H, Fels E (1934). "Reindarstellung der Hormone aus dem Corpusluteum". Berichte Deutsche chemische Gesellschaft 67 (7): 1270–1273. doi:10.1002/cber.19340670729. 
  6. ^ Allen WM (1970). "Progesterone: how did the name originate?". South. Med. J. 63 (10): 1151–5. doi:10.1097/00007611-197010000-00012. PMID 4922128. 
  7. ^ Goodson III WH, Handagama P, Moore II DH, Dairkee S (2007-12-13). "Milk products are a source of dietary progesterone". 30th Annual San Antonio Breast Cancer Symposium. pp. abstract # 2028. Retrieved 2008-03-12. 
  8. ^ Pauli GF, Friesen JB, Gödecke T, Farnsworth NR, Glodny B (January 2010). "Occurrence of Progesterone and Related Animal Steroids in Two Higher Plants". J Nat Prod 73 (3): 338–45. doi:10.1021/np9007415. PMID 20108949. 
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Additional images

Steroidogenesis, showing progesterone among the progestogens in yellow area.


External links