Progesterone Research Papers

Endocrine Reviews, First published online on April 12, 2007 Author Manuscript (PDF)

A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks.
Altern Med Rev. 2006 Sep;11(3):208-23.

Conditional logistic regression analysis found that progesterone is a protective factor only and testosterone is one of the risk factors for hypertension.
International Journal of Epidemiology 1990 Volume 19, Number 2 Pp. 297-302

Serum total cholesterol, low-density lipoprotein cholesterol and the related apolipoprotein B were decreased significantly with 0.35 mmol/l, 0.44 mmol/l and 15 mg/l, respectively, during the luteal phase as compared to the follicular phase (p < or =0.01).
Acta Endocrinol (Copenh). 1993 Aug;129(2):130-3.

Progesterone exerted two effects on macrophages: it acutely inhibited cholesteryl ester (CE) formation, and it prevented glucocorticoid-induced increases in acyl-CoA-cholesterol-acyl transferase gene expression and CE synthesis, estradiol was ineffective.
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 1 265-271

Coronary hyperreactivity, a putative component of coronary artery disease mediated via increased vascular muscle thromboxane prostanoid receptors, can be prevented by subphysiological levels of progesterone, not only in nonatherosclerotic (previously shown) but also in preatherosclerotic primates.
Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:955.

Recent findings suggest that both the production of progesterone during pregnancy and the progesterone endogenously produced or exogenously administered outside pregnancy, does not increase breast cancer risk, and could even be protective.
Journal of Steroid Biochemistry & Molecular Biology 97 (2005) 441-450

Most epidemiological studies have shown an increase in breast cancer risk related to hormone replacement therapy (HRT) use. The risk was significantly greater ( p<0.001) with HRT containing synthetic progestins than with HRT containing micronized progesterone, the RRs being 1.4 [1.2-1.7] and 0.9 [0.7-1.2], respectively.
International Journal of Cancer Volume 114, Issue 3 , Pages 448 - 454

The addition of the synthetic progestin medroxyprogesterone acetate (MPA) to postmenopausal estrogen therapy significantly increases breast cancer risk. These findings suggest that oral micronized progesterone has a more favorable effect on risk biomarkers for postmenopausal breast cancer than medroxyprogesterone acetate.
Breast Cancer Research and Treatment , Volume 101, Number 2, January 2007 , pp. 125-134(10)

These results suggest that prolonged progesterone administration can suppress cell proliferation in endometrial carcinomas through tumor cell differentiation without alterating apoptosis.
Cancer Volume 83, Issue 1 , Pages 111 - 121

Progesterone plays an important role in controlling proliferation and differentiation of the human endometrium.
Reproductive Sciences, Vol. 12, No. 4, 285-292 (2005)

In terms of the pathogenesis of ovarian cancer, we suggest that the additional protective aspect of pregnancy not mediated through suppression of ovulation may be due to the 8-9 months of elevated progesterone.
Journal of the National Cancer Institute, Vol. 90: 1774-86, No. 23, December 2, 1998

In the presence of 20 µg of progesterone per ml, there was significant reduction in the oxidation by resting staphylococcal suspensions or utilization by staphylococci of pyruvate as an energy source during growth.
J Bacteriol. 1966 November; 92(5): 1285-1289

The growth of A. benhamiae + and M. canis, and T. rubrum were all inhibited by progesterone in a dose-responsive manner, with 50% inhibition achieved at concentrations of 9.8 x 10(-6), 1.2 x 10(-5), 1.5 x 10(-5), and 2.7 x 10(-6) M. respectively.
J Clin Microbiol. 1988 October; 26(10): 2110-2115

Vulvovaginal candidiasis (VVC) is an opportunistic mucosal infection caused by Candida albicans…. These results suggest that estrogen, but not progesterone, is an important factor in hormone-associated susceptibility to C. albicans vaginitis.
Infection and Immunity, February 2000, p. 651-657, Vol. 68, No. 2

We have recently described a dose-dependent, endothelium-independent relaxation to progesterone in human placental arteries and veins. This receptor-operated, cAMP-mediated relaxation may be of value in maintaining adequate blood flow in the placental circulation.
Journal of Maternal-Fetal Investigation Volume 8, Number 1 / March, 1998 Pages 27-30

In mild, moderate and severe endometriosis the plasma progesterone concentration did not rise on the first day following the LH peak.
Br J Obstet Gynaecol. 1978 Apr;85(4):246-50.

We have recently documented the presence of matrix metalloproteinases in lesions of endometriosis… suppressing metalloproteinase secretion in vitro with progesterone treatment…..inhibits the formation of ectopic lesions in this experimental model.
J. Clin. Invest. Volume 99, Number 12, June 1997, 2851-2857

In this report, we show that dioxin exposure promotes establishment of experimental endometriosis by interfering with the ability of progesterone to suppress endometrial matrix metalloproteinase expression.
Gynecologic and Obstetric Investigation 1999;48:45-56 (DOI: 10.1159/000052868)

Estrogen is an extremely potent mitogen for endometrium and endometriosis. Progesterone, on the other hand, inhibits the mitogenic action of estrogen on endometrium and enhances differentiation.
Semin Reprod Med 2003; 21: 125-134

The anticonvulsant effects of allopregnanolone against amygdala-kindled seizures in female rats.
Neurosci Lett. 2007 Jan 10;411(2):147-51. Epub 2006 Nov 7.

The anticonvulsant effects of progesterone and its metabolites on amygdala-kindled seizures in male rats.
Brain Res. 2006 Jul 26;1101(1):110-6. Epub 2006 Jun 19.

In a subgroup of catamenial seizure patients on antiepileptic therapy, luteal progesterone levels were remarkably decreased compared to normal and epileptic controls.
Epilepsy Res. 1989 Mar-Apr;3(2):100-6.

Data suggest anti-seizure effects of progesterone may be due, in part, to metabolism to 3alpha,5alpha-THP and subsequent actions at GABA(A) receptor complexes.
Psychoneuroendocrinology. 2000 May;25(4):407-20. Links

Estrogens decrease seizure threshold and increase brain excitability, whereas progesterone has an inhibitory effect and reduces epileptiform activity.
Epilepsia Volume 42 Issue 2 Page 216 - February 2001

Children whose mothers received prenatal progesterone have been shown to be advanced in development at one year and to have greater academic achievement at 9-10 years.
Br J Psychiatry. 1976 Nov;129:438-42.

The Mg2+ concentration in the young men was directly and significantly related to the progesterone level, and the Ca2+/Mg2+ ratio was inversely related to the progesterone level. CONCLUSION(S): Progesterone may be a more important steroid hormone in men than previously believed.
Fertil Steril. 1999 Nov;72(5):817-22.

Progesterone-stimulated [Ca2+] increase was significantly correlated with sperm motility (r = 0.54), sperm concentration (r = 0.96), and sperm morphology (% of normal forms) (r = 0.49). In addition P induced a significant increase of acrosome-reacted spermatozoa in normospermic patients (n = 10),
Journal of Andrology, Vol 14, Issue 1 17-22

Surprisingly, we know little about the physiology, endocrinology, and pharmacology of progesterone and progestins in male gender or men respectively, despite the fact that, as to progesterone secretion and serum progesterone levels, there are no great quantitative differences between men and women (at least outside the luteal phase). Progesterone influences spermiogenesis, sperm capacitation/acrosome reaction and testosterone biosynthesis in the Leydig cells.
The Aging Male , Volume 7, Issue 3September 2004 , pages 236 - 257

Very low doses of natural progesterone, when administered vaginally in a bioadhesive gel, cause secretory endometrial transformation in estrogen-treated postmenopausal women.
Am J Obstet Gynecol 1997;177:937-41.

Although we found no protective effect on bone density after 1 year, we did see a significant improvement in vasomotor symptoms in the treated group.
Obstetrics & Gynecology 1999;94:225-228

Progesterone inhibits mast cell secretion.
These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.
Int J Immunopathol Pharmacol. 2006 Oct-Dec;19(4):787-94.

Chronic progesterone administration apparently does not directly influence aldosterone secretion, but rather acts indirectly to increase aldosterone by mechanisms similar to sodium restriction.
Endocrinology, Vol 137, 4773-4778

Women at menses reported a significantly higher level of physically aggressive behavior than during the midluteal phase.
Aggressive Behavior Volume 29, Issue 6 , Pages 531 - 538

Journal of the Society for Gynecologic Investigation, Vol. 8, No. 5, 295-298 (2001)
The PROGINS Progesterone Receptor Gene Polymorphism and Idiopathic Recurrent Miscarriage. Progesterone inhibits lymphocyte cytotoxicity, natural killer cell degranulation, and release of proinflammatory cytokines and has been shown to protect against spontaneous miscarriage.

The results suggest that progesterone vaginal suppositories are effective in reducing the risk of spontaneous abortions in high-risk patients.
Int J Fertil. 1987 May-Jun;32(3):192-3, 197-9.

The possibility exists therefore that women with recurrent miscarriage may have a need for a greater amount of progesterone to stimulate sufficient PIBF to suppress immune rejection. Progesterone therapy has been demonstrated to reduce the frequency of miscarriage.
Human Reproduction 2005 20(7):2035-2036; doi:10.1093/humrep/deh877

Progesterone inhibits in-vitro embryotoxic Th1 cytokine production to trophoblast in women with recurrent pregnancy loss.
Hum Reprod. 2000 Jun;15 Suppl 1:46-59.

Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity..
American Journal of Obstetrics and Gynecology Volume 188, Issue 2, February 2003, Pages 419-424

Luteal phase support with hCG or progesterone after assisted reproduction results in an increased pregnancy rate.
Cochrane Database Syst Rev. 2004;(3):CD004830.

As cortisol levels rise in the bloodstream, they suppress the production of progesterone, a hormone that is crucial to maintaining a healthy pregnancy.
Exclusive from New Scientist Print Edition. 10:30 12 November 2004

Progesterone is an essential hormone in the process of reproduction. It is involved in the menstrual cycle, implantation and is essential for pregnancy maintenance. This may explain the reduction in the incidence of preterm birth in high risk pregnant women using high-dosage prophylactic progesterone.
BJOG: Volume 112 Issue s1 Page 57-60, March 2005

We describe here the progesterone treatment of a patient with a most likely congenital myopathy and we show that interdisciplinary cooperation can be fruitful.
Acta Obstet Gynecol Scand 2001; 80: 972-973 (original in pdf format)

Plasma Progesterone in the Respiratory Distress Syndrome
Seventeen newborns suffering from RDS (verified by X-ray and clinical parameters) had a mean plasma progesterone of 13.9_+ 1.2ng/ml (mean + S.E.) at 24 h of age. This is only 62% of the normal level (22.6 _+ 1.5 ng/ml).
Eur. J. Pediatr. 132, 7--10(1979) (original in pdf format)

An unusual patient with hypoxemia, hypercapnia, and right ventricular failure is presented. The patient benefited from progesterone therapy. In this unusual patient, mild muscular weakness, caused by diabetes, and central alveolar hypoventilation have acted in synergism to cause abnormal ventilation and right ventricular failure.
Respiration. 1983;44(6):460-5.

Administration of progesterone or its precursor, pregnenolone, to the lesion site increased the extent of myelin sheath formation.
Science 9 June 1995: Vol. 268. no. 5216, pp. 1500 - 1503

The gonadal hormone, progesterone, has been shown to have neuroprotective effects in injured nervous system, including the severity of post injury cerebral edema. These data suggest progesterone has antioxidant effects and support its potential as a treatment for brain injury.
Mol Chem Neuropathol. 1997 May;31(1):1-11. Links

Progesterone has multiple effects on glial cells, it influences growth, differentiation and increases the expression of myelin-specific proteins in oligodendrocytes, and potentiates the formation of new myelin sheaths by Schwann cells in vivo.
J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):97-107.

The loss of progesterone may contribute to the deficits observed after ovariectomy or the increased risk for Alzheimer's disease seen after the menopause.
Ann. N.Y. Acad. Sci. 1052: 145-151 (2005). Volume 1052 published June 2005

The regulation of Tau expression and phosphorylation by progesterone may contribute to the hormonal regulation of cerebellar function by the modification of neuronal cytoskeleton.
Developmental Neurobiology Volume 67, Issue 4 , Pages 510 - 520

The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration.
Journal of Neurobiology Volume 66, Issue 9 , Pages 916 - 928

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism.
Endocr Rev. 1990 May;11(2):386-98.

Progesterone and promegestone increased cell number in human osteoblastic cells after six days of treatment.
Acta Endocrinol (Copenh). 1992 Apr;126(4):329-37.

The administration of progesterone to ovariectomized rats also led to a significant decrease in the parasite load of the animals, thus demonstrating that progesterone induces the increase of the parasiticide activity of the leukocytes involved in the mechanisms of Trichinella spiralis newborn larvae death.
Parasitology (2005), 131: 21 Apr 2005

These results suggest that in women with PCO, the persistent elevation of follicular LH may lead to impaired progesterone production in response to exogenous LH.
J Clin Endocrinol Metab. 1986 Nov;63(5):1156-62.

In summary, it seems that PCOS granulosa cells demonstrate an abnormal capacity to synthesize progesterone in vivo and in vitro. The understanding of granulosa cell function in PCOS may explain the anovulation and miscarriage that occurs in these patients.
Human Reproduction, 1998 Vol 13, 290-293

Women with PCO did not have more variation in cycle length than fertile women with normal ovaries, but there were significantly lower levels of progesterone in the early luteal phase. This may contribute to the delay in conception in these patients.
Human Reproduction, Vol. 17, No. 6, 1459-1463, June 2002

Subjects with PMS manifested lower levels of the anxiolytic metabolite allopregnanolone in the luteal phase when compared with controls.
Obstetrics & Gynecology 1997;90:709-714

Serum allopregnanolone levels were detectable postpartum and were significantly decreased in women with maternity "blues."
Obstetrics & Gynecology 2001;97:77-80

Progesterone has shown to be efficacious when continuation of pregnancy is hampered by immunological factors, luteinic and neuroendocrine deficiencies and myometrial hypercontractility. This may explain the reduction in the incidence of preterm birth in high-risk pregnant women using high-dosage prophylactic progesterone.
Current Opinion in Obstetrics & Gynecology. 17(6):598-600, December 2005.

Progesterone production at the placental level may be responsible, at least in part, for increased production of Th2-type cytokines which have been implied in fetal allograft survival and maintenance of successful pregnancy.
The Journal of Immunology, Vol 155, Issue 1 128-133

Evidence suggests that HLA-G plays a critical role in maternal immune tolerance to the fetus. Progesterone has an up-regulatory effect on HLA-G gene expression in first trimester trophoblasts and JEG-3 cells in vitro.
Human Reproduction 2006 21(1):46-51

Low dose micronized progesterone administered vaginally is simple, easy and well tolerated, it could be recommended as the method of choice for luteal support, (for in-vitro fertilization), especially for high responder patients at risk for ovarian hyperstimulation syndrome.
Human Reproduction, Vol. 14, No. 8, 1944-1948, August 1999

Higher serum concentrations of progesterone and relaxin, but not oestradiol, in early pregnancy were related to lower mean systolic blood pressures in the second and third trimesters.
Human Reproduction, Vol. 16, No. 1, 13-17, January 2001

In assisted reproduction, luteal support is mandatory and progesterone is the most widely used hormone, it can be delivered orally, intramuscularly and vaginally. The oral route is the least efficient but the intramuscular route is as efficient as the vaginal route; however, the latter is more acceptable, especially during prolonged treatments, such as oocyte donation and frozen embryo transfer cycles.
Expert Review of Obstetrics & Gynecology November 2006, Vol. 1, No. 2, Pages 173-182

Conservative treatment with high-dose progesterone for endometrial hyperplasia and well-differentiated early-stage adenocarcinoma, followed by in vitro fertilization and embryo transfer, is an appropriate means for achieving pregnancy.
Gynecologic and Obstetric Investigation 2006;61:21-23

Under conditions in which binding in the 8S region was demonstrable with dihydrotestosterone and testosterone no binding of 3 alpha-androstanediol or progesterone was detectable. Thus, enhancement by 17 beta-estradiol of a prostate cytosol androgen-binding protein occurs under circumstances in which 17 beta-estradiol enhances androgen-mediated prostatic growth.
J Clin Invest. 1979 March; 63(3): 351-357.

The tumor doubling time was more than 4 times longer in rats receiving D-Trp 6 luteinizing hormone-releasing hormone (LH-RH) than in controls. Serum levels of luteinizing hormone and follicle-stimulating hormone were significantly decreased in rats receiving this analogue. In both Fisher 344 and Copenhagen F-1 rats, serum prolactin and testosterone levels were significantly decreased after treatment with D-Trp 6-LH-RH, whereas progesterone levels were increased.
PNAS | October 1, 1981 | vol. 78 | no. 10 | 6509-6512

Of the natural steroids, 17-0H-progesterone was found to have the highest inhibitory effect on 5alpha-R activity (IC 50 =1.35M), followed in decreasing order by progesterone (IC 50 =5.0 M) and 4-androstene-3,17-dione (IC 50 =21.6 M). Oestradiol-1 had practically no inhibitory effect.
International Urology and Nephrology Issue Volume 24, Number 2 / March, 1992

At present, we aim to lower DHT levels in our patients. In the future that may not happen. At the moment we give our patients 1% progesterone to lower their DHT levels. We try not to use 5-alpha reductase inhibitors.
Fellowship in Anti-Aging and Functional Medicine

The modulation of progesterone effects on typical male targets is connected with a great pharmacodynamic variability. The reason for this is that, in men, some important effects of progesterone are mediated non-genomically through different molecular biological modes of action. Therefore, the precise therapeutic manipulation of progesterone actions in the male requires completely new endocrine-pharmacological approaches.
The Aging Male, Volume 7, Issue 3 September 2004 , pages 236 - 257

The present invention provides a method and composition for treatment of benign prostate hyperplasia (BPH) in men via a transscrotal delivery system. The progesterone composition preferably is capable of delivering an effective dosage amount of about 65-100 mg of progesterone per ml when applied directly onto the surface of scrotum.
(WO/2005/079317) PROSTATE HYPERTROPHY TREATMENT COMPOSITION AND METHOD

We have found a consistent pattern of hormonal abnormalities in patients with ERECTILE DYSFUNCTION. Our study group included men from age 21 to 88 years old. By helping to correct the hormonal imbalance of progesterone and testosterone towards normal values, most of the men in our study were able to obtain normal erectile function. By using a progesterone/testosterone cream we were able to help correct the hormonal imbalance commonly found in men with ERECTILE DYSFUNCTION.
United States Patent 20070167418

Low allopregnanolone levels in premenopausal women with PTSD (post traumatic stress disorder) might contribute to an imbalance in inhibitory versus excitatory neurotransmission, resulting in increased PTSD re-experiencing and depressive symptoms.
Biological Psychiatry Volume 60, Issue 7 , 1 October 2006, Pages 704-713

Progesterone delayed resorption of skin allografts placed in the uterine lumen. Results are consistent with the hypothesis that progesterone mediated this effect by stimulating the secretion of immunosuppressive substances into the uterine lumen.
Am J Reprod Immunol Microbiol. 1986 Oct;12(2):48-54. Links

Skin 5 alpha-reductase activity is the major factor influencing the manifestation of androgen excess. We conclude that progesterone and the 19-nor-derivatives inhibit 5 alpha-reductase activity at high doses, whereas medroxyprogesterone acetate does not.
Obstetrics & Gynecology 1991;78:103-107

A 1-year treatment with systemic estrogen alone or combined with progestin does not change the amount of collagen or the rate of collagen synthesis in postmenopausal women.
Maturitas. 1997 Jun;27(2):153-62.

The results of this study demonstrate that topical 2% progesterone acts primarily in increasing elasticity and firmness in the skin of peri- and postmenopausal women. These effects in combination with good tolerability make progesterone a possible treatment agent for slowing down the ageing process of female skin after onset of the menopause. Clinical monitoring showed a greater reduction in wrinkle counts (29.10% vs. 16.50%) and wrinkle depth (9.72% vs. 7.35%) around the right eye, a greater decrease in nasolabial wrinkle depth (9.72% vs. 6.62%) and a significantly higher (P < 0.05) increase in skin firmness (23.61% vs. 13.24%) in the treatment group.
Br J Dermatol. 2005 Sep;153(3):626-34

Significant increases in serum concentrations of progesterone were observed in all of the women studied. The percutaneous absorption of progesterone correlates strongly with the absorption of transdermal 17 beta-estradiol. There is variance in absorption of progesterone just as with 17 beta-estradiol, and the 2 measures are closely correlated. The percutaneous application of progesterone cream appears to be a safe and effective route of administration
American Journal of Obstetrics & Gynecology. 180(6):1504-1511, June 1999.

Natural progesterone given as a vaginal tablet is well tolerated, safe and an easily administered treatment. Even in a non-oestrogenized vagina the absorption was efficient and the 100 mg dosage resulted in adequate serum progesterone concentrations.
Human Reproduction, Vol. 14, No. 3, 606-610, March 1999

Salivary progesterone measurements confirm that topically applied progesterone is absorbed, despite the lack of change in serum progesterone concentrations.
Clinical Endocrinology Volume 53 Issue 5 Page 615 - November 2000

The present study suggests that by expressing PR human keratinocytes act as targets for progesterone action.
J Korean Med Sci. 2000 Dec;15(6):647-54.

These results demonstrate that topically applied progesterone is rapidly absorbed transdermally and that its patterns of distribution and metabolism are comparable to those previously reported for intravascularly administered progesterone.
J Steroid Biochem Mol Biol. 2002 Apr;80(4-5):449-55. Links

A major concern is that serum progesterone levels achieved with progesterone creams are too low to have a secretory effect on the endometrium. However, antiproliferative effects on the endometrium have been demonstrated with progesterone creams when circulating levels of progesterone are low. Thus, effects of topical progesterone creams on the endometrium should not be based on serum progesterone levels, but on histologic examination of the endometrium. Despite the low serum progesterone levels achieved with the creams, salivary progesterone levels are very high, indicating that progesterone levels in serum do not necessarily reflect those in tissues.
Menopause. 12(2):232-237, March/April 2005.

Stress stimulates the adrenal medulla to rapidly secrete catecholamines (CAs), and the adrenal cortex to release progesterone (PROG), which may locally regulate stress-induced CA release. This study supports a role for adrenocortical PROG in the regulation of CA secretion during stress.
Brain Res (2005) 1043: 76-86.

The scientists found evidence that the progesterone metabolite allopregnanolone reduces the brain's response to corticotropin-releasing factor (CRF), a peptide hormone that plays an important role in the stress response in animals.
Emory University Health Sciences Center Article Date: 09 Feb 2005 - 8:00 PST

The gonadal hormone, progesterone, has been shown to have neuroprotective effects in injured nervous system, including the severity of postinjury cerebral edema. These data suggest progesterone has antioxidant effects and support its potential as a treatment for brain injury.
Mol Chem Neuropathol. 1997 May;31(1):1-11.

Systemic injections of the neurosteroid progesterone (P) have been shown to improve cognitive, sensory and motor recovery after traumatic brain injury (TBI). Progesterone withdrawal (PW), however, increases the risk of ischemia, anxiety, seizure, and excitotoxicity.
Georgia Institute of Technology 19-Jul-2005

Approximately 1.5 to 2 million people in the U.S. sustain a TBI each year, leading to 50,000 deaths and 80,000 new cases of long-term disability. Emory's researchers designed a clinical trial to assess the promise of progesterone for treatment of TBI. Their three-year pilot study found a 50 percent reduction in the rate of death in the progesterone-treated group. Furthermore, there was a significant improvement in the functional outcome and level of disability among patients who were enrolled with a moderate brain injury.
Emory University Press release 02 October 2006

Research at Emory and elsewhere indicates that progesterone may limit damage from transient and permanent ischemic stroke. Emory researchers hope to initiate a similar pilot clinical trial to study the effectiveness of progesterone or a progesterone metabolite to treat patients with acute stroke.
Emory University Press release 02 October 2006

Progesterone reduces programmed cell death and the synthesis of inflammatory factors that can kill neurons hours to days after traumatic brain injury.

As an anti-inflammatory agent, progesterone has been shown to reduce the response of natural killer cells as well as other known initiators of inflammation.

Systemic injections of the neurosteroid progesterone given after traumatic brain injury (TBI) have been shown to improve cognitive, sensory and motor recovery, enhancing both short and long term recovery.

Progesterone readily cross the blood brain barrier (BBB) reducing oedema to barely measurable levels.

Reduces lipid peroxidation and the generation of isoprostanes, which contribute to post-injury ischaemic conditions.

Produces metabolites which decrease pro-apoptotic and increase anti-apoptotic enzymes.

Reduces the expression of pro-inflammatory genes and their protein products.

Reduces the area of necrotic cell death and improves behavioural outcomes.

Protects neurons distal to the site of injury which would normally die after TBI.

Enhances remyelination in degenerative disorders.

Produces significant sparing of cognitive, sensory and spatial learning performance after bilateral brain injury.

TBI yielded extremely promising results and found no adverse events attributable to progesterone, unlike oestrogen, which can exacerbate brain injury, especially in animal models of ischaemic stroke. Progesterone can be given to both males and females without affecting gender and sexual functions.

Our own preliminary data show that medroxyprogesterone acetate (MPA) can reduce cerebral oedema after TBI, but unlike progesterone, MPA did not result in any behavioural recovery on the tasks we used.

MPA is used instead of progesterone in mouse models of sexually transmitted diseases to increase infectibility because progesterone does not have this effect. According to one recent paper, MPA increases susceptibility to genital herpes (HSV-2) ten times more than does natural progesterone.
ACNR, Volume 5 Number 4 o September/October 2005