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Pharmacological Reports : PR 2013In this article, we review published preclinical and clinical studies that examine the role of female ovarian steroids (estrogen and progesterone) in epilepsy. Its... (Review)
Review
In this article, we review published preclinical and clinical studies that examine the role of female ovarian steroids (estrogen and progesterone) in epilepsy. Its effects on the reproductive and endocrine system are well known but a large and growing body of evidences indicates that the hormones also exert neuroprotective effects on the central nervous system. Estrogen crosses the blood-brain barrier due to its low molecular weight and lipophilic properties and easily reaches the neuronal tissue. Estrogens and progesterone influence neuronal activity and are important for normal brain functions. It is commonly accepted that estrogens may increase neuronal excitability and thus mediate proconvulsant effects whereas in case of progesterone, various preclinical and clinical studies have proved that progesterone shows anticonvulsant effects. To concise our review we concluded that the effects of estrogens and progesterone on seizures depend on various factors, such as treatment duration and latency prior to the seizure testing, dose, hormonal status, the seizure type/model used and sex.
Topics: Animals; Anticonvulsants; Brain; Epilepsy; Estrogens; Female; Humans; Models, Neurological; Ovary; Progesterone
PubMed: 24145074
DOI: 10.1016/s1734-1140(13)71061-2 -
Journal of the Royal Society of Medicine Jun 1979
Topics: Adolescent; Adult; Child; Female; Humans; Intelligence; Maternal-Fetal Exchange; Pre-Eclampsia; Pregnancy; Progesterone; Time Factors
PubMed: 552532
DOI: 10.1177/014107687907200602 -
Brain Research Jun 2013Both progesterone and estradiol have well-described neuroprotective effects against numerous insults in a variety of cell culture models, animal models and in humans.... (Review)
Review
Both progesterone and estradiol have well-described neuroprotective effects against numerous insults in a variety of cell culture models, animal models and in humans. However, the efficacy of these hormones may depend on a variety of factors, including the type of hormone used (ex. progesterone versus medroxyprogesterone acetate), the duration of the postmenopausal period prior to initiating the hormone intervention, and potentially, the age of the subject. The latter two factors relate to the proposed existence of a "window of therapeutic opportunity" for steroid hormones in the brain. While such a window of opportunity has been described for estrogen, there is a paucity of information to address whether such a window of opportunity exists for progesterone and its related progestins. Here, we review known cellular mechanisms likely to underlie the protective effects of progesterone and furthermore, describe key differences in the neurobiology of progesterone and the synthetic progestin, medroxyprogesterone acetate (MPA). Based on the latter, we offer a model that defines some of the key cellular and molecular players that predict the neuroprotective efficacy of progesterone. Accordingly, we suggest how changes in the expression or function of these cellular and molecular targets of progesterone with age or prolonged duration of hormone withdrawal (such as following surgical or natural menopause) may impact the efficacy of progesterone. This article is part of a Special Issue entitled Hormone Therapy.
Topics: Animals; Disease Models, Animal; Humans; Medroxyprogesterone Acetate; Nervous System Diseases; Neurons; Neuroprotective Agents; Predictive Value of Tests; Progesterone
PubMed: 23340161
DOI: 10.1016/j.brainres.2013.01.027 -
Cells May 2022In mammalian females, after sperm are deposited in the reproductive tract, a fraction of sperm migrates to the lower oviduct (isthmus) and forms a sperm storage site... (Review)
Review
In mammalian females, after sperm are deposited in the reproductive tract, a fraction of sperm migrates to the lower oviduct (isthmus) and forms a sperm storage site known as the functional sperm reservoir. The interactions between sperm membrane proteins and oviduct epithelial cells facilitate sperm binding to the oviductal epithelium and retention in the reservoir. Sperm are bound by glycans that contain specific motifs present on isthmic epithelial cells. Capacitated sperm are released from the reservoir and travel further in the oviduct to the ampulla where fertilization occurs. For decades, researchers have been studying the molecules and mechanisms of sperm release from the oviductal sperm reservoir. However, it is still not clear if the release of sperm is triggered by changes in sperm, oviduct cells, oviduct fluid, or a combination of these. While there is a possibility that more than one of these events are involved in the release of sperm from the reservoir, one activator of sperm release has the largest accumulation of supporting evidence. This mechanism involves the steroid hormone, progesterone, as a signal that induces the release of sperm from the reservoir. This review gathers and synthesizes evidence for the role of progesterone in inducing sperm release from the oviduct functional sperm reservoir.
Topics: Animals; Epithelium; Fallopian Tubes; Female; Humans; Male; Mammals; Oviducts; Progesterone; Spermatozoa
PubMed: 35626659
DOI: 10.3390/cells11101622 -
BioMed Research International 2017To conduct systematic analyses to evaluate the efficacy of progesterone therapy for the prevention of miscarriages in pregnant women experiencing threatened abortion. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct systematic analyses to evaluate the efficacy of progesterone therapy for the prevention of miscarriages in pregnant women experiencing threatened abortion.
METHODS
In November 2016, we performed a systematic literature search and identified 51 articles in PubMed, Embase, and Cochrane databases. We identified nine randomized trials that included 913 pregnant women (including 322 treated with oral dydrogesterone, 213 treated with vaginal progesterone, and 378 control subjects) who met the selection criteria.
RESULTS
The incidence of miscarriage was significantly lower in the total progesterone group than in the control group (13.0% versus 21.7%; odds ratio, 0.53; 95% confidence interval (CI), 0.36 to 0.78; = 0.001; , 0%). Moreover, the incidence of miscarriage was significantly lower in the oral dydrogesterone group than in the control group (11.7% versus 22.6%; odds ratio, 0.43; 95% CI, 0.26 to 0.71; = 0.001; , 0%) and was lower in the vaginal progesterone group than in the control group, although this difference was nonsignificant (15.4% versus 20.3%; odds ratio, 0.72; 95% CI, 0.39 to 1.34; = 0.30; , 0%). However, the incidence of miscarriage was not different between the oral dydrogesterone and vaginal progesterone groups.
CONCLUSION
Progesterone therapy, especially oral dydrogesterone, can effectively prevent miscarriage in pregnant women experiencing threatened abortion.
Topics: Abortion, Threatened; Administration, Oral; Dydrogesterone; Female; Humans; Pregnancy; Progesterone; Vagina
PubMed: 29392134
DOI: 10.1155/2017/3616875 -
Behavioural Brain Research Nov 2015This review explores the effects of female reproductive hormones, estrogens and progestogens, with a focus on progesterone and allopregnanolone, on object memory.... (Review)
Review
This review explores the effects of female reproductive hormones, estrogens and progestogens, with a focus on progesterone and allopregnanolone, on object memory. Progesterone and its metabolites, in particular allopregnanolone, exert various effects on both cognitive and non-mnemonic functions in females. The well-known object recognition task is a valuable experimental paradigm that can be used to determine the effects and mechanisms of progestogens for mnemonic effects across the lifespan, which will be discussed herein. In this task there is little test-decay when different objects are used as targets and baseline valance for objects is controlled. This allows repeated testing, within-subjects designs, and longitudinal assessments, which aid understanding of changes in hormonal milieu. Objects are not aversive or food-based, which are hormone-sensitive factors. This review focuses on published data from our laboratory, and others, using the object recognition task in rodents to assess the role and mechanisms of progestogens throughout the lifespan. Improvements in object recognition performance of rodents are often associated with higher hormone levels in the hippocampus and prefrontal cortex during natural cycles, with hormone replacement following ovariectomy in young animals, or with aging. The capacity for reversal of age- and reproductive senescence-related decline in cognitive performance, and changes in neural plasticity that may be dissociated from peripheral effects with such decline, are discussed. The focus here will be on the effects of brain-derived factors, such as the neurosteroid, allopregnanolone, and other hormones, for enhancing object recognition across the lifespan.
Topics: Aging; Animals; Humans; Memory; Progesterone; Psychological Tests
PubMed: 26235328
DOI: 10.1016/j.bbr.2015.07.057 -
Fertility and Sterility Sep 1999To integrate and evaluate the pharmacokinetic, endocrine, and clinical effects of micronized progesterone formulations. (Comparative Study)
Comparative Study Review
OBJECTIVE
To integrate and evaluate the pharmacokinetic, endocrine, and clinical effects of micronized progesterone formulations.
DESIGN
Published articles concerning the pharmacokinetics of orally administered progesterone and the potential clinical uses of oral micronized progesterone were reviewed. Results concerning their use for secondary amenorrhea, premenopausal bleeding disorders, luteal phase dysfunction, termination of premature labor, hormone replacement therapy, and premenopausal syndrome are summarized. Critical issues to be resolved through ongoing preclinical and clinical research are highlighted.
RESULT(S)
Because of the enhanced bioavailability of oral micronized progesterone, the compound may be useful for a variety of therapeutic indications. Oral micronized progesterone is available in France, and a formulation recently has been approved in the United States for the treatment of secondary amenorrhea and postmenopausal hormone replacement therapy. A large body of evidence, including the Postmenopausal Estrogen/Progestin Interventions study, suggests that the use of a combination of estrogen and oral micronized progesterone is optimal for long-term hormone replacement therapy. There also are data indicating that oral micronized progesterone could be of potential use for the treatment of premenopausal bleeding disorders, luteal phase disorders, and premature labor.
CONCLUSION(S)
Oral micronized progesterone has widespread clinical potential, particularly for the treatment of secondary amenorrhea and dysfunctional premenopausal bleeding, and as a component of postmenopausal hormone replacement therapy.
Topics: Amenorrhea; Biological Availability; Dosage Forms; Female; Hormone Replacement Therapy; Humans; Infertility, Female; Menstruation Disturbances; Pregnancy; Progesterone
PubMed: 10519605
DOI: 10.1016/s0015-0282(99)00272-1 -
Journal of Neuroinflammation Jun 2023Autoimmune uveitis (AU) is the most common ophthalmic autoimmune disease (AD) and is characterized by a complex etiology, high morbidity, and high rate of blindness. AU...
BACKGROUND
Autoimmune uveitis (AU) is the most common ophthalmic autoimmune disease (AD) and is characterized by a complex etiology, high morbidity, and high rate of blindness. AU remission has been observed in pregnant female patients. However, the effects of progesterone (PRG), a critical hormone for reproduction, on the treatment of AU and the regulatory mechanisms remain unclear.
METHODS
To this end, we established experimental autoimmune uveitis (EAU) animal models and constructed a high-dimensional immune atlas of EAU-model mice undergoing PRG treatment to explore the underlying therapeutic mechanisms of PRG using single-cell RNA sequencing.
RESULTS
We found that PRG ameliorated retinal lesions and inflammatory infiltration in EAU-model mice. Further single-cell analysis indicated that PRG reversed the EAU-induced expression of inflammatory genes (AP-1 family, S100a family, and Cxcr4) and pathological processes related to inflammatory cell migration, activation, and differentiation. Notably, PRG was found to regulate the Th17/Treg imbalance by increasing the reduced regulatory functional mediators of Tregs and diminishing the overactivation of pathological Th17 cells. Moreover, the Id2/Pim1 axis, IL-23/Th17/GM-CSF signaling, and enhanced Th17 pathogenicity during EAU were reversed by PRG treatment, resulting in the alleviation of EAU inflammation and treatment of AD.
CONCLUSIONS
Our study provides a comprehensive single-cell map of the immunomodulatory effects of PRG therapy on EAU and elaborates on the possible therapeutic mechanisms, providing novel insights into its application for treating autoimmune diseases.
Topics: Mice; Female; Animals; Progesterone; Th17 Cells; Virulence; Uveitis; Inflammation; Autoimmune Diseases; Disease Models, Animal; Mice, Inbred C57BL
PubMed: 37344856
DOI: 10.1186/s12974-023-02829-3 -
American Journal of Obstetrics and... Sep 2019Characterization of pharmacokinetics is lacking for vaginal progesterone in pregnancy. Dosing of vaginal progesterone for preterm birth prevention has been empirical.... (Clinical Trial)
Clinical Trial
BACKGROUND
Characterization of pharmacokinetics is lacking for vaginal progesterone in pregnancy. Dosing of vaginal progesterone for preterm birth prevention has been empirical. Owing to pregnancy-related changes in vaginal and uterine blood flow, hepatic metabolism, renal clearance, and endogenously elevated serum progesterone, studies outside of pregnancy may not be applicable. The lack of the pharmacokinetics profile of vaginally administered progesterone in pregnancy limits the ability to define the exposure-response relationship needed to optimize dosing, which has implications for its use in research and clinical care regarding management of short cervix, prevention of recurrent preterm birth, and prevention of recurrent miscarriage.
OBJECTIVE
This was a study to establish the feasibility of using serum progesterone to establish basic pharmacokinetic parameters of vaginal progesterone in pregnancy for preterm birth prevention.
STUDY DESIGN
This is a prospective study of 6 low-risk singletons at 18 0/7 to 23 6/7 weeks' gestation with body mass index 20-40. Exclusion criteria were current vaginitis, abnormal Pap smear, prescription medication use, cervical length ≤25 mm, prior preterm birth, and contraindication to progesterone. Participants received a single dose of 200 mg micronized vaginal progesterone and serum progesterone levels were evaluated every 2 hours from 0 to 12 hours and then 24 hours post dose. Primary outcome was concentration/time profile of serum progesterone.
RESULTS
Median (range) maternal age was 27 (21.5-33.3) years, median body mass index was 26.5 (23.3-29.0) kg/m, and median gestational age was 22.9 (21.0-23.4) weeks. Median baseline serum progesterone was 47 (40-52) ng/mL, median peak concentration was 54 (48-68) ng/mL, and median time to peak was 12 (4-15) hours. There was a trend in rising serum progesterone over baseline with a median change in peak concentration of 11 ng/mL and interquartile range of 2-22. Median percent change from baseline was an increase by 24% (interquartile range, 4%-53%). However, there was no clear elimination phase and the median area under the curve was 112 ng*h/mL with an interquartile range of -43 to 239.
CONCLUSION
Unlike in nonpregnant individuals, administration of vaginal progesterone in pregnant individuals only minimally impacts systemic exposure. There is a limited trend of rising serum progesterone over baseline levels, with significant inter-individual variability. Serum progesterone is unlikely to be a good candidate for establishing pharmacokinetics or dosing of vaginal progesterone in pregnancy for preterm birth prevention.
Topics: Administration, Intravaginal; Adult; Biomarkers; Feasibility Studies; Female; Humans; Pregnancy; Premature Birth; Progesterone; Progestins; Prospective Studies
PubMed: 31211965
DOI: 10.1016/j.ajog.2019.06.019 -
Biology of Reproduction Sep 2022The myometrium undergoes progressive tissue remodeling from early to late pregnancy to support fetal growth and transitions to the contractile phase to deliver a baby at...
The myometrium undergoes progressive tissue remodeling from early to late pregnancy to support fetal growth and transitions to the contractile phase to deliver a baby at term. Much of our effort has been focused on understanding the functional role of myometrial smooth muscle cells, but the role of extracellular matrix is not clear. This study was aimed to demonstrate the expression profile of sub-sets of genes involved in the synthesis, processing, and assembly of collagen and elastic fibers, their structural remodeling during pregnancy, and hormonal regulation. Myometrial tissues were isolated from non-pregnant and pregnant mice to analyze gene expression and protein levels of components of collagen and elastic fibers. Second harmonic generation imaging was used to examine the morphology of collagen and elastic fibers. Gene and protein expressions of collagen and elastin were induced very early in pregnancy. Further, the gene expressions of some of the factors involved in the synthesis, processing, and assembly of collagen and elastic fibers were differentially expressed in the pregnant mouse myometrium. Our imaging analysis demonstrated that the collagen and elastic fibers undergo structural reorganization from early to late pregnancy. Collagen and elastin were differentially induced in response to estrogen and progesterone in the myometrium of ovariectomized mice. Collagen was induced by both estrogen and progesterone. By contrast, estrogen induced elastin, but progesterone suppressed its expression. The current study suggests progressive extracellular matrix remodeling and its potential role in the myometrial tissue mechanical function during pregnancy and parturition.
Topics: Animals; Collagen; Elastic Tissue; Elastin; Estrogens; Female; Mice; Myometrium; Pregnancy; Progesterone
PubMed: 35594450
DOI: 10.1093/biolre/ioac102