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The effect of estrogen compared to estrogen plus progesterone on the exercise electrocardiogram.

Bokhari S, Bergmann SR.

Division of Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. sb605 columbia.edu

OBJECTIVES: The objective of this study was to evaluate the effect of estrogen compared to estrogen plus progesterone on the stress electrocardiogram (ECG) in relationship to stress-gated myocardial perfusion imaging (MPI) in postmenopausal women. BACKGROUND: It is generally recognized that estrogen may cause false positive ST depressions on the stress ECG. The effects of estrogen plus progesterone are not known. This study was performed to define the effects of these agents on the stress ECG correlated with results from MPI. METHODS: We evaluated 140 postmenopausal women-31 not taking any hormone replacement therapy (HRT); 75 taking estrogen alone; and 34 taking estrogen plus progesterone. Women with a history of coronary artery disease (CAD), cardiomyopathy, or an abnormal resting ECG were excluded. All women underwent a symptom-limited treadmill test and MPI. RESULTS: The overall sensitivity and specificity of the stress ECG compared to MPI in women not taking HRT was 54% and 78%, respectively. In women taking estrogen or estrogen plus progesterone, the sensitivity was unchanged. The power to detect clinically meaningful sensitivity difference (10%) was poor (p = 0.09). The specificity was reduced to 46% (p < 0.01) in women on estrogen therapy. In women taking estrogen plus progesterone, specificity was 80%. CONCLUSIONS: Our results suggest that estrogen increases the false positive rate of the stress ECG. This decreased specificity is countered by co-administration of progesterone. Nonetheless, because the sensitivity of the stress ECG is only 50% to 57% in postmenopausal women, women at risk should have imaging in conjunction with stress for the optimal detection of CAD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12354433&dopt=Abstract progesterone, progesterone cream



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[Maturation of the follicle-enclosed common frog oocytes stimulated by low progesterone concentrations depends on transcription]

[Article in Russian]

Skoblina MN.

Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, ul. Vavilova 26, Moscow, 119991 Russia. skoblina proxima.idb.ac.ru

The maturation of follicle-enclosed common frog oocytes stimulated by low progesterone concentration is inhibited by actinomycin D (5 micrograms/ml). The concentrations of progesterone, at which oocyte maturation was inhibited by actinomycin D, varied with the season and were different in different females. The inhibitor of steroidogenesis aminogluthetimide (100 micrograms/ml) did not suppress the maturation of follicle-enclosed oocytes in most experiments, which was induced by both high and low progesterone concentrations. The induction of maturation of the defolliculated ("denuded") oocytes required lower progesterone concentrations than of the follicle-enclosed oocytes and, in addition, the maturation of denuded oocytes was not suppressed by actinomycin D. Thus, it was shown for the first time that low doses of progesterone induced the maturation of amphibian oocytes while acting on the follicle wall cells and this process depended on transcription. The factor inducing or enhancing maturation, which is formed in the follicle cells in the presence of low progesterone concentrations, remains as yet unknown.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12722592&dopt=Abstract progesterone, progesterone cream



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Effects of oestradiol and progesterone on secretion of gonadotrophins and health of first wave follicles during the oestrous cycle of beef heifers.

Austin EJ, Mihm M, Evans AC, Ireland JL, Ireland JJ, Roche JF.

Faculty of Veterinary Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Ireland. edward.austin ucd.ie

Antral follicle development in cattle is initially FSH dependent and then LH dependent. The aim of the present study was to determine the effects of oestradiol- and progesterone-induced suppression of FSH and LH on growth and differentiation of first wave follicles. Cyclic heifers (n = 45, n = 6-10 per group) received the following i.m. injections or treatments beginning 30 h after oestrus: (i) saline (controls); (ii) 0.75 mg oestradiol benzoate (ODB); (iii) insertion of a progesterone-releasing intravaginal device (PRID) for 42 h (progesterone); (iv) 0.75 mg oestradiol benzoate plus PRID (ODB plus progesterone); (v) 0.75 mg ODB plus injection of 1 mg Ovagen(TM) at 33, 39 and 45 h after onset of oestrus (ODB plus FSH). In Expt 1, follicle development was monitored by ovarian ultrasonography once a day. In Expt 2, heifers were ovariectomized. Emergence of the first follicle wave and dominant follicle selection were delayed in ODB plus progesterone-treated heifers compared with controls. Interval to nadir FSH concentration was shorter in ODB-, progesterone- and ODB plus progesterone-treated heifers compared with controls. Frequency of LH pulses was unaffected in ODB- or ODB plus FSH-treated heifers, decreased in progesterone-treated heifers and further decreased in ODB plus progesterone-treated heifers. Intrafollicular oestradiol concentrations were lower in the largest follicle from ODB plus progesterone-treated heifers compared with control (66 h) heifers, but follicle diameter and concentrations of insulin-like growth factor binding proteins (IGFBPs) and inhibin forms were unaffected. Treatment with ODB decreased follicular oestradiol concentration in smaller follicles in the cohort. It is concluded that growing cohort follicles are uniformly responsive to increased FSH concentration but differentially responsive to suppressed FSH and LH release, which is consistent with an LH-mediated survival advantage of the largest follicle in the cohort before cessation of the growth of remaining follicles in the cohort occurs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12361472&dopt=Abstract progesterone, progesterone cream



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Effects of prostaglandin F2alpha and progesterone on the ability of bovine luteal cells to stimulate T lymphocyte proliferation.

Cannon MJ, Petroff MG, Pate JL.

Department of Animal Sciences, The Ohio State University/Ohio Agricultural Research and Development Center, Wooster, Ohio 44691, USA.

Bovine luteal cells express class I and II major histocompatibility complex molecules and stimulate T lymphocyte proliferation in vitro. Proliferation of T lymphocytes is greater in cocultures of luteal cells and T lymphocytes collected following administration of a luteolytic dose of prostaglandin (PG) F2alpha to the cow. Whether this results from changes in luteal cells that increase their ability to stimulate T lymphocyte proliferation or from changes in T lymphocytes that enhance their ability to respond to luteal cells is unclear. To determine which is the case, luteal cell-T lymphocyte cocultures were performed using luteal cells and T lymphocytes isolated from the same animals before and 8 h after administration of PGF2alpha. In the presence of T lymphocytes collected before PGF2alpha administration, luteal cells isolated after PGF2alpha were more potent stimulators of T lymphocyte proliferation than were luteal cells collected before PGF2alpha (P<0.05). The effect of progesterone on luteal cell-stimulated T lymphocyte proliferation was also evaluated. Proliferation of T lymphocytes was greater (P<0.05) in cultures containing the cytochrome P450 side-chain cleavage enzyme-inhibitor aminoglutethimide. Exogenous progesterone caused a dose-dependent inhibition of luteal cell-stimulated T lymphocyte proliferation (P<0.05). Progesterone-receptor mRNA was undetectable in peripheral blood mononuclear cells collected before and after PGF2alpha administration, indicating that the effect of progesterone was not mediated via progesterone receptors in lymphocytes. These results imply that specific changes in luteal cells in response to PGF2alpha enhance the ability of these cells to stimulate T lymphocyte proliferation. These results also demonstrate that progesterone can suppress luteal cell-stimulated T lymphocyte proliferation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12724272&dopt=Abstract progesterone, progesterone cream



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Progesterone administration during reperfusion, but not preischemia alone, reduces injury in ovariectomized rats.

Murphy SJ, Littleton-Kearney MT, Hurn PD.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. sjmurphy jhmi.edu

Although progesterone is neuroprotective in traumatic brain injury, its efficacy in stroke is unclear. The authors determined whether there are infarction differences after middle cerebral artery occlusion (MCAO) in ovariectomized rats treated acutely with progesterone before MCAO or both pre- and postischemia. Rats received vehicle, 5 (P5), 10 (P10), or 20 (P20) mg/kg progesterone intraperitoneally 30 minutes before MCAO. In another cohort, animals received vehicle or 5 (P5R) mg/kg progesterone intraperitoneally 30 minutes before MCAO, at reperfusion initiation, and at 6-hour reperfusion. Animals underwent 2-hour MCAO by the intraluminal filament technique, followed by 22-hour reperfusion. Cortical (CTX) and caudate-putamen (CP) infarctions were determined by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis. End-ischemic and early reperfusion regional cerebral blood flow (CBF) was measured by [ C]-iodoantipyrine quantitative autoradiography in vehicle- or progesterone (5 mg/kg)-treated rats. Cortical infarction (% contralateral CTX) was 31 +/- 30% (vehicle), 39 +/- 23% (P5), 41 +/- 14% (P10), and 28 +/- 20% (P20). Caudate-putamen infarction (% contralateral CP) was 45 +/- 37% (vehicle), 62 +/- 34% (P5), 75 +/- 17% (P10), and 52 +/- 30% (P20). In vehicle and P5R groups, CTX infarction was 37 +/- 20% and *20 +/- 17%, respectively (* < 0.05 from vehicle). In vehicle and P5R groups, CP infarction was 63 +/- 26% and 43 +/- 29%, respectively. End-ischemic regional CBF and CBF recovery during initial reperfusion was unaffected by progesterone treatment. These data suggest that progesterone administration both before MCAO and during reperfusion decreases ischemic brain injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12368656&dopt=Abstract progesterone, progesterone cream



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Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations.

Carmody BJ, Arora S, Wakefield MC, Weber M, Fox CJ, Sidawy AN.

Department of Surgery, Veterans Affairs Medical Center, Walter Reed Army Medical Center, USA.

INTRODUCTION: Diabetes mellitus is a significant risk factor for atherosclerotic peripheral vascular disease. Hyperglycemia and hyperinsulinemia, as encountered in patients with type II diabetes, have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation, a paramount feature in atherosclerosis. Female sex hormones, such as estrogen, have been suggested to inhibit VSMC proliferation. However, the role of progesterone, particularly in patients with diabetes mellitus, has not been examined. Therefore, we studied the effect of progesterone on VSMCs exposed to various concentrations of glucose and insulin. METHODS: Human infragenicular VSMCs isolated from the tibial arteries of five male patients with diabetes undergoing lower extremity amputation were used. Immunocytochemical studies with confocal microscopy were performed for progesterone receptor identification in these VSMCs. Cells were grown to subconfluence, followed by exposure to deprived media with various glucose (100 and 200 mg/dL) and insulin (no insulin and 100 ng/mL) concentrations. Cells were then additionally exposed to physiologic progesterone (10 ng/mL, progesterone group) and compared with a no-progesterone group. Cell count and methyl-(3)H-thymidine incorporation were used to determine cellular proliferation. Cell count with hemocytometry was performed on day 6. DNA synthesis as reflected through methyl-(3)H-thymidine incorporation was measured at 24 hours. RESULTS: Immunocytochemical studies with confocal microscopy showed cytosolic progesterone receptors. The no-progesterone group showed a significant rise in cell count (P <.05) at all concentrations of glucose or insulin compared with the control group containing 100 mg/dL glucose concentration. The no-progesterone group also showed a significant rise in thymidine incorporation (P <.05) in the 100 mg/dL glucose-100 ng/mL insulin group and the 200 mg/dL glucose-100 ng/mL insulin group compared with the 100 mg/dL glucose group. In the cell count studies, progesterone significantly inhibited cellular proliferation in several settings. All cell groups cultured with insulin or an elevated glucose concentration showed a significant (P <.05) antiproliferative effect when exposed to progesterone. With thymidine incorporation, progesterone showed a similar antiproliferative effect in cells stimulated with glucose or insulin. CONCLUSION: Significant reductions in cell proliferation as determined with both cell count and thymidine incorporation suggest that progesterone is an inhibitor of VSMC proliferation induced by our in vitro models of hyperglycemia and hyperinsulinemia. Therefore, progesterone may have a protective role against the atherosclerotic changes associated with type II diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12368746&dopt=Abstract progesterone, progesterone cream



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Reproductive responses following royal jelly treatment administered orally or intramuscularly into progesterone-treated Awassi ewes.

Husein MQ, Kridli RT.

Department of Animal Production, Faculty of Agriculture, Jordan University of Science and Technology, PO Box 3030, 22110, Irbid, Jordan. huseinmq just.edu.jo

An experiment was conducted to determine whether natural royal jelly (RJ) paste administered orally or intramuscularly (i.m.) in conjunction with exogenous progesterone is associated with improved reproductive responses in ewes. Thirty 3-6-year-old Awassi ewes were randomly allocated into three (RJ-capsule, RJC; RJ-injection, RJI and control, CON) groups of 10 ewes each. All ewes were treated with intravaginal progesterone sponges for 12 days. Ewes in the RJC and RJI were administered orally or i.m. with a total of 3g of RJ given in 12 equal doses of 250 mg per ewe per day starting at the time of sponge insertion. At the time of sponge withdrawal (day 0, 0 h), ewes were exposed to three rams and checked for breeding marks at 6-h intervals for 3 days. Blood samples were collected from all ewes for analysis of progesterone concentrations. Pretreatment progesterone levels were <0.5 ng x ml(-1) in 16/30 and >1.3 ng x ml(-1) in the remaining ewes indicating luteal function and cyclicity. Similar reproductive responses and progesterone levels occurred in ewes of the RJC and RJI; therefore, data of the two groups were pooled. Following sponge insertion, progesterone levels increased rapidly and reached maximum values of 5.8+/-0.2 ng x ml(-1) within 2 days among ewes of the three groups, and then declined gradually to day 0 values of 1.6+/-0.1 and 1.9+/-0.1 ng x ml(-1) for the RJ-treated and CON ewes, respectively. The rate of progesterone decline was greater (P<0.001) in RJ-treated than in CON. Mean progesterone levels during the 12-day period were lower (P<0.001) in RJ-treated than in CON (2.8+/-0.2 ng x ml(-1) versus 3.3+/-0.2 ng x ml(-1)). Treatment with RJ resulted in greater (P<0.05) incidence of oestrus and shorter (P<0.05) intervals to onset of oestrus than CON. Based upon progesterone levels, ovulation occurred following day 0 in all ewes. Progesterone increased on day 3 in RJ-treated and on day 4 in CON ewes. Progesterone remained elevated through day 18 in 8/20 RJ-treated and 1/10 CON ewes (P=0.09). All pregnant ewes exhibited oestrus 14 h earlier (P<0.02), ovulated approximately 1 day earlier and had higher (P<0.001) luteal phase progesterone levels than non-pregnant ewes. Non-pregnant had higher (P<0.04) body weights than pregnant ewes. In conclusion, results demonstrate that both RJ treatments in conjunction with exogenous progesterone were equally capable of improving oestrus response and pregnancy rate.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12379374&dopt=Abstract progesterone, progesterone cream









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