Comparing the effect of two different hormonal therapy regimens on the activity coagulation factors VII, VIII, IX and serum lipids in menopausal women

During extrinsic coagulation pathway, a complex is developed between factor VII, calcium and tissue factor [a cell membrane lipoprotein that is exposed after cell injury]. Factor VII needs calcium and vitamin K for its biologic activation. Coronary artery disease [CAD] can be induced by increased level and activity of the coagulation factors VII, VIII and IX. In postmenopausal women, estrogen decreases blood lipids and thereby decreases risk of CAD. However, the exact effects of the estrogen on the other predisposing factors of CAD are unknown. This study was conducted to evaluate the effects of oral hormone therapy regimen on fibrinogen and other coagulation factors. Sixty menopausal women with history of hysterectomy were randomly allocated in 2 groups. One group was treated with conjugated estrogen 0.625 mg/day and the other group was treated with conjugated estrogen 0.625 mg/day and medroxyprogesterone 2.5 mg/day. Serum fibrinogen level and activity of coagulation factors VII, VIII and IX and blood lipids level were checked before and 3 months after treatment. In the group treated with estrogen alone, mean factor VII activity showed significant increase 3 months after treatment as compared to before hormone therapy [P<0.05]. There were no significant changes in mean activities of coagulation factors VIII, IX and serum fibrinogen level in patients treated with estrogen or estrogen/medroxyprogesterone after treatment [P>0.05]. In both groups, hormone therapy significantly decreased serum cholesterol level and LDL-C and increased HDL-C [P>0.00], but serum triglyceride level increased in the group only treated with estrogen. Significant increase of coagulation factor VII and serum triglyceride in estrogen-treated patients is logical. This study confirms that hormone therapy with this protocol does not change mean serum fibrinogen levels and activity of coagulation factor VIII and IX. This may be a genuine finding or may be due to inadequacy of samples, given the wide normal range of coagulation factors and serum fibrinogen. Studies with more prolonged follow-up or more samples are warranted

Estrogen receptor profiles: changes in mouse and rat mammary tumors by treatment with selective estrogen receptor modifiers

The aim of this work was to analyze the effect of estradiol [E2], medroxyprogesterone and the two selective estrogen receptor modulators [SERMs] [tamoxifen [Tam] and raloxifene [Ral]] on the estrogen receptor [ER] conformers profile performed by size exclusion HPLC in relation to hormone dependence of mammary tumors. Materials and Two types of mammary tumors were studied: tumors transplanted in BALB/c mice that are medroxyprogesterone acetate [MPA]-dependent for growth, and tumors induced in Sprague-Dawley rats by intraperitoneal injection of N-nitroso-N-methylurea [NMU]. Tumors from mice treated with MPA, E2, Tam or Ral and NMU-treated rats were analyzed and compared to that of control. The tumor conformer profiles were as follows: control and MPA-treated mice showed only one peak [oligomeric form]; E2-treated mice also showed only one peak [dimer]; Tam-treated mice showed one peak corresponding to a possible proteolytic fragment, and Ral-treated mice showed two peaks [oligomeric and a possible proteolytic fragment]. On the other hand, NMU-induced mammary tumors from rats showed three peaks [oligomeric, monomeric and proteolytic]. Our findings may indicate that SERMs affect the aggregation state of ER and thereby its ability to modulate genomic transcription mechanisms related to growth rate

Efectos de los estrógenos conjugados sintéticos en la masa ósea y en los lípidos plasmáticos / Effects of the synthetic conjugated estrogens in the bone mass and plasmatic lipids

Objetivo: Son escasos los estudios que han evaluado los efectos metabólicos de los estrógenos conjugados sintéticos. Como en Chile este tipo de estrógeno son los más usados, decidimos evaluar la respuesta ósea y de los lípidos a estos fármacos. Material y método: 61 pacientes tratadas con estrógenos conjugados sintéticos durante un año; aquellas pacientes que tenían útero y menos de 60 años de edad se le indicó medroxiprogesterona asociada en forma secuencial, a las mayores, se les indicó en forma combinada continua. La masa ósea se evaluó con un equipo de ultrasonografía ósea. DBI-Sonic (Igea, Italia), cuyo bajo coeficiente de variación (0,4 por ciento) permite monitorizar la respuesta terapéutica al año.Los lípidos plasmaticos, se midieron con métodos enzimáticos. Se realizó ultrasonografía ósea y se midió los lípidos plasmáticos al inicio y al final del seguimiento. Resultados: La masa ósea no sufrió la pérdida esperada durante el año de tratamiento. Evaluado con AD-SOS (amplitude-dependent speed of sound), se observa que esta se mantuvo constante: basal: 2014+- 62 m/seg, al año: 2015+- 60m/seg. Tampoco hubo deterioro de microarquitectura ósea como la muestra la UBPS; 39,7 +- 23,7 Y 40,5 +- 20,2 respectivamente (ns). En cuanto a los lípidos, se observaron los beneficios característicos de los estrógenos orales.El colesterol total bajo de 222+- 31 mg/dl a 211+- 28 (p<0,06); el HDL, de 49,5+- 7,9 subió a 55,9+-7,1 (p<0.001); LDL, DE 134+-33 PASÓ A 125+-26(NS). Los triglicéridos bajaron de 188+-85 a 153+-52(p<0,004); mejoría atribuible a la dieta que se indica de rutina de estas pacientes. Conclusiones :los estrógenos conjugados sintéticos evitan la pérdida de masa ósea y mejoran el perfil lipídico

Progesterone and medroxyprogesterone acetate retard the development of amygdala kidling in male rats

The effect of progesterone and medroxyprogesterone acetate [MPA] on the development and expression of amygdala kindled seizures was studied in adult male rats. Rats were treated with either daily intraperitoneal progesterone[60 mg/kg] or weekly intramuscular MPA [25 mg/kg] during the development of kindling. Progesterone retarded both focal and generalization stages of kindling at the 10 min. injection-stimulation interval, while MPA only retarded the generalization stage. However, neither of the drugs had any effect on afterdischarge and stage 5 seizure duration after full kindling. These results suggest that progesterone antiepileptogenic effect results from inhibition of the development of both focal seizures and kindled seizure generalization

Hormone replacement therapy increases trabecular and cortical bone density in osteoporitic women

Twenty five postmenopausal Caucasian women with established osteoporosis or severe osteopenia were treated with continuous combined estrogen/progesterone (2 mg 17 beta estradiol and 5 mg medroxiprogesterone) and 1000 mg of calcium daily. The mean age of the patients was 57 + 6 years (range 44 to 69 years), and the average postmenopausal interval was of 10.7 + 4.2 years. The bone mineral density (BMD) of the lumbar spine and proximal femur was determined using DXA densitometer at baseline, 12 and 24 months of treatment. Serum and urine measurements were done at baseline and 12 months. After 24 months of treatment bone mineral density increased at the trochanter 10.2 per cent p<0.001, lumbar spine 9.6 per cent p<0.001, Ward's triangle 8.6 per cent p<0.005 and femoral neck 5.7 per cent p<0.001 in comparison to basal levels. In the first year of treatment serum alkaline phosphatase and urinary hydroxiproline diminished significantly in comparison to basal levels (p<0.001, for both). In conclusion, this study indicates that continous combined estrogen progesterone therapy descreases bone turnover and increases BMD of the spine, femoral neck and trochanter in established osteoporosis.

Avaliaçäo anátomo histopatológica do efeito do acetato de medroxiprogesterona e do acetato de megestrol sobre o útero de cadelas adultas / Anatomo histopathologic evaluation of the effect of medroxiprogesterone acetate and megestrol acetate on the uterus of adult bitches

No presente experimento foram utlizadas 18 fêmeas caninas adultas, clinicamente sadias, sem sintomas clínicos de estro, as quais foram subdivididas aleatoriamente em 6 grupos contendo 3 animais cada. Após biópsia uterina para controle, foi administrado acetato de medroxiprogesterona nas fêmeas dos grupos I, II e III e acetato de megestrol nas fêmeas dos grupos IV, V, VI. Observou-se que ambas as drogas utilizadas induziram a ocorrência de endometrite, porém este foi mais discreto nos animais dos grupos IV, V e VI. Näo foi registrada a ocorrência de poliúra, polidipsia, distençäo abdominal, corrimento vaginal purulento ou sanguinolento, leucocitose e anemia

Anticoncepcional injetável: modificaçöes nucleares após o uso / Injectable contraceptive: nuclear modifications after use

Foi estudada a açäo contraceptiva hormonal injetável do acetato de medroxiprogesterona-ciprionato de estradiol (MPACE) em órgäos genitais de ratas. As ratas foram divividas em 2 grupos: A e B, respectivamente castradas e näo castradas e, de acordo com o número de doses, subdivididas em 6 subgrupos: A0, A1, A2, A3, A4, A5 e B0, B1, B2, B3, B4 e B5. Foram feitos estudos cariométricos dos núcleos do epitélio de revestimento da túnica mucosa uterina, das glândulas endometriais, miométrio e do epitélio da ectocérvix e da vagina. De cada subgrupo foram selecionadas três ratas e foram analisadas três lâminas para cada uma, em um total de nove observaçöes para cada subgrupo. Foram medidos 20 núcleos em cada lâmina, perfazendo um total de 60 núcleos, quando se tratava de epitélio de revestimento do endométrio, das glândulas endometriais e do miométrio, e um total de 120 núcleos nos casos de epitélio do exocérvix e da vagina, por se tratarem os mesmos de epitélios estratificados. Foram medidos um total de 15.120 núcleos e os resultados submetidos a tratamento estatístico. Observou-se aumento de volume nuclear quase duplicado das ratas na fase estro em relaçäo às castradas-controles. Por outro lado, a maior significância do efeito do MPACE foi encontrada em relaçäo às células do epitélio da túnica mucosa uterina, glândulas endometriais e miométrio. A açäo MPACE nas células da exocérvix e vagina näo foi significante. A análise estatística dos resultados demonstrou que com a associaçäo empregada neste trabalho houve predominância da açäo dos efeitos da fraçäo estrogênica, com aumento do volume nuclear; porém essa açäo foi contrabalançada pela fraçäo progestagênica, pois foram raras as mitoses

Effect of medroxyprogesterone acetate on hepatic lipid profile of female rats under various states of nutrition.

The effect of medroxyprogesterone acetate (MPA) treatment on hepatic lipid profile was studied in female rats kept on protein-deficient diet, on normal restricted diet and on normal, ad libitum diet. A significant decline in total and free cholesterol levels was observed in rats kept on protein-deficient diet and on normal, restricted diet. However, protein-deficient animals exhibited a significant rise in the liver triglyceride level. In rats on normal, ad libitum diet only, MPA treatment resulted in elevated levels of triglycerides and increased esterification of cholesterol. This was mostly due to increased incorporation of acetate into esterified cholesterol and triglyceride as evident from studies using the labelled precursor. Total phospholipid content was found to be unaffected by MPA in all the groups suggesting that the drug and dietary protein level have no effect on hepatic phospholipid content.