Quantitative analysis of collagen fibrillar structure in canine uterus exposed to acetate of medroxyprogesterone using second harmonic generation microscopy / Análisis cuantitativo de la estructura de fibras colágenas en útero canino expuesto a acetato de medroxiprogesterona utilizando generación microscópica de un segundo harmónico

Collagen is the most abundant structural protein found in organs and is responsible for providing tissues with structure and function. In order to investigate in canine uteri the potential effect of medroxyprogesterone acetate (MPA) on the changes in collagen deposition were grouped as nulliparous (n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5 mg/kg; i.m.). The amount of collagen was studied in the fold and basal regions of the endometrium and myometrium using second harmonic generation with a two-photon spectral confocal microscope, quantified using ImageJ software with a color segmentation plugin, was expressed as fraction area (%) and analyzed by ANOVA (p<0,05). No differences were observed between groups in the fold (p=0,3995) or base (p=0,7392) of the endometrium and myometrium (p=0,1781). In conclusion, our data demonstrate that two doses of MPA (5 mg/kg; i.m.) do not affect the total collagen deposition in canine uteri undergoing contraceptive treatment.

El colágeno es la proteína estructural más abundante presente en órganos y es responsable de proporcionar la sostén y función a los tejidos. Para investigar en caninos el efecto potencial del acetato de medroxiprogesterona (MPA) sobre cambios en el depósito de colágeno en útero, éstos fueron agrupados como nulíparos (n = 11), multíparos (n = 11) y tratados con MPA (n = 11, nulíparos con dos tratamientos 5 mg/kg, im). El colágeno fue evaluado en el pliegue y regiones basales del endometrio y en miometrio utilizando la Generación de un Segundo Harmónico con un microscopio confocal espectral y dos fotones y cuantificado utilizando el software ImageJ a partir de la segmentación de colores. Los resultados fueron expresados y analizados como fracción de área (%; ANOVA; p<0,05). No se observaron diferencias entre los grupos en el pliegue (p = 0,3995) y base (p=0,7392) del endometrio y tampoco en miometrio (p=0,1781). En conclusión, nuestra evidencia demuestra que dos dosis de MPA (5 mg/kg, i.m.) no afectan el depósito total de colágeno en úteros caninos expuestos a tratamiento anticonceptivo.

Body composition, resting energy expenditure and inflammatory markers: impact in users of depot medroxyprogesterone acetate after 12 months follow-up

ABSTRACT Objective The aim of this study was to evaluate for 12 months the changes of body weight using Depot Medroxyprogesterone Acetate (DMPA) and if these changes are related to inflammatory markers. Subjects and methods Twenty women of childbearing age who chose the DMPA, without previous use of this method, BMI < 30 kg/m2, and 17 women using IUD TCu 380A, participated in the study. At the baseline and after one year, changes in weight gain, body composition by the bioimpedance electric method, resting energy expenditure (REE) by the indirect calorimetry method, inflammatory markers and HOMA-IR were assessed. Results After 12 months of evaluation, we could observe a significant increase in the DMPA group in weight (3,01 kg) and BMI, while the IUD group’s only significant increase was observed in the BMI. Relative to REE there was an increase of basal metabolic rate (BMR) in both groups after one year. The sub-group DMPA that gained < 3 kg had increased significant weight, BMI and body surface (BS) with respiratory quotient (RQ) reduction, while the sub-group that gained ≥ 3 kg had a significant increase in weight, BMI, BS, fat-free mass, fat mass, BMR, Leptin, HOMA-IR and waist circumference, with RQ significantly reduced. Conclusion Our study found significant changes in weight, body composition and metabolic profile of the population studied in the first 12 months of contraceptive use. These changes mainly increased body weight, leptin levels and HOMA-IR which can contribute to the development of some chronic complications, including obesity, insulin resistance and diabetes mellitus.

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice

PURPOSE: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Postnatal exposure to a progestin does not prevent uterine adenogenesis in domestic dogs

To assess the effects of a single supraphysiological postnatal administration of a progestogen on uterine glands in dogs, 10 females were randomly assigned to a medroxyprogesterone acetate 35 mg (MPA; n = 6) or placebo (n = 4) group within the first 24 h of birth. The safety of the treatment was also evaluated. A transient mild clitoris enlargement appeared in MPA-treated females. Microscopic postpubertal uterine assessment revealed the presence of uterine glands in all cases without significant differences in the area occupied by the glands per µm2 of endometrium nor in the height of the uterine epithelium.

Impacto dos contraceptivos hormonais na densidade óssea: evidências atuais para contracepção na adolescência / Impact of hormonal contraceptives on bone density: current evidences for contraception in adolescence

Devido aos efeitos adversos dos contraceptivos hormonais, algumas mulheres são privadas de seus benefícios, que se estendem além da contracepção. Especialmente em adolescentes, é preocupante o impacto dos hormônios sobre o osso. Buscando reunir evidências nesse sentido, três revisores independentes fizeram buscas nas bases de dados Medline, Lilacs, Ibecs, Scielo e Cochrane, utilizando descritores relacionados à contracepção e densidade óssea. Foram critérios de inclusão: revisões sistemáticas e estudos com nível de evidência A e B. Foram excluídos estudos com contraceptivos utilizados para fins terapêuticos e não contraceptivos. Das 66 publicações encontradas, foram selecionados 15 estudos, e evidenciou-se que compostos com progesterona isolada de depósito e possivelmente os de baixa dose estrogênica têm impacto negativo na fase do pico de massa óssea. Contudo, o efeito esteve restrito à idade de iniciação e ao tempo de uso, havendo recuperação após interrupção da contracepção. Não há evidências de relação entre uso de contraceptivos e fraturas. O aconselhamento contraceptivo deve considerar o efeito negativo que a progesterona isolada de depósito e a baixa dose estrogênica podem ter sobre a massa óssea na adolescência, considerando que tal efeito é reversível e limitado ao tempo de uso

Due to the adverse effects of hormonal contraceptives, some women are deprived of the benefits they provide that extend beyond contraception. In adolescents, the main concern is the impact hormones can have on their bone structure. Three independent reviewers researched the databases Medline, Lilacs, Ibecs, Scielo and Cochrane, by using descriptions related to contraception and bone density. The inclusion criteria were: systematic reviews and studies with levels of evidence A and B. Contraceptives used for therapeutic purposes, other than contraception itself, were excluded from the study. Of the 66 publications found, 15 studies were selected. Compounds isolated from progesterone deposit, and possibly the low-dose estrogen, have a negative impact on the stage the bone mass peaks, but the effect was restricted to the age of initiation and the time of use, with recovery after discontinuation of contraception. There is no evidence of a relationship between the use of contraceptives and bone fractures. The negative effects that the deposit of progesterone and low-dose estrogen may have on bone mass should be taken into account when adolescents engage in the use of contraceptives ? bearing in mind that said effects are reversible and limited to the time of use

Histomorfometria da mama de ratas tratadas com estrogênio e/ou progestagênio / Breast histomorphometry of rats treated with estrogen and/or progestogen

OBJETIVO: Avaliar as alterações histomorfométricas nas mamas de ratas tratadas com estrogênio e/ou progestagênio por curto período de tempo. MÉTODOS: Foram divididas em quatro grupos 40 ratas ooforectomizadas: GC-recebeu veículo; GE-recebeu benzoato de estradiol (37,6 µg/animal); GP-recebeu acetato de medroxiprogesterona (11,28 mg/animal) e, GEP-recebeu benzoato de estradiol (37,6 µg/animal) e acetato de medroxiprogesterona (11,28 mg/animal). No grupo GE, o estradiol foi administrado durante sete dias, por via subcutânea. Já no grupo EP o estradiol foi administrado nos primeiros sete dias e o progestagênio por mais 23 dias, por via subcutânea. Vinte e quatro horas após a última administração dos hormônios, os animais foram anestesiados e o primeiro par de mamas inguinais removido, imerso em formaldeído a 10 por cento e processado para inclusão em parafina, sendo os cortes corados pela Hematoxilina-Eosina. Foram avaliadas a morfologia e a área ocupada pelo parênquima mamário, sendo os dados submetidos à análise de variância complementado pelo teste de Kruskal-Wallis (p < 0,05). RESULTADOS: As mamas no grupo-controle apresentaram-se atrofiadas, sendo que, nos animais dos grupos GE e GEP, nota-se a presença de alvéolos típicos contendo secreção no seu interior, já nos animais tratados somente com progestagênio (GP) notam-se alvéolos formados por células volumosas que ocupam praticamente todo o lúmen alveolar. A morfometria mostrou haver maior área de parênquima mamário nos animais tratados com hormônios (GE = GP > GEP > GC; p < 0,05) CONCLUSÃO: O estradiol e o progestagênio apresentaram efeito proliferativo no parênquima mamário. No entanto, a administração prévia de estradiol modifica a ação do progestagênio no tecido mamário da rata.

OBJECTIVE: To evaluate the breast histomorphometric changes in rats treated with estrogen and/or progestogen for a short period of time. METHODS: Forty oophorectomized rats were divided into four groups: GC, vehicle; GE, treated with estradiol benzoate (37.6 mg/animal); GP, treated with medroxyprogesterone acetate (11.2 mg/animal) and GEP, treated with estradiol benzoate (37.6 mg/animal) plus medroxyprogesterone acetate (11.28 mg/animal). In GE group, estradiol was administered subcutaneously for seven days; in GEP group, estradiol was administered once in a day for the first seven days and the progestogen over the next 23 days both subcutaneously. Twenty-four hours after the last hormone administration, the animals were killed upon deep anesthesia and the first inguinal breasts were removed, fixed in 10 percent formaldehyde and processed to be included in paraffin, with the sections being stained by hematoxylin-eosin. Morphology and the area occupied by mammary parenchyma were assessed, with the data undergoing analysis of variance followed by the Kruskal-Wallis test (p < 0.05). RESULTS: The control group breasts were found atrophic and, in GE and GEP group animals, typical alveoli with secretion inside are present; in progestogen-treated animals (GP), alveoli formed by large cells occupying almost the entire alveolar lumen are noted. Morphometric analysis showed a larger mammary parenchyma area in hormone-treated animals (GE = GP > GEP > GC; p < 0.05). CONCLUSION: Estradiol and progestogen had a proliferative effect on mammary parenchyma. However, prior estradiol administration changes the progestogen action on rat mammary tissue.

Variação de peso de usuárias de acetato de medroxiprogesterona de depósito segundo índice de massa corporal em seguimento de seis anos / Variation of weigth among users of the contraceptive with depot-medroxyprogesterone acetate according to body mass index in a six-year follow-up

OBJETIVO: determinar a variação de peso de mulheres com diferentes Índices de Massa Corporal (IMC), usuárias do injetável trimestral de acetato de medroxiprogesterona de depósito (AMPD) e compará-la à de mulheres em uso de método não hormonal. MÉTODOS: Estudo retrospectivo com revisão de prontuários de 226 usuárias de AMPD e 603 controles usuárias de DIU TCu380A. As mulheres foram distribuídas conforme o IMC inicial nas categorias de peso normal (<25 kg/m²), sobrepeso (25 a 29,9 kg/m²) e obesas (>30 kg/m²) e seguidas anualmente durante seis anos com medidas de peso e IMC. Aplicou-se o teste estatístico ANOVA para medir a variação de peso entre os grupos em cada categoria de IMC a cada ano. RESULTADOS: a média de idade no início do uso do método foi maior no grupo de estudo do que no controle em todas as categorias de IMC 31,6 ± DP 7,1 X 27,4 ± DP 5,5 na categoria peso normal (p<0,0001); 37,3 ± DP 6,8 X 29,2± DP 6,0 na categoria sobrepeso (p<0,0001); e 35,3 ± DP 6,4 X 29,7 ± DP 5,8 na categoria obesas (p<0,0001). As usuárias de AMPD tiveram elevação de peso em relação às controles na categoria de sobrepeso (p=0,0082); e o aumento de peso em relação ao tempo também foi maior no grupo de usuárias de AMPD do que nas controles para as categorias de peso normal (p<0,0001) e sobrepeso (p=0,0008). No grupo de obesas não houve variação do IMC entre os grupos nem em relação ao tempo de uso do método. CONCLUSÕES: não houve variação de ganho de peso em mulheres obesas usuárias de AMPD. Estudos prospectivos deverão ser realizados com testes metabólicos para determinar os fatores desencadeadores do ganho de peso em mulheres com peso normal e sobrepeso.

PURPOSE: to determine weight variation in women with different Body Mass Index (BMI) in use of trimestral injections of depot-medroxyprogesterone acetate (DMPA), and compare it to women users of a non-hormonal method. METHODS: retrospective study with the chart review of 226 DMPA users and 603 controls, users of DIU TCu380A. Women were distributed in categories, according to their initial BMI, as having normal weight (<25 kg/m²), overweight (25 to 29,9 kg/m²) and being obese (>30 kg/m²), and were followed-up for six years, with yearly measurements of weight and BMI. The statistic test ANOVA was used to measure the weight variation among the groups in each BMI category every year. RESULTS: the average age at the onset of the method employed was higher in the study group than in the controls, in all the BMI categories: 31.6±SD 7.1 X 27.4±SD 5.5 in the normal weight category (p<0.0001); 37.3±SD 6.8 X 29.2±SD 6.0 in the overweight category (p<0.0001); and 35.3±SD 6.4 X 29.7±SD 5.8 among obese women (p<0.0001). DMPA users showed weight increase as compared to the controls in the overweight category (p=0.0082); and the weight increase along the observation period was also higher among the DMPA users than among the controls, for the normal weight (p<0.0001) and overweight (p=0.0008) categories. In the obese group, there was no BMI variation between the groups, nor along the period during which they were using the method. CONCLUSIONS: there was no change in weight gain among DMPA users from the obese category. Prospective studies should be done with metabolic tests to establish the determining factors of weight gain in normal and overweight women.

Efficacy comparison of Pueraria mirifica (PM) against conjugated equine estrogen (CEE) with/without medroxyprogesterone acetate (MPA) in the treatment of climacteric symptoms in perimenopausal women: phase III study.

OBJECTIVE: To evaluate the efficacy comparison of Pueraria mirifica (PM), name in Thai is Kwao Kruea Khao, against conjugated equine estrogen (CEE) with/without medroxyprogesterone acetate (MPA) in the treatment of perimenopuasal women with climacteric symptoms. MATERIAL AND METHOD: Perimenopausal women attending the Menopausal clinic of Hat Yai Regional Hospital were voluntarily recruited. The vasomotor symptoms such as hot flushes and night sweats, as well as other unpleasant symptoms, urogenital and psychological symptoms, were also assessed. Patients were voluntarily enrolled and randomly received daily 50 mg raw material of PM, Group A, or daily 0.625 mg of conjugated equine estrogen (CEE) with/without 2.5 mg of medroxyprogesterone acetate (MPA), Group B, depend on non-hysterectomized/hysterectomized condition. RESULTS: Seventy-one patients were enrolled. Eleven of those were excluded for failing to complete the initial work-up and follow-up. Sixty cases were evaluated, 30 cases in Group A and 30 cases in Group B. After medication, the mean of modified Greene climacteric scale (MGCS) in Group A/Group B had decreased from 29.0/32.26 to 17.86/18.1, 12.56/9.57 and 9.9/8.16 at 1-, 3-, and 6- month respectively. The clinical satisfaction using MGCS was not statistically significant between PM (Group A) and CEE with/without MPA (Group B) in the alleviation of climacteric symptoms (p-value > 0.05). There were no statistically significant changes of three serum markers: estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) between both groups. CONCLUSION: PM, containing phytoestrogens, has estrogenic effect as similar as CEE, and can alleviate the climacteric symptoms in perimenopausal women. PM demonstrates great promise in the treatment of climacteric symptoms. However, optimal doses should be clinically assessed to meet appropriate individual responses.

Regulatory effect of estrogen, progestin and HB-EGF on the expression of HOXA10 gene in Ishikawa cells / 华中科技大学学报（医学）（英德文版）

HOXA10 gene plays an essential role in differentiation of the endometrium and in human reproduction. The aim of this study was to investigate the regulatory effect of sex steroids and HB-EGF on HOXA10 gene in Ishikawa cells. Ishikawa cells were incubated with 17-beta estradiol (10(-8) mol/L), medroxyprogesterone acetate (MPA) (10(-6) mol/L), RU486 (10(-5) mol/L) or HB-EGF (10 ng/mL) for 48 h respectively. The expression of HOXA10 gene was detected by immunofluorescence, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Our results showed that either estrogen alone, progestin alone or progestin combined with estrogen could significantly increase the expression of HOXA10 gene 48 h after the treatment (P<0.05). But estrogen combined with progestin and RU486 could inhibit the up-regulation by estrogen and progestin. HB-EGF could elevate the expression of HOXA10 gene 48 h after the treatment (P<0.05). It is concluded that both estrogen and progestin can up-regulate the expression of HOXA10 gene in Ishikawa cells, but RU486 can inhibit the effect and HB-EGF can elevate the expression level of HOXA10 gene.

The expression of cyclooxygenase-2 in cervical cancers and Hela cells was regulated by estrogen/progestogen / 华中科技大学学报（医学）（英德文版）

To investigate the relationship between the expression of cyclooxygenase-2 (COX-2) and menstrual cycle, the regulatory effects of 17-beta-estradiol (E(2)) and medroxyprogesterone acetate (MPA) on the expression of COX-2 in cervical cancer Hela cells were examined. Cervical cancer specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE staining of uterine endometrium. COX-2 was immunohistochemically stained by SABC staining and the staining intensity was determined with computerized image analysis system. Hela cells were incubated with alcohol, E(2), E(2)+MPA, MPA for 12, 24 and 48 h respectively. The expression of COX-2 in Hela cells was detected by Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Our results showed that the expression of COX-2 was significantly higher during proliferative phase than secretory phase (P0.05). Incubation with E(2) could significantly enhance the expression of COX-2 continually. On the contrary, E(2)+MPA and MPA alone could decrease the expression of COX-2 as compared with the control and E(2) group (P<0.05 and P<0.01 respectively). It is concluded that the expression of COX-2 in cervical cancer of pre-menopausal patients and Hela cells was regulated by estrogen/progestogen.

Effects of prolonged use of injectable hormonal contraceptive on serum lipid profile.

The current study was carried out to determine serum levels of total cholesterol, triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in human female volunteers taking injectable hormonal contraceptives. For this purpose, 200 (two hundred) subjects with age range of 20-35 years were selected. Out of them, 140 (one hundred and forty) were experimental subjects and 60 (sixty) were control. Women without hormonal contraceptive were selected as the subjects of control group. The experimental subjects were taking injectable hormonal contraceptive, DMPA (depo-medroxyprogesterone acetate) for 3-5 years uninterruptedly. The mean serum total cholesterol and mean serum triacylglycerol levels of the DMPA users were significantly (P<O.05 and P<0.01 respectively) elevated in comparison to that of the non-users. The mean serum HDL-cholesterol was decreased in subjects using DMPA in comparison to that of the control group. But the decrease was not significant (P>0.05). The mean serum LDL-cholesterol level of the subjects of DMPA users was significantly (P<0.05) elevated in comparison to that of the control.

effect of medroxyprogesterone acetate on the structure of adrenal cortex [zona fasciculata] of adult female albino rat. Light and electron microscopic studies

The injectable contraceptive medroxyprogesterone acetate [MPA] is an internationally established option of birth control. To evaluate the possible effects of MPA on the structure of zona fasciculata cells, the adrenals of forty adult female albino rats were used. The experimental animals were divided into four groups treated as follows: group I was kept as control, groups II and III were injected intramusculary with MPA for 2 and 4 months respectively. Animals of group IV were injected for 4 months and sacrificed one month after the last injection. Specimens from the adrenal gland were taken and processed for light and electron microscopic examination. It has been found that MPA caused an increase in the thickness of zona fasciculate and activation of the cells when administered for 2 months. The cells showed numerous lipid droplets, large number of mitochondria and prominent smooth endoplasmic reticulum. However, MPA administration for 4 months resulted in reduction in the thickness of zona fasciculata with degenerative changes in its cells. The cells appeared small and separated from each other and exhibited many lysosomes and intracellular vacuolar spaces. After withdrawal, most of the cells appeared more or less normal and few cells showed some structural changes. These findings indicated that MPA at first caused activation of fasciculata cells and increased steroidogenesis, but prolonged use of MPA induced inactivation and degenerative changes in these cells. However some of these changes were reversible on withdrawal of the drug. Therefore precaution and follow up must be considered with prescribing this drug for prolonged periods

Effect of oral and injectable contraceptive on serum cacium magnesium and phosphorus in women

This study aims at evaluating serum calcium, magnesium and phosphorus levels in women taking oral and injectable contraceptives. Serum calcium, magnesium and phosphorus were measured in 50 women taking oral contraceptives [Lofeminal] and 50 women taking injectable contraceptive [Depo-medroxy progesterone acetate and Norigest]. These women were used as controls before starting these contraceptives. There was significant decrease in serum levels of calcium, magnesium and phosphorus in women taking oral contraceptives but there was significant increase in these minerals in women taking injectable contraceptives. Conclusions: It is suggested that these contraceptives should be used with due care and with proper investigations of the women before and during the therapy

Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats

Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0.25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro

Effects of depot medroxyprogesterone acetate on the calcium metabolism of adult ovariectomized rats

This paper describes experiments designed to test the effect of depot medroxyprogesterone acetate (DMPA) on calcium metabolism of adult ovariectomized rats. The 24 animals were randomly assigned to control or treated groups. Treated rats received 15 mg of DMPA i.m. per week, during four or twelve weeks. Controls received solvent alone. The variables characterizing the metabolism of Ca (daily rates of intestinal absorption and excretion, bone accretion and resorption and the sizes of the exchangeable pools and their rate constants) were measured with the aid of 45Ca according to Aubert and Milhaud. No effects were observed at four weeks of treatment. After twelve weeks, treatment produced serum levels of 46.5 ñ 5.6 nmoles of medroxyprogesterone/L, reduction of bone turnover (Ca accretion and resorption rates) and of the size of the slow exchanging Ca compartment. The increase in true Ca intestinal absorption was compensated by the increased endogenous fecal Ca excretion. The mass of body Ca was not affected by treatment.

Importância do fator de crescimento epidérmico (EGF) e seu receptor (EGF-R) no tecido endometrial / Epidermal growth factor (EGF) and its receptor (EGF-R) importance in the endometrial tissue

Os autores fazem uma revisäo sobre a influência que o EGF e seu receptor (EGF-R) exercem no tecido endometrial, enfocando sua possível regulaçäo pelos esteróides e seus receptores e sua importância nos processos de transformaçäo secretora e de decidualizaçäo.

Efeitos da terapia de reposiçäo hormonal na densidade mamográfica de mulheres na pós-menopausa / Effects of HRT on mammography density in post-menopausal women

Avaliar a influência da terapia de reposiçäo hormonal (TRH) no comportamento da densidade mamográfica em mulheres na pós-menopausa. Foi realizado um estudo de coorte com 81 usuárias de TRH e 46 näo-usuárias. As mamografias foram reavaliadas e classificadas segundo os critérios de Wolfe (1976). O aumento da densidade mamográfica foi avaliado em usuárias e näo-usuárias de TRH. Foram também avaliados para o grupo de usuárias de TRH (estrógeno ou estrógenos associados a progestágenos) a influência do tipo e o esquema em uso. Para este estudo utilizou-se os testes de Qui-Quadrado, Exato de Fisher e t de Student. Foi observado 12,4 por cento de aumento de densidade mamográfica em usuárias de TRH. O tipo, o esquema e a dose de progesterona utilizados no grupo de usuárias de TRH näo influenciaram o aumento de densidade mamográfica. As implicaçöes desta situaçäo devem ser consideradas.

Effect of medroxy progesterone acetate and testosterone enanthate on vas deferens of rats.

Effects of medroxy progesterone acetate (MPA; 5 mg/kg) and MPA + testosterone enanthate (TE) (3 mg + 2 mg/kg) were investigated in vas deferens and on fertility (along with reversibility study) for 60 days through histopathology, morphometric and certain biochemical parameters such as total proteins, sialic acid, ATPase, SDH and testosterone. The study revealed for altered histopathology and contratile pattern of vas deferens resulting in reduced fertility. The study also indicated androgen antagonistic effect. These effects were found to be reversible 4 and 3 months after withdrawal of MPA and MPA + TE injections respectively. Thus, both types generated functional sterility in the rat, but MPA affected histophysiology of vasal tissue.

Hormonoterapia de reemplazo con dos esquemas de terapia combinada continua / Estrogen replacement therapy with 2 combined continued therapy schedules

El propósito del estudio fue evaluar los patrones de sangrado con dos regímenes de TCC con diferentes dosis de progestina. En un estudio prospectivo, randomizado, de doce meses de duración analizamos 78 mujeres climatéricas (con amenorrea >6 meses, test de progesterona negativo y grosor endometrial igual o menor que 6 mm). Las pacientes fueron divididas en dos grupos: grupo A (n= 41) que recibió diariamente 2 mg de estradiol (E2) oral más 2,5 mg de medroxiprogesterona acetato (MPA) y el grupo B (n= 37) 2 mg de estradiol (E2) más 5 mg de MPA. En ambos grupos el número de mujeres en amenorrea aumentó progresivamente en los trimestres sucesivos de tratamiento. En el grupo A el porcentaje aumentó de un 26,9 por ciento en el primer trimestre a un 60,9 por ciento en el cuarto (p< 0,05) y en el grupo B de un 21,6 por ciento a un 73 por ciento (p< 0,001), respectivamente. El grupo B alcanzó un porcentaje de amenorrea más significativo.El análisis combinado de ambos grupos mostró un significativo descenso en el promedio de días con sangrado o con goteo en los trimestres sucesivos: de 10.05 (0-62) días en el primer trimestre a 4,34 (0-42) días en el cuarto (p< 0,01). El grosor endometrial no experimentó cambios significativos en ninguno de ambos grupos. Los patrones de sangrado individuales no mostraron correlación con la edad, peso, grosor endometrial, ni con los meses transcurridos desde la menopausia (NS). Ambos regímenes ensayados indujeron amenorrea progresiva, la que fue significativamente mayor en el grupo B, que recibió la dosis más alta de MPA

Efectos sobre la sintomatología climatérica, pérfil lipídico y patrones mamográficos / Effects on climacteric sintomatology, lipid profile and mammography patterns

Se compara dos esquemas de HTR-CC por vía oral con el objeto de evaluar su eficacia clínica, modificaciones del pérfil lipídico y de los patrones mamográficos. Estudio prospectivo, doble ciego de 12 meses de duración en mujeres con sintomatología climatérica, amenorrea mayor que 6 meses y prueba de progesterona negativa. Se evalúa 78 mujeres que completaron el estudio, divididas en dos grupos: grupo A (n= 41) que recibió diariamente 2 mg de estradiol (E2) oral más 2,5 mg de medroxiprogesterona acetato (MPA) y el grupo B: 2 mg de estradiol (E2) más 5 mg de MPA. Ambos grupos terapéuticos demostraron similar eficacia en la disminución de los síntomas vasomotores (SVM) con una reducción del 92 por ciento y del 93 por ciento, respectivamente (p< 0,001); de los síntomas urogenitales: 84 por ciento en ambos grupos (p< 0,01) y de los síntomas funcionales: 75 por ciento en ambos grupos (p< 0,01). El colesterol total disminuyó 12,04 por ciento en el grupo A (p< 0,001) y 7,06 por ciento en el B (p< 0,05), siendo su descenso más significativo en el grupo A, con menor dosis de MPA. El HDL-colesterol aumentó significativamente en ambos grupos, en forma marcada en el grupo A: 12,3 por ciento (p< 0,001) que en el B: 8,5 por ciento (p< 0,05). Los niveles de triglicéridos no experimentaron cambios significativos. Al ingreso un 37,2 por ciento de las mujeres, en forma global, tenía elevado el índice de riesgo cardiovascular (> 5), el número de mujeres con factor de riesgo disminuyó al 7,7 por ciento después de los doce meses de terapia. Un 56 por ciento en el grupo A y un 40,6 por ciento en el grupo B presentaron un leve a moderado aumento de la densidad mamaria, las restantes mujeres no experimentaron modificaciones de sus patrones mamográficos. Ambos esquemas demostraron similar eficacia en el control de la sintomatología climatérica, independientemente de la dosis de MPA empleada. El agregado de MPA continua, no contrarrestó los efectos beneficiosos del E2 sobre el colesterol total y el HDL-colesterol, si bien los resultados fueron mejores al utilizar la dosis más baja de 2,5 mg