Hydroxylation of Progesterone and Its Derivatives by the Entomopathogenic Strain Isaria farinosa KCh KW1.1.

Progesterone biotransformation is worth studying because of the high industrial value of its derivatives. This study investigated the catalytic ability of the entomopathogenic filamentous fungus strain Isaria farinosa KCh KW1.1 to transform progesterone derivatives: 11α-hydroxyprogesterone, 17α-hydroxyprogesterone, 16α,17α-epoxyprogesterone and pregnenolone. In the culture of Isaria farinosa KCh KW1.1, 11α-hydroxyprogesterone was effectively transformed into only one product: 6ß,11α-dihydroxyprogesterone. Transformation of 17α-hydroxyprogesterone gave three hydroxy derivatives: 6ß,17α-dihydroxyprogesterone, 12ß,17α-dihydroxyprogesterone and 6ß,12ß,17α-trihydroxyprogesterone. Two products: 6ß-hydroxy-16α,17α-epoxyprogesterone and 6ß,11α-dihydroxy-16α,17α-epoxyprogesterone, were obtained from the 16α,17α-epoxyprogesterone transformation. We isolated two compounds from the biotransformation medium with pregnenolone: 11α-hydroxy-7-oxopregnenolone and 5α,6α-epoxy-3ß,11α-dihydroxypregnan-7,20-dione. In this study, we observed only mono- and dihydroxy derivatives of the tested substrates, and the number of obtained products for each biotransformation did not exceed three.

Personality traits change after an opportunity to mate.

There is growing evidence that personality traits can change throughout the life course in humans and nonhuman animals. However, the proximate and ultimate causes of personality trait change are largely unknown, especially in adults. In a controlled, longitudinal experiment, we tested whether a key life event for adults--mating--can cause personality traits to change in female threespine sticklebacks. We confirmed that there are consistent individual differences in activity, sociability and risk-taking, and then compared these personality traits among three groups of females: (i) control females; (ii) females that had physically mated, and (iii) females that had socially experienced courtship but did not mate. Both the physical experience of mating and the social experience of courtship caused females to become less willing to take risks and less social. To understand the proximate mechanisms underlying these changes, we measured levels of excreted steroids. Both the physical experience of mating and the social experience of courtship caused levels of dihydroxyprogesterone (17α,20ß-P) to increase, and females with higher 17α,20ß-P were less willing to take risks and less social. These results provide experimental evidence that personality traits and their underlying neuroendocrine correlates are influenced by formative social and life-history experiences well into adulthood.

Does the bone morphogenetic protein 7 inhibit oocyte maturation by autocrine/paracrine in mud crab?

A bone morphogenetic protein ligand (BMP7) and its two receptors (BMPRIB and BMPRII) were recently cloned and characterized in the mud crab, Scylla paramamosain. However specific functions of BMP7 and the mechanistic pathways regulating its function are largely unidentified. In the present study, we separated oocytes and follicle cells from the ovarian explants of S. paramamosain. Subsequent analysis using semi-quantitative PCR demonstrated that the mRNA of Sp-BMP7 was exclusively expressed in follicle cells while Sp-BMPRs were expressed in both oocytes and follicle cells. In vitro experiments further showed that the mRNA and protein levels of Cyclin B increased but Sp-BMP7 declined in 17α, 20ß-Dihydroxyprogesterone (DHP)-induced oocytes. Furthermore, the inhibitory effects of Sp-BMP7 were not affected by the elimination of the contact/gap junction-mediated communication between oocytes and follicle cells. Our data indicate that BMP7 may play a role in the suppression of DHP-induced oocyte maturation by affecting autocrine/paracrine pathways in S. paramamosain.

Estrías generalizadas secundarias a tratamiento tópico con clobetasol y minoxidil en un paciente con psoriasis / Generalized striae rubra due to cronic abuse of clobetasol and minoxidil formule in a patient with psoriasis

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Cloning and pattern of gsdf mRNA during gonadal development in the protogynous Epinephelus akaara.

Gonadal soma-derived factor (gsdf) is a teleost- and gonad-specific growth factor involved in early germ cell development. The red spotted grouper, Epinephelus akaara, as a protogynous hermaphrodite, provides a novel model for understanding the mechanisms of sex determination and differentiation in teleosts. In the present study, a 2307-bp long gsdf gene was cloned from E. akaara and there was further analysis of its tissue distribution and gonadal patterns of gene expression during the female phase and sex change developmental stages. The cellular localization of gsdf at the late transitional developmental stage was also analyzed. In addition, the concentrations of serum sex steroid hormones (E2, 11-KT and DHP) were determined. The gsdf transcripts were exclusively localized in the gonad. During the female phase at an early developmental stage, when the ovotestis contained mainly oogonia and primary growth oocytes, the gsdf mRNA was relatively more abundant. The relative abundance of gsdf decreased, however, and the lesser amount was sustained with the advancement of oocyte development. During the transitional phase, the relative abundance of gsdf mRNA increased slightly at the early developmental stage and there were further increases in relative abundance in the late developmental stage, and the gsdf transcripts were observed in the Sertoli cells surrounding early developing spermatogonia. Among the sex steroids, 11-KT concentrations were positively correlated with amount of gsdf mRNA during sex change. These results suggest that gsdf could have roles in regulating pre-meiotic germ cell proliferation and be involved in sex change in E. akaara.

Combination injectable contraceptives for contraception.

BACKGROUND: Combination injectable contraceptives (CICs) provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of CICs. SEARCH METHODS: In January and February 2013, we searched for randomized controlled trials (RCTs) of combination injectable contraceptives.Databases include MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS.We searched for current trials in ClinicalTrials.gov and ICTRP.Earlier searches also included AIM and IMEMR. For the initial review, we also assessed the references listed in review articles and in the eligible trial reports. SELECTION CRITERIA: RCTs were eligible if they compared a combination injectable contraceptive with any other contraceptive method (e.g., a second CIC,a progestin-only injectable contraceptive, another hormonal contraceptive or a barrier method) or a placebo. We limited the review to marketed CICs. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on contraceptive efficacy, bleeding patterns, continuation, and side effects. We calculated the Peto odds ratio or mean difference with 95% confidence interval for dichotomous or continuous outcome, respectively. Survival analysis estimates for method discontinuation were presented where available. MAIN RESULTS: Twelve trials met the inclusion criteria. Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA)25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons.Acceptability results favored the CIC in one study and the progestin-only in another.Studies comparing two CICs found that NET-EN 50 mg plus E(2)V (5)mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials.The NET-EN plus E (2) V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward improving the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

Combination injectable contraceptives for contraception.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: One author evaluated all titles and abstracts from the literature searches to determine their eligibility. Two authors independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons. Acceptability results favored the combination injectable in one study and the progestin-only in another.Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials. The NET-EN plus E(2)V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

Combination injectable contraceptives for contraception.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

Microbial transformations of steroids-XI. Progesterone transformation by Streptomyces roseochromogenes-purification and characterisation of the 16alpha-hydroxylase system.

Streptomyces roseochromogenes, NCIB 10984, contains a cytochrome P450 which, in conjunction with two indigenous electron transfer proteins, roseoredoxin and roseoredoxin reductase, hydroxylates exogenous progesterone firstly to 16alpha-hydroxyprogesterone and thereafter in a second phase bioconversion to 2beta,16alpha-dihydroxyprogesterone. The progesterone 16alpha-hydroxylase P450 and the two electron transfer proteins have been purified to homogeneity. A reconstituted incubation containing these three purified proteins and NADH, the natural electron donor, produced identical hydroxy-progesterone metabolites as in intact cells. Peroxy and hydroperoxy compounds act in a shortened form of the cycle known as the 'peroxide shunt' by replacing the natural pathway requirement for the electron donor NADH, the electron transfer proteins and molecular O2, the terminal electron acceptor. In an NaIO4 supported incubation, the initial rate of progesterone hydroxylation was marginally higher (1.62 mmol progesterone/mmol P-450/h) than in the reconstituted natural incubation (1.18 mmol progesterone/mmol P-450/h) but the product yield was significantly lower, 0.45 mol hydroxyprogesterone produced/mol P-450 compared to 6.0 mol hydroxyprogesterone produced/mol P-450. These yield data show that in the reconstituted natural pathway, progesterone 16alpha-hydroxylase P450 supports multiple rounds of hydroxylation in contrast to a likely single oxygenation by a minority of P450s in the peroxide shunt pathway.

Effects of peripheral-type benzodiazepine receptor antisense knockout on MA-10 Leydig cell proliferation and steroidogenesis.

The peripheral-type benzodiazepine receptor (PBR) is not only widely expressed throughout the body, but it is also genetically conserved from bacteria to humans. Many functions have been attributed to it, but its primary role remains a puzzle. In the current study, we stably transfected cultures of MA-10 Leydig cells with either control or 18-kDa PBR antisense knockout plasmids. The antisense knockout vector was driven by the human enkephalin promoter, which contains two cAMP response elements, such that cAMP treatment of transfected cells could superinduce 18-kDa PBR antisense RNA transcription and, hence, down-regulate endogenous 18-kDa PBR mRNA levels. Control and knockout MA-10 cell lines were then compared at the level of receptor binding, thymidine incorporation, and steroid biosynthesis. Eighteen-kilodalton PBR knockout reduced the maximal binding capacity of tritium-labeled PBR ligands, and the affinity of receptors to the ligands remained unaltered. Additionally, 24-h accumulation of progesterone was lower in the knockout cells. Exposure of the two cell types to 8-bromo-cAMP resulted in a robust increase in steroid production. However, a complex pattern of steroid accumulation was observed, in which further progestin metabolism was indicated. The later decline in accumulated progesterone as well as the synthesis of androstenedione were different in the two cell types. At the level of cell proliferation, reduction of 18-kDa PBR mRNA showed no effect. Thus, we conclude that the 18-kDa PBR may have a more important role in steroidogenesis than in proliferation in this Leydig cell line.

Proliferation of pancreatic islet-cells in cyclic and pregnant rats after treatment with progesterone.

The effect of progesterone (P) on pancreatic islet-cell proliferation and function of cyclic and pregnant rats was investigated in vivo. Silastic tubes containing P were inserted s.c. in cyclic rats for 7 or 14 days and in pregnant rats from day 7 to 14, from day 14 to 21 or from day 7 to 21 of pregnancy. 5-Bromo-2-deoxyuridine (BrdU) was infused during the last 24h of the treatment; the proportion of dividing islet-cells was determined in pancreatic sections, which were immunostained for BrdU. Islet-cell function was determined by measuring glucose and insulin response to a standard intravenous glucose challenge. P treatment increased P and 20alpha-dihydroprogesterone (20alpha-OHP) levels in cyclic rats; in pregnant rats, only the plasma levels of 20alpha-OHP were elevated. Both 7 and 14 days of P treatment stimulated islet-cell proliferation in cyclic rats. In pregnant rats, P treatment increased islet-cell proliferation on day 14, but not on day 21 after either 7 or 14 days of P treatment. P did not affect plasma lactogenic activity in pregnant rats; plasma concentrations of prolactin were decreased after 14 days of P treatment in cyclic rats, but were not affected in pregnant rats. P treatment had no effect on glucose tolerance and glucose-stimulated insulin secretion in any of the groups. It was concluded that: 1. in vivo P stimulates islet-cell proliferation, but does not affect islet-cell function, 2. the stimulatory effects of P are indirect and possibly mediated by the P metabolite 20alpha-OHP and 3. at the end of gestation, stimulation of islet-cell proliferation is inhibited by some factor, which is not identical to P.

Endogenous steroid metabolism is indicated by fluctuations of endogenous steroid and steroid glucuronide levels in early development of the steelhead trout (Oncorhynchus mykiss).

Concentrations of endogenous steroids and their glucuronide conjugates fluctuated during early development in steelhead trout Oncorhynchus mykiss. Whole body content of sex steroids and steroid glucuronides of both bisexual and gynogenetic (all female) steelhead trout were quantified by radioimmunoassay. Concentrations of 17beta-estradiol (E2) and cortisol increased 2-4 days before hatch. Two days after hatch, 11-ketotestosterone (11KT) increased in concentrations in both gynogenetic and bisexual populations, and 11KT glucuronide concentrations increased in the gynogenetic population. Testosterone (T) and E2 concentrations were at their lowest at 39 days postfertilization (dpf) for T and 39 and 61 dpf for E2. Changes in levels of steroid glucuronides were not consistently parallel to free steroids through time. T-, E2-, and 17alpha, 20beta dihydroxyprogesterone glucuronides declined slower than their free forms. Based on fluctuating concentrations of all steroid glucuronides, both populations of fish demonstrated an ability to form glucuronide conjugates of all steroids at the embryonic stage. The changes in levels of both free steroids and their glucuronides during early development of the trout indicate that steroid metabolism is active during development. This study also implicates steroid metabolism as an integral part of embryonic and postembryonic development.

Subclinical changes in luteal function in cynomolgus monkeys with moderate blood lead levels.

The objective of the present study was to investigate luteal function in cynomolgus monkeys (n = 32), aged 15-20 years with blood lead levels (BLLs) in the range of < 3.0 micrograms dl-1 (control, n = 20), 10-15 micrograms dl-1 (low, n = 7) and 25-30 micrograms dl-1 (moderate, n = 5). Sampling was performed daily beginning with day 10 of the menstrual cycle and concluding on the first day of the subsequent menstrual cycle. Circulating levels of oestradiol (E2), progesterone (P4) and 20 alpha-hydroxyprogesterone (20-OHP) were normalized to the day of the ovulatory E2 surge. The area under the concentration curve (AUC) for P4 was significantly lower in monkeys with moderate BLLs compared to the control group (P = 0.04). The number of days for which circulating levels of P4 were greater than 1.0 ng ml-1 were also significantly fewer (P = 0.03) in monkeys with moderate BLLs compared to controls. There was no statistical evidence of a lead effect on circulating levels of E2, 20-OHP or menstrual cycle characteristics. These data suggest that chronic lead exposure suppresses corpora luteal production of P4 in the monkey at circulating BLLs lower than previously reported and relevant to humans with occupational exposure to lead.

Increased substrate concentration causes a shift from production of 11-oxygenated androgens to 17,20-dihydroxyprogestogens during the in vitro metabolism of 17-hydroxyprogesterone by goldfish testes.

Goldfish testes were incubated with [3H]17-hydroxyprogesterone in the presence of 0 to 100 micrograms/ml of unlabeled substrate and metabolites examined by thin-layer and high performance liquid chromatography. Conjugated steroids, predominantly sulfates, accounted for 50% of recovered activity with radiolabeled substrate alone, but percentage yields decreased to very low levels with substrate concentrations of 1 micrograms/ml and above. The 11-oxygenated androgens, androstenetrione and 11-ketotestosterone, were the major products with 0 to 0.1 micrograms/ml substrate, but at concentrations of 1 to 100 micrograms/ml the major products were 17,20 alpha-dihydroxy-4-pregnen-3-one (30% of recovered activity) with smaller amounts of the 20 beta-epimer. 11-Deoxycortisol was a minor product at all substrate concentrations. Production of 11-oxygenated androgens in the medium reached a maximum value of 40 ng/100 mg tissue/3 hr with 2 micrograms substrate, but progestogen production continued to increase up to the maximum substrate used (30 micrograms at 200 micrograms substrate). The results demonstrate a clear switch from production of 11-oxygenated androgens to that of 20-reduced progestogens with increased substrate concentration. This switch shows similarities to that observed for in vivo plasma steroid concentrations during the prespawning period of many male teleosts and it is suggested that this, at least in part, may be due to increased substrate availability resulting from elevated gonadotropin secretion.

Plasma membrane cholesterol is utilized as steroidogenic substrate in Y-1 mouse adrenal tumor cells and normal sheep adrenal cells.

Previous studies from this laboratory indicate that plasma membrane cholesterol acts as an important source of steroidogenic substrate for MA-10 Leydig tumor cells. The present studies were designed to generalize these findings to other steroidogenic cells and to another species. Studies were performed using the Y-1 murine adrenal tumor cell line and primary cultures of sheep adrenocortical cells. Treating Y-1 cells with the acyl coenzyme A:cholesterol acyltransferase inhibitor, 58-035, caused cellular cholesteryl ester depletion and rendered more apparent the effect of dibutyryl-cAMP to cause cellular free cholesterol depletion. Radioactive 20 alpha-dihydroprogesterone was synthesized by Y-1 cells that had been plasma membrane-labeled with [3H]-cholesterol. Primary sheep adrenal cultures that had been cholesteryl ester-depleted also demonstrated cellular free cholesterol depletion after stimulation with dibutyryl cAMP. Plasma membrane label was converted to steroid hormones in these cells as well. Taken together, these data indicate that the use of plasma cholesterol is not restricted to the MA-10 cells. The present data indicate that both neoplastic mouse adrenal tumor cells and normal sheep adrenal cells utilize plasma membrane cholesterol.

Two novel microbial conversion products of progesterone derivatives.

Two novel microbial steroid hydroxylations were found in a screening of 131 microorganisms under aerobic conditions. 17 alpha-Hydroxyprogesterone was hydroxylated in the 8 beta-position by Corynespora melonis CBS 16260, and fermentation of 17 alpha-acetoxyprogesterone with Pycnosporium species ATCC 12231 yielded 11 beta-hydroxy- and 11 beta, 12 beta-dihydroxy-17 alpha-acetoxyprogesterone. The known 11 beta-hydroxy compound could be obtained as a single product with Trichothecium roseum ATCC 12519.

Accumulation and mobilization of triglycerides and cholesteryl esters in Leydig tumor cells.

Incubating MA-10 Leydig tumor cells with sodium oleate led to the accumulation of triglyceride within the cells. Triglycerides were deposited in a time- and dose-dependent fashion. Cellular triglyceride promoted storage of cholesteryl ester. As much cholesteryl ester was stored in oleate-treated cells as in cells treated with saturating concentrations of low density lipoprotein. Addition of both oleate and low density lipoprotein resulted in additive accumulation of cholesteryl esters. Cholesteryl esters in cells loaded with triglyceride by oleate treatment were mobilized in response to dibutyryl-cAMP to an extent similar to that in cells containing low triglyceride concentrations. Dibutyryl-cAMP stimulated cholesteryl ester mobilization under all conditions, and stimulated triglyceride mobilization when adequate fatty acid acceptors were available. The results indicate that while triglyceride accumulation in MA-10 cells promoted cholesteryl ester deposition, it did not impair cAMP-dependent cholesteryl ester hydrolysis or steroid hormone production.

Estudo clínico multicêntrico sobre o efeito metabólico do contraceptivo mensal injetável contendo acetofenido de dihidroxiprogesterona 150 mg + enantato de estradiol 10 mg / A multicenter clinical trial on the metabolic effect of an injectable monthly contraceptive containing dihydroxyprogesterone acetophenide 150 mg + estradiol enanthate 10 mg

O efeito metabólico do contraceptivo mensal injetável contendo acetofenido de dihidroxiprogesterona (DHPA) 150 mg + enantato de estradiol (Een) 10 mg foi comparado ao de outros métodos anticoncepcionais comumente utilizados (pílulas contendo: etinilestradiol (EEn) 0,050 mg + levonogestrel (LNG) 0,250 mg, EE 0,030 + LNG 0,150 mg; e EE 0,030/0,040/0,030mmg + LNG 0,050/0,075/0,0125 mg; enantato de noretisterona (NEE) 200 mg via i.m.; e métodos nao-hormonais. Foram determinados os triglicerídeos séricos, colesterol HDL/LDL, cobre, ceruloplasmina, cortisol total e livre, CBG e testosterona total e livre e SHBG de usu rios crônicas. Este estudo contou com a participaçäo do total de 237 mulheres. As usuárias de métodos nao-hormonais utilizadas como controle apresentaram níveis mais altos de triglicerídeos. Os níveis de testosterona total e livre foram mais baixos em mulheres que utilizavam DHPA 150 mg + Een 10 mg e nas que tomavam pílulas anticoncepcionais (p<0,05 - 0,01). Tais alteraçöes foram levemente menores no grupo que utilizou o injetável. Os efeitos do DHPA 150 mg + EEn 10 mg sobre o colesterol HDL/LDL, cobre, ceruloplasmina, CBG, cortisol total e livre e SHBG foram raros ou inexistentes. Entretanto, com as pílulas anticoncepcionais (mesmo as de formulaçäo de baixa dosagem) ocorreram alteraçöes em todas essas vari eis, que foram altamente significativas na comparaçäo com o método injetável (p< 0,01) e com os métodos nao-hormonais (p<0,01); näo houve diferenças entre estes dois últimos métodos. Os resultados sugerem que o efeito metabólico da injeçäo mensal i.m. de DHPA 150 mg + Een 10 mg näo é superior aos dos anticoncepcionais orais comumente utilizados. Estes resultados também nao sugerem que a dose contida nesse injetável seja excessiva. Nao há qualquer evidência de que ele produza efeito cumulativo no organismo. Esses achados devem ser levados em consideraçäo com relaçäo à segurança do uso a longo prazo desse injetável.

Luteolytic effect of the antiprogestin and antiglucocorticoid agent RU486 in rats.

Ovarian cells of pregnant rats were cultured with synthetic progestins (R5020, R2323), dexamethasone and RU486. Progesterone and 20 alpha-hydroxy-pregn-4-en-3-one (20 alpha-dihydroprogesterone) in the medium were measured by specific radioimmunoassay. Both R5020 and R2323 increased concentrations of these intrinsic progestins. RU486 decreased concentrations of progesterone, however, the addition of R5020 or R2323 counteracted this action. Immature hypophysectomized rats treated with pregnant mare serum gonadotropin (PMS) and human chorionic gonadotropin (hCG) were administered with RU486; the serum levels of progesterone and 20 alpha-dihydroprogesterone tended to decrease. R5020 and R2323 inhibited the effect of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), whereas RU486 did not. Inhibition of the cholesterol side chain cleavage enzyme (CSCC) by RU486 was more marked than that by R5020 or R2323. These results show that RU486 decreases progesterone synthesis in cultured ovarian cells. A part of the mechanism may involve an inhibition of CSCC.

Multicentred clinical study of the metabolic effect of the monthly injectable contraceptive containing dihydroxyprogesterone acetophenide 150 mg + estradiol enanthate 10 mg.

The metabolic effect of the monthly injectable contraceptive containing dihydroxyprogesterone acetophenide (DHPA) 150 mg + estradiol enanthate (EEn) 10 mg was compared to that of other regularly used contraceptive methods (pills containing: ethinylestradiol (EE) 0.050 mg + levonorgestrel (LNG) 0.250 mg, EE 0.030 mg + LNG 0.150 mg; EE 0.030/0.040/0.030 mg + LNG 0.050/0.075/0.0125 mg; norethisterone enanthate (NEE) 200 mg i.m.; non-hormonal methods). Serum triglycerides, HDL/LDL-cholesterol, copper, ceruloplasmin, total and free cortisol, CBG, total and free testosterone and SHBG in chronic users were determined. A total of 237 women took part in this study. Taking users of non-hormonal methods as control, triglyceride levels were higher, and total and free testosterone levels were lower in women using DHPA 150 mg + EEn 10 mg and in those taking contraceptive pills (p less than 0.05 - 0.01). Such modifications were slightly less in the group using the injectable. The effects of DHPA 150 mg + EEn 10 mg on HDL/LDL-cholesterol copper, ceruloplasmin, CBG, total and free cortisol and SHBG were rare or non-existent. Nevertheless, the contraceptive pills (even the low-dose formulations) correlate with modifications of all those variables, which were highly significant in comparison with the injectable (p less than 0.01) and with non-hormonal methods (p less than 0.01); there were no differences between the last two methods. The results suggest that the metabolic effect of DHPA 150 mg + EEn 10 mg is not higher than that of the commonly used oral contraceptives. On the other hand, they do not suggest that the dose contained in this injectable is exaggerated. There is no evidence that it produces accumulation of effects in the organism. These findings should be taken into account when referring to the long-term safety of this injectable.