RESUMO
Hormone-associated meningiomas tend to stop growing or decrease in size after cessation of certain progestins, mainly cyproterone acetate. We report three observations on the natural history of hormone-associated intraosseous meningiomas, showing in a first patient that those tumors may grow rapidly under nomegestrol. We then demonstrate the sustained growth of intraosseous hormone-associated meningiomas after cessation of promesgestone and nomegestrol, independently of the intracranial portion, which concurrently decreased in size in the second case or was resected at the time of nomegestrol withdrawal in the third case, thus giving new insights into the tumorigenesis mechanisms of hormone-associated intraosseous meningiomas.
Assuntos
Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/patologia , Meningioma/tratamento farmacológico , Meningioma/patologia , Progestinas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Acetato de Ciproterona/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Megestrol/análogos & derivados , Megestrol/uso terapêutico , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: A few observational studies have suggested that progesterone and dydrogesterone may have a lower risk of breast cancer than other progestogens. In our earlier xenograft animal experiments, progesterone did not stimulate breast tumors. The aim of this study was to test dydrogesterone for the first time. The study also evaluated the effects of PGRMC1 on proliferation with progestogens. METHODS (1): In-vitro study. The proliferative effects of dydrogesterone and of progesterone were assessed in vitro using T47D cells transfected with PGRMC1 or empty vector in the presence or absence of estradiol. Additionally, to find the strongest proliferator for inclusion as a comparator in the xenograft animal study, norethisterone, levonorgestrel, desogestrel, dienogest, drospirenone, nomegestrol, and cyproterone acetate were tested. METHODS (2): Xenograft main study. PGRMC1-transfected or empty-vector T47D and MCF7 xenotransplants were each treated with four different hormonal preparations: E2+placebo; E2+dydrogesterone; E2+progesterone; E2+norethisterone. A total of 112 castrated mice were randomly allocated to the 16 groups. This was thus a prospective, randomized, blinded, placebo-controlled four-arm study (45-50 days) with the two T47D and two MCF7 xenografts. Tumor volumes were monitored twice weekly. RESULTS (1): In-vitro study. The strongest proliferation was with norethisterone, but only with PGRMC1-transfected cells. There was significant proliferation with dydrogesterone, but not with progesterone in the absence of estradiol. However, no increase in proliferation was achieved by adding dydrogesterone to estradiol compared with the proliferation induced with estradiol alone, in contrast to norethisterone. RESULTS (2): Xenograft main study. There was significantly faster tumor growth with norethisterone + E2 than with E2+placebo in T47D and MCF7 PGRMC1 xenografts, but not with dydrogesterone + E2 or progesterone + E2. There was less tumor growth in empty-vector xenografts, without between-group differences. CONCLUSION: PGRMC1 increases the breast-cell proliferation effects of certain progestogens, including dydrogesterone, in contrast to progesterone, but not during estradiol-induced proliferation, either in vitro or in a xenograft animal model, in contrast to norethisterone. Thus the proliferative potency of dydrogesterone may be similar to that of progesterone. Clinical studies in women overexpressing PGRMC1 are recommended.
Assuntos
Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Progestinas/farmacologia , Receptores de Progesterona/metabolismo , Androstenos/farmacologia , Animais , Acetato de Ciproterona/farmacologia , Didrogesterona/farmacologia , Estradiol/farmacologia , Feminino , Xenoenxertos , Humanos , Técnicas In Vitro , Células MCF-7 , Megestrol/análogos & derivados , Megestrol/farmacologia , Camundongos , Camundongos Nus , Nandrolona/análogos & derivados , Nandrolona/farmacologia , Noretindrona/farmacologia , Progesterona/farmacologia , Estudos ProspectivosRESUMO
Endocrine disruptors in water are contaminants of emerging concern due to the potential risks they pose to the environment and to the aquatic ecosystems. In this study, a solar photocatalytic treatment process in a pilot-scale compound parabolic collector (CPC) was used to remove commercial estradiol formulations (17-ß estradiol and nomegestrol acetate) from water. Photolysis alone degraded up to 50% of estradiol and removed 11% of the total organic carbon (TOC). In contrast, solar photocatalysis degraded up to 57% of estrogens and the TOC removal was 31%, with 0.6 g/L of catalyst load (TiO2 Aeroxide P-25) and 213.6 ppm of TOC as initial concentration of the commercial estradiols formulation. The adsorption of estrogens over the catalyst was insignificant and was modeled by the Langmuir isotherm. The TOC removal via photocatalysis in the photoreactor was modeled considering the reactor fluid-dynamics, the radiation field, the estrogens mass balance, and a modified Langmuir-Hinshelwood rate law, that was expressed in terms of the rate of photon adsorption. The optimum removal of the estrogens and TOC was achieved at a catalyst concentration of 0.4 g/L in 29 mm diameter tubular CPC reactors which approached the optimum catalyst concentration and optical thickness determined from the modeling of the absorption of solar radiation in the CPC, by the six-flux absorption-scattering model (SFM).
Assuntos
Anticoncepcionais Orais/química , Estradiol/química , Megestrol/análogos & derivados , Processos Fotoquímicos , Energia Solar , Água/química , Catálise , Megestrol/químicaRESUMO
OBJECTIVE: Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers. METHODS: A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill. RESULTS: The haemostatic impact of E2 pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG. CONCLUSION: E2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed.
Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Anticoncepcionais Orais Combinados/farmacologia , Hemostasia/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Androstenos/farmacologia , Combinação de Medicamentos , Quimioterapia Combinada , Estradiol/análogos & derivados , Estradiol/farmacologia , Estrogênios/farmacologia , Etinilestradiol/farmacologia , Feminino , Humanos , Levanogestrel/farmacologia , Megestrol/análogos & derivados , Megestrol/farmacologia , Nandrolona/análogos & derivados , Nandrolona/farmacologia , Tromboembolia Venosa/induzido quimicamenteRESUMO
Nomegestrol acetate (NOMAC) is a 19-norprogesterone derivative with high biological activity at the progesterone receptor, a weak anti-androgenic effect, but with no binding to estrogen, glucocorticoid or mineralocorticoid receptors. At dosages of 1.5mg/day or more, NOMAC effectively suppresses gonadotropic activity and ovulation in women of reproductive age. Hemostasis, lipids and carbohydrate metabolism remain largely unchanged. In normal and cancerous human breast cells, NOMAC has shown favorable effects on estrogen metabolism. Like natural progesterone (but in contrast to some other synthetic progestogens), it does not appear stimulate the proliferation of cancerous breast cells. While there has been some experience of the use of NOMAC in combination with estrogens as a hormone replacement therapy, most of the data on the compound are reported in the context of its inclusion as a component of a new contraceptive pill comprising 2.5mg NOMAC combined with 1.5mg estradiol. Because of its strong endometrial efficacy, and due to its high antigonadotropic activity and long elimination half-life (about 50h), the contraceptive efficacy of the new pill is maintained even when dosages are missed. Furthermore, for the first time with a monophasic 24/4 regimen containing estradiol, cyclical stability can be achieved comparable with that obtained using pills containing ethinyl estradiol and progestogens like levonorgestrel or drospirenone. The addition of NOMAC to estradiol means that the beneficial effects of estrogen are not lost, which is of especial importance in relation to the cardiovascular system. On the basis both of its pharmacology and of studies performed during the development of the NOMAC/estradiol pill, involving some 4000 women in total, good long-term tolerability can be expected for NOMAC, although its safety profile is still to be fully ascertained, as the clinical endpoint studies are yet to be completed.
Assuntos
Anticoncepcionais Orais/farmacologia , Estrogênios/metabolismo , Megestrol/análogos & derivados , Ciclo Menstrual/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Congêneres da Progesterona/farmacologia , Progestinas/farmacologia , Antagonistas de Androgênios/farmacologia , Endométrio/efeitos dos fármacos , Feminino , Gonadotropinas/metabolismo , Humanos , Megestrol/farmacologia , Norprogesteronas/farmacologiaRESUMO
No evidence of an advantage over standard oestrogen-progestin combinations, but as many serious adverse effects as with ethinylestradiol + drospirenone.
Assuntos
Androstenos/uso terapêutico , Anticoncepcionais Orais Combinados/uso terapêutico , Estradiol/uso terapêutico , Etinilestradiol/uso terapêutico , Megestrol/análogos & derivados , Androstenos/administração & dosagem , Androstenos/efeitos adversos , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/efeitos adversos , Quimioterapia Combinada , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Humanos , Megestrol/administração & dosagem , Megestrol/efeitos adversos , Megestrol/uso terapêuticoRESUMO
OBJECTIVES: Premature ovarian failure (POF) is a consequence of gonadotoxic chemoradiotherapy given in antyneoplasia treatment. In young women it will correlate with menopausal symptoms which tend to appear due to depleted ovarian follicle reserve. DESIGN: It was a case series study that included women 18-50 years old who were treated for malignancy with gonadotoxic chemioradiotherapy. We have measured blood hormonal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone within one month of various hormone replacement therapy (HRT). RESULTS: We have observed different kind of hormonal reaction according to FSH, LH, estradiol and progesterone levels due to various hormonal replacement therapy. The administration of various HRT regimens presented with a decrease in the blood concentration of estradiol E2 and progesterone and a concomitant increase of FSH and LH. These findings demonstrate a shift to physiological ranges and a simultaneous improvement of symptoms associated with CI-POF. CONCLUSIONS: The most appropriate therapy needs to be selected according to the patient's alleviation of symptoms and correction of blood hormone levels.
Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Hematológicas/terapia , Terapia de Reposição Hormonal/métodos , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Adolescente , Adulto , Anticoncepcionais Femininos/administração & dosagem , Combinação de Medicamentos , Didrogesterona/administração & dosagem , Estradiol/administração & dosagem , Estradiol/sangue , Estriol/administração & dosagem , Feminino , Hormônio Foliculoestimulante Humano/sangue , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/tratamento farmacológico , Hormônio Luteinizante/sangue , Acetato de Medroxiprogesterona/administração & dosagem , Megestrol/administração & dosagem , Megestrol/análogos & derivados , Pessoa de Meia-Idade , Folículo Ovariano/efeitos dos fármacos , Insuficiência Ovariana Primária/sangue , Progesterona/sangue , Congêneres da Progesterona/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Activity of nomegestrol acetate (NOMAC), levonorgestrel (LNG), drospirenone (DRSP), dienogest (DNG) and progesterone on human steroid receptor transactivation was investigated. Ovulation inhibition by NOMAC, LNG and progesterone was tested. STUDY DESIGN: The progestogen receptor profile was determined in Chinese hamster ovary cells transfected with human progesterone B (PRB), androgen, estrogen (ER(α) and ER(ß)), glucocorticoid (GR) and mineralocorticoid (MR) receptors, respectively. Ovulation inhibition was tested in rats and monkeys. RESULTS: Agonistic potency rankings for PRB were LNG=NOMACâ«progesteroneâ«DRSP>DNG. No antagonistic activity at PRB was observed. Only LNG had androgenic activity. Antiandrogenic potency rankings were LNGâ«NOMAC>progesterone>DNG>DRSP. All agents were devoid of activity at ER(α), ER(ß) and GR. Only progesterone, DRSP and LNG had anti-MR activity. The NOMAC dose inhibiting ovulation at 50% ranged from 0.14 mg/kg (monkey) to 1.25 to 5.0 mg/kg (rat). CONCLUSION: Nomegestrol acetate is a selective progestogen and a potent inhibitor of ovulation in the rat and monkey.
Assuntos
Megestrol/análogos & derivados , Ovulação/efeitos dos fármacos , Congêneres da Progesterona/farmacologia , Receptores de Esteroides/agonistas , Animais , Células CHO , Cricetinae , Cricetulus , Feminino , Humanos , Macaca fascicularis , Megestrol/farmacologia , Ratos , Ratos Wistar , Receptores de Esteroides/antagonistas & inibidoresRESUMO
BACKGROUND: In postmenopausal women, an increase in insulin resistance is associated with an increased risk of diabetes, cardiovascular disease and breast cancer. Hormone replacement therapy (HRT) can reduce insulin resistance and coffee use is reported to decrease the incidence of diabetes. The aim of our study was to assess possible concurrent effects of HRT and espresso coffee intake on insulin resistance and on interdependent nutritional and clinical features. METHODS: A total of 478 healthy postmenopausal, non-diabetic women (aged 54.5 +/- 4.2 years) were studied: 360 had been on HRT for at least 2 years and 118 were not treated. Insulin resistance was assessed by a conventional homeostasis model (HOMA-IR). RESULTS: Insulin resistance is directly related to body mass index (p < 0.0001), and not with age and blood pressure; hypertensive menopausal women have a slightly higher body mass index but the same degree of insulin resistance as normotensive women. Women on HRT show lower insulin resistance, but not lower prevalence of arterial hypertension. Coffee use is associated with a decrease in insulin resistance in non-obese women receiving HRT, but not in other subsets. CONCLUSIONS: The combination of coffee consumption and HRT could lower insulin resistance in postmenopausal women. In overweight women, greater insulin sensitivity is associated with intake of espresso coffee and not with HRT; in normal weight women, only HRT is associated with lower insulin resistance.
Assuntos
Café , Terapia de Reposição de Estrogênios , Resistência à Insulina , Pós-Menopausa , Índice de Massa Corporal , Anticoncepcionais Orais Sintéticos/administração & dosagem , Estudos Transversais , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Feminino , Humanos , Hipertensão/epidemiologia , Megestrol/administração & dosagem , Megestrol/análogos & derivados , Pessoa de Meia-IdadeRESUMO
AIM: The purpose of this paper was to estimate the effectiveness of the use of acetate nomegestrol in relation to indicator hematochemical parameters and bone mineral density (BMD) regarding patients in physiological menopause treated with hormone replacement therapy (HRT), compared to patients in surgical menopause treated with HRT by only administering transdermally hemi hydrate estradiol (estrogen replacement therapy, ERT). METHODS: Sixty women in menopause for at least 6 months ago, aged between 40 and 55 years, were recruited. Thirty of them were given HRT with acetate nomegestrol, and 30 were given only ERT, because they were subjected to general hysterectomy with bilateral adnexectomy. The standards for inclusion were: level of FSH >or= to 30 UI beta-estradiol Assuntos
Densidade Óssea/efeitos dos fármacos
, Estradiol/uso terapêutico
, Megestrol/análogos & derivados
, Menopausa/efeitos dos fármacos
, Adulto
, Biomarcadores/sangue
, Terapia de Reposição de Estrogênios/métodos
, Estrogênios/sangue
, Feminino
, Hormônio Foliculoestimulante/sangue
, Seguimentos
, Humanos
, Megestrol/uso terapêutico
, Menopausa/sangue
, Pessoa de Meia-Idade
, Qualidade de Vida
, Resultado do Tratamento
RESUMO
OBJECTIVE: To evaluate total and site-specific bone mineral density (BMD) and serum leptin levels in postmenopausal women treated with a calcium supplement and in postmenopausal women receiving estrogen plus progestin therapy. DESIGN: Forty-four women were randomized to receive either calcium supplementation (group A, n = 22) or transdermal 17beta-estradiol at a dose of 50 mug/day in a continuous regimen and nomegestrol at a dose of 5 mg/day for 12 days per month in a sequential regimen (group B, n = 22). All women underwent dual-energy x-ray absorptiometry determination of BMD and blood sampling in the morning at the beginning of the study and after 12 months. Leptin was determined by radioimmunoassay in all samples. RESULTS: After 12 months, serum leptin levels were significantly higher in group A (control) in comparison with group B and baseline values, whereas both total and pelvic BMDs were significantly lower in group A in comparison with group B and baseline values. At baseline, a significant correlation was found between leptin levels, body mass index, and total-body BMD. After 12 months, leptin was still correlated to body mass index in both groups, but the association with BMD was lost. CONCLUSIONS: This study confirms previous evidence of a significant correlation between serum leptin and BMD in early postmenopausal women. Furthermore, this correlation is lost over time during the progression of the postmenopausal period, independently from the administration of estrogen-progestin therapy. Further studies and longer follow-up periods are needed to better understand theses issues.
Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Cálcio da Dieta/metabolismo , Estradiol/administração & dosagem , Leptina/sangue , Megestrol/análogos & derivados , Pós-Menopausa/metabolismo , Absorciometria de Fóton , Densidade Óssea , Relação Dose-Resposta a Droga , Terapia de Reposição de Estrogênios , Feminino , Seguimentos , Humanos , Megestrol/administração & dosagem , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To confirm the effect of postmenopausal hypoestrogenism and hormone therapy (HT) on body composition and serum leptin levels. DESIGN: Prospective, longitudinal study evaluating body composition (body mass index, and total and percent fat mass and lean mass measured at the arms, legs and trunk) with dual-energy x-ray absorptiometry and serum leptin levels by radioimmunoassay in 44 healthy postmenopausal women randomized to receive either no treatment (n = 22) or transdermal 17beta-estradiol (50 microg/day) in continuous regimen and nomegestrol (5 mg/day for 12 days/month) in a sequential regimen (n = 22). RESULTS: One year after the beginning of the study, in untreated women, total and trunk fat mass and percent fat were significantly increased, whereas trunk lean mass was significantly decreased. On the contrary, women treated with HT did not show any significant difference in body composition parameters. In untreated women, serum leptin levels were significantly increased at the end of the study in comparison with baseline values. Serum leptin levels at the other times evaluated were not significantly different from baseline values. In women treated with HT, serum leptin levels did not show significant changes throughout the study. CONCLUSIONS: Untreated postmenopausal women show an increase in total and percent fat mass and a centralization of fat distribution. Serum leptin levels parallel this increase, resulting in significantly higher levels 1 year after the study. Women treated with HT are protected against these changes. This may represent a protective mechanism against cardiovascular diseases.
Assuntos
Composição Corporal , Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Leptina/sangue , Megestrol/análogos & derivados , Megestrol/farmacologia , Pós-Menopausa/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Congêneres da Progesterona/farmacologia , Estudos Prospectivos , RadioimunoensaioRESUMO
OBJECTIVE: To study the adhesion molecule pattern in postmenopausal women who were not receiving hormone replacement therapy (HRT), HRT users, and fertile women. DESIGN: Case-control study. SETTING: Second University of Naples, Naples, Italy. PATIENT(S): Fifty healthy naturally postmenopausal women and 20 fertile women. INTERVENTION(S): Twenty-six women received no HRT and 24 received continuous transdermal 17 beta-estradiol, 0.05 mg/d, plus oral acetate nomegestrol, 5 mg/d. MAIN OUTCOME MEASURE(S): Levels of the soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin. RESULT(S): Women who did not received HRT showed a trend toward higher levels of soluble E-selectin and had significantly higher levels of soluble P-selectin than did fertile women. Levels of soluble E-selectin and soluble P-selectin were significantly lower in HRT users than in nonusers. Levels of VCAM-1 levels were significantly higher in HRT users than in fertile women, but no significant differences in CAM concentrations were found between the other groups. CONCLUSION(S): Menopause may lead to increased levels of soluble E- and soluble P-selectin, whereas long-term HRT is associated with lower selectin concentrations. This suggests that HRT may have a beneficial effect on endothelial function.
Assuntos
Selectina E/sangue , Terapia de Reposição Hormonal , Megestrol/análogos & derivados , Selectina-P/sangue , Pós-Menopausa/sangue , Administração Cutânea , Estudos de Casos e Controles , Selectina E/biossíntese , Estradiol/administração & dosagem , Feminino , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/sangue , Megestrol/administração & dosagem , Selectina-P/biossíntese , Molécula 1 de Adesão de Célula Vascular/biossíntese , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
The experience of 6 million Norplant users has led to several more advanced implants. Implanon is a single-rod implant system containing a low androgenic progestin and requires 1 to 2 minutes for insertion and removal. Like other implants, Implanon prevents pregnancy by changing the character of the cervical mucus and interfering with luteal function. Unlike Norplant, though, Implanon is designed to prevent ovulation for the full duration of use. Implant contraception has several advantages over other types of contraception including high efficacy, minimal required maintenance, absence of estrogen, and rapid return of fertility after discontinuation. Implants can be a good choice for adolescents; women with hypertension, diabetes, anemia, endometriosis, or other medical problems; and women who are breast-feeding. Irregular bleeding is the most common adverse effect of implants and can be treated with several medication regimens. Preinsertion counseling, however, is the most important factor in ensuring satisfaction with implants. Unfortunately, no implant system is currently available in the United States since August 2000, but Implanon is expected to reach the U.S. market within the next 2 years.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Desogestrel , Implantes de Medicamento/administração & dosagem , Megestrol/análogos & derivados , Congêneres da Progesterona/administração & dosagem , Muco do Colo Uterino/efeitos dos fármacos , Ensaios Clínicos como Assunto , Anticoncepcionais Femininos/economia , Anticoncepcionais Femininos/farmacologia , Aconselhamento , Endométrio/efeitos dos fármacos , Feminino , Humanos , Levanogestrel/administração & dosagem , Levanogestrel/farmacologia , Megestrol/administração & dosagem , Megestrol/farmacologia , Norprogesteronas/administração & dosagem , Norprogesteronas/farmacologia , Ovulação/efeitos dos fármacos , Satisfação do Paciente , Gravidez , Congêneres da Progesterona/economia , Congêneres da Progesterona/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Compostos de Vinila/administração & dosagem , Compostos de Vinila/farmacologiaRESUMO
OBJECTIVE: To research the nongenital audiological target for gonadal steroids in postmenopausal women who are treated with hormone replacement therapy. DESIGN: Fifty postmenopausal volunteers were treated with hormone replacement therapy. Women with an intact uterus had sequential weekly transdermal estradiol plus nomegestrole acetate 5 mg orally for 12 days per month or a continuous daily oral dose of conjugated estrogen 0.625 mg and medroxyprogesterone acetate 5 mg tablet. Eighteen surgically postmenopausal women received a weekly transdermal estradiol system. Twenty-five postmenopausal volunteers-5 with a natural menopause and 10 with a surgical menopause-and 20 premenopausal normally cycling women were used as a control group. Each woman performed auditory brainstem response by auditory-evoked potentials for waves I, III, and V and for interpeak I-III, I-V, and III-V intervals. RESULTS: Women who were treated with hormone replacement therapy showed wave latencies and interpeak latencies shorter than those for postmenopausal women in the control group (p < or = 0.05), overlapping those of the premenopausal women (p > 0.05). Women who were treated with estrogen replacement therapy showed shorter time latencies than those treated with combined hormone replacement therapy (p < or = 0.05). CONCLUSIONS: Our data suggest that fluctuating hormone levels cause changes in auditory brain-stem response waves, even if the exact mechanism of activity of the gonadal steroids is not clear. However, we believe that estrogen may influence the neuronal plasticity, the metabolic levels of neurotransmitters, and thus the neuronal conduction time into the audiological system.
Assuntos
Terapia de Reposição de Estrogênios , Potenciais Evocados Auditivos do Tronco Encefálico , Pós-Menopausa , Administração Cutânea , Adulto , Envelhecimento , Estradiol/administração & dosagem , Feminino , Humanos , Megestrol/administração & dosagem , Megestrol/análogos & derivados , Pessoa de Meia-Idade , Projetos Piloto , Congêneres da Progesterona/administração & dosagemRESUMO
A case of recurrent bleeding from a probable left thalamic cavernoma in a 26 year old woman taking hormonal treatment is reported. Four episodes of bleeding were clinically and radiologically documented, prior to her referral to our institution. Interestingly, each episode occurred three weeks after starting hormonal treatment, dydrogesterone, desogestrel ethinylestradiol, chlormadin, nomegestrel acetate). The patient was not operated because of the deep situation of the cavernoma which was remote from the thalamic surface within the third ventricle. There was no recurrent bleeding after the onset hormonal treatment was discontinued. Although no similar case has been found in the literature, we believe that this case gives further argumentation in favor of a role of hormonal factors influencing the biological behavior of cavernous angiomas which has been previously suggested in pregnant females with bleeding cavernous angiomas.
Assuntos
Neoplasias Encefálicas/complicações , Hemorragia Cerebral/etiologia , Anticoncepcionais Orais Combinados/efeitos adversos , Desogestrel/efeitos adversos , Didrogesterona/efeitos adversos , Etinilestradiol/efeitos adversos , Hemangioma Cavernoso/complicações , Megestrol/análogos & derivados , Distúrbios Menstruais/tratamento farmacológico , Congêneres da Progesterona/efeitos adversos , Tálamo , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Adulto , Neoplasias Encefálicas/diagnóstico , Artérias Cerebrais/efeitos dos fármacos , Hemorragia Cerebral/induzido quimicamente , Anticoncepcionais Orais Combinados/uso terapêutico , Desogestrel/uso terapêutico , Combinação de Medicamentos , Didrogesterona/uso terapêutico , Etinilestradiol/uso terapêutico , Feminino , Cefaleia/etiologia , Hemangioma Cavernoso/diagnóstico , Hematoma/etiologia , Hemiplegia/etiologia , Humanos , Imageamento por Ressonância Magnética , Megestrol/efeitos adversos , Megestrol/uso terapêutico , Distúrbios Menstruais/complicações , Metrorragia/complicações , Metrorragia/tratamento farmacológico , Parestesia/etiologia , Congêneres da Progesterona/uso terapêutico , Tálamo/irrigação sanguíneaRESUMO
OBJECTIVE: New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 beta-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects. METHODS: Postmenopausal women (n = 30) were randomly divided into three groups (ten women for each group); all women received continuous 17 beta-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream). A group of healthy fertile women (n = 8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once. RESULTS: Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma beta-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score. CONCLUSIONS: The present study indicates that sequential treatment with transdermal 17 beta-estradiol and progestin, no matter which progestin was used, restores the beta-END release, improves vasomotor and psychological symptoms.
Assuntos
Terapia de Reposição de Estrogênios/métodos , Sistemas Neurossecretores/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , beta-Endorfina/efeitos dos fármacos , Administração Cutânea , Administração Oral , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/uso terapêutico , Clonidina/farmacologia , Estudos de Coortes , Ciproterona/administração & dosagem , Ciproterona/uso terapêutico , Estradiol/administração & dosagem , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Megestrol/administração & dosagem , Megestrol/análogos & derivados , Megestrol/uso terapêutico , Pessoa de Meia-Idade , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Sistemas Neurossecretores/fisiologia , Pós-Menopausa/sangue , Progesterona/administração & dosagem , Progesterona/uso terapêutico , Congêneres da Progesterona/administração & dosagem , Congêneres da Progesterona/uso terapêutico , Simpatolíticos/farmacologia , Cremes, Espumas e Géis Vaginais , Sistema Vasomotor/efeitos dos fármacos , Sistema Vasomotor/fisiologia , beta-Endorfina/sangue , beta-Endorfina/metabolismoRESUMO
BACKGROUND: Recently, the extracellular domain of the c-erbB-2 oncogene product (HER-2/neu) has been reported to be elevated in the serum of one-fourth of patients with metastatic breast carcinoma. The role of serum c-erbB-2 as a tumor marker, however, is still poorly defined. The purpose of this study was to evaluate the utility of serial serum c-erbB-2 levels as a tumor marker in patients with metastatic breast carcinoma. METHODS: c-erbB-2 levels in the sera of patients with breast carcinoma were determined by an enzyme immunoassay that detects the extracellular domain of c-erbB-2. Serum c-erbB-2 levels were evaluated prior to treatment as well as throughout the course of treatment with second-line hormonal therapy employing either megestrol acetate or fadrozole, an experimental aromatase inhibitor. RESULTS: Fifty-eight of 300 patients (19.3%) had elevated pretreatment serum c-erbB-2 levels. Of these 58 patients with elevated pretreatment c-erbB-2, 48 had more than 1 visit which enabled us to quantitate serial c-erbB-2 levels throughout the course of treatment. Of these 48 patients, 28 (58.3%) had serial c-erbB-2 values that correlated with the clinical course. CONCLUSIONS: Serial serum c-erbB-2 levels did not show a high overall correlation with the clinical course in this group of patients with metastatic breast carcinoma treated with second-line hormonal therapy.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Carcinoma/sangue , Receptor ErbB-2/sangue , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Fadrozol/administração & dosagem , Fadrozol/uso terapêutico , Feminino , Humanos , Megestrol/administração & dosagem , Megestrol/análogos & derivados , Megestrol/uso terapêutico , Acetato de Megestrol , Placebos , Prognóstico , Indução de Remissão , Resultado do TratamentoRESUMO
PURPOSE: To compare the efficacy and tolerability of anastrozole (1 and 10 mg once daily), a selective, oral, nonsteroidal aromatase inhibitor, and megestrol acetate (40 mg four times daily), in postmenopausal women who progressed following tamoxifen treatment. PATIENTS AND METHODS: Two randomized, double-blind for anastrozole, open-label for megestrol acetate, parallel-group, multicenter trials were conducted in 764 patients. Because both trials were identical in design, an analysis of the combined results was performed to strengthen interpretation of results from each trial. RESULTS: The median follow-up duration was approximately 6 months. The estimated progression hazards ratios were 0.97 (97.5% confidence interval [CI], 0.75 to 1.24) for anastrozole 1 mg versus megestrol acetate and 0.92 (97.5% CI, 0.71 to 1.19) for anastrozole 10 mg versus megestrol acetate. The overall median time to progression was approximately 21 weeks. Approximately one third of patients in each group benefited from treatment. Twenty-seven patients (10.3%) in the anastrozole 1-mg group, 22 (8.9%) in the anastrozole 10-mg group, and 20 (7.9%) in the megestrol acetate group had a complete or partial response, and 66 (25.1%), 56 (22.6%), and 66 (26.1%) patients, respectively, had stable disease for > or = 24 weeks. For all end points, individual trial results were similar to the results of the combined analysis. Anastrozole and megestrol acetate were well tolerated. Gastrointestinal disturbance was more common among patients in the anastrozole groups than the megestrol acetate group; the difference between the anastrozole 10 mg and megestrol acetate groups was significant (P = .005). Significantly fewer patients in the anastrozole 1-mg (P < .0001) and 10-mg (P < .002) groups had weight gain than in the megestrol acetate group. More than 30% of megestrol acetate-treated patients had weight gain > or = 5%, and 10% of patients had weight gain > or = 10%. Patients who received megestrol acetate continued to gain weight over time. CONCLUSION: Anastrozole, 1 and 10 mg once daily, is well tolerated and as effective as megestrol acetate in the treatment of postmenopausal women with advanced breast cancer who progressed following tamoxifen treatment. Moreover, anastrozole therapy avoids the weight gain associated with megestrol acetate treatment.