RESUMO
BACKGROUND: Despite their high effectiveness, progestin-only contraceptives are considered less than ideal by the many women who experience disruption of their normal vaginal bleeding pattern when using these methods. Current treatments to control these bleeding irregularities are not sufficiently effective. OBJECTIVES: We evaluated preventive and therapeutic interventions of bleeding irregularities associated with the use of progestin-only contraceptives. SEARCH STRATEGY: Literature was identified through database searches, reference lists, organisations and individuals, covering the period until December 2006. SELECTION CRITERIA: Trials with random or alternate allocation, testing interventions for the prevention or treatment of bleeding irregularities associated with the use of progestin-only contraceptives were eligible. DATA COLLECTION AND ANALYSIS: Results are expressed as relative risks (RR) with 95 % confidence interval (CI) for categorical data and as weighted mean difference (WMD) with 95 % CI for continuous data. When we encountered heterogeneity (visual or statistical) we used the random-effects model (quantitative) or did not produce a summary estimate (qualitative). MAIN RESULTS: 19 Randomised controlled trials including 2290 participants were included. Over 60% of these trials had low to moderate risk of bias. Estrogen treatments reduced the number of days of an ongoing bleeding episode in DMPA users and had a positive therapeutic effect in Norplant users. However, treatment frequently led to discontinuation due to gastrointestinal upset. Combinations of oral ethinyl estradiol and levonorgestrel taken by Norplant users experiencing bleeding irregularities, improved bleeding patterns but method discontinuation rates remained the same. Norplant users administered the anti-progestin mifepristone therapeutically reported fewer days of bleeding than those given placebo. Prophylactic oral mifepristone used monthly by new Norplant users reduced bleeding, when compared to placebo.Ibuprofen was reported to decrease the length of bleeding episodes over a year, but the data were not presented in a suitable format for our analysis. Mefenamic acid reduced continued irregular bleeding during treatment in Norplant users, but not among DMPA users. Vitamin E and aspirin had no effect on bleeding patterns in a large trial of women using Norplant. Norplant users receiving tamoxifen had less unacceptable bleeding after treatment and were more likely to continue using Norplant than those receiving placebo. AUTHORS' CONCLUSIONS: Some women may benefit from the interventions described, particularly with cessation of an ongoing bleeding episode. Several regimens offer promise in regulating bleeding, but findings need to be reproduced in larger scale trials. Intermittent treatment with an agent may help some women to continue the use of a progestin-only contraceptive. The results of this review do not support routine clinical use of any of the regimens included in the trials, particularly for long-term effect.
Assuntos
Anticoncepcionais Femininos/uso terapêutico , Distúrbios Menstruais/tratamento farmacológico , Progestinas/uso terapêutico , Anticoncepcionais Orais Sintéticos/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Levanogestrel/uso terapêutico , Acetato de Medroxiprogesterona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Despite their high effectiveness, progestin-only contraceptives are considered less than ideal by the many women who experience irregular vaginal bleeding when using them. Current treatments to control these bleeding problems are not sufficiently effective. OBJECTIVES: We evaluated preventive and therapeutic approaches to normalise bleeding irregularities associated with the use of progestin-only contraceptives. SEARCH STRATEGY: Literature was identified through database searches, reference lists, organisations and individuals, covering the period until December 2006. SELECTION CRITERIA: Trials with random or alternate allocation, testing interventions for the prevention or treatment of bleeding irregularities associated with the use of progestin-only contraceptives were eligible. DATA COLLECTION AND ANALYSIS: Results are expressed as relative risks (RR) with 95% confidence interval (CI) for categorical data and as weighted mean difference (WMD) with 95% CI for continuous data. When we encountered heterogeneity (visual or statistical) we used the random-effects model (quantitative) or did not produce a summary estimate (qualitative). MAIN RESULTS: Twenty three randomised controlled trials enrolling 2674 participants were included. Seventy per cent were determined to reflect low to moderate risk of bias. Estrogen treatments reduced the number of days of an ongoing bleeding episode in DMPA and Norplant users. However, treatment frequently led to study discontinuation due to gastrointestinal upset. Combinations of oral ethinyl estradiol and levonorgestrel improved bleeding patterns in Norplant users, but method discontinuation rates were unchanged. One trial reported successful use of combined oral contraceptives in treating amenorrhea among DMPA users. Norplant users, but not Implanon users, administered the anti-progestin mifepristone reported fewer days of bleeding than those given placebo. Mifepristone used monthly by new Norplant acceptors reduced bleeding, when compared to placebo.A variety of NSAIDS have been evaluated for their ability to treat abnormal bleeding, with mixed results. Norplant users receiving tamoxifen had less unacceptable bleeding after treatment and were more likely to continue using Norplant than those receiving placebo. Tranexamic acid, mifepristone combined with an estrogen and doxycycline were more effective than placebo in terminating an episode of bleeding in women using progestin-only contraceptives, according to three small studies. AUTHORS' CONCLUSIONS: Some women may benefit from the interventions described, particularly with cessation of current bleeding. Several regimens offer promise in regulating bleeding, but findings need to be reproduced in larger trials. The results of this review do not support routine clinical use of any of the regimens included in the trials, particularly for long-term effect.
Assuntos
Anticoncepcionais Femininos/uso terapêutico , Distúrbios Menstruais/tratamento farmacológico , Progestinas/efeitos adversos , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Sintéticos/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Levanogestrel/efeitos adversos , Acetato de Medroxiprogesterona/uso terapêutico , Distúrbios Menstruais/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Intrauterine devices (IUD) are safe and effective methods of long term reversible contraception. The design, and copper content as well as placement of the copper on IUDs could affect their effectiveness and side-effect profile. OBJECTIVES: We compared different copper IUDs for their effectiveness and side effects. SEARCH STRATEGY: Multiple electronic databases were searched with appropriate key words and names of the IUDs known to be in the market. We searched the reference lists of papers identified and contacted trialists when possible. There was no language restriction. SELECTION CRITERIA: Randomised controlled trials comparing different IUDs were considered. Trials needed to report on clinical outcomes. DATA COLLECTION AND ANALYSIS: Data on outcomes and trial characteristics were extracted in duplicate and independently by two reviewers. Meta-analysis results are expressed as rate difference (RD) using a fixed-effects model with 95% confidence interval (CI). In the presence of significant heterogeneity a random-effects model was applied. MAIN RESULTS: We included 35 trials, resulting in 18 comparisons of 10 different IUDs in approximately 48,000 women. TCu380A was more effective in preventing pregnancy than MLCu375 (RD 1.70%, 95% CI 0.07% to 2.95% after 4 years of use). TCu380A was also more effective than MLCu250, TCu220 and TCu200. There tended to be fewer pregnancies with TCu380S compared to TCu380A after the first year of use, a difference which was statistically significant in the fourth year (RD -1.62%, 95% CI -3.00% to -0.24%). This occurred despite more expulsions with TCu380S (RD 3.50%, 95% CI 0.36% to 6.63% at 4 years). MLCu375 was no more effective than TCu220 at 1 year of use, or MLCu250 and NovaT up to 3 years. Compared to TCu380A or TCu380S, none of the IUDs showed any benefits in terms of bleeding or pain, or any of the other reasons for early discontinuation. None of the trials that reported events at insertion found one IUD easier to insert than another or caused less pain at insertion. There is no evidence that uterine perforation rates vary by type of device. There are minimal randomised data on IUD use in nulliparous women. AUTHORS' CONCLUSIONS: TCu380A or TCu380S appear to be more effective than other IUDs. No IUD showed consistently lower removal rates for bleeding and pain in comparison to other IUDs. There is no evidence that any particular framed copper device is better suited to women who have not had children.
Assuntos
Anticoncepção/instrumentação , Dispositivos Intrauterinos de Cobre , Feminino , Humanos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Intrauterine devices (IUD) are safe and effective methods of long term reversible contraception. Design and copper content of IUDs could affect their effectiveness and side-effect profile. OBJECTIVES: We compared different copper IUDs for their effectiveness and side effects. SEARCH STRATEGY: Multiple electronic databases were searched with appropriate key words and names of the IUDs known to be in the market. We searched the reference lists of papers identified and contacted trialists when possible. SELECTION CRITERIA: Randomised controlled trials comparing different IUDs were considered. Trials needed to report on clinical outcomes. DATA COLLECTION AND ANALYSIS: Data on outcomes and trial characteristics were extracted in duplicate and independently by two reviewers. Meta-analysis results are expressed as rate difference (RD) using a fixed-effects model with 95% confidence interval (CI). In the presence of significant heterogeneity a random-effects model was applied. MAIN RESULTS: We included 34 trials, resulting in 16 comparisons of different IUDs. TCu380A was more effective than MLCu375, MLCu250, TCu220 and TCu200. Changing the position of the copper on the arm of the IUD for TCu380S did not improve the efficacy of TCu380A. MLCu375 was no more effective than TCu220, at 1 year, MLCu250 to 3 years or NovaT to 3 years Compared to TCu380A, none of the IUDs showed any benefits in terms of bleeding or pain, or any of the other reasons for early discontinuation. AUTHORS' CONCLUSIONS: TCu380A is more effective compared to other IUDs. There is no data available comparing different IUDs in special subgroups, such as nulliparous women.
Assuntos
Anticoncepção/instrumentação , Dispositivos Intrauterinos de Cobre , Feminino , Humanos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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.
Assuntos
Anticoncepção/métodos , Anticoncepcionais Femininos/administração & dosagem , Algestona/administração & dosagem , Combinação de Medicamentos , Estradiol/administração & dosagem , Feminino , Humanos , Injeções , Medroxiprogesterona/administração & dosagem , Acetato de Megestrol/administração & dosagem , Noretindrona/administração & dosagemRESUMO
This manuscript describes euthyroid hyperthyroxinemia secondary to elevated serum T4-binding prealbumin (TBPA) concentrations in a patient with islet cell carcinoma and reports serum TBPA measurements in other patients with islet cell carcinoma. A 73-yr-old man with a 17-yr history of metastatic islet cell carcinoma was found to have hyperthyroxinemia. His total serum T4 concentration was 18.5 micrograms/dl (normal, 5.5-11.5). Eight years previously, his serum T4 concentration was normal. His free T4 concentration, as determined by equilibrium dialysis, was 1.3 ng/dl (normal, 0.9-2.1). Serum T3, TSH, and T4-binding globulin (TBG) concentrations were normal, as was the TSH response to TRH administration. Polyacrylamide gel electrophoresis of the patient's serum in the presence of tracer amounts of [125I]T4 revealed that, compared to normal sera, [125I]T4 binding to TBPA was increased from 30.0 +/- 6.0% (mean +/- SD) to 52.0%. The distribution of [125I]T3 amont albumin, TBG, and TBPA was normal in this electrophoretic procedure. The concentration of TBPA in the patient's serum was 189 mg/dl. In contrast, the mean serum TBPA concentration in normal men was 40 +/- 4 (mean +/- SD) mg/dl, and that in normal women was 18 +/- 4 mg/dl. Sera from the patient's daughter, his brother, 2 sisters, and 2 male paternal cousins contained normal amounts of TBPA, ranging from 34-47 mg/dl in his male relatives and from 26-30 mg/dl in his female relatives. Serum free T4 index determinations in his relatives also were normal. Serum TBPA concentrations were determined in 14 additional patients with islet cell carcinoma. In 1 of these patients, a man with an insulinoma, serum TBPA was elevated (66 mg/dl). This patient's serum T4 level was 7.3 micrograms/dl, and his free T4 index was 7.0. These data and another study suggest that islet cell carcinoma may rarely produce a TBPA-like protein resulting in an elevated serum TBPA concentration. Markedly elevated serum TBPA is associated with euthyroid hyperthyroxinemia.
Assuntos
Adenoma de Células das Ilhotas Pancreáticas/sangue , Neoplasias Pancreáticas/sangue , Pré-Albumina/metabolismo , Proteínas de Ligação a Tiroxina/metabolismo , Tiroxina/sangue , Adenoma de Células das Ilhotas Pancreáticas/genética , Idoso , Feminino , Humanos , Masculino , Neoplasias Pancreáticas/genética , Ligação Proteica , Valores de Referência , Albumina Sérica/metabolismo , Tri-Iodotironina/sangueRESUMO
A fifty-year-old male patient with bilateral cryptorchidism and abdominal mass due to a large seminoma was found to have persistent müllerian duct derivatives: uterus and fallopian tubes. The patient underwent total hysterosalpingectomy and bilateral intra-abdominal orchidectomy of a seminoma and testes. He was given maintenance testosterone and pelvic irradiation.
Assuntos
Transtornos do Desenvolvimento Sexual/complicações , Disgerminoma/complicações , Genitália Feminina/anormalidades , Neoplasias Testiculares/complicações , Abdome/patologia , Transtornos do Desenvolvimento Sexual/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Paramesonéfricos/patologia , Ductos Mesonéfricos/patologiaRESUMO
OBJECTIVE: To assess whether women who were administered the first injection of DMPA+E(2)C on day 7 of their menstrual cycle (delayed injection) exhibit the same degree of ovarian suppression as women who receive it on day 5 of their menstrual cycle. DESIGN: Multicenter, randomized controlled trial. SETTING: Reproductive health clinics. PATIENT(S): Women aged between 18 and 38 years (inclusive) willing to use DMPA+E(2)C as their method of contraception. INTERVENTION(S): Participants received a DMPA+E(2)C injection on day 5 (control group, n = 41) or day 7 (delayed-injection group, n = 117) of their menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian activity and follicular development determined by serial serum progesterone levels and vaginal ultrasound. RESULT(S): Participants who received DMPA+E(2)C on day 5 of their menstrual cycle (control group) exhibited no more than limited follicular growth (no follicle >16 mm). Of those women who received DMPA+E(2)C on day 7 of their menstrual cycle (delayed-injection group), 21 (18%) showed some follicular growth, of whom 4 (3%) ovulated. CONCLUSION(S): The first injection of DMPA+E(2)C given on day 7 of a menstrual cycle does not provide the same inhibition of ovarian activity as that observed when it is administered on day 5 of the menstrual cycle.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Estradiol/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Ovário/fisiologia , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Preparações de Ação Retardada , Estradiol/análogos & derivados , Feminino , Humanos , Ciclo Menstrual , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Ovário/diagnóstico por imagem , Ovário/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Progesterona/sangue , UltrassonografiaRESUMO
Focus group research was conducted in four countries to understand how couples who use calendar methods determine when they are at risk of pregnancy, what behavior they adopt during the fertile phase, and whether or not they are satisfied with their method. Calendar and periodic abstinence method users do not all know how to make correct calendar calculations of the fertile period, report being sexually active during the fertile period, and desire a more comprehensive approach to sexual behavior during the fertile period. Men's roles in the methods should be enhanced, and credible resources in the community should be enlisted to improve education, information, and communication.
Assuntos
Serviços de Planejamento Familiar/educação , Métodos Naturais de Planejamento Familiar , Abstinência Sexual , Adolescente , Adulto , Anticoncepção , Feminino , Grupos Focais , Educação em Saúde , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Peru/epidemiologia , Filipinas/epidemiologia , Sri Lanka/epidemiologiaRESUMO
An annotated bibliography of 123 references and review papers on graphical description and statistical analysis of vaginal bleeding patterns is presented.
Assuntos
Bibliografias como Assunto , Menstruação , Estatística como Assunto , Anticoncepção/métodos , Feminino , Humanos , Projetos de PesquisaRESUMO
Contraceptive methods often induce disturbances in vaginal bleeding patterns which are the main reason for women to discontinue method use. Knowledge of these changes is essential for effective counselling and product development and necessitates adequate methods of collection and analysis of vaginal bleeding data. These issues were reviewed by clinicians, medical statisticians and computer analysts during several consultations organized by the World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction and their discussions are summarized in this paper. Recommendations are made on the use of menstrual diary cards for data collection. It is suggested that the analysis of menstrual patterns be based on the reference period method developed by Rodriguez et al. in 1976 to which several modifications in terminology and choice of summary statistics are proposed. While these are presented as the minimum required for the comparability of studies, other points of analysis are identified which need further study, in an attempt to stimulate research in this field by other investigators.
Assuntos
Anticoncepcionais Femininos/efeitos adversos , Coleta de Dados , Hemorragia Uterina/induzido quimicamente , Ensaios Clínicos como Assunto , Coleta de Dados/métodos , Coleta de Dados/normas , Feminino , Humanos , Ciclo Menstrual , Estatística como AssuntoRESUMO
Menstrual diary records were obtained from women using either a natural method of contraception, a combined or progestogen-only oral contraceptive, a vaginal ring, or a long-acting injectable (DMPA). Within each method group, multiple regression analysis was used to examine the relationships between the subjects' bleeding patterns and their age, age at menarche, ponderal index, obstetric and contraceptive history and ethnic origin. The influence of ethnic origin was described in the preceding paper. Among combined pill users, increasing age was associated with more frequent spotting episodes. In both the untreated and combined pill groups, women with a higher ponderal index had less variable bleeding-free intervals; in the vaginal ring and DMPA groups, the more obese women had shorter bleeding/spotting episodes and longer bleeding-free intervals. Among combined oral contraceptive users, the most influential variable was the time since the end of the woman's last pregnancy: subjects who had been more recently pregnant had longer, less predictable episodes and shorter intervals. Previous oral contraceptive use was associated with more predictable bleeding patterns among women currently using either type of oral pill. In the vaginal ring and DMPA groups, subjects whose last pregnancy had ended in abortion had more bleeding/spotting days and episodes than those who had had a live birth. As reported previously, bleeding patterns were more closely related to the woman's geographical region of residence than to any other factor. The associations found with other individual characteristics were often inconsistent or difficult to interpret. A number of variables which could potentially influence menstrual bleeding patterns, such as nutritional status, were not measured and therefore could not be included in the analysis. However, contraceptive method and ethnic origin may be predominant influences, overriding any other factor.
Assuntos
Anticoncepção/métodos , Menstruação , Aborto Induzido , Administração Intravaginal , Adulto , Fatores Etários , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Hormonais/farmacologia , Feminino , Humanos , Levanogestrel , Medroxiprogesterona/análogos & derivados , Medroxiprogesterona/farmacologia , Acetato de Medroxiprogesterona , Menstruação/efeitos dos fármacos , Norgestrel/farmacologia , Paridade , Gravidez , Fatores de TempoRESUMO
In clinical trials comparing alternative contraceptive methods, women often discontinue for disturbances in menstrual bleeding patterns. Vaginal bleeding diaries have been used to monitor these patterns, and this paper suggests two new methods of analysis of these data. One analysis measures trends over time in the occurrence of specific patterns and, a second analysis, the relation between a woman's current experience and the probability of continuing method use. Contrasts between these approaches and the reference period method of analysis are made. A randomised clinical trial of the relative efficacy of 100 and 150 mg doses of depot-medroxyprogesterone acetate (DMPA) is used for illustration.
PIP: Researchers recruited 1216 females to study changes in amenorrhea patterns with successive injections of the long acting injectable contraceptive depot-medroxyprogesterone acetate (DMPA). The women received an injection of either 100 mg or 150 mg DMPA on the day of randomization and 3 additional injections at 90 day intervals. 1151 (94.7%) women completed a menstrual diary that could be used, but only diaries of at least 60 days were considered in each reference period (90 days). Of the 99 who received only 1 100mg injection, 23 had amenorrhea. Of the 361 receiving 4 injections, 142 experienced no amenorrhea in any of the injection intervals and 30 had amenorrhea in all 4 intervals. Overall 281 women out of 576 who received 1-4 injections of 100 mg DMPA did not experience amenorrhea at all. For those in the 150 mg sample receiving 1-4 injections, 237 out of 575 women did not have amenorrhea. Analysis of change over time suggested an increase incidence of amenorrhea following the 2nd injection. In terms of the probability of a woman accepting a injection, women who experienced amenorrhea with the 1st injection were less likely to accept a 2nd, especially in the 150 mg DMPA group. Additionally, the trend in amenorrhea pattern demonstrated that a 3rd injection was adversely affected by amenorrhea in the 2nd injection interval in the 150 mg group but not the 100 mg group. Nevertheless, the decision to have a 4th injection appeared adversely affected by amenorrhea in the 3rd injection interval in both groups. The conditional probabilities used in this research can also be applied to examine continuation or survival rates in a follow-up study based on any prognostic factors.
Assuntos
Amenorreia/induzido quimicamente , Medroxiprogesterona/análogos & derivados , Ensaios Clínicos como Assunto , Feminino , Humanos , Prontuários Médicos , Medroxiprogesterona/administração & dosagem , Medroxiprogesterona/efeitos adversos , Acetato de Medroxiprogesterona , Cooperação do Paciente , Distribuição Aleatória , Estatística como AssuntoRESUMO
A total of 100 women who were using depot medroxyprogesterone acetate (DMPA) for contraception and who had experienced at least 6 months of drug induced amenorrhea, were randomized to either switching their method of contraception to Cyclofem, or continuing with DMPA. At the end of 6 months, 82% of the Cyclofem users had experienced some vaginal bleeding, compared with 10% of DMPA users. Time to resumption of vaginal bleeding was related to the duration of DMPA use to the duration of DMPA induced amenorrhea, and to the body mass index of the user. Over the 6 months of follow-up, 94% of Cyclofem users complained of some side effects, compared with 22% of DMPA users. The most frequently cited problems among Cyclofem users included breast tenderness, abdominal pain, and dysmenorrhea; yet a third of these women opted to stay on Cyclofem at the end of the study. It is concluded that switching to Cyclofem is a new option for DMPA users who are concerned about amenorrhea. Although using Cyclofem in this setting will not meet the needs of all such women, its effectiveness in inducing vaginal bleeding justifies a trial in those who have no contraindication to estrogen treatment.
PIP: Substantial numbers of women experience amenorrhea while using the injectable contraceptive depot medroxyprogesterone acetate (DMPA) and this represents a major cause of method discontinuation. In the present study, 100 DMPA acceptors from Bangkok, Thailand, with a history of at least 6 months of drug-induced amenorrhea were randomly assigned to switch their contraceptive method to Cyclofem (a combination of 25 mg of DMPA and 5 mg of estradiol cypionate) or continue with DMPA (150 mg). After 6 months, 82% of Cyclofem users compared with only 10% of DMPA users had experienced some vaginal bleeding. The median time to resumption of vaginal bleeding was 8 weeks in the Cyclofem group. Resumption time was related to the duration of DMPA use, the duration of DMPA-induced amenorrhea, and the user's body mass index. Although 94% of Cyclofem users compared with only 22% of DMPA users experienced minor side effects (breast tenderness, abdominal pain, dysmenorrhea) during the 6-month study period, 34% of these women elected to remain on Cyclofem at the end of the study. On the other hand, 90% of DMPA users opted to continue method use despite amenorrhea. The proven efficacy of Cyclofem justifies a trial in DMPA users concerned about their amenorrhea. This regimen can be expected to induce vaginal bleeding in more than 80% of users after 1-3 months of treatment.
Assuntos
Amenorreia/tratamento farmacológico , Anticoncepcionais Femininos/uso terapêutico , Estradiol/análogos & derivados , Acetato de Medroxiprogesterona/efeitos adversos , Acetato de Medroxiprogesterona/uso terapêutico , Congêneres da Progesterona/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Adulto , Amenorreia/induzido quimicamente , Estudos de Coortes , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Combinados/uso terapêutico , Preparações de Ação Retardada , Combinação de Medicamentos , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estradiol/uso terapêutico , Feminino , Seguimentos , Humanos , Incidência , Acetato de Medroxiprogesterona/administração & dosagem , Pacientes Desistentes do Tratamento , Congêneres da Progesterona/administração & dosagem , Fatores de Tempo , Hemorragia Uterina/epidemiologiaRESUMO
Arachidonic acid metabolites produced by primary cultures of human endometrial cells derived from biopsies obtained before and after exposure to 20 micrograms/day levonorgestrel for 84 +/- 1 days were analysed by reverse phase HPLC. This revealed a significant increase in PGF1 alpha and an epoxide metabolite upon levonorgestrel stimulation. The proportion of epoxide metabolite, PGF1 alpha and PGE2 were positively correlated with serum levonorgestrel levels while HETES, PGE2 and epoxide were similarly correlated with serum oestradiol. The extent of intermenstrual bleeding during exposure to levonorgestrel was correlated with the proportion of epoxide and HETES products in vitro which is discussed in relation to their physiological function.
PIP: Reverse phase high-performance liquid chromatography was used to analyze arachidonic acid metabolites produced by human endometrial cell cultures before and after long-term exposure to 20 mg/day of levonorgestrel released from a released from a vaginal ring. Biopsy specimens were obtained on day 24 of a control menstrual cycle and again 84 days after insertion of the vaginal ring. Significant changes resulting from levonorgestrel exposure were recorded in only 2 of the 14 products of synthesis resolved--6-keto-prostaglandin F 1-alpha at 24 hours and epoxide at 48 hours. There were dose-dependent decreases in all cyclo-oxygenase products and an increase in epoxygenase enzyme levels. Hydroxyeicosatetraenoic acid (HETES) production, on the other hand, was strongly associated with estradiol and thus appears to be under estrogenic control. Intermenstrual bleeding during the study period was correlated with the proportion of epoxide and HETES products in vitro. Investigation of the role of the epoxygenase metabolite identified in this study in the regulation of uterine vasculature is urged.
Assuntos
Anticoncepcionais/farmacologia , Endométrio/metabolismo , Norgestrel/farmacologia , Prostaglandinas/biossíntese , 6-Cetoprostaglandina F1 alfa/biossíntese , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Biópsia , Cromatografia Líquida de Alta Pressão , Dispositivos Anticoncepcionais Femininos , Dinoprostona/biossíntese , Endométrio/efeitos dos fármacos , Feminino , Humanos , Ácidos Hidroxieicosatetraenoicos/biossíntese , Técnicas In Vitro , Leucotrieno B4/biossíntese , Levanogestrel , Tromboxano B2/biossínteseRESUMO
The objectives of this study were to assess whether women who were administered the first injection of the once-a-month contraceptive containing estradiol cypionate and 25 mg depot-medroxyprogesterone acetate (MPA+E(2)C) on Day 7 of their menstrual cycle (delayed injection) exhibit the same degree of cervical mucus changes as women who receive it on Day 5 of their menstrual cycle. This was a multicenter, randomized, controlled clinical trial. A total of 158 women, aged between 18 and 38 years (inclusive), who, were willing to use MPA+E(2)C as their contraceptive method participated in the trial. Participants received a MPA+E(2)C injection on Day 5 (control group, n = 41) or Day 7 (delayed-injection group, n = 117) of their menstrual cycle. Participants who received MPA+E(2)C on Day 5 of their menstrual cycle (control group) exhibited fair or poor mucus quality and poor sperm penetration. Of those women who received MPA+E(2)C on Day 7 of their menstrual cycle (delayed-injection group), 3 (3%) showed good mucus or good sperm penetration at some time point during follow-up. It is possible to conclude that the first injection of MPA+E(2)C given on Day 7 of a menstrual cycle does not provide the same degree of inhibition of mucus quality and sperm penetration as that observed if it is administered on Day 5. However, the theoretical risk of pregnancy after receiving MPA+E(2)C on Day 7 would be expected to be low.
Assuntos
Muco do Colo Uterino/efeitos dos fármacos , Anticoncepcionais Femininos/farmacologia , Anticoncepcionais Orais Combinados/farmacologia , Estradiol/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Adulto , Muco do Colo Uterino/fisiologia , Preparações de Ação Retardada/farmacologia , Esquema de Medicação , Combinação de Medicamentos , Estradiol/análogos & derivados , Estradiol/sangue , Feminino , Humanos , Injeções Intramusculares , Ovário/efeitos dos fármacos , Ovário/fisiologia , Interações Espermatozoide-Óvulo/efeitos dos fármacos , Fatores de TempoRESUMO
The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.
Assuntos
Anticoncepcionais Femininos/farmacologia , Dispositivos Anticoncepcionais Femininos , Endométrio/efeitos dos fármacos , Norgestrel/farmacologia , Endométrio/citologia , Estradiol/sangue , Feminino , Humanos , Levanogestrel , Menstruação/efeitos dos fármacos , Norgestrel/farmacocinética , Progesterona/sangue , Globulina de Ligação a Hormônio Sexual/metabolismoRESUMO
Little is known about the effects of contraceptive vaginal rings on the vaginal surface epithelium, although most studies have not demonstrated any significant deleterious effect. However, one study found that some medium-to-long-term levonorgestrel-releasing ring users developed chronic erythematous and ulcerative lesions in the posterior vaginal fornix. Subsequently, this ring was completely redesigned (IVR-2) with different dimensions and much greater flexibility. The first version of IVR-2 was designed as a placebo ring to explore effects on the vagina and cervix without addition of a progestogen. One-hundred-sixty-six healthy sexually active women volunteers were recruited in four centers and randomly assigned for 6 months to either placebo ring use or control (non-use) using a predetermined randomization code generated by WHO in a 2:1 ratio. Careful inspections of the vaginal and cervical epithelium were performed with a colposcope at admission and at 2-month intervals. No clinically significant lesions were detected in any center either among ring users or controls. However, a number of minor changes in appearance of the vaginal and cervical epithelium (erythema, petechiae, ecchymosis, and minor aceto-white changes) were described from the Sydney Center, some of which were present on admission and some of which were found on subsequent examination. Ten of eleven "red" changes on the cervix and vagina were noted in IVR-2 users, and only one in the controls, suggesting a contribution by the IVR-2 to minor epithelial surface changes. Five of ten resolved completely with continued ring use. There was no correlation in this study between epithelial changes and cigarette smoking or frequency of intercourse in the 14 days prior to colposcopic examination but a significant relationship between tampon use in the last 7 days and all epithelial changes (p = 0.05) and especially red changes (p = 0. 027) was noted. Red changes were significantly less likely to be found among condom users (p = 0.007). The IVR-2 placebo ring did not produce clinically significant changes in the vaginal epithelium and cervical mucosa and a carefully controlled and randomized study should be considered to compare the epithelial appearances in women using a placebo IVR-2 and one releasing 20 microg levonorgestrel.
Assuntos
Colo do Útero/patologia , Dispositivos Anticoncepcionais Femininos/efeitos adversos , Pessários/efeitos adversos , Biópsia , Muco do Colo Uterino/química , Epitélio/patologia , Feminino , Humanos , Mucosa/patologia , Vagina/patologiaRESUMO
Normal postpartum women, who had a spontaneous vaginal delivery of one full-term male infant, free of congenital abnormalities and other diseases, were recruited for this study. Thirteen women received 150 mg depot-medroxy-progesterone acetate (DMPA), intramuscularly on days 42 + 1 and 126 + 1 postpartum. Infants of nine mothers, who did not receive DMPA, served as controls. Blood samples were collected from treated mothers on days 44, 47, 74, 124, 128, and 130 postpartum for medroxyprogesterone acetate (MPA) measurements. Four-hour urine collections were obtained from all 22 infants in the morning on days 38, 40, 42, 44, 46, 53, 60, 67, 74, 88, 102, 116, 122, 124, 126, 128, 130, and 137. Urinary follicle stimulating hormone (FSH), luteinizing hormone (LH), unconjugated testosterone, and unconjugated cortisol were measured by radioimmunoassay, and serum MPA and urinary MPA metabolites were measured by gas chromatography-mass spectrometry (GC-MS). No MPA metabolites could be detected in the urine of the infants from the DMPA-receiving mothers. Hormonal profiles in the urine samples were not suppressed in comparison with those of the control infants. The present study demonstrates that DMPA, administered to the mother, does not influence the hormonal regulation of the breast-fed normal male infant.