RESUMO
Healthy, regularly menstruating women, aged 14-38 years, were enrolled in a comparative, double-blind, phase III, clinical trial to evaluate the contraceptive efficacy and acceptability of a combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate compared to the commercially available contraceptive combination of 150 mg dihydroxyprogesterone acetophenide with 10 mg estradiol enanthate. Subjects received the contraceptive combination intramuscularly, between the 7th and 10th day of each menstrual cycle, during 12 consecutive menstrual cycles. Approximately 60% of the subjects in both groups completed the study. Principal reasons for discontinuation were personal, nonmedical reasons. Principal medical reasons for discontinuation were menstrual-related, irregular bleeding being the most frequent. Differences in menstrual patterns between the two groups did not lead to differences in discontinuation rates. Three contraceptive failures occurred during the trial, one in Group A (90/6 mg) and two in Group B (150/10 mg), indicating that the lower dose formulation is at least as efficient as the higher dose.
Assuntos
Acetofenida de Algestona/efeitos adversos , Anticoncepcionais/efeitos adversos , Estradiol/análogos & derivados , Menstruação/efeitos dos fármacos , Congêneres da Progesterona/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Adolescente , Adulto , Acetofenida de Algestona/administração & dosagem , Peso Corporal , Brasil , Estudos de Coortes , Anticoncepcionais/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Feminino , Humanos , Incidência , Menstruação/fisiologia , Aceitação pelo Paciente de Cuidados de Saúde , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Congêneres da Progesterona/administração & dosagem , Hemorragia Uterina/epidemiologiaRESUMO
The addition of a short- or medium-acting estrogen ester to the long-acting progestins depot-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) to produce "combined" injectable formulations has proved a successful strategy in the development of once-a-month injectable contraceptives. Recent clinical pharmacokinetic studies undertaken on once-a-month injectable contraceptives in various WHO Collaborating Centers have guided the selection of the estrogen-progestogen combinations, ratios and dose schedules. At least three combined once-a-month injectable preparations exhibit acceptable pharmacokinetic and pharmacodynamic profiles; however, further improvement in the design of optimal estrogen/progestin injectables are expected during this decade.
PIP: The World Health Organization [WHO] Special Programme of Research, Development and Research Training in Human Reproduction has coordinated the developmental strategy of combined once-a-month injectable contraceptives. The strategy consists of the selection, based on pharmacokinetic data, of appropriate long-acting progestin-estrogen combinations to develop at least 2 sustained-release formulations; assessment of safety and effectiveness of these formulations in clinical research facilities; and their evaluation at field level through service facilities of national family planning programs. WHO Collaborating Centers were involved in selecting the estrogen-progestogen combinations, ratios, and dose schedules. Research has found at least 3 combined once-a-month injectable contraceptives that demonstrate acceptable pharmacokinetic and pharmacodynamic profiles. 2 safe and effective once-a-month contraceptive formulations (Cyclofem and Mesigyna) can join the existing choice of contraceptive methods. WHO expects more improvement in the design of optimal estrogen/progestin injectables in the 1990s.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/farmacocinética , Adolescente , Adulto , Preparações de Ação Retardada , Estrogênios/administração & dosagem , Estrogênios/farmacocinética , Feminino , Humanos , Injeções Intramusculares , Progestinas/administração & dosagem , Progestinas/farmacocinéticaRESUMO
Following the development and widespread use of oral hormonal contraceptives, it became evident that alternative long-acting delivery systems would be required to improve contraceptive practice in some cultural settings where injectable or subdermal routes of administration are preferred. Nowadays, long-acting contraceptives constitute an important option in family planning services in many parts of the world. Indeed, two long-acting injectable contraceptives containing just a synthetic progestogen (depot-medroxyprogesterone acetate (DMPA) and norethisterone enantate (NET-EN)) have been in clinical practice for more than 20 years. The World Health Organization's (WHO) Special Programme of Research in Human Reproduction, in collaboration with the U.S. National Institute of Child Health and Human Development (NICHD) and universities primarily in developing countries undertook a synthesis programme aimed at producing an improved injectable preparation by developing new derivatives of known steroids. One such compound (levonorgestrel 17-butanoate) is now at the stage of Phase II clinical testing. In addition, the Special Programme has developed and improved once-a-month injectable formulations and assessed their safety and efficacy in different countries worldwide. After large scale clinical testing, at least two progestogen-estrogen combinations have reached the point of introductory trials.
PIP: A survey of recent trials of new injectable hormonal contraceptives, progestogen-only, levonorgestrel esters, and once monthly injectables, follows a brief review of all the experimental long-acting contraceptive modalities, injectables, implants, vaginal rings, and hormone-releasing IUDs. Currently medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) are being used by 7 million women. WHO is conducting dose reduction trials and studies of bioavailability in various national populations. Even though a dose of 100 mg DMPA every 3 months has been satisfactory for contraception, 150 mg is still recommended until further pharmacodynamic data are available. Some populations, notably Thais and Mexican women, have higher peaks and more rapid elimination rates of DMPA, while Chinese women show slower elimination and higher blood levels of NET-EN. Extensive studies of new synthetic esters of levonorgestrel have proceeded to Phase II clinical trials with levonorgestrel butanoate. This ester is an effective contraceptive for 3 months at 12.5 mg, or 5-6 months at a dose of 25 or 50 mg. Trials of combined estrogen and progestogen injectables once-monthly have been ongoing for 10 years. The ratio of the 2 components is as important as the amounts. 2328 women from 12 countries participated in trials of DMPA 25 mg-estradiol cypionate 5 mg, and NET-EN 50 mg-estradiol valerate 5 mg. The continuation rate was better than that for 3-monthly progestogen-only injectables, because of less irregular bleeding. A combined injectable called Cyclofem, DMPA 25 mg-estradiol cypionate is being introduced in several countries. The steadily increasing demand for long-acting injectables prompts development of better formulations.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Noretindrona/análogos & derivados , Compostos de Anilina/administração & dosagem , Compostos de Anilina/farmacocinética , Anticoncepcionais Femininos/farmacocinética , Preparações de Ação Retardada , Implantes de Medicamento , Feminino , Humanos , Levanogestrel/administração & dosagem , Noretindrona/administração & dosagem , Noretindrona/farmacocinética , Acetato de Noretindrona , Ovulação/efeitos dos fármacosRESUMO
In three ongoing open studies conducted by 50 investigators in Europe, South America, and New Zealand, 639 subjects followed a new triphasic regimen of gestodene (GTD) and ethinyl estradiol (EE) for 3,020 cycles. One study used GTD + EE only, but in each of the other two studies a comparator oral contraceptive (OC) also was given: norethisterone (NET) + EE in one and desogestrel (DSG) + EE in the other. The objective of all three studies was to assess the efficacy, cycle control, and safety of the triphasic GTD + EE. The following is a report of the interim results. Statistical analysis was performed only on differences between groups in the incidences of bleeding irregularities. During six treatment cycles, subjects either followed the GTD + EE regimen (50 micrograms GTD + 30 micrograms EE for 6 days, 70 micrograms GTD + 40 micrograms EE for 5 days, and 100 micrograms GTD + 30 micrograms EE for 10 days) or took triphasic NET + EE or monophasic DSG + EE. Each cycle concluded with a seven-day hiatus in study medication. No pregnancies occurred with any of the contraceptive preparations (Pearl Index = 0). Compliance was good in all studies and a majority of subjects were still participants at cycle 6. Normal bleeding was reported during 92% of the total evaluable cycles of GTD + EE use. Cycle control with GTD + EE was superior to that with NET + EE or DSG + EE: Breakthrough bleeding occurred in 1.5% of the pooled GTD + EE cycles versus 6.6% of the NET + EE cycles and 2.6% of the DSG + EE cycles; spotting occurred in 4.5% of the GTD + EE cycles versus 9.7% of the NET + EE cycles and 10.3% of the DSG + EE cycles; and breakthrough bleeding plus spotting occurred in 2.1% of the GTD + EE cycles versus 8.1% of the NET + EE cycles and 4.6% of the DSG + EE cycles. Amenorrhea occurred in 2.0% of the cycles with NET + EE, but was reported by only 0.3% of all the subjects given GTD + EE and 0.7% of those given DSG + EE. Cycle length and intensity of bleeding changed little during the use of any of the study preparations. Mean length of withdrawal bleeding during the GTD + EE regimen shortened from 4.5 days (prestudy) to 4.0 days. With each OC, the subjects' mean weight during cycles 3 and 6 differed less than 0.5 kg from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Anticoncepcionais Orais Combinados/farmacologia , Etinilestradiol/farmacologia , Ciclo Menstrual/efeitos dos fármacos , Norpregnenos/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Anticoncepcionais Orais Combinados/efeitos adversos , Desogestrel , Etinilestradiol/efeitos adversos , Europa (Continente) , Feminino , Humanos , Estudos Multicêntricos como Assunto , Nova Zelândia , Noretindrona/efeitos adversos , Noretindrona/farmacologia , Norpregnenos/efeitos adversos , Cooperação do Paciente , América do SulRESUMO
PIP: The article describes the results obtained over a period of 10 years with contraception by monthly injection of 150 mg of dihydroxyprogesterone acetophenide, and 10 mg of estradiol enanthate. 100 fertile patients were observed, for a total of 8074 cycles. There were no pregnancies, and only minimal side effects. No changes were observed in blood profile, urine and hepatic function, and in blood coagulation; there were no instances of breast or uterine cancer. In 10 years only 15% of patients abandoned this method because of changes in the menstrual cycle, changes which were expected, but which had not been explained to the patients.^ieng
Assuntos
Acetofenida de Algestona , Injeções , Distúrbios Menstruais , Pesquisa , Tempo , Anticoncepção , Anticoncepcionais , Anticoncepcionais Femininos , Anticoncepcionais Orais Hormonais , Demografia , Doença , Serviços de Planejamento Familiar , População , Dinâmica Populacional , Fatores de TempoRESUMO
PIP: 75 women of proven fertility were treated as a contraceptive measure with an injection of 75 mg. of duhydroxyprogesterone acetophenide, and of 5 mg. of estradiol enanthate. Doses were half of what regularly used, and were injected between the 7th and the 9th day of the cycle. Total number of cycles studied was 859. Most important side effects of the treatment was headache in 28.3% of patients, spotting in 15.5%, and emotional instability in 10.5%. Metabolic and hematologic data were unchanged, and vaginal cytology was negative. There were no pregnancies. It must be remembered that, in every contraceptive treatment, lower doses are always preferable when equally effective. (Summary in ENG).^ieng
Assuntos
20-alfa-Di-Hidroprogesterona/efeitos adversos , Estradiol/efeitos adversos , Progesterona/análogos & derivados , Protrombina/análise , 20-alfa-Di-Hidroprogesterona/metabolismo , Glicemia/análise , Colesterol/análise , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Estradiol/metabolismo , Feminino , Humanos , Injeções Intramusculares , Gravidez , Tempo de ProtrombinaRESUMO
PIP: Since recent recommendations advocate that smaller doses of estrogen should be used, a combination of .5 mg of norethindrone and .015 mg ethinyl estradiol was tested on 198 patients for a total of 2546 cycles, the longest usage being over 2 years. The women ranged from 15 to 45 years of age, the average age being 28, and the average number of pregnancies, 5.2. The medication was taken daily for 21 days and then stopped for 7. The group was controlled for secondary effects, bleeding, weight changes, and nucleal or hormonal changes. 14.2% stopped taking it because of secondary problems like spotting, nausea, transhormonal bleeding, and depression. The only pregnancy was due to inadequate attention to the prescription by the patient. Tolerance of the medication was quite good overall and no severe difficulties resulted.^ieng
Assuntos
Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais/administração & dosagem , Etinilestradiol/administração & dosagem , Noretindrona/administração & dosagem , Adolescente , Adulto , Ensaios Clínicos como Assunto , Anticoncepcionais Orais Combinados/efeitos adversos , Avaliação de Medicamentos , Etinilestradiol/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Noretindrona/efeitos adversos , GravidezRESUMO
PIP: 135 women who had had at least 1 child were treated with 80 mg of mestranol and 1 mg of lynestrenol on a 22 day on, 6 day off basis for a total of 800 cycles of observation. Follow-up was done monthly. Endometrial and cervical biopsies were done and levels of pregnanediol in the urine were tested. Cycles were between 25-31 days with an average of 28. Flow averaged 3 days' duration and was slight in 53.1% of the cycles, normal in 39.3% and heavy in 2.1%. 48.3% of the cycles were characterized by no dysmenorrhea, 35.7% by slight, 11% by moderate, and 1.8% by severe. Incidence of spotting and breakthrough bleeding was slight. Side effects were also slight; nausea was present in 7.6% of the cycles, hypogastric tension in 6.6%, chloasma in 5.9%, and severe headache in 4.3%. Headaches were the only side effect reported with any regularity. No pregnancies occurred. Only 14 patients discontinued. Test results indicated that under medication the amount of pregnanediol diminished, the endometrium modified its ovulatory functions, the cervical mucus lost it ability to crystallize or stretch, and vaginal shedding was slightly modified.^ieng