RESUMO
The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only one man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects on the 7.5 mg/day dose group, 12 recovered sperm counts >20 million/mL within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. Eight of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.
PIP: The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only 1 man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects in the 7.5 mg/day dose group, 12 recovered sperm counts higher than 20 million/ml within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. 8 of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.
Assuntos
Anticoncepcionais Masculinos/sangue , Gossipol/sangue , Espermatogênese/efeitos dos fármacos , Adulto , Brasil , China , Anticoncepcionais Masculinos/administração & dosagem , Anticoncepcionais Masculinos/efeitos adversos , Hormônio Foliculoestimulante/sangue , Gossipol/administração & dosagem , Gossipol/efeitos adversos , Humanos , Quênia , Cinética , Masculino , Nigéria , Potássio/sangue , Testículo/anatomia & histologiaRESUMO
A study of the acceptability of Uniplant, a 12-month single implant of nomegestrol acetate, included 819 women from Africa, Latin America, and China, participating in a clinical trial of Uniplant. A standard, pre-coded questionnaire was specially designed for this purpose and applied at the moment of removal of implant, either at the end of 12 months of use or at the time of discontinuation for whatever reason. The level of satisfaction proved high when users' comparison with their previous contraceptive method, users' recommendation of Uniplant to others, users' intention to use the method in the future, and service satisfaction were taken into consideration. Uniplant was considered easy to use, safe (low risk of pregnancy), and also to cause fewer side effects than other methods. When asked about the least liked feature of Uniplant, almost half the respondents said that there was nothing that they disliked and about one-third mentioned the changes in their menstrual pattern. However, according to the clinical trial, over half of the Uniplant users have bleeding patterns similar to untreated cycles. The majority of respondents did not feel any discomfort during the procedure of insertion and removal of the implant. About 70% of patients in the study stated that they required contraception for more than one year and most of these women said that they did not mind having to change the implant every year.
Assuntos
Megestrol/análogos & derivados , Satisfação do Paciente , Congêneres da Progesterona , Adulto , Implantes de Medicamento , Feminino , Humanos , Entrevistas como Assunto , Megestrol/administração & dosagem , Megestrol/efeitos adversos , Satisfação do Paciente/estatística & dados numéricos , Congêneres da Progesterona/administração & dosagem , Congêneres da Progesterona/efeitos adversos , Inquéritos e QuestionáriosRESUMO
Uniplant, a single Silastic implant containing nomegestrol acetate, provides contraceptive efficacy for one year. Uniplant use for one year was studied in 1,803 healthy women of reproductive age, enrolled from 10 centers in 9 countries, after informed consent. Implants were placed subdermally either in the upper arm or in the gluteal region. Two-hundred-seventy-six subjects discontinued prior to completing one year of study. Cumulative discontinuation rate at 12 months was 15.72%. Medical reasons for discontinuation were principally menstrual-related. Fifteen pregnancies occurred during the one year study period, resulting in a 12-month net cumulative pregnancy rate of 0.94%. Approximately 56% of subjects using Uniplant had bleeding patterns similar to normal menstruation. Results from this study confirm that Uniplant is an efficient, well tolerated, 12-month contraceptive implant, with the advantage of easier insertion and removal of the single implant compared to other multiple implant methods.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Megestrol , Norpregnadienos/administração & dosagem , Adulto , Anticoncepcionais Femininos/efeitos adversos , Implantes de Medicamento , Feminino , Humanos , Norpregnadienos/efeitos adversos , Gravidez , Congêneres da Progesterona/administração & dosagem , Congêneres da Progesterona/efeitos adversos , Hemorragia Uterina/induzido quimicamenteRESUMO
A multicenter, international, randomized, comparative trial was conducted to assess the acceptability, efficacy and safety of two different schedules of a contraceptive pill, containing 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol, administered by the vaginal route. One schedule of daily administration for 21 days with a seven-day interruption to allow withdrawal bleeding was compared to daily administration without interruption for bleeding. A total of 900 women were recruited in three countries, Brazil, Egypt and China; 7,090 women-months of vaginal pill use were recorded (3,364 using the pills intermittently and 3,726 continuously). Four undesired pregnancies occurred, one in Egypt and three in China, all four in women using the pills intermittently. There was a statistically significant difference (p = 0.486) in pregnancy rate between the two groups. There were no other significant differences in discontinuation rates despite marked differences in bleeding patterns, amenorrhea predominating in the continuous use group. Hemoglobin levels increased significantly in the two groups but hematocrit was significantly higher in the continuous use group.
PIP: 900 healthy women 16-42 years old were recruited in Brazil, China, and Egypt for a multicenter, randomized, comparative clinical trial to determine the acceptability, efficacy, and safety of two different schedules of a contraceptive pill with 250 mcg levonorgestrel and 50 mcg ethinyl estradiol administered vaginally. The two schedules were: 1) daily vaginal use of the pill for 21 days, followed by withdrawal for regular bleeding, and restarted 7 days later, and 2) use of the pill by the vaginal route nonstop for one year. There were no significant difference in cumulative discontinuation rates between the two groups (total, 15.5 for intermittent group and 14.64 for continuous group), except for unwanted pregnancy. The only unwanted pregnancies occurred to 4 women in the intermittent group (1.04%) (p = 0.0486). Women in the continuous use group were more likely than those in the intermittent group to have spotting at least once (20.6% vs. 4.4%; p 0.001). Women in the continuous group were more likely than those in the intermittent group to have amenorrhea. For example, the mean number of bleeding/spotting days during all time intervals was lower for the continuous group than for the intermittent group (p 0.001; last interval, 0.97 vs. 12.83). Hemoglobin levels increased considerably in both groups between baseline and one year of use (11.61 vs. 11.9 g/dl for intermittent group and 11.54 vs. 11.81 g/dl for continuous use; p 0.001). The mean value of hematocrit at 12 months for the continuous group was higher than that at baseline (38.8% vs. 38.2%; p = 0.011). It did not increase in the intermittent group, however. Women in both groups gained weight during the 12 months of pill use. The weight gain was significant for the continuous group only. These findings suggest that continuous use of vaginal contraceptive pills may be more advantageous than intermittent use oral contraceptives and may benefit anemic women and those who bleed heavily during menstruation.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Congêneres do Estradiol/administração & dosagem , Etinilestradiol/administração & dosagem , Levanogestrel/administração & dosagem , Administração Intravaginal , Adolescente , Adulto , Brasil , China , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Femininos/normas , Formas de Dosagem , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Egito , Contagem de Eritrócitos , Congêneres do Estradiol/efeitos adversos , Congêneres do Estradiol/normas , Etinilestradiol/efeitos adversos , Etinilestradiol/normas , Feminino , Hematócrito , Hemoglobinas/análise , Humanos , Cooperação Internacional , Levanogestrel/efeitos adversos , Levanogestrel/normas , Fatores de TempoRESUMO
The objective of this multicenter randomized clinical trial was to compare the efficacy, acceptability, and occurrence of side effects associated with the oral versus vaginal route of administration of contraceptive pills. Eight hundred nineteen healthy, parous women of reproductive age were recruited at family planning clinics and research centers, members of the South to South Cooperation in Reproductive Health, in seven countries of the developing world. These women were randomly assigned to use either oral or vaginal administration of the same contraceptive pill, which contained 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol. No statistically significant differences were found in discontinuation rates between the two groups after 1 year. Involuntary pregnancy rates after 1 year were not statistically significantly different between the two groups. The vaginal route of administration appears to be as acceptable and efficacious as the oral route.
PIP: The objective of this multicenter randomized clinical trail was to compare the efficacy, acceptability, and occurrence of side effects associated with the oral versus vaginal route of administration of contraceptive pills. This study started in June, 1987, and data collection extended up to April, 1992, at family planning clinics and research centers, members of the South to South Cooperation in Reproductive Health, in seven countries of the developing world. The 819 subjects were from 17 to 39 years of age, had already had at least one pregnancy, had had regular menstrual cycles for 3 months before, were exposed to the risk of pregnancy, and were not using any other method of contraception. 424 were randomly assigned to use the pills orally (which contained 250 mcg levonorgestrel and 50 mcg ethinyl estradiol), whereas 395 inserted the pills vaginally. 625 subjects completed at least 6 months of use, 326 used the pills orally and 299 used the pills vaginally. 385 subjects completed 1 year of pills use, 201 in the oral group and 184 in the vaginal group. The 1-year discontinuation rate per 100 subjects per year for the oral group was 34.71 +or- 2.42, while it was 36.35 +or- 2.53 for the vaginal group. This difference was not statistically significant. The only single reason of statistically significant difference for discontinuation was "desire for pregnancy" (p = 0.444). Paired value analysis of subjects completing 12 months of study showed that women in the oral group had a statistically significant increase in weight, from a mean of 55.8 kg at admission to a mean of 56.9 kg at 6 months (p 0.05) and 57.3 kg at 1 year (p = 0.05). The mean weight of the vaginal group increased from 56.52 kg to 57.22 kg (p = 0.036) at 12 months. Significantly more complaints of vaginal discharge were recorded in women using the pills by the vaginal route (p = 0.001). However, only one subject discontinued the pills because of vaginal discharge.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Orais Hormonais , Administração Intravaginal , Adolescente , Adulto , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Países em Desenvolvimento , Feminino , Humanos , Cooperação do PacienteRESUMO
Hypokalemia has been associated with the taking of gossypol, a potential oral antifertility drug for men. Because the frequency of this response differed in different parts of the world, this study was done to learn if "normal" serum [K+] also differed. [K+] was measured by flame photometry in serum from apparently normal men from Austria (n = 30), China (53), Brazil (100), the Dominican Republic (38), and the US (103), and in plasma from Nigerian men (82). The mean (SD) for [K+] in Chinese men, 3.82 (0.27) mmol/L, was lower than that in Brazilians [4.06 (0.29) mmol/L], Austrians [4.14 (0.44) mmol/L], Dominicans [4.37 (0.33) mmol/L], or Americans [4.38 (0.37) mmol/L]. Apparently there are regional differences in average serum [K+], with men in China having lower serum [K+] than men elsewhere. This may predispose them to hypokalemia.