RESUMO
The objective of this study was to evaluate the contraceptive efficacy and clinical performance of a Nestorone subdermal implant (NES) in the postpartum period. NES (n = 100) and Copper T intrauterine device (T-Cu; n = 100) acceptors initiated contraception at 8 weeks postpartum and were followed at monthly intervals during the first year and at 3-month intervals thereafter. Pregnancy rates, breastfeeding performance, infant growth, bleeding pattern, and side effects were assessed. Blood and milk NES concentration were measured. No pregnancy occurred in 2195 and 2145 woman-months of NES implant and T-Cu use, respectively. No effect of NES on lactation and infant growth and no serious adverse events were observed. Lactational amenorrhea was significantly longer in NES users (353 +/- 20 days) than in T-Cu users (201 +/- 11 days). More NES users (55.8%) experienced prolonged bleedings than did T-Cu users (36.2%). Concentrations of NES in breast milk ranged between 54-135 pmol/liter. The Nestorone implant is a highly effective contraceptive, safe for breastfed infants because the steroid is inactive by the oral route.
Assuntos
Anticoncepção , Anticoncepcionais Femininos/administração & dosagem , Lactação/efeitos dos fármacos , Norprogesteronas/administração & dosagem , Adolescente , Adulto , Amenorreia/fisiopatologia , Aleitamento Materno , Chile , Anticoncepcionais Femininos/metabolismo , Implantes de Medicamento , Feminino , Seguimentos , Humanos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Leite Humano/efeitos dos fármacos , Leite Humano/metabolismo , Norprogesteronas/efeitos adversos , Norprogesteronas/metabolismo , Pacientes Desistentes do Tratamento , Período Pós-Parto/efeitos dos fármacos , Fatores de Tempo , Hemorragia Uterina/induzido quimicamente , DesmameRESUMO
Nestorone(R) progestin (NES) is a potent 19-nor-progesterone derivative which is biologically inactive when administered orally; however, it is an excellent option for implant contraception. The objective of this study was to evaluate ovarian function during use of either one 4-cm or two 3-cm NES implants for 24 months. A total of 60 volunteers were enrolled in each dose group. Vaginal ultrasound (VUS) and blood sampling for determinations of estradiol (E(2)), progesterone (P) and NES serum levels were carried out twice a week for 6 consecutive weeks, beginning in months 1, 6, 12, 18, and 24 of implant use. Serum levels of NES declined with time, with a more pronounced decrease during the first 18 months of implant use; thereafter, NES levels remained stable until the end of the study at 24 months. Luteal activity was very infrequent during the first year of use (<3%) but increased during the second year, occurring in 27% and 35% of the sampling periods in the 1-implant group, and 2% and 16% of the sampling periods in the 2-implant group, at months 18 and 24 of use, respectively. No luteal activity was observed with NES levels above 80 pmol/L. Serum P levels in periods of luteal activity were significantly lower than those of controls. Persistent anovulatory follicles were the most common VUS finding and this was associated with E(2) levels that remained within the normal range (101-1500 pmol/L) in the majority of the sampling periods studied. Considering that a single implant offers advantage for insertion and removal, a new single NES implant is being developed with a slightly higher release rate, to reduce effectively the incidence of ovulation and provide a greater margin of safety beyond 2 years.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Norprogesteronas/administração & dosagem , Ovário/efeitos dos fármacos , Ovário/fisiologia , Adolescente , Adulto , Anticoncepcionais Femininos/sangue , Relação Dose-Resposta a Droga , Implantes de Medicamento , Estradiol/sangue , Feminino , Humanos , Norprogesteronas/sangue , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Ovário/diagnóstico por imagem , Ovulação/efeitos dos fármacos , Progesterona/sangue , UltrassonografiaRESUMO
The relationship between ovarian hormones and bleeding patterns during continuous progestin contraception was studied in 29 women who used Nestorone (NES) releasing implants. Oestradiol and progesterone were measured in blood samples taken twice a week for 6 consecutive weeks, during months 6, 12, 18 and 24 of implant use. Retrospectively, the association between hormonal concentrations and bleeding patterns was evaluated. Twenty-four short (
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Glândulas Endócrinas/efeitos dos fármacos , Menstruação/efeitos dos fármacos , Norprogesteronas/administração & dosagem , Adolescente , Adulto , Amenorreia/sangue , Anticoncepcionais Femininos/farmacologia , Implantes de Medicamento , Glândulas Endócrinas/fisiologia , Estradiol/sangue , Feminino , Humanos , Ciclo Menstrual/sangue , Menstruação/sangue , Norprogesteronas/farmacologia , Concentração Osmolar , Progesterona/sangue , Estudos Retrospectivos , Fatores de TempoRESUMO
The synthetic androgen 7alpha-methyl-19-nortestosterone (MENT) is a potent suppressor of gonadotrophin that has several advantages for long term administration to normal or hypoandrogenic men. The aim of this study was to examine MENT serum concentrations following subdermal insertion of MENT acetate (MENT Ac) implants and their effects on gonadotrophins, testosterone, dihydrotestosterone (DHT), sex hormone-binding globulin, prostate specific antigen and insulin-like growth factor-1 serum concentrations in normal men. A total of 45 healthy men were recruited at three clinics. Each subject received one, two or four implants for 28 days. Serum samples were obtained before insertion and on days 8, 15, 22, 29, 36 and 43 after implant insertion. The average daily dose delivered in vivo by one implant was approximately 500 microg. One, two or four MENT Ac implants produced dose dependent and sustained serum MENT concentrations for the entire duration of treatment of 0.7 +/- 0.1, 1.2 +/- 0.1 and 2.0 +/- 0.1 nmol/l respectively. This treatment induced a dose dependent decrease in gonadotrophin and androgen serum levels. Two and four implants induced maximal suppression that was maintained throughout treatment and was completely reversed after removal of the implants. The mean decreases were 93 +/- 1% for testosterone, 80 +/- 3% for DHT, 97 +/- 1% for luteinizing hormone and 95 +/- 1% for follicle stimulating hormone. No serious adverse reactions were reported by the volunteers and no consistent changes in clinical chemistry and haematology were found. These results indicate that MENT Ac implants are an efficient way of MENT administration and confirm the potent gonadotrophin and androgen suppressive effect of this drug.
Assuntos
Estrenos/administração & dosagem , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Testosterona/sangue , Adulto , Di-Hidrotestosterona/sangue , Implantes de Medicamento , Estrenos/farmacocinética , Estrenos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Congêneres da Progesterona/administração & dosagem , Congêneres da Progesterona/farmacocinética , Congêneres da Progesterona/farmacologia , Antígeno Prostático Específico/sangue , Globulina de Ligação a Hormônio Sexual/metabolismoRESUMO
The clinical performance and the in vivo release rate of a single 4-cm Nestorone subdermal implant were investigated. Implants manufactured by two different procedures were compared. Volunteers were 70 healthy women of proven fertility. Forty women provided blood samples twice a week in the pretreatment cycle and for 5-6 weeks at 6-month intervals during treatment. Additional control cycles (n = 31) were studied in 19 Copper T users. No pregnancy occurred in 1570 woman-months. Nestorone plasma levels (x +/- S.E.) declined from 112 +/- 8 to 86 +/- 3 pmol/L (Implant A) and from 145 +/- 8 to 57 +/- 5 pmol/L (Implant B) from the first to the 24th month. Progesterone levels were < 9.5 nmol/L in 166 (93%) of 178 blood samplings taken during treatment. Progesterone levels > 16 nmol/L were found in only 7 sampling periods (3.9%) in treated women and in 70 (98.6%) out of 71 control cycles. No ovulation occurred with Nestorone plasma levels above 105 pmol/L. No abnormal changes were observed in plasma lipoproteins or other clinical chemistry parameters during treatment. The implants were well tolerated. The most frequent complaint was the occurrence of irregular bleeding. Enlarged follicles found during pelvic examination in 8 subjects (11.4%) disappeared spontaneously in 10 days to 6 weeks. Implants were removed because of medical (n = 10, 14.3%) or personal reasons (n = 6, 8.6%) or at the 24th month of treatment (n = 54, 77.1%). The estimated average daily in vivo release rate of Nestorone was 45-50 micrograms/day. A single Nestorone subdermal implant affords efficient contraceptive protection during two years.