gestodene and Uterine-Hemorrhage

The objective of this study was to compare cycle control, tolerability and sexual well-being with the use of three hormonal contraceptives.. In this prospective randomized study, the effects of two combined oral contraceptives [20 microg of ethinylestradiol (EE)/100 microg of levonorgestrel and 15 microg of EE/60 microg of gestodene] were compared with those of the vaginal ring (15 microg of EE/120 microg of etonogestrel). One-year data from 280 women were obtained. We investigated the pattern of menstrual cycle and the incidence of weight gain, nausea, headache, breast tenderness, irritability, depression and vaginal dryness. Moreover, desire and sexual satisfaction were evaluated. Finally, the cumulative rate of discontinuation in the three groups was estimated.. The analysis of adverse events revealed two crucial points for acceptability, compliance and continuation: poor cycle control and disturbance of sexual intercourse due to vaginal dryness and loss of desire.

Topics: Administration, Intravaginal; Adult; Affect; Contraceptive Agents, Female; Contraceptives, Oral; Desogestrel; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Libido; Menstrual Cycle; Norpregnenes; Prospective Studies; Reproduction; Uterine Hemorrhage

This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) or 20 microg ethinyl estradiol and 150 microg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-microg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel.

Topics: Adult; Blood Glucose; C-Peptide; Contraceptives, Oral, Combined; Desogestrel; Ethinyl Estradiol; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Norpregnenes; Uterine Hemorrhage

Postmenopausal women taking oestradiol 17-beta 2 mg daily were randomized to receive either 25 or 50 microg gestodene from day 17 to 28 of the cycle in a double-blind study. Placental protein P14 (PP14) and CA 125 concentrations in uterine flushing, endometrial morphology and irregular bleeding after 12 cycles of study were observed. Eleven and 12 women in the 25 and 50 microg groups respectively completed the study. There were no significant differences in pre-treatment biochemical and morphological indices between the groups. The median PP14 concentration increased from 332 to 5800 ng/ml (P < 0.001) and from 145 to 27 160 ng/ml (P < 0.001) in the 25 and 50 microg gestodene groups respectively. No between-group significant rise of PP14 was observed. Similarly, no significant change was seen between the initial and post-treatment concentrations of CA 125 for either group. All biopsies were atrophic at inception of the study, and both regimens produced secretory endometrial transformation in the majority of biopsies. No between-group difference was observed in the morphometric indices measured, or any significant correlation between the concentrations of PP14 or CA 125 and morphology. The mean number of days of withdrawal bleeding (3.8 and 4.2 days for 25 and 50 microg respectively) were similar. In conclusion, both regimens produced a significant rise in uterine flushing concentrations of PP14, but not CA 125. PP14 is a sensitive biochemical marker in the assessment of endometrial response to hormone replacement therapy.

Topics: Adult; CA-125 Antigen; Double-Blind Method; Endometrium; Estradiol; Estrogen Replacement Therapy; Female; Glycodelin; Glycoproteins; Humans; Middle Aged; Norpregnenes; Postmenopause; Pregnancy Proteins; Progesterone Congeners; Prospective Studies; Therapeutic Irrigation; Uterine Hemorrhage; Uterus

This prospective, double-blind, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day versus a 21-day oral contraceptive regimen containing 20 microg ethinyl estradiol and 75 microg gestodene. Participants took trial medication daily for 28 days, either 23 tablets with active substances plus 5 placebo tablets or 21 tablets with active substances plus 7 placebo tablets. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 4,878 treatment cycles (23-day regimen: 2,362 cycles; 21-day regimen: 2,516 cycles) were obtained from 703 participants (23-day regimen, n = 342; 21-day regimen, n = 361). Both preparations proved to be effective contraceptives and provided good cycle control. One pregnancy because of method failure was recorded in each treatment group. This resulted in a study Pearl Index of 0.5 for each treatment. For the 23-day regimen, 36.0% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 37.1% in the 21-day regimen. In the 23-day regimen group, intracyclic bleeding episodes were reported by 42.4% of the participants in Cycle 1 but only in 14% in Cycle 7 and in the 21-day regimen group by 44.6% in Cycle 1 and only 17.3% in Cycle 7. Overall, intracyclic bleeding was reported in 21.9% of the 23-day regimen cycles and in 22.7% of the 21-day regimen cycles.A greater number of 23-day regimen participants had shorter withdrawal bleeding periods than with the 21-day regimen. In significantly (p <0.0001) more cycles in the 23-day regimen group, participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day regimen group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day regimen group was 4 days and in the 21-day regimen group 5 days. Both preparations were well tolerated and showed a similar adverse events pattern. The discontinuation rate because of adverse events was low (23-day regimen, 6%; 21-day regimen, 4%). No serious vascular adverse events were reported. More than 75% of the women in both groups either lost more than 2 kg of weight or did not gain weight during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study.

Topics: Contraceptives, Oral; Double-Blind Method; Ethinyl Estradiol; Female; Humans; Menstrual Cycle; Norpregnenes; Placebos; Pregnancy; Prospective Studies; Time Factors; Uterine Hemorrhage

This prospective, open, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day regimen with 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) and a 21-day regimen with 20 microg EE and 150 microg desogestrel (DSG). Participants took either 23 tablets with active substances plus 5 placebo tablets (23-day EE/GSD) or 21 tablets with active substances followed by 7 days without pill-taking (21-day EE/DSG). Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 5967 treatment cycles (23-day EE/GSD: 2975 cycles; 21-day EE/DSG: 2992 cycles) were obtained from 890 participants (445 in each group). Both preparations proved to be effective contraceptives and provided good cycle control. No pregnancy during treatment was recorded. This resulted in a study Pearl Index of 0.0 for both treatments. For 23-day EE/GSD, 32.4% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 31.5% for 21-day EE/DSG. In the 23-day EE/GSD group, intracyclic bleeding episodes were reported by 48.8% of the participants in Cycle 1 but in only 15.1% in Cycle 7, and in the 21-day regimen group by 43.4% in Cycle 1 and only 14.2% in Cycle 7. Overall, intracyclic bleeding was reported in 20.9% of cycles for both treatments.A greater number of 23-day EE/GSD participants had shorter withdrawal bleeding periods than with 21-day EE/DSG. In significantly (p <0.0001) more cycles in the 23-day EE/GSD group participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day EE/DSG group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day EE/GSD group was 4 days and in the 21-day EE/DSG group 5 days. Both preparations were well tolerated and showed a similar adverse events pattern. The discontinuation rate because of adverse events was low (23-day EE/GSD: 6.1%; 21-day EE/DSG: 5.6%). No serious vascular adverse events were reported. More than 82% in the 23-day EE/GSD group and 79% in the 21-day EE/DSG group either lost more than 2 kg of weight or did not gain weight during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study compared to baseline.

Topics: Adolescent; Adult; Blood Pressure; Body Weight; Contraceptives, Oral, Combined; Desogestrel; Ethinyl Estradiol; Female; Humans; Menstrual Cycle; Norpregnenes; Time Factors; Treatment Outcome; Uterine Hemorrhage

This was an open-label multicenter study to compare the cycle control and effect on well-being of two oral contraceptives containing gestodene and one containing desogestrel. A total of 2419 healthy women < or = 41 years of age were randomized to receive oral contraceptives containing monophasic gestodene (Minulet; n = 806, mean age 24.5 years), triphasic gestodene (Tri-Minulet; n = 808, mean age 24.6 years) or monophasic desogestrel (Mercilon; n = 805, mean age 24.6 years). Subjects were to participate in the study for up to 13 treatment cycles. A modified Moos Menstrual Distress Questionnaire was used to evaluate menstrual symptoms and to assess overall well-being. A total of 698 women were withdrawn from the study, 154 due to adverse events. Cycle control with gestodene was superior to that with desogestrel at almost all time points, particularly for breakthrough bleeding and/or spotting, which occurred significantly less frequently with gestodene than with desogestrel at cycles 1-7 and 9-11 (p < 0.05). Generally, the proportion of subjects with breakthrough bleeding and/or spotting was almost twice as great with desogestrel as with gestodene. The duration of bleeding was not consistently different between the gestodene and desogestrel groups; however, the intensity of bleeding was greater with gestodene at all time points (p < 0.05). The latent period before withdrawal bleeding was significantly longer for monophasic gestodene at cycles 1-5 and 8-10 (p < 0.05). Treatment significantly improved overall well-being at cycles 6 and 9 with triphasic gestodene and at cycle 13 with desogestrel; however, no statistically significant differences among treatment groups in overall well-being scores or individual factors of well-being could be identified. All three treatments were well tolerated. The most common drug-related adverse events were headache (14.2%), breast pain (6.2%), nausea (4.1%), metrorrhagia (3.9%) and abdominal pain (3.5%). The incidence of adverse events in all treatment groups was similar, with the exception of metrorrhagia, which occurred in more patients in the desogestrel group than in the gestodene treatment groups (p < 0.05).

Topics: Adolescent; Adult; Affect; Contraceptives, Oral, Synthetic; Desogestrel; Female; Humans; Menstrual Cycle; Norpregnenes; Patient Satisfaction; Progesterone Congeners; Uterine Hemorrhage

The aim of the study was to assess the dose-response effects on the postmenopausal endometrium of 3 sequential combined hormone replacement regimens and 1 continuous combined hormone replacement regimen of estradiol and gestodene.. In this 2-year double-blind, placebo-controlled study, 278 healthy postmenopausal women received either 2 mg estradiol sequentially combined with 50 microg or 25 microg gestodene, 1 mg estradiol sequentially or continuously combined with 25 microg gestodene, or placebo.. All 4 hormone treatment regimens produced a safe endometrial histologic appearance. The regimens that were based on the lower dose of 1 mg estradiol was associated with less uterine bleeding than were those that were based on 2 mg estradiol. For sequentially opposing the 2 mg dose of estradiol, the dose of 25 microg gestodene was less efficient in producing secretory activity than was the dose of 50 microg gestodene. The measurement of placental protein 14 in serum reflected the secretory transformation of the endometrial buildup.. The reduction in bleeding episodes associated with regimens with lower estradiol doses may lead to improved long-term therapy compliance by menopausal women. The potency of progestogens can be assessed by measuring the serum concentration of placental protein 14.

Topics: Dose-Response Relationship, Drug; Double-Blind Method; Endometrium; Estradiol; Female; Glycodelin; Glycoproteins; Hormone Replacement Therapy; Humans; Middle Aged; Norpregnenes; Postmenopause; Pregnancy Proteins; Progesterone Congeners; Uterine Hemorrhage

This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene (EE/GSD) or 150 micrograms of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/DSG. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.. This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 mcg of ethinyl estradiol combined with either 75 mcg of gestodene (EE/GSD) or 150 mcg of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/GSD. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.

Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Desogestrel; Estradiol Congeners; Ethinyl Estradiol; Female; Humans; Menstrual Cycle; Norpregnenes; Pregnancy; Progesterone Congeners; Prospective Studies; Uterine Hemorrhage

To assess the contraceptive efficacy, cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene.. In a randomized, open-label, six-cycle, group-comparative, multicenter study performed in Brazil, pregnancies, cycle-control parameters, incidence of side-effects and the presence and severity of acne vulgaris were assessed, and blood pressure and body weight were measured at pretreatment and after one, three and six cycles of oral contraceptive use.. Of the 595 women enrolled, 274 (86.7%) in the desogestrel/ethinylestradiol group and 227 (81.4%) in the gestodene/ethinylestradiol group completed the six cycles, providing data for 1753 and 1487 treatment cycles, respectively. Two pregnancies occurred, one of which (in the desogestrel/ethinylestradiol group) was attributed to user failure, whilst the other (in the gestodene/ethinylestradiol group) was thought to result from method failure. Cycle control was observed to be excellent; the incidences of irregular bleeding and minor side-effects were low in both groups and decreased after an initial increase in the first cycle. Pre-existing acne improved in both groups, whereas blood pressure and body weight remained essentially unchanged.. Both desogestrel/ethinylestradiol and gestodene/ethinylestradiol provide effective oral contraception with comparable cycle control and acceptability.

Topics: Acne Vulgaris; Adult; Blood Pressure; Body Weight; Brazil; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Estradiol Congeners; Ethinyl Estradiol; Female; Humans; Menstrual Cycle; Norpregnenes; Progesterone Congeners; Severity of Illness Index; Uterine Hemorrhage

The aim of this study was to compare contraceptive reliability, cycle control, and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol (EE2) and 75 micrograms gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive. For the 20 micrograms EE2 preparation, 47.4% of all women reported spotting at least once over a period of 12 treatment cycles, whereas this figure was 35.5% for the 30 micrograms EE2 pill (p < 0.05). However, the incidence was within a range that corresponds to that of other OCs. The cumulative breakthrough bleeding rates (at least once during the one year of treatment) of 14.5% (20 micrograms EE2) and 11.8% (30 micrograms EE2) of women were not significantly different. In relation to all cycles, the intermenstrual bleeding rates were remarkably lower, indicating that the majority of the volunteers experienced such events only in few cycles under treatment: the spotting rate was 11.5% (20 micrograms EE2) and 7.2% (30 micrograms EE2) of all cycles, and the breakthrough bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 micrograms EE2 + 75 micrograms GSD group, two in the 30 micrograms EE2 + 75 micrograms GSD group). All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect. The influence of both treatments on the blood pressure and body weight proved to be extremely slight. Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent. The discontinuation rate due to adverse events, including intermenstrual bleeding, was low (9.8% for 20 micrograms EE2 + 75 micrograms GSD, and 7.2% for 30 micrograms EE2 + 75 micrograms GSD) and was in the lower range known for other oral contraceptives. Both preparations were well accepted by the volunteers. The data obtained demonstrate clinically acceptable cycle control, good tolerance, and a high standard of contraceptive reliability for both drugs. Prescription of the 20 micrograms EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible. In case of persistent cycle control problems, a switch to the 30 micrograms EE2 drug should be considered.. A double-blind, comparative study of oral contraceptives (OCs) containing 75 mcg of gestodene and either 20 mcg or 30 mcg of ethinyl estradiol (EE2) indicates that the lower-dose formulation neither compromises contraceptive effectiveness nor produces unacceptable cycle control. Study subjects included 649 randomly selected healthy women requesting contraception from 10 family planning centers in Germany; the 20 mcg EE2 pill was evaluated in 428 women for a total of 4470 cycles, while the 30 mcg preparation was tested in 221 women for 2377 cycles. During the 12-month study period, the incidence of at least 1 episode of intermenstrual bleeding (generally in the first cycle) was significantly greater in the 20 mcg EE2 group (47.4%) than in the 30 mcg group (35.5%); however, the cumulative breakthrough bleeding rates (14.5% and 11.8%, respectively) were not dissimilar. In relation to the sum of all cycles, the spotting rates were 11.5% for the 20 mcg EE2 OC and 7.2% for the 30 mcg OC, and the breakthrough bleeding rates were 2.6% and 1.6%, respectively. The 3 pregnancies that occurred all involved user failure. The discontinuation rates due to side effects, including spotting, were 9.8% in the 20 mcg EE2 group and 7.2% in the 30 mcg group. 66.6% of women in the former group and 71.0% of those in the latter group never complained of an adverse effect during the study. The incidences of spotting and discontinuation were well within the range reported for other OCs. These findings indicate that the 20 mcg EE2 preparation should be prescribed first; if cycle control problems persist, a 30 mcg EE2 OC can be considered.

Topics: Adult; Amenorrhea; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Double-Blind Method; Estradiol Congeners; Ethinyl Estradiol; Female; Germany; Humans; Incidence; Menstruation; Norpregnenes; Time Factors; Uterine Hemorrhage

This long-term, open-label multicenter study investigated the clinical efficacy and tolerability of a monophasic oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene. A total of 670 women between the ages of 18 and 45 years received the trial preparation over a 3-year period, giving 19,095 evaluable cycles. Of the 670 participants in the study, 75% completed at least 24 cycles with the trial preparation and 46% remained in the study for the full 3 years. One pregnancy occurred during the study which was considered by the investigator to be the result of misuse of the drug, giving an uncorrected Pearl Index of 0.07. Cycle control with the trial preparation was good, especially in women who did not miss any pills. By cycle 3, only 10.2% of women who had not missed pills reported intermenstrual bleeding (scanty or medium/excessive bleeding) and this decreased to 2.3% by cycle 36. The preparation was well tolerated, with a low incidence of unprompted adverse events. There were no clinically significant changes in mean body weight or blood pressure. Over the 3 years of the study, 10% of women withdrew from the study for reasons related mostly to mild adverse events. Results from this study demonstrate that the trial preparation is a reliable and well-tolerated oral contraceptive that provides good cycle control.

Topics: Adolescent; Adult; Amenorrhea; Contraceptives, Oral, Combined; Dysmenorrhea; Ethinyl Estradiol; Female; Humans; Menstrual Cycle; Norpregnenes; Patient Compliance; Pregnancy; Uterine Hemorrhage

The aim of the study was to investigate the endometrial histology and the bleeding pattern under a hormone replacement therapy regimen with continuous estrogen quarterly (3-monthly) combined with a progestogen.. In a prospective, double-blind, randomised clinical trial, 30 healthy, postmenopausal women were allocated to one of the three trial preparations. Group I was treated with 1 mg micronized 17 beta-estradiol continuously, group II took 2 mg micronized 17 beta-estradiol continuously and group III took 1 mg and 2 mg 17 beta-estradiol alternating every 42 days (step-up regimen). One treatment cycle was 84 days, during the last 12 days estradiol was combined with 50 micrograms gestodene. The total treatment period comprised two cycles of 12 weeks each. With regard to endometrial histology, the second cycle was the actual study cycle. In each patient endometrial samples were obtained at the following time points: after the withdrawal bleeding in the beginning (day 8-11) of cycle II (Vabra-method), at the end of the estrogen mono-phase (day 70-72) of cycle II(Pipelle-method), and 8-11 days after cessation of all medication (Vabra-method). Histopathological classification was done by two experienced gynaecological pathologists. All patients kept record of their bleeding events in a diary. Analysis of variance and Kruskal-Wallis test were used for statistical analysis of the data.. 29 patients were evaluable for the assessment of endometrial histology. Only one sampling procedure (1.2%) yielded an insufficient amount of tissue. In each treatment group, simple (cystic) hyperplasia was observed exclusively at the end of the estrogen mono-phase (in total 4/29 patients, 14.8%). Hyperplasia disappeared in all cases after the combined estrogen-progestogen phase. No cytological atypia was seen. Fifty-five cycles were evaluable for the bleeding pattern. The onset of the scheduled bleeding (withdrawal bleeding) was in all cycles on day 11 of the combined phase or beyond. Unlike the duration, the severity of the scheduled bleeding episodes was estrogen-dose dependent. In the entire treatment period of 2 x 84 days, breakthrough bleeding occurred in 3 women, totalling 9 days. Spotting occurred rarely and was equally divided among the treatment groups.. A quarterly sequential hormone replacement therapy regimen for women with anintact uterus gives rise to the development of simple hyperplasia without cytological atypia at the end of the unopposed estrogen phase. This occurs independent of the estrogen dose and can be reverted to inactive or atrophic endometrium by the addition of gestodene during 12 days. The combination offers good cycle control. The safety aspects should be investigated further in long-term studies before this regimen can be advocated for routine use.

Topics: Analysis of Variance; Biopsy; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Endometrial Hyperplasia; Endometrium; Estradiol; Estrogen Replacement Therapy; Female; Follow-Up Studies; Humans; Middle Aged; Norpregnenes; Postmenopause; Progesterone Congeners; Prospective Studies; Safety; Uterine Hemorrhage

Spotting and bleeding are among the most common side effects associated with oral contraceptive (OC) use and their occurrence is a prime determinant of whether a new user will continue to use OCs. Desogestrel and gestodene are two new progestins that were developed in part to minimize the occurrence of these side effects. Assessing the effect of these progestins is difficult, however, in part because their effects may be subtle, requiring a large sample size and possibly being overshadowed by other factors. To address these issues, we analyzed data from two comparative multicenter clinical trials that included 15,421 cycles among 2767 women. One study compared 75 micrograms gestodene + 30 micrograms ethinyl estradiol (EE) with 150 micrograms desogestrel + 30 micrograms EE, the other compared the same gestodene preparation with 150 micrograms desogestrel + 20 micrograms EE. Both studies found a higher risk of spotting or bleeding in all cycles among users of the desogestrel-containing preparation, with the differences ranging between 20% and 70% higher for the first study and 40% and 140% in the second. These differences were statistically significant in four of six cycles in each study and persisted after controlling for consistency and recency of OC use as well as smoking. After pooling the data and controlling for estrogen dose, the desogestrel-containing preparation was significantly associated with more frequent spotting or bleeding in five of six cycles. Smoking and consistency and recency of OC use were also independent predictors of spotting or bleeding.

Topics: Adolescent; Adult; Contraceptives, Oral; Desogestrel; Ethinyl Estradiol; Female; Humans; Norpregnenes; Progesterone Congeners; Smoking; Uterine Hemorrhage

To assess the effect of oral contraception started on the first day of menses and the fifth day following its onset, on women's compliance and the incidence of early breakthrough bleeding.. Oral contraceptives (OCs) containing 30 micrograms ethinylestradiol and 75 micrograms gestodene were prescribed to 100 consecutive, healthy women for whom OCs were found to be the most suitable method of contraception. In the first 50 women, OCs were started on the first day of menses (day 1 group), while in the remaining 50 women, OCs were started on the fifth day after the onset of menses (day 5 group).. The day 5 group had better compliance and a reduced incidence of breakthrough bleeding. No differences were observed between the two groups regarding age, parity and gravity.. Starting an OC regimen should include initiation on the fifth day following the onset of menses. This regimen might increase patient compliance and lower the incidence of breakthrough bleeding.

Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Drug Administration Schedule; Estradiol Congeners; Ethinyl Estradiol; Female; Humans; Incidence; Infant, Newborn; Menstrual Cycle; Norpregnenes; Patient Compliance; Progesterone Congeners; Time Factors; Uterine Hemorrhage

The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospective, open, group-comparative, randomized, multicenter trial of women asking for contraception. In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thailand, 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were randomly allocated to one of the two study groups. An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles. Criteria of cycle control, side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1, 3 and 6. Furthermore, the efficacy was evaluated after the last cycle. No pregnancies occurred with either of the contraceptives. The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle. Acne improved in both groups. Blood pressure and body weight remained unchanged. The two oral contraceptives were found to be effective and acceptable in Thai women. Compared to Caucasian women, the incidences of irregular bleeding and side effects were apparently lower in these Asian women. Furthermore, the effects of both oral contraceptives were comparable.. During October 1988-April 1990, clinicians randomly allocated 783 healthy women attending six family planning centers and outpatient gynecological clinics in urban areas of Thailand to either the group using a 30 mcg ethinyl estradiol (EE) combined oral contraceptive (OC) with 150 mcg desogestrel (DSG) (394 women) or an OC with 75 mcg gestodene (GSD) (389 women). Researchers aimed to evaluate the efficacy and acceptability of these two third-generation OCs. After six cycles of OC use, the continuation rate was 87.6% for DSG/EE and 85.9% for GSD/EE. No one from either group became pregnant. Women forgot to take the pills during 1.8% of the cycles with DSG/EE and 2% of the cycles with GSD/EE. Breakthrough bleeding was more common than spotting in both groups (0.8-5.4% vs. 0.6-2% for DSG/EE; 0.8-4.4% vs. 0-4.4% for GSD/EE), while in Caucasian women spotting was more common. Breakthrough bleeding and spotting rates were comparable in both groups. Irregular bleeding initially increased, then fell with time. Irregular bleeding for both OC groups was less common than it is in Northern European women. No one experienced any serious side effects. The most common minor side effects were nausea, headache, and breast tenderness. The incidences increased in the first cycle, then fell. They were comparable for both groups. Acne was less frequent after OC use (20.7% at baseline vs. 17.1% at 6 months for DSG/EE and 22% at baseline vs. 16.9% at 6 months for GSD/EE). Neither OC influenced the mean body weight or the mean blood pressure. These findings indicated that both OCs are very effective, provide excellent cycle control, and produce a low incidence of side effects. They also protect against acne.

Topics: Adult; Contraceptives, Oral; Desogestrel; Ethinyl Estradiol; Female; Humans; Multicenter Studies as Topic; Norpregnenes; Prospective Studies; Thailand; Uterine Hemorrhage

This clinical investigation of a low-dose, monophasic gestodene-containing oral contraceptive (75 micrograms gestodene/30 micrograms ethinylestradiol), investigated contraceptive efficacy, tolerability, cycle control and compliance in 5602 adolescents. The investigation was carried out over a period of 6 cycles. The average age of the study population was 16.4 years; however, only 12 women (0.2%) were under the age of 14. With regard to contraceptive efficacy, during the course of the study there were 5 pregnancies, of which 3 were attributed to user failure. Two pregnancies were recorded as method failure, giving a Pearl Index of 0.08. Cycle control with monophasic gestodene was observed to be excellent. The incidence of spotting and breakthrough bleeding was low and declined during the course of the study, as did amenorrhea. The preparation was tolerated well and the incidence of side-effects was low, with only 4.4% of women withdrawing from the study due to adverse events. An increase in body weight was uncommon, and, at cycle 6, 91.2% of women had not gained weight. At the end of the study, 85.0% of women rated monophasic gestodene as good and 9.6% as satisfactory.

Topics: Adolescent; Blood Pressure; Contraceptives, Oral; Female; Humans; Menstrual Cycle; Norpregnenes; Pregnancy; Uterine Hemorrhage; Weight Gain

During one year of treatment with oral contraceptives containing 30 micrograms ethinylestradiol and 150 micrograms desogestrel (EE/DG) or 30 micrograms EE and 75 micrograms gestodene (EE/GSD), the serum concentrations of EE, 3-keto-desogestrel (KDG) and GSD were determined on day 1, 10 and 21 of the 1st, 3rd, 6th and 12th cycle. The areas under the time-versus-concentration curves were calculated from the levels before and 0.5, 1, 1.5, 2, 3, 4 and 24 hours after intake of a tablet. There were large intra- and interindividual variations both revealing coefficients of variation (C.V.) between 25% and 80% (EE),, 30% and 50% (KDG) and 30% and 65% (GSD). During each cycle, the EE levels increased significantly between day 1 and 10 by 70% on average reaching a steady-state, while the progestogen concentrations rose by 100% (KDG) and 150% (GSD) up to a steady-state between day 10 and 21. After reaching the steady-state, the C.V. were generally lower. The ratios between the levels of EE and the progestogens showed still higher variations indicating different influences on the estrogen and progestogen component. There was no correlation between the steroid levels and weight, height or age. In spite of the large intraindividual variations, most of the women showed a distinct pattern of the levels of EE and the progestogens throughout the year of treatment indicating a genetic or acquired predisposition. The difference in the average AUC of EE, KDG and GSD between the women was 300% at most. During the first cycle of treatment with EE/DG and EE/GSD, about half of the women recorded intermenstrual bleedings which decreased thereafter. There was no relation between the occurrence of irregular bleedings and the average serum levels of EE and the progestogens of the individual women, neither during the first cycle nor during the whole treatment period of 12 cycles. It is concluded that spottings or breakthrough bleedings during treatment with oral contraceptives are not dependent on a distinct pattern of the serum levels of EE and the progestogen.

Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Desogestrel; Ethinyl Estradiol; Female; Humans; Multivariate Analysis; Norpregnenes; Progesterone Congeners; Uterine Hemorrhage

To study the influence of smoking on uterine bleeding patterns during sequentially administered oral hormone therapy (HT).. Using a post-hoc strategy, we included four sequential oral HT groups from two studies. The therapies consisted of estradiol from days 1 to 28 (estradiol or estradiol valerate) and progestogen (levonorgestrel or gestodene) on days 17-28. A total of 111 healthy, early postmenopausal women (38 smokers and 73 non-smokers) followed for 2 years were included in the analyses. Uterine bleeding data were collected from bleeding calendars.. On the regimen containing levonorgestrel, smoking women had a cyclical bleeding significantly earlier than non-smoking women (about 2 days' difference). Moreover, smoking women had significantly longer bleeding than non-smoking women (about 1 day in difference). This was in contrast to the three regimens containing gestodene, where smoking seemed to have far less influence on uterine bleeding.. On a regimen containing levonorgestrel, smokers exhibit an earlier and longer uterine bleeding than do non-smokers. This is in contrast to regimens containing gestodene, where smoking women are less likely to differ from non-smoking women with regard to bleeding. This indicates that smoking influences progestogen metabolism, and that this influence may vary with different progestogens. Further studies are needed.

Topics: Administration, Oral; Contraceptive Agents; Estradiol; Estrogen Replacement Therapy; Female; Humans; Levonorgestrel; Middle Aged; Norpregnenes; Postmenopause; Randomized Controlled Trials as Topic; Smoking; Uterine Hemorrhage

A prospective, open-label, noncomparative, multicenter study was carried out in 163 women aged 18-39 (mean 25+/-5 years), who used an ultra-low-dose oral contraceptive pill (OCP) containing gestodene (GTD) 60 mug/ethinylestradiol (EE) 15 mug for 6 months. The objective of the study was to evaluate the acceptability, safety, bleeding patterns and premenstrual symptomatology in these women.. Patients used the OCP from Days 1-24, followed by a 4-day pill-free interval from Days 25-28 of the menstrual cycle. Physical and gynecological examinations were carried out at baseline and after 3 and 6 months, at which time blood pressure, weight, hemoglobin, hematocrit, SGOT, SGPT and urinalysis were also assessed. The Moos Menstrual Distress Questionnaire (MDQ) was completed on three consecutive days (Days 25-27 of the cycle) at baseline and at the end of the third and sixth cycles. Patients kept a menstrual diary throughout the study.. A total of 146 women completed the study. Ten women discontinued because of adverse events and one undesired pregnancy occurred during treatment. No adverse metabolic effects were observed. The adverse event most frequently reported was breakthrough bleeding, which diminished, however, as the time of OC use increased. Cycle length and duration of bleeding decreased significantly with OC use (p<.01 and p<.05, respectively, after 6 months). Intensity of menstrual bleeding tended to decrease with OC use, but this difference was not statistically significant. Systolic and diastolic blood pressure were significantly lower after 6 months of OC use compared to baseline (p<.02). No alterations were recorded in body weight or laboratory evaluations. Statistically significant changes were found both in the total MDQ score and in several of the factors evaluated, and patients showed a statistically significant improvement in well-being with respect to premenstrual complaints and symptoms.. This OC regimen is safe, well-accepted and well-tolerated, affects menstrual patterns beneficially by reducing both the intensity and duration of bleeding, provides good cycle control and improves premenstrual symptomatology.

Topics: Adolescent; Adult; Blood Pressure; Contraceptives, Oral; Ethinyl Estradiol; Female; Humans; Menstrual Cycle; Menstruation Disturbances; Norpregnenes; Pregnancy; Prospective Studies; Uterine Hemorrhage

The purpose of this study was to compare cycle control, efficacy and side effects of an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene, with a reference preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. From the study, it was demonstrated that the two regimens had no difference in cycle control, efficacy, and side effects. The occurrence of spotting and breakthrough bleeding was low and was not different between these two preparations. The most common adverse events in both treatment groups were nausea, vomiting, dizziness, and chloasma. There were no statistically significant change in body weight and blood pressure in both groups at the end of study. It is concluded that both preparations are good cycle control, reliable and low side effects oral contraceptives.

Topics: Adult; Blood Pressure; Body Weight; Contraceptives, Oral; Dizziness; Ethinyl Estradiol; Female; Humans; Melanosis; Menstrual Cycle; Nausea; Norpregnenes; Thailand; Uterine Hemorrhage; Vomiting

To compare the effect of starting oral contraceptives on the first day of menses with the effect of starting on the day of menses' cessation (but no later than the 5th day following its onset), on the incidence of early breakthrough bleeding.. Oral contraceptives containing 30 micrograms ethinylestradiol and 75 micrograms gestodene were prescribed to 200 consecutive healthy women in whom oral contraceptives were found to be the most suitable method of contraception. In the first 100 women, treatment was started on the 1st day after the onset of menses (Day 1 group), and in the remainder, treatment was started on the day of menses' cessation, but no later than the 5th day following its onset (Flexible group).. The Flexible group had better compliance and a reduced incidence of breakthrough bleeding. No differences were observed between the two groups for age, parity and gravity, or contraceptive failure.. Oral contraceptives may be initiated on the day of menses' cessation, but no later than the 5th day following its onset. This regimen might increase patient compliance and lower the incidence of breakthrough bleeding, probably without adversely affecting contraceptive efficacy.

Topics: Adolescent; Adult; Case-Control Studies; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Drug Administration Schedule; Estradiol Congeners; Ethinyl Estradiol; Female; Humans; Incidence; Menstrual Cycle; Norpregnenes; Patient Compliance; Progesterone Congeners; Prospective Studies; Uterine Hemorrhage

Ability of progesterone, gestodene, promegestone and cyproterone acetate (CPA) to reverse antigestagenic action of onapristone in adult female guinea pigs was investigated. Onapristone (10 mg/kg, s.c.) administered on post-conception days 8-11 caused resorption of implantations and vaginal bleeding in all animals. Simultaneous administration of progesterone, gestodene or promegestone on days 7-13 successfully reversed antigestagenic action of this antiprogestin, since most animals supplemented with these progestagens had viable implantations at autopsy on day 14. CPA was, however, ineffective and animals supplemented with it had only resorbed implantations and blood in uterus and vagina like that in onapristone per se treated animals. High plasma progesterone and low PGFM concentration were generally observed in all pregnant animals bearing viable implantations. PGFM (13, 14-dihydro-15-keto PGF2 alpha) was significantly elevated by day 14 in onapristone-treated (Group II) and CPA-supplemented (Group X) animals. No discernible effect on pregnancy or post-implantation embryonic development was observed in animals treated per se with these progestagens.

Topics: Animals; Corpus Luteum; Embryo Implantation; Embryonic and Fetal Development; Female; Fetal Resorption; Gestational Age; Gonanes; Guinea Pigs; Hormone Antagonists; Norpregnenes; Pregnancy; Progesterone; Progesterone Congeners; Progestins; Promegestone; Uterine Hemorrhage