Bleeding pattern with drospirenone 3 mg+ethinyl estradiol 20 mcg 24/4 combined oral contraceptive compared with desogestrel 150 mcg+ethinyl estradiol 20 mcg 21/7 combined oral contraceptive

Background

The study was conducted to compare cycle control, bleeding pattern and efficacy of two low-dose combined oral contraceptives.

Study Design

Four hundred fifty-three women were randomized to receive a 24/4 regimen of drospirenone 3 mg/ethinyl estradiol 20 mcg (drsp 3 mg/EE 20 mcg; n=230) or a 21/7 regimen of desogestrel 150 mcg/EE 20 mcg (DSG 150 mcg/EE 20 mcg; n=223), and recorded bleeding daily over 7 treatment cycles.

Results

The duration [mean 4.7 (SD 1.5)-5.2 (SD 2.2) days in the drsp 3 mg/EE 20 mcg 24/4 group and 5.1 (SD 1.5)-5.4 (SD 2.1) days in the DSG 150 mcg/ EE 20 mcg group] and maximum intensity (“normal bleeding” for >50% of all subjects) of scheduled bleeding in Cycles 1-6 was comparable between treatment groups. The incidence of unscheduled bleeding during Cycles 2-6 was also similar between the two groups (drsp 3 mg/EE 20 mcg, 8.8-17.3%; DSG 150 mcg/ EE 20 mcg, 9.4-16.3%).

Conclusion

Drsp 3 mg/EE 20 mcg 24/4 achieved an acceptable bleeding profile with reliable cycle control, comparable with an established formulation.     

Efficacy and safety of a 28-day oral contraceptive with 7 days of low-dose estrogen in place of placebo

BACKGROUND: The study was conducted to evaluate the efficacy and safety for the prevention of pregnancy of a 28-day oral contraceptive (OC) containing 150 mcg desogestrel (DSG)/20 mcg ethinyl estradiol (EE) for 21 days followed by 7 days of 10 mcg EE (Cette-28). STUDY DESIGN: A 6-month, prospective, multicenter, single-arm study was conducted in 1302 women aged 18-45 years. RESULTS: Over six cycles of treatment, the cumulative risk of pregnancy among all treated subjects (n=1262) was 0.9%. The Pearl Index for women 18-35 years of age (n=1042) was 2.20, including 9 pregnancies with estimated conception dates during active drug ingestion or up to 7 days after the last combination tablet. The rate of unscheduled bleeding was low and the duration of scheduled bleeding was approximately 2 days during each of the six treatment cycles. The safety profile was similar to what has been reported for other OCs. CONCLUSION: This low-dose, 28-day OC incorporating 7 days of 10 mcg EE during the hormone free interval is effective and safe for the prevention of pregnancy and is well-tolerated by women.     

Influence of the LH-RH analogue buserelin on cyclic ovarian function and on endometrium. A new approach to fertility control?

The long-acting stimulatory luteinizing hormone - releasing hormone analogue D-Ser(TBU)6-EA10-LH-RH (buserelin) was administered intranasally once daily in a dose of 400 mcg to 24 normally ovulating women and to 4 women with pre-existing endocrine dysregulation. Ovulation was inhibited in 136 out of 156 treatment months. In 20 treatment months, progesterone values temporarily increased indicating luteinization of follicles or ovulation with defective corpus luteum function. Estradiol secretion showed a tendency to lower values as treatment progressed but individually indicated follicle maturation until the end of the observed medication period. Bleeding pattern ranged from menses-like bleeding in regular as well as irregular intervals to amenorrhea. The morphological findings of 31 endometrial biopsies of 20 volunteers ranged from atrophy (n = 4) to proliferation (n = 25) with early signs of hyperplasia as well as early secretory transformation (n = 2). The morphological alterations indicate that unopposed estrogen stimulation of the endometrium is the main problem of long-term contraception with the dose schedule of buserelin used.     

Clinical studies with a low dose estrogen-progestogen combination

Nine hundred and thirty women were followed for 7,197 cycles of treatment with a combination of levonorgestrel 150 mcg and ethinyl estradiol 30 mcg. Seven pregnancies were recorded, only one of them probably a drug failure (corrected Pearl Index 0.17). The cumulative termination rate for pregnancies (life-table) was 0.01 after 12 cycles. The total cumulative rate for terminations was 0.47 after 12 cycles. Cycle control was good in “new” patients, “switchers” and lactating women, but the incidence of breakthrough bleeding was higher in the latter group. In only 5.2% of the cycles more than 6 days of bleeding (including menses, BTB and spotting) were recorded. The incidence of subjective side effects was low. The group of patients on the average did not gain weight nor had any clinically significant increase in diastolic blood pressure.     

Two oral contraceptives with the same gestagen and different estrogen: A controlled clinical trial

A total of 237 healthy women have participated in a controlled double-blind comparison between two oral contraceptive preparations; A: Norethisterone 1 mg + mestranol 50 mcg (Plan mite R) and B: Norethisterone 1 mg + ethinyl estradiol 50 mcg (test preparation). The object of the trial was to investigate whether two preparations containing the same gestagen but a different estrogen are clinically different.Fifty women were excluded from the statistical analysis, 8 of them because of various side-effects (including bleeding disturbances).During a total of 1,345 cycles, 187 women participated. No significant difference was found between the two preparations, neither as regards their effect on the bleeding pattern (duration and amount), cycle control (number of women with spottings, breakthrough bleedings or amenorrhoea), frequency of nausea, weight increase, nor change in blood pressure. There was a tendency towards fewer bleeding disturbances and occurrences of nausea with norethisterone + mestranol.In women who had not been using oral contraceptives within the last three months before start of the trial, a significant weight increase was found during the first three cycles, and the duration and amount of the bleeding was also reduced.No pregnancies or cases of hypertension occurred during the trial.     

Second-trimester pregnancy termination with 600-microg vs. 400-microg vaginal misoprostol and systematic curettage postexpulsion: a randomized trial

BACKGROUND: This study was conducted to compare efficacy and safety of 600 mcg of misoprostol vaginally every 6 h up to four doses vs. 400 mcg of misoprostol vaginally every 4 h up to five doses, followed by systematic curettage of the uterine cavity, for pregnancy termination between 12 and 20 weeks' gestation. STUDY DESIGN: We used a randomized clinical trial conducted at Hospital Gineco-Obstétrico "Eusebio Hernández", Havana, Cuba. Subjects were women requesting voluntary termination of pregnancies between 12 and 20 weeks' gestation. Two hundred ten women were randomly assigned to receive 600 mcg of vaginal misoprostol every 6 h up to four doses (Group I) vs. 400 mcg of vaginal misoprostol every 4 h up to five doses (Group II), followed by curettage 1 h after expulsion. The main outcomes measured were successful abortion rate and mean expulsion time. RESULTS: Successful abortion occurred in 103/105 women (98.1%) in Group I and in 99/105 (94.3%) in Group II [p=.279, relative risk (RR)=3.121 and 95% confidence interval for RR=0.615 to 15.833]. Fetus mean expulsion time was 10.7+/-1.3 (SD) h in Group I and 11.5+/-5.0 (SD) h in Group II (p=.209). CONCLUSIONS: Six hundred micrograms of misoprostol administered vaginally every 6 h was as effective as 400 mcg of misoprostol every 4 h for second-trimester pregnancy termination.     

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel

Background

This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17β-estradiol.

Study design

This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years.

Results

Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3±10.4 vs. 21.5±8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4±9.vs. 15.9±7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG.

Conclusions

A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.     

Open prospective multicenter trial with a new monophasic contraceptive combination containing gestodene

In a large and open prospective multicenter trial of 12,250 cycles from 2,378 women, contraceptive efficacy, clinical tolerance and acceptability of a new monophasic contraceptive combination containing 75 mcg gestodene (delta-5-levonorgestrel) and 30 mcg ethinyl oestradiol were studied. The objective was to assess efficacy, safety, side effects and cycle control of this oral contraceptive on healthy women using no other additional birth control methods. Two women became pregnant (0.016%) during the trial; both were patient failures. There was no effect on systolic or diastolic pressures. An average weight increase of 0.3 kg was noted. Cycle control was excellent with 95% of the cycles free of spotting and 98% free of breakthrough bleeding after six cycles. No serious complications occurred. There was an overall incidence of 14% reported side effects (after six cycles), indicating that the hormonal combination is well tolerated. It should be noted that 41.4% of the patients had some complaint before starting the treatment. For all complaints, a highly significant improvement was seen during the treatment.     

Peptide contraception in women: Inhibition of ovulation by chronic intranasal LRH agonist therapy

Seventy-one healthy female volunteers used the LRH superagonist D-Ser(TBU) ⁶-EA¹⁰-LRH (buserelin) for contraception during 3–26 months. One daily dose of 200–600 μg was administered by the nasal route. No pregnancy occurred during the 628 treatment months. The bleeding pattern varied from fairly regular menstrual bleedings (n = 26) to oligomenorrhoea (n = 27) and amenorrhoea (n = 18). No severe or dysfunctional bleeding disturbances were observed. No signs of hyperplastic changes of the endometrium were found in 57 endometrial biopsies. After cessation of the long-term treatment normal ovulation and menstruation returned after 41.3 days, on average. Thus, intranasal administration of an LRH agonist for inhibition of ovulation is a promising new contraceptive method for women.     

Continuous,daily levonorgestrel/ethinyl estradiol vs. 21-day,cyclic levonorgestrel/ethinyl estradiol: efficacy,safety and bleeding in a randomized,open-label trial

BackgroundThis Phase 3, randomized, open-label, multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous, daily regimen of levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg compared with a 21-day, cyclic LNG 100 mcg/EE 20 mcg regimen.Study DesignThree hundred twenty-three healthy women were randomized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year (13 pill packs). Pearl index, adverse event (AE) incidence and bleeding profiles were assessed.ResultsNo pregnancies occurred with the continuous oral contraceptive (OC) (Pearl index=0.00). As the study progressed, the percentage of women who achieved amenorrhea during each 28-day pill pack increased: 40% at pill pack 7, 53% at pill pack 13. The percentage of women with no bleeding [with or without spotting (defined as not requiring sanitary protection)] was 50%, 69% and 79% at pill packs 3, 7 and 13, respectively. The incidence of AEs was similar to that of the cyclic OC (except for metrorrhagia and vaginal bleeding in the first 6 months).ConclusionsContinuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC. Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous, low-dose OC.     

Effects of a luteinizing hormone-releasing hormone agonist on luteal function in women

The potent stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)⁶-EA¹⁰-LRH was administered once daily during the luteal phase of the human menstrual cycle. The treatment was instituted in the early or mid-luteal phase of the cycle. Early luteal phase institution of intranasal treatment with 600 μg of the LRH agonist once daily reduced the basal progesterone levels during the luteal phase in 4 women but did not cause premature onset of menstruation. Mid-luteal phase institution of subcutaneous treatment with 10 μg of the LRH agonist once daily did not affect the progesterone levels or reduce the length of the luteal phase in 5 women. Thus, daily postovulatory administration of the LRH agonist D-Ser (TBU)⁶-EA¹⁰-LRH did not cause luteolysis in normally cycling women.     

Efficacy, safety and sustainability of treatment continuation and results of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg chlormadinone acetate, in long-term usage (up to 45 cycles)--an open-label, prospective, noncontrolled, office-based Phase III study

BACKGROUND: This open-label, noncontrolled study assessed the long-term efficacy and tolerability of the monophasic combined low-dose oral contraceptive (OC) ethinyl estradiol (EE) 30 mcg+chlormadinone acetate (CMA) 2 mg (Belara). STUDY DESIGN: In total, 781 women who had already taken EE 30 mcg+CMA 2 mg for 24 cycles in a previous Phase III study were assessed for up to 45 cycles. RESULTS: Over 23,033 cycles, the Pearl Index was 0.16 (95% confidence interval, 0.04-0.42). Approximately 86% of women had regular withdrawal bleeding in each cycle, while incidence of intracyclic bleedings (1.6-6.4%) and proportion of women with amenorrhea (4%) were low. The incidence of acne decreased from 13.8% to 5.7%, while rates of hirsutism, alopecia and seborrhea remained low (< or =4%) throughout this study. The most frequent adverse events were consistent with OC treatment, and no unexpected events occurred. No changes in mean blood pressure and pulse rate were observed during the study, and there were no clinically relevant changes in liver or hematological parameters, hemostasis or carbohydrate metabolism. The incidence of pathological findings in gynecological examination was low and decreased over time. CONCLUSION: EE 30 mcg+CMA 2 mg was an effective and well-tolerated OC, with beneficial effects on cycle stability, intracyclic bleeding, amenorrhea and signs of androgenization that were maintained during long-term treatment for up to 5 years. There was no evidence of an increased risk of thromboembolic events, atherogenic disease or cervical cancer, suggesting that 30 EE mcg+CMA 2 mg is highly suitable for long-term use.     

Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial

Background

This Phase 3, randomized, open-label, multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous, daily regimen of levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg compared with a 21-day, cyclic LNG 100 mcg/EE 20 mcg regimen.

Study Design

Three hundred twenty-three healthy women were randomized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year (13 pill packs). Pearl index, adverse event (AE) incidence and bleeding profiles were assessed.

Results

No pregnancies occurred with the continuous oral contraceptive (OC) (Pearl index=0.00). As the study progressed, the percentage of women who achieved amenorrhea during each 28-day pill pack increased: 40% at pill pack 7, 53% at pill pack 13. The percentage of women with no bleeding [with or without spotting (defined as not requiring sanitary protection)] was 50%, 69% and 79% at pill packs 3, 7 and 13, respectively. The incidence of AEs was similar to that of the cyclic OC (except for metrorrhagia and vaginal bleeding in the first 6 months).

Conclusions

Continuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC. Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous, low-dose OC.     

Matched-pairs analysis of ovarian suppression during oral vs. vaginal hormonal contraceptive use

Background

This study was conducted to compare ovarian suppression during oral vs. vaginal hormonal contraceptive use. Secondary aims included comparison of endometrial thickness and bleeding patterns.

Methods

In two open-label trials assessing ovarian suppression, 33 compliant women completed both studies. They first used oral contraceptive pills (OCs) [randomized to either 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) or 30 mcg EE/150 mcg LNG] and subsequently used contraceptive vaginal rings (CVRs) (daily release of 15 mcg EE/120 mcg etonogestrel), all 21/7-day regimens. Participants had at least one run-in cycle using each contraceptive method prior to evaluation. During one cycle of each method, women underwent biweekly transvaginal sonography to measure ovarian follicular diameters and endometrial thickness. We also noted presence of a corpus luteum or a ruptured follicle as a marker of ovulation. Participants recorded bleeding days on paper calendars. We used matched-pairs analyses as appropriate.

Results

During follow-up, we identified at least one ovarian follicle ≥8 mm in 20/33 (61%) OC users and 12/33 (36%) CVR users (matched-pairs analysis, p=.02). Similar trends were seen for larger follicles; however, we had limited statistical power to evaluate these differences. Median follicular diameter among OC users was larger than median follicular diameter among CVR users (p=.01). We did not observe a corpus luteum or ruptured follicle in any participant during either study. Endometrial thickness was similar during OC and CVR use (mean 4.1±1.4 vs. 4.1±1.6 mm, p=.9), as was the number of bleeding or spotting days (mean 2.1±2.4 vs. 1.9±2.1, p=.8). Oral contraceptive pill dose was unrelated to follicle diameter, endometrial thickness or bleeding.

Conclusions

Ovarian follicles ≥8 mm were more common in 33 compliant women during OC use than during CVR use, indicating that CVR use results in greater ovarian suppression than OC use.     

Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol 20 mcg based on 2 years of clinical trial data in Canada

BackgroundThe study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg.Study DesignHealthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events.ResultsSeventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively.ConclusionsContinuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting.     

The vaginal contraceptive pill

Vaginal administration of oral contraceptives (OCs) has been shown to be an acceptable and effective method of contraception. The most widely tested vaginal contraceptive pill (VCP) contains 500 mcg of d-1 norgestrel and 50 mcg of ethinyl estradiol (EE) and is administered on the same 21-day schedule as the oral contraceptive. Other combination OCs used vaginally include 1 mg of norethisterone plus 50 mcg of mestranol, 250 mcg of levonorgestrel plus 50 mcg of EE, and 2 mg of cyproterone acetate plus 50 mcg of EE. Gestrinone, a potent antiestrogenic progestin, has also been used with success. Comparative studies of the various combination pills and Gestrinone revealed that plasma levels of the progestins rose at a slower pace and to a lower peak value after vaginal administration than after ingestion, but ovulation was suppressed in most cycles. Fertility control compared favorably with most low-dosage combined pills taken by mouth. No pregnancies occurred in a group of 124 women who used the vaginal route for 6-20 months totalling 1438 woman-months of use. Cycle control was good, and bleeding episodes occurred following discontinuation and lasted 3-5 days in 98% of cycles. Amenorrhea was rare, and breakthrough bleeding and spotting occurred in fewer than 10% of women. 22% of the women gained more than 2 kg and 9% lost weight. Blood pressure remained unchanged in most women, and fewer than 10% had headache, nausea, acne, nervousness, or mastalgia. Fewer than 20% had vaginal discharge requiring treatment, with Trichomonas vaginalis being the most common pathogenic agent. In 1 study, 44 women discontinued VCP use before completing 1 year of use, 7 for medical reasons (2 for mastalgia, 2 for vaginal irritation, 3 for vaginal discharge unresponsive to treatment), 6 to achieve pregnancy, and the remaining 31 to avoid daily vaginal insertion. The VCP achieved the same results as OCs with a minimum of side effects due to the low steroid levels and because VCPs bypass the liver on the 1st pass. The vaginal ring shares these advantages of the VCPs, but the bulky silastic rubber structure of the ring may cause erosion of the vaginal wall, interfere with coitus, and absorb release unpleasant odors. Problems with vaginal rings also include expulsion, difficulty of insertion and removal, and storage. The VCP may be a better alternative than the OC as the 1st prescribed contraceptive for family planning clinics because the low blood levels of steroid will reduce the occurrence of side effects in longterm use.     

Reproductive endocrine effects of intranasal administration of norethisterone (NET) to women

Four consecutive menstrual cycles were studied in six healthy parous women. A solvent mixture comprising propylene glycol:ethanol:water (3:3:4) was sprayed intranasally daily using a glass atomizer between days 5 and 24 of the first (control) menstrual cycle. NET was dissolved in the solvent and similarly administered at a daily dose of 100 mcg during the second and third menstrual cycles. Nasal sprays were not administered during the fourth post-treatment cycle. Blood samples were taken during four consecutive cycles between days 8 and 15 and again between days 20 and 24 of the cycle to estimate levels of estradiol (E2), FSH, LH and progesterone (P). These studies revealed that nasal sprays of NET were well accepted and that no adverse clinical effects or menstrual disturbances occurred. NET inhibited ovulation in one cycle. The E2-induced mid-cycle rise in FSH and LH was either suppressed or inhibited in nine out of the 12 treated cycles. P levels in three treated cycles were indicative of luteal inadequacy. These endocrine effects of NET persisted into the post-treatment cycle in two cases.     

Two routes of administration for misoprostol in the treatment of incomplete abortion: a randomized clinical trial

Background

This study was conducted to compare the safety, effectiveness and acceptability of 400 mcg sublingual misoprostol and 600 mcg oral misoprostol for treatment of incomplete abortion.

Study Design

We used an open-label randomized controlled trial conducted from July 2005 to August 2006 in a large tertiary level maternity hospital in Antananarivo, Madagascar, and a large tertiary level hospital in Chisinau, Moldova. Three hundred consenting women seeking treatment for clinically diagnosed incomplete abortion with uterine size ≤12 weeks since last menstrual period were randomized to misoprostol either 600 mcg orally or 400 mcg sublingually. The primary outcome measure was the complete resolution of clinical signs and symptoms of incomplete abortion without need for surgical intervention. Women were seen for follow-up on Day 7 and, if necessary, on Day 14 to assess abortion status. The study was powered to detect a 7% difference in efficacy with a total of 142 women required in each arm.

Results

Efficacy rates were 94.6% and 94.5%, for the oral and sublingual routes, respectively (RR: 1.00, 95% CI=0.95–1.06, p=.98). At 1 week follow-up, more than 80% of women had completed abortions (77.8% oral and 84.8% sublingual, p=.12). Mean pain scores were 2.95 and 3.04, respectively, for the oral and sublingual groups. Side effects included abdominal pain, bleeding, headaches and dizziness/weakness with no differences reported between the two groups. Acceptability and satisfaction were high for both routes and women indicated a preference for medical versus surgical treatment if ever needed in the future.

Conclusions

Both treatment regimens were very effective. Four hundred micrograms of sublingual misoprostol and 600 mcg oral misoprostol appear to have similar safety and effectiveness profiles when used for the treatment of incomplete abortion. A lower 400-mcg misoprostol dose may provide an alternative treatment option as well as have potential benefits in terms of cost.     

Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol 20 mcg based on 2 years of clinical trial data in Canada

Background

The study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg.

Study Design

Healthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events.

Results

Seventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively.

Conclusions

Continuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting.     

Inhibition of ovulation in women by chronic treatment with a stimulatory lrh analogue — A new approach to birth control?

A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser (TBU)⁶-EA¹⁰-LRH was administered subcutaneously once daily in a dose of 5 ug to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22 – 30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular maturation and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.