Incidence Of Breakthrough Bleeding Research Articles

Incidence of breakthrough bleeding in transgender and gender-diverse individuals on long-term testosterone

BackgroundLittle is known about maintenance of amenorrhea in transgender and gender diverse individuals with uteri using long-term testosterone gender-affirming hormone therapy. Emerging data describes breakthrough bleeding in adolescents on long-term testosterone, as well as in adults seeking gender affirming hysterectomy. More studies are needed to better understand breakthrough bleeding patterns in transgender and gender diverse individuals on testosterone with uteri, including the frequency, timing, and etiology, and how these may differ in adults compared to younger populations. ObjectivesThe primary aim of this study was to characterize the incidence and patterns of breakthrough bleeding in a cohort of transgender and gender diverse individuals who had been on testosterone for greater than 12 months and had uteri in situ. Secondary aims included identifying the time to first bleed for those who experienced breakthrough bleeding as well as risk factors associated with breakthrough bleeding on testosterone. Study DesignThis was an IRB approved, single tertiary center, retrospective chart review of transgender and gender diverse individuals who had been on testosterone for at least one year. A primary survival analysis looking at the incidence of bleeding was combined with descriptive analyses and evaluation of factors associated with bleeding. ResultsOf the 279 patients included in the analysis, the median age of testosterone initiation was 22 years (IQR 19-41), with the median follow-up time 34 months (range 12-278). The absolute proportion of individuals who ever experienced breakthrough bleeding on testosterone was 34% (n=96, 95% CI [29, 40]). Patients who experienced breakthrough bleeding initiated testosterone at a younger age (20.5 vs 22.0 years, p=0.04), had lower mean serum testosterone levels (389.14 vs 512.7 ng/dL, p=0.001), were more likely to have a mean testosterone level <320ng/dL (52% vs 48% , p=.001), and had higher mean estradiol levels (62% vs 49%, p=0.003). Survival analyses estimated a breakthrough bleeding incidence rate of 0.09 per year (95% CI [.07-1.0]). While 58 people underwent a hysterectomy during the follow-up period, 64% of the cohort who maintained a uterus eventually experienced breakthrough bleeding. The median time to the initial bleeding episode was 22 (IQR 12-201) months after testosterone initiation. Conclusion(s)These results suggest a substantial fraction of transgender and gender diverse individuals using testosterone will experience at least one episode of breakthrough bleeding, even after their initial year using testosterone. We recommend that clinicians counsel all patients that breakthrough bleeding is a common occurrence, even after the first year on testosterone.

Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 μg ethinylestradiol and 150 μg levonorgestrel: a randomized trial

This trial was conducted to compare cycle control with vaginal ring a combined contraceptive vaginal ring, and a combined oral contraceptive (COC) delivering 30 mug ethinylestradiol (EE) and 150 mug levonorgestrel. This open-label, randomized, multi-centre, Phase III study involved adult women from 11 countries. Subjects were treated with either vaginal ring or a COC for 13 cycles (12 months). A total of 1030 subjects (vaginal ring, n=512; COC, n=518) comprised the intention-to-treat (ITT) population. The percentage of women in the ITT population who completed the trial was 70.9% for vaginal ring and 71.2% for the COC group. The incidence of breakthrough bleeding and spotting over cycles 2-13, the primary efficacy parameter, was lower with vaginal ring (range 2.0-6.4%) than the COC (range 3.5-12.6%), and for cycles 2 and 9 the lower incidence with vaginal ring was confirmed as statistically significant (P=0.003 and P=0.002 respectively). The incidence of intended bleeding was significantly higher over all cycles with vaginal ring (58.8-72.8%) than with the COC (43.4-57.9%). Cycle control with vaginal ring was excellent and superior to that of a COC containing 30 mug EE.

Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate

Depo-medroxyprogesterone acetate (DMPA) is an effective injectable contraceptive with worldwide availability. However, it is associated with a high incidence of breakthrough bleeding (BTB) during the first 6 months of use which often leads to discontinuation. Mifepristone is a progesterone receptor antagonist that has been demonstrated to decrease BTB caused by the levonorgestrel subdermal implant (Norplant™). The purpose of this study was to determine if mifepristone would decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo every 2 weeks for 24 weeks. Percent days of BTB and number of cycles with bleeding intervals ≥8 and ≥14 days were evaluated using daily bleeding diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites of estrogen and progesterone. Endometrial concentrations of ER and PR were determined by immunohistochemistry. Mifepristone significantly decreased the percent days of BTB and the number of cycles with prolonged bleeding intervals when compared to placebo. No subject ovulated in either group. ER immunostaining increased and PR immunostaining decreased after mifepristone treatment. In conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the incidence of BTB in new starters of DMPA. This effect may be due to modulation of endometrial estrogen and progesterone receptors.

A prospective, randomized, placebo-controlled trial of mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate (DMPA)

Objective: The clinical application of DMPA for contraception is associated with excellent contraceptive protection; a significant proportion of users experience breakthrough bleeding (BTB) which may lead to discontinuation of therapy. Our objective was to determine if a twice monthly oral dose of mifepristone will decrease the incidence of BTB in new starters of DMPA and to determine the effects of mifepristone on endometrial sex steroid receptors following DMPA and mifepristone administration.

Contraceptive efficacy and cycle control with the Ortho Evra™/Evra™ transdermal system: the analysis of pooled data

Objective: To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra™/Evra™). Design: Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles. Setting: 183 centers. Patient(s): 3,319 women. Intervention(s): Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle. Main Outcome Measure(s): Contraceptive efficacy and cycle control. Result(s): Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%–1.3%) and 0.6% (95% CI, 0.2%–0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44–1.33) and 0.7 (95% CI, 0.31–1.10). Contraceptive failure among women with a body weight <90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight ≥90 kg (≥198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time. Conclusion(s): In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women <90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women ≥90 kg (≥198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.

Efficacy and Safety of a Transdermal Contraceptive System

In Brief OBJECTIVES To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 μg and ethinyl estradiol 20 μg daily. METHODS In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. RESULTS The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). CONCLUSIONS The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics. The weekly transdermal contraceptive patch provides excellent contraceptive efficacy, cycle control, compliance, safety, and tolerability as shown in this open-label, international study.

Efficacy and safety of a transdermal contraceptive system

OBJECTIVES: To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 μg and ethinyl estradiol 20 μg daily. METHODS: In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six ( n = 1171) or 13 cycles ( n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. RESULTS: The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). CONCLUSIONS: The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

Transdermal Progesterone or Synthetic Progestogens

The increasing use of transdermal progesterone creams and gels and the introduction of transdermal patches containing the progestogens norethisterone and levonorgestrel has led to a group of problems, concerns and enthusiastic claims for transdermal therapy regimens which require careful scrutiny and evaluation. From a review of the literature it appears that transdermal progesterone creams are poorly absorbed and, at the doses presently used for therapy regimens, do not achieve plasma levels sufficient to protect the endometrium from oestrogen-induced proliferation. On the other hand transdermal progestogen in the form of norethisterone is absorbed and achieves blood levels sufficient to inhibit mitosis or to induce a secretory change in the endometrium. Transdermal progestogens may not result in some of the adverse responses associated with oral therapy and therefore are likely to be the preferred route of delivery for those women who suffer from problems associated with oral preparations. Transdermal progestogen regimens achieve a constant low blood level rather than a high initial level followed by the rapid degradation, which is associated with oral progestogen therapy. This lower constant level may explain why transdermal progestogens may be associated with fewer adverse reactions than oral administration, and why the transdermal combined patches have a higher incidence of breakthrough bleeding.

Multicenter study of the efficacy, cycle control and tolerability of a phasic desogestrel-containing oral contraceptive

Objective To investigate the efficacy, cycle control and tolerability of a phasic oral contraceptive containing ethinylestradiol 35/30/30 μg and desogestrel 50/100/150 μg.Methods A multicenter study was conducted involving 2070 healthy, fertile women, who received study treatment for six treatment cycles.Results Most of the participants (79%) had previously been using an alternative oral contraceptive. In 10 408 treatment cycles, two women became pregnant while on treatment (Pearl index, 0.25). The incidence of irregular bleeding was 10% before treatment, rising to 27% at cycle 1, and decreasing to 11% by cycle 6. Irregular bleeding was mainly due to spotting rather than breakthrough bleeding and the incidence of breakthrough bleeding remained below 2.2% for most of the study period. Only 1.8% of women withdrew due to bleeding irregularities. First-time oral contraceptive users initially experienced more irregular bleeding than switchers but these differences lessened over time. The most common adverse events during treatment were headache, breast tenderness and nausea. The incidence of these adverse events fell to below pretreatment levels with continued use.Conclusion The phasic preparation was effective and well tolerated.

Cycle control, safety and efficacy of a 24-day regimen of gestodene 60 µg/ ethinylestradiol 15 µg and a 21-day regimen of desogestrel 150 µg/ethinylestradiol 20 µg

Objectives: This multicenter, open-label study was conducted to compare the cycle control, efficacy and safety of a 24-day regimen of a new ultra-low-dose oral contraceptive containing gestodene (GTD) 60 µg/ethinylestradiol (EE) 15 µg and a 21-day regimen of desogestrel (DSG) 150 µg/EE 20 µg.Methods: Healthy women at least 18 years of age who had had regular menstrual cycles for the prior 3 months were randomly assigned to treatment for six cycles.Results: Data from 1074 women were included in the analyses. Overall, 65% of cycles were normal with GTD/EE and 78% with DSG/EE. The overall incidence of breakthrough bleeding and/or spotting was 29% with GTD/EE and 20% with DSG/EE, with absence of bleeding occurring in 6% of cycles in the GTD/EE group and 1% of cycles in the DSG/EE group. The GTD/EE group had a significantly shorter length of bleeding episodes (4 vs. 5 days, p < 0.001), a significantly lower intensity of bleeding (p < 0.01) and a significantly shorter time for onset of withdrawal bleeding than the DSG/EE group (p < 0.001). Safety profiles for the two treatment groups were similar. Significantly more subjects in the DSG/ EE group withdrew because of breast pain (p = 0.03) and nausea or vomiting (p = 0.05). One pregnancy occurred in each treatment group.Conclusions: The 24-day regimen of GTD 60 µg/EE 15 µg provided good efficacy, acceptable cycle control and a favorable safety profile compared with DSG/EE. This ultra-low-dose formulation offers unique advantages in efficacy and safety for oral contraception.

Flexible starting schedule for oral contraception: effect on the incidence of breakthrough bleeding and compliance

Objective 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.Method Oral contraceptives containing 30 μg ethinylestradiol and 75 μg 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).Results 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.Conclusions 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.

The pharmacodynamic effects of an oral contraceptive containing 3 mg micronized 17β-estradiol and 0.150 mg desogestrel for 21 days, followed by 0.030 mg desogestrel only for 7 days

During oral treatment with 3 mg micronized 17β-estradiol and 0.150 mg desogestrel for 21 days followed by 0.030 mg (A) desogestrel (15 women) or placebo (B) (14 women) for 7 days, ovarian function, bleeding pattern and estradiol levels were evaluated. The study was performed in a group-comparative, double-blind fashion. During a pre-treatment control cycle, using ultrasound scan, follicular diameter was measured on cycle days 10–16 and endometrial thickness on one of cycle days 22–26. Estradiol was measured at time of ultrasound scan and progesterone three times in the luteal phase. During three treatment cycles, follicular diameter and endometrial thickness were monitored three times weekly and at the same time, estradiol and progesterone were measured. Treatment resulted in anovulation in all women. Maximum and mean estradiol levels were approximately 900 pmol/l and 550 pmol/l during treatment, respectively, and approximately 200 pmol/l during the estradiol-free weeks in both groups. Ten women showed ovarian activity (follicle size ≥ 15 mm) during treatment, seven in group A and three in group B. Endometrial thickness decreased approximately 3 mm during treatment in both groups. The incidence of breakthrough bleeding and spotting was higher in group A when compared to group B. The study indicates that the combination of 3.0 mg micronized estradiol and 0.150 mg desogestrel is an effective and safe contraceptive, offering an acceptable cycle control. The addition of a low dose of desogestrel during the pill-free period did not further suppress ovarian activity nor improve the bleeding pattern. The results of this study should be interpreted with great care, since the number of women studied is relatively small.

P230 Incidence of breakthrough bleeding after changing from cyclical HRT to tibolone

P230 Incidence of breakthrough bleeding after changing from cyclical HRT to tibolone

Monophasic gestodene and ethinylestradiol in oral contraception: A multicenter open study

A low-dose monophasic oral contraceptive containing 75μg of gestodene and 30μg of ethinylestradiol was evaluated for contraceptive reliability, cycle control and tolerability. The study was designed as a multicenter, open-label trial and involved a total of 285 women, aged 18 to 35 years, in nine centers, over six cycles. Contraceptive reliability was good and there were no pregnancies. Cycle control was excellent, as demonstrated by the decline in the incidence of breakthrough bleeding and spotting, culminating in their eventual absence by the end of cycle 6. Amenorrhea did not occur. There was significant moderation in cycle length, and duration and intensity of menstrual flow during the course of the study (p < 0.05). Treatment-related adverse events were reported by 37 (13%) subjects and were the cause of only one (0.3%) subject withdrawal. The most frequently reported were nausea (4.9%) and headache (3.9%). The occurrence of side-effects most commonly associated with oral contraception showed a decli...

Multicenter evaluation of a new low-dose triphasic oral contraceptive containing ethinylestradiol and gestodene (Tri-Minulet®), and its effect on the quality of life

To evaluate the effect of a low-dose, triphasic oral contraceptive containing gestodene and ethinylestradiol (Tri-Minulet®) on the subjective quality of life and general well-being of women, and to evaluate its efficacy, safety and cycle control, a total of 724 women, aged from 14 to 41 years, were enrolled in this open-label, non-comparative, multicenter study which was conducted over six cycles.Contraceptive reliability was good, and there were no pregnancies during the study. The duration and amount of menstrual flow decreased, and cycle control was good (4% spotting and 1.4% breakthrough bleeding at cycle 6 of the study). The incidence of breakthrough bleeding decreased significantly as did spotting, for all cycles compared to cycle 1 (p < 0.001 and p < 0.05, respectively). The study preparation was well tolerated. At the first assessment phase during study medication intake at cycle 3, 197 of 696 women (28.3%) reported adverse events. Tliis incidence declined to 11.9% (68 of 573 women) at cycle 6. Of...

Long oestradiol replacement in an oocyte donation programme.

The objective of this study was to optimize, in terms of endometrial receptivity (embryo implantation), the limits of unopposed administration of oestrogens beyond 35 days in an in-vitro fertilization (IVF) and ovum donation programme. Oocytes donated by 182 women undergoing IVF were distributed among 186 women treated by ovum donation. Five groups of recipients were established according to the duration of oestradiol valerate administration, in a 'prolonged follicular phase' protocol, before embryo replacement, employing oestradiol valerate at increasing doses up to 6 mg/day. Gonadotrophin-releasing hormone analogues (GnRHa) were simultaneously administered in ovulatory patients. The dosage of oestradiol valerate was maintained until oocytes were available for insemination and subsequent transfer. Donors and recipients were equally distributed among groups in terms of age and cause of infertility. There was no difference among groups in serum oestradiol concentration the day in which progesterone was added to obtain a secretory transformation of the endometrium. An analysis of the ovum donation cycles showed no difference among groups in pregnancy and implantation rates after the replacement of a similar number of embryos. Successful implantation was observed even after 100 days of unopposed oestradiol valerate administration. Break-through bleeding increasingly appeared according to the duration of oestrogen replacement. These clinical observations provide evidence that the concept of 'prolonged follicular phase' oestrogen replacement for ovum donation can be maintained, at least as long as 15 weeks. However, because of the high (> 44%) incidence of break-through bleeding after 9 weeks, it is advisable to stop oestrogen treatment at this point.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate

Both monophasic and triphasic formulations of ethinyl estradiol plus nor9estimate, a pro9estin with marked pro9esterone-receptor affinity and minimal androgen-receptor affinity, have been evaluated in numerous clinical studies designed to determine if nor9estimate's receptor-binding profile provides enhanced safety without a reduction in efficacy. To date clinical trials have shown that both formulations of ethinyl estradiol/nor9estimate offer contraceptive efficacy equivalent to that of other oral contraceptives. Monophasic ethinyl estradiol/nor9estimate was associated with an incidence of breakthrough bleeding and spotting similar to that of monophasic ethinyl estradiol/norgestrel and an incidence of amenorrhea less than that of ethinyl estradiol/norgestrel. Cycle control with triphasic ethinyl estradiol/nor9estimate was similar to that with monophasic ethinyl estradiol/nor9estimate. Weight gain and elevated blood pressure were insignificant in clinical trials with both fixed-dose and phasic ethinyl estradiol/nor9estimate formulations. Perhaps of greatest importance, both monophasic and triphasic ethinyl estradiol/nor9estimate formulations consistently showed favorable impact on metabolic parameters including elevations in serum high-density lipoprotein cholesterol, and reductions in the low-density lipoprotein/high-density lipoprotein ratio, the parameter considered most sensitive for atherosclerotic risk. Both monophasic and triphasic ethinyl estradiol/nor9estimate formulations were associated with minimal and clinically neutral effects on carbohydrate metabolism.

Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate

Both monophasic and triphasic formulations of ethinyl estradiol plus norgestimate, a progestin with marked progesterone-receptor affinity and minimal androgen-receptor affinity, have been evaluated in numerous clinical studies designed to determine if norgestimate's receptor-binding profile provides enhanced safety without a reduction in efficacy. To date clinical trials have shown that both formulations of ethinyl estradiol/norgestimate offer contraceptive efficacy equivalent to that of other oral contraceptives. Monophasic ethinyl estradiol/norgestimate was associated with an incidence of breakthrough bleeding and spotting similar to that of monophasic ethinyl estradiol/norgestrel and an incidence of amenorrhea less than that of ethinyl estradiol/norgestrel. Cycle control with triphasic ethinyl estradiol/norgestimate was similar to that with monophasic ethinyl estradiol/norgestimate. Weight gain and elevated blood pressure were insignificant in clinical trials with both fixed-dose and phasic ethinyl estradiol/norgestimate formulations. Perhaps of greatest importance, both monophasic and triphasic ethinyl estradiol/norgestimate formulations consistently showed favorable impact on metabolic parameters, including elevations in serum high-density lipoprotein cholesterol, and reductions in the low-density lipoprotein/high-density lipoprotein ratio, the parameter considered most sensitive for atherosclerotic risk. Both monophasic and triphasic ethinyl estradiol/norgestimate formulations were associated with minimal and clinically neutral effects on carbohydrate metabolism.

Norgestimate: A clinical overview of a new progestin

The efficacy and safety of a new monophasic oral contraceptive, norgestimate/ethinyl estradiol, containing the third-generation progestin, norgestimate (250 &#x03BC;g), and ethinyl estradiol (35 μg), are reviewed. Norgestimate/ethinyl estradiol demonstrates excellent contraceptive efficacy, with a Pearl index of 0.25. Cycle control is reliable, with a low incidence of breakthrough bleeding and spotting. Because of the minimal androgenicity of norgestimate, norgestimate/ethinyl estradiol has a low impact on carbohydrate and lipid metabolism. It neither reduces the vasodilatory and antiaggregatory prostacyclin nor increases its endogenous antagonist, thromboxane. Norgestimate/ethinyl estradiol has no significant effect on blood coagulation factors. All these characteristics suggest that norgestimate/ethinyl estradiol may be associated with a lower risk of cardiovascular disease than other oral contraceptives currently available. Epidemiologic data, however, are not available, and physicians should be reluctant to prescribe it or any oral contraceptive to patients who have a history of vascular or thrombotic disorders.

Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen.

The performance of a new low-dose oral contraceptive (Mercilon) containing only 20 micrograms ethinyloestradiol combined with 150 micrograms desogestrel is reviewed. Eight multicentre clinical trials have been completed and provide information on 10,672 women studied over 73,477 cycles. The high efficacy of Mercilon was indicated by the finding that only 10 pregnancies were reported; nine of these occurred in women who omitted to take Mercilon on a number of days and only one in a woman who took all the tablets according to instructions. Cycle control was good; as with all oral contraceptives, the incidence of breakthrough bleeding and spotting was highest in the first treatment cycle and by the sixth treatment cycle the values were usually < 5% and < 7%. More than 80% of women had regular cycles. Side effects were few, the most common being headache, nausea and breast tenderness with incidences in the sixth treatment cycle of less than 2%, 6% and 6%, respectively. There were no significant changes in body weight or blood pressure. Pharmacodynamic investigations showed no adverse effects. Only 1 of 5 studies found an increased response to a glucose tolerance test compared to the pretreatment test. In 8 of 10 studies, serum HDL-C concentrations increased on treatment and this was associated with increases in apoproteins A1 and A2. Serum triglyceride levels also increased but no change occurred in serum cholesterol or LDL-C levels. Haematological factors were assessed in 8 studies and only minor changes were observed. Serum binding protein (SHBG, CBG, caeruloplasmin) concentrations increased and serum androgen levels decreased. Measurements of blood FSH, LH, oestradiol and progesterone indicated adequate inhibition of ovulation. Mercilon is the only oral contraceptive containing 20 micrograms ethinyloestradiol to have high efficacy, to have no adverse pharmacodynamic effects and, importantly, to produce an acceptable bleeding pattern not significantly different from that of oral contraceptives with a higher content of ethinyloestradiol.