Triphasic Levonorgestrel Research Articles

A comparison between monophasic levonorgestrel–ethinyl estradiol 150/30 and triphasic levonorgestrel–ethinyl estradiol 50–75–125/30–40–30 contraceptive pills for side effects and patient satisfaction: A study in Iran

Objective Oral contraceptive pills (OCPs) are one of the most effective reversible and accessible contraceptives, and patient acceptance for their use depends partly on the unfavorable adverse effects. The present study compared the two kinds of OCPs (monophasic; levonorgestrel (LNG)–ethinyl estradiol (EE) 150/30 versus triphasic; LNG–EE 50–75–125/30–40–30) for adverse effects and patient satisfaction. Study design A randomized clinical trial was performed on 314 women who used OCPs for the first time, as their contraception, for 6 months. Overall, 1884 cycles were studied. In the monophasic group ( n = 159 who finally finished the study), monophasic pills LNG–EE 150/30 mcg, and in the triphasic group ( n = 155 who finally finished the study), triphasic pills LNG–EE 50–75–125/30–40–30 mcg were used. Statistical analysis was performed using SPSS 10: Chi square test, Fisher exact test and Student's t-test were used. Results There were no significant differences between the two groups for common side effects, including nausea, headache, nervousness, facial hyperpigmentation (chloasma), and body weight (increase or decrease) but breakthrough bleeding and spotting (BTB/S) were less in the triphasic group, occurring in 30 cycles (18.86%) versus 10 cycles (6.45%), P = 0.009*. Patient satisfaction for the two OCPs was similar and high. The rates of side effects were low. Conclusion It seems that the monophasic and triphasic pills are similar according to patient satisfaction and side effects; therefore there is no benefit of one over the other except for BTB/S, for which triphasic is superior.

Biphasic versus triphasic oral contraceptives for contraception

Side effects caused by oral contraceptives discourage compliance with, and continuation of, oral contraceptives. A suggested disadvantage of biphasic compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage. To compare biphasic with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. We searched MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. We searched the reference lists of relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. We included randomized controlled trials comparing any biphasic with any triphasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the searches for possible inclusion and assessed methodological quality using Cochrane guidelines. We contacted the authors of included studies and of possibly randomized studies for supplemental information about the methods and outcomes. We entered the data into RevMan. We calculated Peto odds ratios for incidence of discontinuation due to medical reasons, intermenstrual bleeding, and absence of withdrawal bleeding. Only two trials of limited quality met our inclusion criteria. Larranaga 1978 compared two biphasic pills and one triphasic pill, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. Percival-Smith 1990 compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and with another triphasic containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic. The odds ratio of cycles with intermenstrual bleeding was 1.7 (95% CI 1.3 to 2.2) for the biphasic compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95% CI 3.1 to 13). In contrast, cycle control with the biphasic pill was comparable to that of the triphasic containing the same progestin (norethindrone). The available evidence is limited and the internal validity of these trials is questionable. Given the high losses to follow up, these reports may even be considered observational. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. The choice of progestin may be more important than the phasic regimen in determining bleeding patterns.

Biphasic versus triphasic oral contraceptives for contraception.

Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. A suggested disadvantage of biphasic oral contraceptive pills as compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage. To compare biphasic oral contraceptives with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. We searched computerized databases MEDLINE, EMBASE, POPLINE and the Cochrane Controlled Trial Register. Additionally we searched the reference lists of potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the U.S. We included randomized controlled trial comparing any biphasic oral contraceptive with any triphasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplemental information about the study methods and outcomes. We entered the data in RevMan 3.1 and later imported them into RevMan 4.1. We calculated Peto odds ratios for incidence of incidence of discontinuation due to medical reasons, intermenstrual bleeding, absence of withdrawal bleeding, and discontinuation due to intermenstrual bleeding. Only two trials of limited quality met our inclusion criteria. Larranaga (1978) compared two biphasic and one triphasic pills, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. Percival Smith (1990) compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic pill. The odds ratio of cycles with intermenstrual bleeding was 1.7 (95%CI 1.3-2.2) for the biphasic pill compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95%CI 3.1-13). In contrast, cycle control with the biphasic pill was comparable to that with the triphasic pill containing the same progestin (norethindrone). The available evidence is limited and of poor quality; the internal validity of these trials is questionable. Given the high losses to follow-up after randomization, these reports may be better considered observational in nature. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. This suggests that the choice of progestin may be more important that the phasic regimen in determining bleeding patterns.

The effects of monophasic and triphasic oral contraceptives on ovarian function and endometrial thickness

Objective To analyze and compare the effects of seven low-dose oral contraceptives (OCs) on ovarian function and endometrial thickness.Methods Cross-sectional study of users of one of five monophasic OCs, one of two triphasic OCs and a control group of non-users. Ovarian function, endometrial thickness and serum hormone levels were monitored during days 10–12 and 16–18 of the cycle.Results Serum estradiol was suppressed in OC users to a greater degree during days 16–18 than during days 10–12, whereas serum progesterone during days 16–18 was in the anovulatory range with each preparation. Ovarian activity as measured by follicular size was lowest with desogestrel-containing OCs, whereas greater activity was seen with triphasic levonorgestrel/ ethinylestradiol and triphasic norgestimate/ethinylestradiol. Endometrial thickness in OC users was significantly smaller than in controls.Conclusions All preparations demonstrated profound suppression of ovarian activity and effectively prevented ovulation. Ovarian suppression with desogestrel/ethinylestradiol 150/ 20 did not differ from that of other OCs despite its lower ethinylestradiol content. The use of both triphasic OCs, having a relatively low progestogenic activity, was associated with a higher ovarian activity than that of the monophasic OCs.

The role of triphasic levonorgestrel in oral contraception: a review of metabolic and hemostatic effects.

Epidemiological studies suggesting a possible association between the use of combined oral contraceptives and an increased risk of cardiovascular disease have led to extensive investigations into the effect of oral contraceptives on lipid and carbohydrate metabolism, and on hemostasis. Since this association was originally suggested, the steroid dose in oral contraceptives has been significantly reduced and new progestogens have been developed. Also, triphasic formulations have been introduced which offer a well-balanced estrogen/progestogen ratio, allowing a further reduction in the progestogen dose per cycle, and thus helping to minimize unwanted metabolic and hemostatic effects. The metabolic interactions of triphasic levonorgestrel, the first triphasic formulation to be introduced, have received particular attention. Lipid metabolism appears to be largely unaffected by triphasic levonorgestrel, most studies reporting no significant change in high- (HDL-C) or low-density lipoprotein-cholesterol (LDL-C) levels. Several studies have reported a decrease in the lipoprotein subfraction HDL2-C levels, but in most cases measurements of the LDL-C/HDL-C and apolipoprotein A-1/B ratios reveal no clinically significant effects. Concerning lipids, most studies suggest that triphasic levonorgestrel has less metabolic impact than the monophasic formulation. In common with all currently available oral contraceptives, triphasic levonorgestrel appears to have some effect on carbohydrate metabolism. The study results vary, however; some investigators have found an impairment of glucose tolerance, whereas others have not detected any significant effect. Compared with lipid and carbohydrate metabolism, fewer studies have investigated the effect of triphasic levonorgestrel on hemostasis. In common with all estrogen-containing oral contraceptives, levonorgestrel appears to stimulate some procoagulant activity, elevating the levels of factors VII and X, and fibrinogen. However, the effect of triphasic levonorgestrel appears to be balanced, with most studies reporting a corresponding increase in anti-coagulant-fibrinolytic activity. Although most of the studies reviewed here reported some statistically significant metabolic interactions, many authors comment that the changes are probably not clinically relevant in terms of an altered risk of cardiovascular disease. The true risk of vascular disease associated with modern low-dose oral contraceptives remains to be confirmed when sufficient epidemiological data eventually become available.

Interaction of oral contraceptive use with the effects of age, exercise habits and other cardiovascular risk modifiers on metabolic risk markers

An analysis was undertaken to determine whether combined oral contraceptive (OC) use interacts with the effects of potential cardiovascular risk modifiers (age, body mass index, cigarette smoking, alcohol intake, exercise habit, family histories of heart disease or diabetes, number of pregnancies and duration of OC use) on blood pressure and lipid, lipoprotein, glucose and insulin risk markers for cardiovascular disease. Relationships between risk modifiers and risk markers were compared between non-users (n = 418) and users of low-estrogen dose OC (n = 925, categorised according to progestin content as monophasic levonorgestrel, triphasic levonorgestrel, norethindrone or desogestrel). OC use diminished the adverse effects of age on glucose tolerance. Aerobic exercise had a particularly beneficial effect on triglyceride levels and OGTT insulin response in OC users. The rise in HDL and HDL 2 cholesterol concentrations with alcohol intake seen in non-users was diminished in OC users. Increasing duration of use of a desogestrel combination was associated with increasing HDL cholesterol concentrations. No adverse effects of risk modifiers on metabolic risk markers and blood pressure were augmented by OC use, and some were even diminished.

Ovarian activity suppression by two different low-dose triphasic oral contraceptives

In an open, randomized study in an outpatient clinic of a large teaching hospital, thirty-one female volunteers with regular cycles and established ovulation by ultrasonography were given one of two triphasic oral contraceptives containing ethinylestradiol combined with levonorgestrel or desogestrel during six cycles of treatment. The main outcome measures were transvaginal ultrasonography and serum E 2 and P measurements in pill cycles 1, 3 and 6. No ovarian activity was found in 10 subjects. Among the remaining 21 women who showed ovarian activity, most follicle-like structures developed in the pill-free week and decreased in size or disappeared in the first pill week. One women taking triphasic desogestrel had evidence of a luteinized unruptured follicle and one women taking triphasic levonorgestrel had a possible ovulation. The latter women also showed symptoms of lower abdominal pain. A statistically significant difference in ovarian activity between the two oral contraceptives could not be established. The two triphasic oral contraceptives suppressed ovarian activity to the same degree. A trend was seen towards increasing ovarian activity with duration of use in both treatment groups.

Relationships between blood pressure, oral contraceptive use and metabolic risk markers for cardiovascular disease

Data from a previous study, designed to compare metabolic risk markers for cardiovascular disease in non-users and oral contraceptive (OC) users, were analysed to evaluate the influence of OC composition on blood pressure. Healthy, female volunteers (1189 women) either not using OC (non-users) or currently using one of six different combined formulations (users) were compared. Combinations studied contained 30–40 μg ethinyl estradiol combined with the progestins levonorgestrel, norethindrone (at two and three different doses, respectively) or desogestrel. After statistical standardisation to account for the significantly greater age of the non-users and longer duration of OC use amongst the levonorgestrel combination users, mean blood pressure was higher, compared with non-users, in users of monophasic or triphasic levonorgestrel combinations (systolic: +4.3 mmHg (p < 0.001) and +2.7 mmHg (p < 0.001), respectively; diastolic: +2.6 mmHg (p < 0.001) and +2.3 mmHg (p < 0.05), respectively). Blood pressures in users of monophasic norethindrone and desogestrel combinations were not significantly raised and there was no increase in the proportion of women with abnormal values. Diastolic and systolic blood pressures were positively associated with oral glucose tolerance test insulin response (r = 0.11 (p < 0.01) and r = 0.15 (p < 0.001), respectively) in users but not in non-users. Currently used OC containing norethindrone or desogestrel progestins have little impact on blood pressure. Their correlated reduction in impact on insulin concentrations, though small, suggests common mechanisms through which OC affect blood pressure and insulin.

Gestodene

The newer progestogens gestodene, desogestrel and norgestimate were developed in an attempt to produce agents with more selective progestational activity that would improve cycle control and minimise metabolic changes and adverse events while effectively preventing pregnancy. In clinical practice, gestodene is combined with ethinylestradiol in monophasic or triphasic combined oral contraceptive preparations. The drug has pharmacokinetic advantages over the other new progestogens in that it is active per se (the others are prodrugs) and has high bioavailability (approximately 100%). The ability of gestodene-containing oral contraceptives to inhibit ovulation is similar to that of preparations containing other progestogens although the required dosage is lower. In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism. The effects of gestodene preparations on coagulation parameters, like those of desogestrel and levonorgestrel, are balanced by changes in the fibrinolytic system. Although the impact of these changes on clinical cardiovascular end-points has not been determined, the altered lipid profile is not likely to have significant clinical relevance because of the predominantly thrombogenic nature of cardiovascular disease in oral contraceptive users. Pregnancy rates and Pearl Indices with gestodene-containing preparations are low and similar to those with preparations containing other progestogens. Most pregnancies are attributable to user failure. Cycle control appears to be better with gestodene preparations than with levonorgestrel preparations, and available data suggest that cycle control may also be better with monophasic gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate-containing preparations, and better with triphasic gestodene- than with triphasic levonorgestrel- or norgestimate-containing preparations. However, differences between the new progestogen-containing preparations need to be confirmed in further large-scale trials. The most common adverse events with gestodene/ethinylestradiol are headaches and breast tension; the incidence of short term adverse events, including acne, is similar to that with preparations containing other progestogens. Changes in blood pressure and bodyweight are negligible. There are no comparative data on the incidence of cardiovascular events with gestodene-containing and other combined preparations. While the risk of breast cancer appears to be increased with long term combined oral contraceptive use in certain patient subgroups, this risk needs to be balanced against the noncontraceptive benefits of these preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Triphasic levonorgestrel

The triphasic levonorgestrel oral contraceptive preparation was introduced in the late 1970s and today it is available in more than 90 countries. The substantial volume of clinical experience now available has established that not only is this preparation clinically effective but that it also provides excellent cycle control. In this paper, results of efficacy, cycle control and patient acceptability/compliance are reviewed, drawing together the considerable clinical experience that now exists.All studies confirm the contraceptive reliability of triphasic levonorgestrel and report good patient compliance. Good patient compliance is, in part, due to the low incidence of breakthrough bleeding and spotting (intermenstrual bleeding) as well as the low incidence of failure of withdrawal menses (amenorrhea) that is achieved with this oral contraceptive, even in the first few cycles. The side-effect profile of triphasic levonorgestrel is also good and most studies report it to be well tolerated. When compared both with monophasic and other triphasic preparations, several studies show that triphasic levonorgestrel is associated with better cycle control. A further non-contraceptive benefit of triphasic levonorgestrel is reported in patients with acne vulgaris, which has been shown to improve in the majority of patients treated.

Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

Three low-dose oral contraceptives Trinordiol ®, Gynatrol ®, and Marvelon ®, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DSG), respectively, were given to 65 healthy women, n = 21–22 in each group. Blood levels of antithrombin III (AT III), α 2-macroglobulin ( α 2M) α1-antitrypsin ( α 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during the first and third treatment cycles. AT III levels decreased and α 1at levels increased in all three groups during treatment. α 2M increased during cycle 3 in the Trinordiol and Gynatrol groups. CBG, PZP and SHBG levels increased in all 3 groups, the CBG and PZP increase being higher in the Marvelon group than in the Gynatrol group. Increases in SHBG levels were found in the order Marvelon > Trinordiol > Gynatrol. Plasma levels of complement factors B, C3 and C4 remained unchanged. It is concluded that the increase in α 1at partly compensates for the fall in AT III, that the rise in PZP presumably enhances fibrinolysis, and that LNg has higher anti-estrogenicity and androgenicity than DSG.

Oral contraceptives in premenstrual syndrome: A randomized comparison of triphasic and monophasic preparations

Thirty-seven women with cyclical mood changes, either only in the premenstrual phase (‘pure PMS’) or during the entire cycle with premenstrual aggravation (‘PMA’), were recruited to participate in a randomized study investigating the effect of three different oral contraceptives (OCs) on mood symptoms; 32 out of the 37 women completed the study. The monophasic ethinylestradiol (EE)/desogestrel (DSG) OC was compared, in a single (doctor)-blind cross-over design, with a monophasic and a triphasic levonorgestrel (LNG)-containing combined OC. The women kept a record of their symptoms and complaints by noting daily ratings using a validated visual analogue scale. One pretreatment cycle was followed by four treatment cycles, two cycles on each OC. All OCs had a beneficial effect on the PMS symptoms compared to the pre-treatment period. There were no changes between consecutive cycles. Cyclical symptom changes were noted during all OC treatment. The monophasic desogestrel pill provoked less changes in mood parameters than the monophasic and triphasic levonorgestrel OCs. However, physical complaints were less frequently reported during the use of the triphasic preparation as compared to the monophasic desogestrel preparation. Women with ‘pure’ PMS (premenstrual syndrome) were more consistent in their reactions on OCs compared to women with PMA.

Pharmacokinetics of Levonorgestrel in 18 Women after 1 Month of Treatment with a Triphasic Oral Contraceptive

A triphasic levonorgestrel (LNG)- and ethinylestradiol-containing oral contraceptive was administered to 18 women. Plasma samples were obtained throughout a treatment cycle just before drug administration and on the last treatment day (day 21), several plasma samples were collected from each individual up to 48 h postadministration. LNG was determined by radioimmunoassay in all plasma samples. In addition, the concentration of sex-hormone-binding globulin (SHBG) was determined in plasma samples collected from the same subjects during treatment, as well as during a pre- and a posttreatment cycle. During the treatment cycle, plasma levels of LNG determined just before drug administration increased and reached steady state at about day 16. This increase was due to an increased dose of LNG according to the triphasic dose regimen, a concomitantly ethinylestradiol-induced increase in SHBG and due to pharmacokinetic accumulation, since LNG had a terminal half-life of approximately 28.5 h and the dosing interval was 24 h. Steady-state levels and pharmacokinetic parameters of LNG determined on the last day of treatment were in good accordance with previously published results.

Effects of three combined oral contraceptive preparations containing desogestrel plus ethinyI estradiol on lipid metabolism in comparison with two levonorgestrel preparations

The effects of three different desogestrel-containing combined oral contraceptive preparations on lipid metabolism were compared with those of two levonorgestrel preparations. The following preparations were studied: (1) monophasic desogestrel (150/30), (2) monophasic desogestrel (150/20, containing 20 fLg of ethinyl estradiol instead of 30 fLg of ethinyl estradiol, (3) biphasic desogestrel, (4) monophasic levonorgestrel (150/30), and (5) triphasic levonorgestrel. The effects of these preparations were assessed on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein B, the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol, and the ratio of apolipoprotein A-I to apolipoprotein B after 3 months of treatment, and the percentage changes with regard to pretreatment were calculated. The monophasic desogestrel (150/30) and biphasic desogestrel preparations induced higher high-density lipoprotein cholesterol and apolipoprotein A-I levels than did their levonorgestrel-containing counterparts. Low-density lipoprotein cholesterol levels were increased in monophasic levonorgestrel and clearly decreased in the lowest ethinyl estradiol-containing monophasic desogestrel (150/20) and biphasic desogestrel preparations. Apolipoprotein B increased in all preparations. The antiatherogenic indexes (ratios of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol and apolipoprotein A-I to apolipoprotein B were higher for monophasic desogestrel (150/30) and biphasic desogestrel than for comparable levonorgestrel-containing preparations. The differences seen between the desogestrel and levonorgestrel preparations can best be explained by the lower intrinsic androgenicity of 3-keto-desogestrel (active metabolite of desogestrel) than that of levonorgestrel. (Am J Obstet Gynecol 1990;163:370-373.)

Effects of seven low-dose combined contraceptives on vitamin B 6 status

The effect of seven low-dose oral contraceptive preparations on vitamin B 6 status was investigated in 55 women. All preparations contained about the same amount of ethinylestradiol but differed in the content and type of progestagen. The following preparations were investigated: monophasic and triphasic levonorgestrel, monophasic and biphasic desogestrel, monophasic norethisterone, monophasic cyproterone acetate and triphasic gestodene. The vitamin B 6 status was evaluated by measuring erythrocyte glutamate oxaloacetate transaminase (EGOT) activity and its degree of in vitro stimulation. From these two variables the total EGOT activity was calculated. In addition plasma pyridoxal-5′-phosphate (PLP) levels were estimated. After six months' treatment, EGOT activity and the calculated total EGOT activity were increased, but no changes were observed in the degree of in vitro stimulation (which is a more reliable parameter). Plasma PLP levels initially decreased during the first three months of treatment but after six months a return to normal levels was observed. Differences between the seven preparations were not found. We conclude from these results that the low-dose preparations investigated in this study have no any adverse effects on vitamin B 6 status.

Clinical aspects of three new progestogens: Desogestrel, gestodene, and norgestimate

Three new 19-nortestosterone progestogens, which are chemically related to levonorgestrel, are now clinically available in combination oral contraceptives in Europe. Desogestrel and norgestimate must be transformed to metabolites for all or part of their biologic activity; gestodene is active in its original form. Compared with present low-dose monophasic and triphasic levonorgestrel formulations, the new combinations appear to be equivalent in efficacy and type and frequency of side effects. Cycle control may be slightly improved with the gestodene preparation and somewhat poorer with the desogestrel regimen. As with the present triphasics, most changes reported in toagulation indexes for the new combinations remained within normal limits, as did changes in carbohydrate and lipid metabolism. There is no present evidence that either the norgestimate or oesogestrel formulation provides a clinical improvement over the levonorgestrel triphasic. In the gestodene combination, the progestogen's increased biologic activity allows further reduction of total steroid dose.

Effects of seven low dose combined oral contraceptives on high density lipoprotein subfractions.

The effects on lipid metabolism of seven combined oral contraceptives were investigated, particularly the effects on high density lipoprotein (HDL) subfractions, which were separated by density gradient ultracentrifugation. There were no differences between the preparations in the effects on the LDL fraction, the so-called atherogenic particle, but there were marked differences in the effects on the anti-atherogenic HDL fraction, of which the effects on HDL-2 were most pronounced. After treatment with monophasic cyproterone acetate and biphasic desogestrel, the cholesterol and phospholipid contents of the HDL-2 fraction were significantly higher than those found after treatment with the other preparations. The lowest values were found after treatment with monophasic levonorgestrel, whereas monophasic desogestrel, triphasic levonorgestrel, monophasic norethisterone and triphasic gestoden induced intermediate values for these variables. The levels of HDL-2 reflect the intrinsic androgenicity of the various progestogens used in the preparations.

Effects of the Oral Contraceptive Combination 0.150 mg Desogestrel + 0.020 mg Ethinylestradiol on Serum Lipids Including the HDL Subfractions

The effects of the low‐dose oral contraceptive combination 0.150 mg desogestrel plus 0.020 mg ethinylestradiol (EE) on lipid metabolism was investigated in two independent studies. In one study the effects of this preparation on lipid parameters in a group of 10 women were compared with those of a triphasic levonorgestrel plus EE preparation in a group of 13 women. In a second study the effects of 0.150 mg desogestrel plus 0.020 mg EE on the lipid composition of VLDL, LDL, HDL‐2 and HDL‐3 were investigated in a group of 10 volunteers. The assessments were made in blood samples taken before treatment, after 3 treatment cycles and one or two cycles after treatment was stopped. The desogestrel preparation induced an increase in triglycerides, phospholipids and apolipoprotein B. HDL‐cholesterol did not change, but the structural parts of the HDL particle, apolipoprotein A‐I and phospholipids, showed a marked increase in the group treated with the desogestrel preparation. In the comparative study there was no difference between the combination 0.150 mg desogest‐reI+0.020 mg EE and the triphasic levonorgestrel+EE preparation. The lipid compositions of VLDL, LDL, HDL‐2, HDL‐3 and VHDL did not change during treatment with the combination 0.150 mg desogestrel+0.020 mg EE. It can be concluded from this study that the combination 0.150 mg desogestrel+0.020 mg EE does not adversely affect lipid metabolism after 3 months of treatment.

Comparative effects of monophasic desogestrel plus ethinyloestradiol and triphasic levonorgestrel plus ethinyloestradiol on lipid metabolism

The effects of the monophasic oral contraceptive preparation desogestrel plus ethinyloestradiol (EE) and triphasic levonorgestrel plus EE on lipid metabolism were compared. Sixteen young healthy female volunteers received monophasic desogestrel plus EE ( 21 × 150 30 ), whereas eighteen women received triphasic levonorgestrel plus EE ( 6 × 50 30 + 5 × 75 40 + 10 × 125 30 ) for six consecutive cycles. The lipid composition of the various lipoprotein fractions was estimated after separation in a density gradient by ultracentrifugation. In addition, the apolipoproteins A-I and B were assessed. HDL-cholesterol (precipitation method), HDL-2 cholesterol, HDL-2 phospholipids and the ratio apolipoprotein A-I to apolipoprotein B were significantly higher in the monophasic desogestrel group than in the triphasic levonorgestrel group after three and six treatment cycles. HDL-cholesterol (gradient), HDL-phospholipids (gradient), HDL-3 phospholipids and apolipoprotein A-I were only significantly higher after six treatment cycles. No differences between the groups were observed for the other lipid variables studied including triglycerides and VLDL-triglycerides.

Two oral contraceptives, efficacy, serum proteins, and lipid metabolism: A comparative multicentre study on a triphasic and a fixed dose combination

A triphasic, combined oral contraceptive containing 30 — 40 — 30 μg ethinyloestradiol (EE), and 50 — 75 — 125 μg levonorgestrel was compared with a fixed dose combination containing 30 μg EE and 150 μg desogestrel in a randomized multicentre trial in 193/199 women and 1063/1073 cycles, respectively. The duration of the trial was six months. Eleven centres in Denmark, Sweden, and Norway participated. Contraceptive reliability, bleeding control and side effects were evaluated. Influence on serum sex hormone binding globulin (SHBG) and transcortin was assayed as well as lipid metabolism. Three pregnancies occurred in the group using the triphasic regimen but none in the fixed dose regimen. Two of the three pregnancies were considered drug failures and the third a possible interaction. Possible reasons for the triphasic contraceptive failure are discussed with special reference to a British report on eight pregnancies. Bleeding control appeared to be equally good for the two preparations. However, the number of cycles with spotting, breakthrough bleeding and missed withdrawal bleeding were above the levels reported earlier on the triphasic regimen. About 80 per cent of the women completed the planned six months on either combination. Side effects were generally mild and in accordance with earlier reports on low dose oral contraceptives. Metabolically the triphasic levonorgestrel combination increased SHBG 100 per cent versus 200 per cent for the fixed desogestrel combination. Transcortin rose about 98 and 110 per cent, respectively. Both preparations induced similar changes in the levels of lipids and lipoproteins with the exception of a significant increase in the arachidonic content of cholesterol during treatment with the desogestrel-containing preparation.