Biphasic Oral Contraceptives Research Articles

Biphasic versus monophasic oral contraceptives for contraception

Side effects caused by oral contraceptives discourage compliance with, and continuation of, oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. To compare biphasic with monophasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. Our a priori hypotheses were: (a) biphasic oral contraceptives are less effective than monophasic oral contraceptives in preventing pregnancy; (b) biphasic oral contraceptives cause more side effects, give poorer cycle control, and have lower continuation rates. We searched the computerized databases MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. In addition, we searched the reference lists of all potentially 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 monophasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the various literature searches for possible inclusion and assessed their methodology using Cochrane guidelines. We contacted the authors of all included studies and possibly randomized studies for supplemental information about methodology and outcome. We entered the data into RevMan, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding, and study discontinuation due to intermenstrual bleeding. Only one trial of limited quality compared a biphasic and monophasic preparation. Percival-Smith 1990 examined 533 user cycles of a biphasic pill (500 microg norethindrone/35 microg ethinyl estradiol for 10 days, followed by 1000 microg norethindrone/35 microg ethinyl estradiol for 11 days; Ortho 10/11) and 481 user cycles of a monophasic contraceptive pill (1500 microg norethindrone acetate/30 microg ethinyl estradiol daily; Loestrin). The study found no significant differences in intermenstrual bleeding, amenorrhea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial, and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Effects of two different oral contraceptives on homocysteine metabolism in women with polycystic ovary syndrome

Purpose This study was conducted to evaluate the effects of two different oral contraceptives (OCs) on homocysteine (Hcy) metabolism in 20 women with polycystic ovary syndrome (PCOS). Methods Women were randomly allocated to receive either the biphasic OC containing 40/30 μg ethynylestradiol (EE)+25/125 μg desogestrel (DSG; n=10) or the monophasic OC containing 35 μg EE and 2 mg cyproterone acetate (CPA; n=10). Investigations were performed before and after 6 months of treatment. Fasting vitamin B 12, folate, Hcy and insulin sensitivity (SI), and glucose utilization independent of insulin (Sg), by the minimal model method, were evaluated. Results Folate and vitamin B 12 were not significantly modified by either OC. EE/DSG decreased SI (2.53±0.35 vs . 1.68±0.45; p<.05), without modifying Hcy (9.54±0.7 μmol/L vs. 9.18±0.6 μmol/L). EE/CPA improved SI (1.47±0.38 vs . 3.27±0.48; p<.04) and decreased Hcy (9.8±1.9 μmol/L vs. 7.9±0.9 μmol/L; p<.05). This study indicates that in women with PCOS, EE/CPA, but not EE/DSG, improves IS and decreases fasting Hcy.

Biphasic versus monophasic oral contraceptives for contraception: a Cochrane review.

Side-effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. We compared biphasic oral contraceptives with monophasic oral contraceptives in terms of efficacy, cycle control and discontinuation due to side-effects. Our a priori hypotheses were: (i) biphasic oral contraceptives are less effective in preventing pregnancy than monophasic oral contraceptives, and (ii) biphasic oral contraceptives cause more side-effects, give poorer cycle control and have lower continuation rates. We searched computerized databases Medline, Embase, Popline and the Cochrane Controlled Trial Register. Additionally, we searched the reference lists of all potentially 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 oral contraceptive with any monophasic 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 supplementary information about the study methods and outcomes. We entered the data in RevMan 3.1, imported the data into RevMan 4.1, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding and study discontinuation due to intermenstrual bleeding. Only one trial of limited quality compared a biphasic and monophasic preparation. This trial examined 533 user cycles of a biphasic pill (norethindrone 500 microg/ethinyl estradiol 35 microg for 10 days, followed by norethindrone 1000 microg/ethinyl estradiol 35 microg for 11 days) and 481 user cycles of a monophasic contraceptive pill (norethindrone acetate 1500 microg/ethinyl estradiol 30 microg daily). The study found no significant differences in intermenstrual bleeding, amenorrhoea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Efficacy on hyperandrogenism and safety of a new oral contraceptive biphasic formulation containing desogestrel

A new biphasic oral contraceptive (OC) containing ethinylestradiol and desogestrel (DGS) in both phases of the cycle (7 days 40 25 μg + 15 days 30 125 μg) was tested for its reliability, tolerability, safety and effectiveness on endocrine correlates of hyperandrogenism and acne in normal women ( n = 30) and women suffering from acne ( n = 33). Contraceptive efficacy was absolute and, despite 3 drop-outs in the group with acne (4.7% of total patients), subjective complaints were limited to a small number of women. Cycle control was satisfactory in both groups. Fibrinopeptide A remained stable under the treatment, whereas HDL-chol increased and the ratio between LDL-chol and HDL-chol decreased during pill intake. Other advantageous effects were obtained on the circulating androgen profile with increased sex hormone binding globulin concentrations coupled with significantly reduced total and free testosterone levels. In 23 out of 30 patients with acne (76.6%) the skin disease disappeared after 9 months of therapy and in 3 severely affected subjects the pathology changed into a pattern of mild or moderate degree. Our results indicate that the tested new biphasic OC combination is reliable, well tolerated, safe and effective against hyperandrogenism.

Serum concentrations of ethinylestradiol, 3-keto-desogestrel, SHBG, CBG and gonadotropins during treatment with a biphasic oral contraceptive containing desogestrel.

During a cross-over study, the pharmacokinetics of ethinylestradiol (EE) and 3-keto-desogestrel (KDG) were investigated on days 7 and 22 of one cycle of treatment with two biphasic formulations containing 50 micrograms EE (7 tablets) and 50 micrograms EE + 125 micrograms desogestrel (DG) (15 tablets) (50/50 EE) or 40 micrograms EE + 25 micrograms DG (7 tablets) and 30 micrograms EE + 125 micrograms DG (15 tablets) (40/30 EE). Peak serum levels and areas under the curve of EE increased significantly by 50% between days 7 and 22 of those taking 50/50 EE, while during treatment with 40/30 EE, no difference was found between days 7 and 22. Both formulations caused identical KDG levels on day 22. There were only slight differences in the effects of both preparations on sex-hormone-binding globulin (SHBG; +150 to +160%) and on corticosteroid-binding globulin (CBG; +130 to +150%) on day 7. On day 22, the changes were more pronounced with 50/50 EE (SHBG, +310%; CBG, +240%) than with 40/30 EE (SHBG, +250%; CBG, +180%). On day 22 after discontinuation of treatment, the SHBG and CBG levels were still significantly above the control values. Using both formulations, LH and FSH levels were significantly suppressed on day 22, while on day 7 no significant reduction was observed. The rise in the EE levels between days 7 and 22 of 50/50 EE intake and the time course of the EE concentrations during treatment with 40/30 EE appear to be due to an inhibition of hepatic metabolism by the contraceptive steroids, as EE is nearly exclusively bound to albumin which does not change.

Biphasic oral contraceptives.

This article briefly summarizes the action and uses administration contraindications and nursing implications of biphasic oral contraceptives (OCs). Biphasic contraceptives which provide an appropriate hormonal balance for both the follicular and luteal phases of the menstrual cycle permit the use of low doses of estrogen and progestogen while minimizing the incidence of breakthrough bleeding. The contraceptives are available in both a 21-tablet and a 28-tablet regimen (containing 7 tablets of inert ingredients). Absolute contraindications to combined OCs include thromboembolic disorder cerebrovascular accident coronary artery disease impaired liver function hepatic adenoma malignancy of the breast or reproductive system and pregnancy. Some relatively strong contraindicated include severe headaches hyertension diabetes prediabetes gallbladder disease previous cholestasis during pregnancy acute mononucleosis sickle-cell disease undiagnosed abnormal vaginal bleeding long leg casts elective surgery planned within 4 weeks over 40 years of age heavy smokers over 25 years of age or impaired liver function during the previous year. Nurses should advise women who use biphasic OCs that some spotting and missed menstrual periods can be expected. A wait-and-see approach with adequate supervision is recommended. Women should also be advised about the warning signs that may indicate discontinuation of the preparation: severe abdominal pain severe chest pain eye problems and severe leg pain in either the calf or thigh.

Hormonal contraception, tryptophan metabolism and depression

The effects of mono- and biphasic oral contraceptives on the metabol ism of L-tryptophan (2g) were studied in 11 women at midcycle. In 4 women the tryptophan load was continued for 15 cycles with a daily Vitamin-B6 supplement. 9 untreated women served as controls. Urinary excretion of xanthuric acid was much greater at 12 hours in treated than in untreated women. During daily treatment with Vitamin-B6 however xanthuric acid excretion was reduced to normal levels. Urinary Kynuric acid levels were also slightly higher in treated women but the difference was not significant. These metabolic changes are related to a secondary reduction in cerebral serotonin levels which may provide an explanation of the depressions sometimes observed during hormonal contraception.