Bleeding by RegimenProgestin ActivityExtended Regiment BleedingWeight EfficacyProgestin Exposure
Perception: The 24/4 regimens improve the bleeding profile of low dose oral contraceptives (OC).

PROOF: Intracyclic bleeding data from Phase III and independent studies show no significant difference between 24/4 and 21/7 regimens.

Phase III studies of 24-day and 21-day drospirenone (DRSP)/ethinyl estradiol (EE) regimens showed comparable intracyclic bleeding results
  • When comparing the combined data from 2 Phase III studies of 3 mg drospirenone/20 mcg ethinyl estradiol in a 24-day regimen trial (N=1027) and a 21-day regimen trial (N=516), the percent of subjects experiencing intracyclic bleeding was similar for both regimens1
In 2 independent studies, Loestrin® Fe* demonstrated similar rates of intracyclic (unscheduled) bleeding compared to the 21-day regimen



*Loestrin® Fe 1/20.
Loestrin Fe (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets) is a registered trademark of Warner Chilcott.

    References:
  1. YAZ Summary of Approval [US Food and Drug Administration Web site]. Available at: http://www.fda.gov/cder/foi/nda/2006/021676s000MEDR_pt1.pdf. Accessed January 25, 2008.
  2. Nakajima ST, Archer DF, Ellman H. Efficacy and safety of a new 24-day oral contraceptive regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 µg (Loestrin® 24 Fe). Contraception. 2007;75:16-22.
  3. Rible RD, Taylor D, Wilson ML, Stanczyk FZ, Mishell DR Jr. In press. Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate. Contraception. 2009:1-7.
Perception: Total hormone exposure relates only to estrogen dose and regimen.

PROOF: Criteria for choosing an optimal OC may include prescribing an effective OC with the lowest progestin activity level and dose.1

  • In addition, triphasic design also helps to minimize overall exposure to progestin2
  • Selecting a triphasic OC containing a low-activity progestin and a lower overall progestin dose may therefore reduce undesirable side effects1
  • Progestin-related side effects include1:
      - acne/oily skin   - weight gain   - hirsutism
*Drospirenone also exhibits anti-mineralocorticoid activity, which may be associated with increased potassium levels.3 As such, product labeling recommends restricting use with certain patients or in combination with certain drugs.4 Drugs that may increase serum potassium when taken daily and for long-term chronic conditions include ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, heparin, aldosterone antagonists, and NSAIDs.
    References:
  1. Dickey RP. Managing Contraceptive Pill Patients. 12th ed. New Orleans, La: Emis Medical Publishers; 2004.
  2. Cedars MI. Triphasic oral contraceptives: review and comparison of various regimens. Fertil Steril. 2002;77:1-14.
  3. Yasmin – an oral contraceptive with a new progestin. Med Lett Drugs Ther. 2002;44:55-57.
  4. Yasmin® (drospirenone and ethinyl estradiol) [prescribing information]. Montville, NJ: Berlex, Inc.
Perception: Extended OC regimens offer a more favorable bleeding profile than cyclic regimens.

PROOF: Unscheduled bleeding occurs more often with extended-cycle regimens than with cyclic regimens.1,2

  • Numerous studies have demonstrated that patients on extended OC regimens may experience an increased rate of BTB/S vs those patients on conventional cyclic OC regimens1,2
  • In one study, patients on an extended-cycle OC had more than twice as many BTB/S days compared to patients on a cyclic regimen1
In a separate, noncomparative trial evaluating a continuous daily regimen of levonorgestrel/ethinyl estradiol, 21% of patients continued to experience BTB/S after 1 year of treatment3
  • The average number of BTB/S days was 10.8 in Cycle 13 of the study3
  • The overall discontinuation rate was 57%
*Results from a parallel, randomized, multicenter, open-label, 1-year study of the OC Seasonale® [30 mcg ethinyl estradiol (EE)/150 mcg levonorgestrel (LNG), and Nordette®-28 (30 mcg EE/150 mcg LNG)] in sexually active, adult women.
    References:
  1. Anderson FD, Hait H, the Seasonale-301 Study Group. A multicenter, randomized study of an extended cycle oral contraceptive. Contraception. 2003;68:89-96.
  2. Cachrimanidou A-C, Hellberg D, Nilsson S, Waldenström U, Olsson S-E, Sikström B. Long-interval treatment regimen with a desogestrel-containing oral contraceptive. Contraception. 1993;48:205-216.
  3. Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006;74:439-445.
Seasonale is a registered trademark of Duramed Pharmaceuticals, Inc.
Nordette is a registered trademark of Wyeth-Ayerst, Inc.
Perception: Low-dose OCs are less effective in women with higher body weight.

PROOF: Historically, clinical trials tended to enroll few overweight women.1 However, there is evidence of comparable contraceptive efficacy with a 25-mcg OC in women with increased body weight.
  • Research suggests that higher body weight (>155 lb) may compromise the efficacy of birth control pills2
  • Overall, assumptions about OC efficacy in heavier women cannot be made unless studies specifically include women >155 lb
25-mcg triphasic efficacy
  • A 25-mcg triphasic pill was studied in women >155 lb and is equally effective in heavier women (up to 240 lb)
    • There was no association found between pregnancy risk and body weight (n=1671)3
  • Retrospective analysis of this 25-mcg triphasic pill Phase 3 efficacy data showed no statistically significant difference in pregnancy risk among all weight groups3
  • Weight ranged from 90 to 240 lb3
    • Approximately 26% of patients weighed >155 lb (n=435)
  • Therefore, existing data offer no support to the hypothesis that the risk of pregnancy is related to body weight in women using a 25-mcg triphasic OC3,4
    References:
  1. Creinin MD. Oral contraceptive prescribing: should body weight influence choice of pill? Questions and answers with associate editor Mitchell D. Creinin, MD. Contracept Rep. 2004;14:11-15.
  2. Holt VL, Cushing-Haugen KL, Daling JR. Body weight and risk of oral contraceptive failure. Obstet Gynecol. 2002;99:820-827.
  3. Zhang HF, LaGuardia KD, Creanga DL. Higher body weight and BMI are not associated with reduced efficacy in Ortho Tri-Cyclen Lo users. Poster presented at: 54th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists; May 6-10, 2006; Wash DC.
  4. Vessey M, Painter R. Oral contraceptive failures and body weight: findings in a large cohort study. J Fam Plann Reprod Health Care. 2001;27:90-91.
Perception: Pills with phasic design are associated with hormonal fluctuation.

PROOF: Hormone doses in newer triphasics are associated with smaller dropoff or escalation than older formulations.1,2
  • Triphasics also provide less overall total progestin exposure than monophasics1,3
  • Week 2 is 100% increase from Week 1
  • Week 3 is 50% dropoff from Week 2
  • Week 2 is 50% increase from Week 1
  • Week 3 is 33% increase from Week 2
  • Week 2 is 19% increase from Week 1
  • Week 3 is 16% increase from Week 2
*Charts are representative of percent change, but are not to actual size.
    References:
  1. Cedars MI. Triphasic oral contraceptives: review and comparison of various regimens. Fertil Steril. 2002;77:1-14.
  2. Corson SL. Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate. Am J Obstet Gynecol. 1994;170:1556-1561.
  3. Letterie GS. Reproductive health issues: contemporary contraceptive practices in clinical care. In: Lemcke DP, Marshall LA, Pattison J, Cowley DS, eds. Current Care of Women: Diagnosis & Treatment. New York, NY: Lange Medical Books/McGraw-Hill; 2004:547-562.