Oral contraceptives and breakthrough bleeding: What patients need to know

,

Applied Evidence

Oral contraceptives and breakthrough bleeding: What patients need to know

J Fam Pract. 2006 October;55(10):872-880

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References

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Type of progestin may affect breakthrough bleeding. All combination OCs contain either EE or mestranol. However, a variety of progestins have come into use. The 2 most common contraceptive progestins are derived from 19-nortestosterone, and are classified as gonanes or estranes ( TABLE 2 ).²²

Estranes include norethindrone and its derivatives, norethindrone acetate and ethinyodiol diacetate. Gonanes include levonorgestrel, norgestrel, desogestrel, gestodene, and norgestimate.

Each progestin differs in half-life, estrogenic, progestogenic, and androgenic properties, and these variations may explain differing rates of breakthrough bleeding among formulations.⁴ As shown by Endrikat et al,¹² pills with the same quantity of EE but different progestins can have marked differences in breakthrough bleeding rates.

FAST TRACK

Though women may experience more breakthrough bleeding on extended-cycle regimens, the number of planned and unplanned bleeding days may still decrease

Although gonanes have greater progestational activity, no trial has determined which progestin has the best bleeding profile. A recent Cochrane review comparing different progestins did find that, compared with pills containing levonorgestrel, those containing gestodene may be associated with less intermenstrual bleeding.²³

Regardless of the progestin used or the quantity of EE, breakthrough bleeding generally decreases with each successive cycle. One study that compared 2 combination OCs composed of EE/norgestimate and EE/norgestrel demonstrated bleeding rates of 11.3% and 10.6% during the first 6 cycles, that decreased to 5.1% and 6.3% in Cycles 13 to 24, respectively.²⁴ Additionally, all women using OCs can experience some cycles without a withdrawal bleed—a menstrual abnormality that may be concerning to those who desire a menstrual period as confirmation that they are not pregnant.

Comparing regimens. OC regimens are available as biphasic, triphasic, extended-cycle, and continuous use. Women using extended-cycle contraceptives may experience more breakthrough bleeding than those using a standard 28-day pill. However, in a 3-month cycle, there are only 7 days of planned bleeding. This is in contrast to 28-day cycles during 3 months in which there are 21 days of planned bleeding.

Though women on extended-cycle regimens may initially experience more breakthrough bleeding than women using 28-day regimens, the total number of planned and unplanned bleeding days may still decrease. Women using a 3-month cycle OC (30 μg EE/150 μg levonorgestrel) experienced more unscheduled bleeding than women using a standard 28-day cycle OC of the same formulation and dose.²⁶ The number of bleeding days decreased with each cycle. Another study examined continuous OC use (20 μg EE/100 μg levonorgestrel) over a period of 1 year, and reported a decreasing number of bleeding days over time.²⁷ In the case of continuous use, all bleeding is unscheduled, and any bleeding is considered breakthrough bleeding.

Multiphasic OC regimens were developed with the intention of decreasing breakthrough bleeding by mimicking the rising and falling pattern of estrogen and progesterone in the normal menstrual cycle.²⁸ After the introduction of the biphasic pill, an increase in breakthrough bleeding was noted, which led to the development of the triphasic pill.²⁹ Though the multiphasic hypothesis is physiologically plausible, recent reviews of the literature have found the evidence for its efficacy too limited and methodologically flawed to draw any definitive conclusions about a decrease in breakthrough bleeding.^30,31

TABLE 1
Available OCs by formulation and regimen

TRADE NAME	GENERIC NAME(S)	TROGEN (DOSE)	PROGESTIN (DOSE)
MONOPHASIC
Alesse, Levlite	Aviane, Lessina	Ethinyl estradiol (20 μg)	Levonorgestrel (0.1 mg)
Mircette	Kariva	Ethinyl estradiol (20 μg×21 days +10 μg×5 days during placebo week)	Desogestrel (0.15 mg)
Loestrin FE	Microgestin FE 1/20, June FE 1/20	Ethinyl estradiol (20 μg)	Norethindrone acetate (1 mg)
Yaz		Ethinyl estradiol (20 μg)	Drospirenone (3 mg)
Levlen, Nordette	Levora, Portia	Ethinyl estradiol (30 μg)	Levonorgestrel (0.15 mg)
Lo/Ovral	Low-ogestrel, Cryselle	Ethinyl estradiol (30 μg)	Norgestrel (0.3 mg)
Desogen, Ortho-cept	Apri	Ethinyl estradiol (30 μg)	Desogestrel (0.15 mg)
Loestrin 211/5/30	Microgestin, Junel Fe	Ethinyl estradiol (30 μg)	Norethindrone acetate (1.5 mg)
Yasmin		Ethinyl estradiol (30 μg)	Drospirenone (3 mg)
Ovcon 35		Ethinyl estradiol (35 μg)	Norethindrone (0.4 mg)
Ortho-Cyclen	Mononesessa, Sprintec	Ethinyl estradiol (35 μg)	Norgestimate (0.25 mg)
Brevicon, Modicon	Nortrel, Necon 0.5/35	Ethinyl estradiol (35 μg)	Norethindrone (0.5 mg)
Demulen 1/35	Zovia 1/35	Ethinyl estradiol (35 μg)	Ethynodiol diacetate (1 mg)
Ortho-Novum 1/35, Norinyl 1+35	Necon 1/35, Nortrel	Ethinyl estradiol (35 μg)	Norethindrone (1 mg)
Ortho-Novum 1/50	Necon 1/50	Ethinyl estradiol (50 μg)	Norethindrone (1 mg)
Ovral	Ogestrel	Ethinyl estradiol (50 μg)	Norgestrel (0.5 mg)
Ovcon 50		Ethinyl estradiol (50 μg)	Norethindrone (1 mg)
Demulen 1/50	Zovia 1/50	Ethinyl estradiol (50 μg)	Ethynodiol diacetate (1 mg)
Norinyl 1/50		Mestranol (50 μg)	Norethindrone (1 mg)
BIPHASIC
Ortho-Novum 10/11, Jenest	Necon 10/11, Nelova 10/11	Ethinyl estradiol (35 μg)	Norethindrone (0.5 mg×10 days, 1 mg×11 days)
TRIPHASIC
Ortho Tri-Cyclen Lo		Ethinyl estradiol (25 μg)	Norgestimate (0.18 mg×7 days, 0.215 mg×7 days, 0.25 mg×7 days)
Cyclessa	Velivet	Ethinyl estradiol (25 μg)	Desogestrel (0.1 mg×7 days, 0.125×7 days, 0.15 mg×7 days)
T riphasil, Tri-Levlen	Trivora, Enpresse	Ethinyl estradiol (30 μg×6 days, 40 μg×5 days, 30 μg×10 days)	Levonorgestrel (0.05 mg×6 days, 0.075 mg×5 days, 0.125 mg×10 days)
Tri-Norinyl		Ethinyl estradiol (35 μg)	Norethindrone (0.5 mg×7 days, 1 mg×9 days, 0.5 mg×5 days)
Ortho Tri-Cyclen	Tri-Sprintec, Trinessa *	Ethinyl estradiol (35 μg)	Norgestimate (0.18 mg×7 days, 0.215 mg×7 days, 0.25 mg×7 days)
Ortho-Novum 7/7/7	Nortrel 7/7/7, Necon 7/7/7	Ethinyl estradiol (35 μg)	Norethindrone (0.5 mg×7 days, 0.75 mg×7 days, 1 mg×7 days)
Estrostep FE		Ethinyl estradiol (20 μg×5 days, 30 μg×7 days, 35 μg×9 days)	Norethindrone acetate (1 mg)
EXTENDED CYCLE
Seasonale		Ethinyl estradiol (30 μg×84 days followed by 7 placebo pills)	Levonorgestrel (0.15 mg)
Seasonique		Ethinyl estradiol (30 μg×84 days followed by 10 μg×7 days)	Levonorgestrel (0.15 mg)